Hyperbaric oxygen therapy (HBOT) may have a role in treating calciphylaxis, with benefits in both mortality and wound healing, report Daniela Kroshinsky, MD, MPH, of the department of dermatology at Massachusetts General Hospital, Boston, and colleagues.

Although intravenous sodium thiosulfate (IV STS) is considered standard care in the treatment of calciphylaxis, HBOT has been reported to have beneficial effects, they noted.

In their study, the researchers retrospectively reviewed records of 93 patients newly diagnosed with calciphylaxis, seen at Massachusetts General Hospital, between January 2006 and December 2021. They compared mortality and wound healing outcomes for 57 patients treated with IV STS only (control group) with those of 36 patients treated with HBOT plus IV STS (treatment group). Traditional survival analyses and Cox proportional hazard modeling were used to examine mortality data, and mixed effects modeling was used to analyze longitudinal wound outcomes. The study was published in the Journal of the American Academy of Dermatology.

Univariate survival analyses showed that HBOT plus IV STS was associated with significantly longer survival time than IV STS alone (P = .016), particularly for those with nonnephrogenic calciphylaxis (P < .0001), they report. An increased number of HBOT sessions conferred improved mortality outcomes, with 1, 5, 10, and 20 sessions yielding decreasing hazard ratios.

There was also a significant positive association between an increasing number of HBOT sessions and increased wound score (P = .042). Increases were seen with each session.

Anxiety/claustrophobia was the most common side effect reported among those in the HBOT group (22%).

“Given the proposed benefits and seemingly low side effect profile, it is the authors’ recommendation that HBOT be offered as an additional intervention to patients with calciphylaxis, especially if they have open wounds, to improve outcomes and expedite wound healing,” the researchers concluded.

Limitations, they noted, included the small sample size, retrospective design, and the potential for not adequately capturing patients who received external care. They were also unable to match patients by disease or wound severity. Large prospective trials would help clarify the role of HBOT for calciphylaxis, they added.

The researchers reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Hyperbaric oxygen therapy (HBOT) may have a role in treating calciphylaxis, with benefits in both mortality and wound healing, report Daniela Kroshinsky, MD, MPH, of the department of dermatology at Massachusetts General Hospital, Boston, and colleagues.

Although intravenous sodium thiosulfate (IV STS) is considered standard care in the treatment of calciphylaxis, HBOT has been reported to have beneficial effects, they noted.

In their study, the researchers retrospectively reviewed records of 93 patients newly diagnosed with calciphylaxis, seen at Massachusetts General Hospital, between January 2006 and December 2021. They compared mortality and wound healing outcomes for 57 patients treated with IV STS only (control group) with those of 36 patients treated with HBOT plus IV STS (treatment group). Traditional survival analyses and Cox proportional hazard modeling were used to examine mortality data, and mixed effects modeling was used to analyze longitudinal wound outcomes. The study was published in the Journal of the American Academy of Dermatology.

Univariate survival analyses showed that HBOT plus IV STS was associated with significantly longer survival time than IV STS alone (P = .016), particularly for those with nonnephrogenic calciphylaxis (P < .0001), they report. An increased number of HBOT sessions conferred improved mortality outcomes, with 1, 5, 10, and 20 sessions yielding decreasing hazard ratios.

There was also a significant positive association between an increasing number of HBOT sessions and increased wound score (P = .042). Increases were seen with each session.

Anxiety/claustrophobia was the most common side effect reported among those in the HBOT group (22%).

“Given the proposed benefits and seemingly low side effect profile, it is the authors’ recommendation that HBOT be offered as an additional intervention to patients with calciphylaxis, especially if they have open wounds, to improve outcomes and expedite wound healing,” the researchers concluded.

Limitations, they noted, included the small sample size, retrospective design, and the potential for not adequately capturing patients who received external care. They were also unable to match patients by disease or wound severity. Large prospective trials would help clarify the role of HBOT for calciphylaxis, they added.

The researchers reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Hyperbaric oxygen therapy (HBOT) may have a role in treating calciphylaxis, with benefits in both mortality and wound healing, report Daniela Kroshinsky, MD, MPH, of the department of dermatology at Massachusetts General Hospital, Boston, and colleagues.

Although intravenous sodium thiosulfate (IV STS) is considered standard care in the treatment of calciphylaxis, HBOT has been reported to have beneficial effects, they noted.

In their study, the researchers retrospectively reviewed records of 93 patients newly diagnosed with calciphylaxis, seen at Massachusetts General Hospital, between January 2006 and December 2021. They compared mortality and wound healing outcomes for 57 patients treated with IV STS only (control group) with those of 36 patients treated with HBOT plus IV STS (treatment group). Traditional survival analyses and Cox proportional hazard modeling were used to examine mortality data, and mixed effects modeling was used to analyze longitudinal wound outcomes. The study was published in the Journal of the American Academy of Dermatology.

Univariate survival analyses showed that HBOT plus IV STS was associated with significantly longer survival time than IV STS alone (P = .016), particularly for those with nonnephrogenic calciphylaxis (P < .0001), they report. An increased number of HBOT sessions conferred improved mortality outcomes, with 1, 5, 10, and 20 sessions yielding decreasing hazard ratios.

There was also a significant positive association between an increasing number of HBOT sessions and increased wound score (P = .042). Increases were seen with each session.

Anxiety/claustrophobia was the most common side effect reported among those in the HBOT group (22%).

“Given the proposed benefits and seemingly low side effect profile, it is the authors’ recommendation that HBOT be offered as an additional intervention to patients with calciphylaxis, especially if they have open wounds, to improve outcomes and expedite wound healing,” the researchers concluded.

Limitations, they noted, included the small sample size, retrospective design, and the potential for not adequately capturing patients who received external care. They were also unable to match patients by disease or wound severity. Large prospective trials would help clarify the role of HBOT for calciphylaxis, they added.

The researchers reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

INTRODUCTION

Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.

CASE PRESENTATION

A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.

DISCUSSION

EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.

CONCLUSIONS

Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.

INTRODUCTION

Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.

CASE PRESENTATION

A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.

DISCUSSION

EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.

CONCLUSIONS

Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.

INTRODUCTION

Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.

CASE PRESENTATION

A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.

DISCUSSION

EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.

CONCLUSIONS

Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.

In resectable non–small cell lung cancer (NSCLC), neoadjuvant durvalumab in combination with chemotherapy had no effect on surgical outcomes, according to the most recent analysis of data from the phase 3 AEGEAN study.

“In terms of cancellation of surgery, surgical delay, surgically related adverse events, complications, operation time, and operation procedure, there was no difference between the durvalumab group and the placebo group. In addition, the R0 resection rate was numerically higher in the durvalumab group. These [results] indicate that adding perioperative durvalumab did not adversely affect surgical outcomes,” wrote Tetsuya Mitsudomi, MD, PhD, who presented the new results at the annual World Conference on Lung Cancer, in an email. The topline results of AEGEAN were presented earlier this year at AACR 2023, which showed that the regimen combined with adjuvant durvalumab improved event-free survival (EFS) and pathologic complete response (pCR), compared with chemotherapy plus placebo.

Dr. Mitsudomi also pointed out that AEGEAN is one of the first studies looking at immune checkpoint inhibitors (ICI) in the perioperative settings that demonstrated improved EFS and pCR with no effect on surgical outcomes. Previously, the CheckMate 816 study demonstrated efficacy of neoadjuvant ICI alone.

“The AEGEAN study showed that neoadjuvant plus adjuvant ICI is another option for these patients. However, no one knows who should receive the postoperative ICI in addition to neoadjuvant ICI, because there are no trials including ongoing ones that ask this question,” wrote Dr. Mitsudomi.

The phase 3 AEGEAN study included 740 patients who were randomized to durvalumab or placebo. The median age was 65.0 years in both groups, and 33.3% and 33.4% of patients in each group respectively had fewer than 1% of tumor cells that expressed PD-L1. Expression in 1-49% of tumor cells occurred in 36.9% and 38.0% respectively, and expression ≥ 50% occurred in 29.8% and 28.6%.

Prior to surgery, 84.7% of the durvalumab arm completed four cycles of chemotherapy, as did 87.2% in the placebo arm. The proportion of patients undergoing surgery was 80.6% and 80.7% in the two arms, respectively, and surgical completion was achieved in 77.6% and 76.7%. The durvalumab arm and placebo arm had similar median times from last neoadjuvant treatment to surgery (34.0 days for both) and median time from surgery to first adjuvant dose (50.0 versus 52.0 days).

Among patients with stage II NSCLC, 84.3% in the durvalumab arm underwent surgery, versus 88.9% in the placebo arm. Among patients with stage III disease, the numbers were 79.2% and 77.4%, respectively. There was no surgical delay in 82.7% of patients in the durvalumab arm, compared with 77.8% in the placebo arm. The most common reason for surgical delay was logistical reasons. Mediastinal lymph node dissection was completed in 86.6% of the durvalumab arm and 84.7% of the placebo arm. In both groups where surgery was completed, R0 resection rates were over 90% overall as well as in both stage I and stage II patients. Following surgery, adverse events possibly related to surgery occurred in 40.2% of the durvalumab group and 39.2% of the placebo group. The most common surgical adverse events occurred at similar frequency between groups.

After the presentation, Solange Peters, MD, PhD, served as a discussant. She pointed out other studies that have examined ICI therapy for NSCLC in both the neoadjuvant and adjuvant setting, including Keynote-671 (pembrolizumab), Neotorch (toripalimab), CheckMate 77T (nivolumab), and Impower030 (atezolizumab). She pointed out that AEGEAN, Keynote-671, CheckMate 816, and NeoTorch all had similar trial designs and showed similar magnitude of benefit. “We have a growing paradigm [for combining neoadjuvant and adjuvant ICI therapy]. We are quite all convinced in the community that there is a biological rationale to use neoadjuvant immunotherapy because of the fit immune system, because of the presence of the neoantigens within the tumor at the time of the start of neoadjuvant treatment, [leading to] better priming of immune cells,” said Dr. Peters, who is a professor of medical oncology at University Hospital of Lausanne, Switzerland.

About one in five patients across the trials who would be eligible for surgery never undergo it, but there is promising data from CheckMate 816 that neoadjuvant ICB may improve the odds of surgery, according to Dr. Solange. The AEGEAN data produced some “quite interesting” data about the reasons that patients don’t make it to surgery, as it showed that 8%-10% of patients don’t reach surgery because of progression, but 10%-15% may fall out because they turned out not to be a good candidate for surgery. “I think we probably have to blame the enthusiasm we have to add all these patients into the trial, hoping for the best for the patient but maybe making a wrong selection,” said Dr. Peters.

The study was funded by AstraZeneca. Dr. Mitsudomi has received speaker fees, honoraria, or research funding from AstraZeneca, Chugai, Ono, Bristol Myers Squibb, and MSD. Dr. Peters has financial relationships with AstraZeneca as well as a wide range of other pharmaceutical companies.

In resectable non–small cell lung cancer (NSCLC), neoadjuvant durvalumab in combination with chemotherapy had no effect on surgical outcomes, according to the most recent analysis of data from the phase 3 AEGEAN study.

“In terms of cancellation of surgery, surgical delay, surgically related adverse events, complications, operation time, and operation procedure, there was no difference between the durvalumab group and the placebo group. In addition, the R0 resection rate was numerically higher in the durvalumab group. These [results] indicate that adding perioperative durvalumab did not adversely affect surgical outcomes,” wrote Tetsuya Mitsudomi, MD, PhD, who presented the new results at the annual World Conference on Lung Cancer, in an email. The topline results of AEGEAN were presented earlier this year at AACR 2023, which showed that the regimen combined with adjuvant durvalumab improved event-free survival (EFS) and pathologic complete response (pCR), compared with chemotherapy plus placebo.

Dr. Mitsudomi also pointed out that AEGEAN is one of the first studies looking at immune checkpoint inhibitors (ICI) in the perioperative settings that demonstrated improved EFS and pCR with no effect on surgical outcomes. Previously, the CheckMate 816 study demonstrated efficacy of neoadjuvant ICI alone.

“The AEGEAN study showed that neoadjuvant plus adjuvant ICI is another option for these patients. However, no one knows who should receive the postoperative ICI in addition to neoadjuvant ICI, because there are no trials including ongoing ones that ask this question,” wrote Dr. Mitsudomi.

The phase 3 AEGEAN study included 740 patients who were randomized to durvalumab or placebo. The median age was 65.0 years in both groups, and 33.3% and 33.4% of patients in each group respectively had fewer than 1% of tumor cells that expressed PD-L1. Expression in 1-49% of tumor cells occurred in 36.9% and 38.0% respectively, and expression ≥ 50% occurred in 29.8% and 28.6%.

Prior to surgery, 84.7% of the durvalumab arm completed four cycles of chemotherapy, as did 87.2% in the placebo arm. The proportion of patients undergoing surgery was 80.6% and 80.7% in the two arms, respectively, and surgical completion was achieved in 77.6% and 76.7%. The durvalumab arm and placebo arm had similar median times from last neoadjuvant treatment to surgery (34.0 days for both) and median time from surgery to first adjuvant dose (50.0 versus 52.0 days).

Among patients with stage II NSCLC, 84.3% in the durvalumab arm underwent surgery, versus 88.9% in the placebo arm. Among patients with stage III disease, the numbers were 79.2% and 77.4%, respectively. There was no surgical delay in 82.7% of patients in the durvalumab arm, compared with 77.8% in the placebo arm. The most common reason for surgical delay was logistical reasons. Mediastinal lymph node dissection was completed in 86.6% of the durvalumab arm and 84.7% of the placebo arm. In both groups where surgery was completed, R0 resection rates were over 90% overall as well as in both stage I and stage II patients. Following surgery, adverse events possibly related to surgery occurred in 40.2% of the durvalumab group and 39.2% of the placebo group. The most common surgical adverse events occurred at similar frequency between groups.

After the presentation, Solange Peters, MD, PhD, served as a discussant. She pointed out other studies that have examined ICI therapy for NSCLC in both the neoadjuvant and adjuvant setting, including Keynote-671 (pembrolizumab), Neotorch (toripalimab), CheckMate 77T (nivolumab), and Impower030 (atezolizumab). She pointed out that AEGEAN, Keynote-671, CheckMate 816, and NeoTorch all had similar trial designs and showed similar magnitude of benefit. “We have a growing paradigm [for combining neoadjuvant and adjuvant ICI therapy]. We are quite all convinced in the community that there is a biological rationale to use neoadjuvant immunotherapy because of the fit immune system, because of the presence of the neoantigens within the tumor at the time of the start of neoadjuvant treatment, [leading to] better priming of immune cells,” said Dr. Peters, who is a professor of medical oncology at University Hospital of Lausanne, Switzerland.

About one in five patients across the trials who would be eligible for surgery never undergo it, but there is promising data from CheckMate 816 that neoadjuvant ICB may improve the odds of surgery, according to Dr. Solange. The AEGEAN data produced some “quite interesting” data about the reasons that patients don’t make it to surgery, as it showed that 8%-10% of patients don’t reach surgery because of progression, but 10%-15% may fall out because they turned out not to be a good candidate for surgery. “I think we probably have to blame the enthusiasm we have to add all these patients into the trial, hoping for the best for the patient but maybe making a wrong selection,” said Dr. Peters.

The study was funded by AstraZeneca. Dr. Mitsudomi has received speaker fees, honoraria, or research funding from AstraZeneca, Chugai, Ono, Bristol Myers Squibb, and MSD. Dr. Peters has financial relationships with AstraZeneca as well as a wide range of other pharmaceutical companies.

In resectable non–small cell lung cancer (NSCLC), neoadjuvant durvalumab in combination with chemotherapy had no effect on surgical outcomes, according to the most recent analysis of data from the phase 3 AEGEAN study.

“In terms of cancellation of surgery, surgical delay, surgically related adverse events, complications, operation time, and operation procedure, there was no difference between the durvalumab group and the placebo group. In addition, the R0 resection rate was numerically higher in the durvalumab group. These [results] indicate that adding perioperative durvalumab did not adversely affect surgical outcomes,” wrote Tetsuya Mitsudomi, MD, PhD, who presented the new results at the annual World Conference on Lung Cancer, in an email. The topline results of AEGEAN were presented earlier this year at AACR 2023, which showed that the regimen combined with adjuvant durvalumab improved event-free survival (EFS) and pathologic complete response (pCR), compared with chemotherapy plus placebo.

Dr. Mitsudomi also pointed out that AEGEAN is one of the first studies looking at immune checkpoint inhibitors (ICI) in the perioperative settings that demonstrated improved EFS and pCR with no effect on surgical outcomes. Previously, the CheckMate 816 study demonstrated efficacy of neoadjuvant ICI alone.

“The AEGEAN study showed that neoadjuvant plus adjuvant ICI is another option for these patients. However, no one knows who should receive the postoperative ICI in addition to neoadjuvant ICI, because there are no trials including ongoing ones that ask this question,” wrote Dr. Mitsudomi.

The phase 3 AEGEAN study included 740 patients who were randomized to durvalumab or placebo. The median age was 65.0 years in both groups, and 33.3% and 33.4% of patients in each group respectively had fewer than 1% of tumor cells that expressed PD-L1. Expression in 1-49% of tumor cells occurred in 36.9% and 38.0% respectively, and expression ≥ 50% occurred in 29.8% and 28.6%.

Prior to surgery, 84.7% of the durvalumab arm completed four cycles of chemotherapy, as did 87.2% in the placebo arm. The proportion of patients undergoing surgery was 80.6% and 80.7% in the two arms, respectively, and surgical completion was achieved in 77.6% and 76.7%. The durvalumab arm and placebo arm had similar median times from last neoadjuvant treatment to surgery (34.0 days for both) and median time from surgery to first adjuvant dose (50.0 versus 52.0 days).

Among patients with stage II NSCLC, 84.3% in the durvalumab arm underwent surgery, versus 88.9% in the placebo arm. Among patients with stage III disease, the numbers were 79.2% and 77.4%, respectively. There was no surgical delay in 82.7% of patients in the durvalumab arm, compared with 77.8% in the placebo arm. The most common reason for surgical delay was logistical reasons. Mediastinal lymph node dissection was completed in 86.6% of the durvalumab arm and 84.7% of the placebo arm. In both groups where surgery was completed, R0 resection rates were over 90% overall as well as in both stage I and stage II patients. Following surgery, adverse events possibly related to surgery occurred in 40.2% of the durvalumab group and 39.2% of the placebo group. The most common surgical adverse events occurred at similar frequency between groups.

After the presentation, Solange Peters, MD, PhD, served as a discussant. She pointed out other studies that have examined ICI therapy for NSCLC in both the neoadjuvant and adjuvant setting, including Keynote-671 (pembrolizumab), Neotorch (toripalimab), CheckMate 77T (nivolumab), and Impower030 (atezolizumab). She pointed out that AEGEAN, Keynote-671, CheckMate 816, and NeoTorch all had similar trial designs and showed similar magnitude of benefit. “We have a growing paradigm [for combining neoadjuvant and adjuvant ICI therapy]. We are quite all convinced in the community that there is a biological rationale to use neoadjuvant immunotherapy because of the fit immune system, because of the presence of the neoantigens within the tumor at the time of the start of neoadjuvant treatment, [leading to] better priming of immune cells,” said Dr. Peters, who is a professor of medical oncology at University Hospital of Lausanne, Switzerland.

About one in five patients across the trials who would be eligible for surgery never undergo it, but there is promising data from CheckMate 816 that neoadjuvant ICB may improve the odds of surgery, according to Dr. Solange. The AEGEAN data produced some “quite interesting” data about the reasons that patients don’t make it to surgery, as it showed that 8%-10% of patients don’t reach surgery because of progression, but 10%-15% may fall out because they turned out not to be a good candidate for surgery. “I think we probably have to blame the enthusiasm we have to add all these patients into the trial, hoping for the best for the patient but maybe making a wrong selection,” said Dr. Peters.

The study was funded by AstraZeneca. Dr. Mitsudomi has received speaker fees, honoraria, or research funding from AstraZeneca, Chugai, Ono, Bristol Myers Squibb, and MSD. Dr. Peters has financial relationships with AstraZeneca as well as a wide range of other pharmaceutical companies.

A debate in Houston at the annual meeting of the Society of Hematologic Oncology tackled a vexing issue in hematology: Should smoldering myeloma be treated?

Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.

The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.

In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.

“I’m taking this as a win,” Dr. Lonial said.

Different interpretations of two trials

The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.

At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.

The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.

Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.

However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.

About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.

Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.

“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”

Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.

“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.

Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.

“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”

He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.

He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.

Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.

A debate in Houston at the annual meeting of the Society of Hematologic Oncology tackled a vexing issue in hematology: Should smoldering myeloma be treated?

Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.

The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.

In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.

“I’m taking this as a win,” Dr. Lonial said.

Different interpretations of two trials

The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.

At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.

The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.

Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.

However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.

About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.

Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.

“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”

Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.

“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.

Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.

“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”

He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.

He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.

Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.

A debate in Houston at the annual meeting of the Society of Hematologic Oncology tackled a vexing issue in hematology: Should smoldering myeloma be treated?

Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.

The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.

In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.

“I’m taking this as a win,” Dr. Lonial said.

Different interpretations of two trials

The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.

At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.

The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.

Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.

However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.

About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.

Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.

“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”

Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.

“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.

Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.

“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”

He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.

He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.

Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.

Two shave biopsies were taken, 1 in the center of a previous SCC site with hyperkeratosis, the other in a site not previously affected by SCC but with the physical features of a pustule. Biopsy results from both sites were consistent with erosive pustular dermatosis, an unusual inflammatory disorder that mimics SCC.

Erosive pustular dermatosis of the scalp is an uncommon dermatitis that usually affects older women but may appear in men and women of all ages. It can mimic many other conditions that can affect the scalp, including seborrheic dermatitis, psoriasis, actinic keratosis, and SCC.

The exact causative mechanism is not understood, and cases may develop spontaneously. Rough papules, pustules, crusts, and ulcers develop and (apart from the pustules) share many features of actinic keratoses, SCCs, and field cancerization. The presence of pustules helps point to the diagnosis.

Triggers include previous surgery or physical trauma, burns, skin or hair grafts, and treatment of actinic keratoses with imiquimod, 5-fluourouracil, or photodynamic therapy. Some autoimmune diseases (including Hashimoto thyroiditis, autoimmune hepatitis, and rheumatoid arthritis) have been linked to disease occurrence and severity.¹

Treatment includes potent or super-potent topical steroids such as clobetasol 0.05% ointment. Topical tacrolimus 0.1% ointment and calcipotriene 0.005% cream have been reported as steroid alternatives. Paradoxically, photodynamic therapy, while associated with triggering disease, has also been used therapeutically. Systemic immunomodulators such as cyclosporine 3 mg/kg/d or prednisone 0.5 to 1 mg/kg/d may be needed in severe cases. Antibiotics including topical dapsone 5% gel, systemic dapsone from 50 mg bid to tid, and doxycycline have been helpful due, in part, to their immunomodulatory effects.^1,2

This patient was told to apply topical triamcinolone 0.1% ointment around and over ulcers and pustules and to take doxycycline 100 mg twice daily. The patient cleared well after 6 weeks. He continued to apply topical triamcinolone every few days as maintenance therapy.

He had some mild recurrence after discontinuing all topical and oral therapy, so he currently is being maintained on topical clobetasol 0.05% ointment every other day. He comes in for follow-up appointments every 3 months to monitor for control of the erosive pustular dermatosis of the scalp and for skin cancer surveillance.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME

Two shave biopsies were taken, 1 in the center of a previous SCC site with hyperkeratosis, the other in a site not previously affected by SCC but with the physical features of a pustule. Biopsy results from both sites were consistent with erosive pustular dermatosis, an unusual inflammatory disorder that mimics SCC.

Erosive pustular dermatosis of the scalp is an uncommon dermatitis that usually affects older women but may appear in men and women of all ages. It can mimic many other conditions that can affect the scalp, including seborrheic dermatitis, psoriasis, actinic keratosis, and SCC.

The exact causative mechanism is not understood, and cases may develop spontaneously. Rough papules, pustules, crusts, and ulcers develop and (apart from the pustules) share many features of actinic keratoses, SCCs, and field cancerization. The presence of pustules helps point to the diagnosis.

Triggers include previous surgery or physical trauma, burns, skin or hair grafts, and treatment of actinic keratoses with imiquimod, 5-fluourouracil, or photodynamic therapy. Some autoimmune diseases (including Hashimoto thyroiditis, autoimmune hepatitis, and rheumatoid arthritis) have been linked to disease occurrence and severity.¹

Treatment includes potent or super-potent topical steroids such as clobetasol 0.05% ointment. Topical tacrolimus 0.1% ointment and calcipotriene 0.005% cream have been reported as steroid alternatives. Paradoxically, photodynamic therapy, while associated with triggering disease, has also been used therapeutically. Systemic immunomodulators such as cyclosporine 3 mg/kg/d or prednisone 0.5 to 1 mg/kg/d may be needed in severe cases. Antibiotics including topical dapsone 5% gel, systemic dapsone from 50 mg bid to tid, and doxycycline have been helpful due, in part, to their immunomodulatory effects.^1,2

This patient was told to apply topical triamcinolone 0.1% ointment around and over ulcers and pustules and to take doxycycline 100 mg twice daily. The patient cleared well after 6 weeks. He continued to apply topical triamcinolone every few days as maintenance therapy.

He had some mild recurrence after discontinuing all topical and oral therapy, so he currently is being maintained on topical clobetasol 0.05% ointment every other day. He comes in for follow-up appointments every 3 months to monitor for control of the erosive pustular dermatosis of the scalp and for skin cancer surveillance.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME

Two shave biopsies were taken, 1 in the center of a previous SCC site with hyperkeratosis, the other in a site not previously affected by SCC but with the physical features of a pustule. Biopsy results from both sites were consistent with erosive pustular dermatosis, an unusual inflammatory disorder that mimics SCC.

Erosive pustular dermatosis of the scalp is an uncommon dermatitis that usually affects older women but may appear in men and women of all ages. It can mimic many other conditions that can affect the scalp, including seborrheic dermatitis, psoriasis, actinic keratosis, and SCC.

The exact causative mechanism is not understood, and cases may develop spontaneously. Rough papules, pustules, crusts, and ulcers develop and (apart from the pustules) share many features of actinic keratoses, SCCs, and field cancerization. The presence of pustules helps point to the diagnosis.

Triggers include previous surgery or physical trauma, burns, skin or hair grafts, and treatment of actinic keratoses with imiquimod, 5-fluourouracil, or photodynamic therapy. Some autoimmune diseases (including Hashimoto thyroiditis, autoimmune hepatitis, and rheumatoid arthritis) have been linked to disease occurrence and severity.¹

Treatment includes potent or super-potent topical steroids such as clobetasol 0.05% ointment. Topical tacrolimus 0.1% ointment and calcipotriene 0.005% cream have been reported as steroid alternatives. Paradoxically, photodynamic therapy, while associated with triggering disease, has also been used therapeutically. Systemic immunomodulators such as cyclosporine 3 mg/kg/d or prednisone 0.5 to 1 mg/kg/d may be needed in severe cases. Antibiotics including topical dapsone 5% gel, systemic dapsone from 50 mg bid to tid, and doxycycline have been helpful due, in part, to their immunomodulatory effects.^1,2

This patient was told to apply topical triamcinolone 0.1% ointment around and over ulcers and pustules and to take doxycycline 100 mg twice daily. The patient cleared well after 6 weeks. He continued to apply topical triamcinolone every few days as maintenance therapy.

He had some mild recurrence after discontinuing all topical and oral therapy, so he currently is being maintained on topical clobetasol 0.05% ointment every other day. He comes in for follow-up appointments every 3 months to monitor for control of the erosive pustular dermatosis of the scalp and for skin cancer surveillance.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME

This transcript has been edited for clarity.

Today, I’d like to talk about private parts. You know: the genitals, down there.

I hate all of that. I really wish that we can get to a place where we can talk about genitals and sexual health the same way we do about high blood pressure and diabetes. In fact, when a new patient comes in and they get a new diagnosis of diabetes, you spend time explaining to them how their pancreas works. I don’t remember all the details because I’m a urologist. But you explain the details of diabetes, how it works, why therapy is important, and how it’s very important for quality of life.

I would like us to take that same understanding of anatomy and physiology and use it to explain to patients how their sexual health works because when they understand it, they then have the tools to make it better. I say to patients, “You have to know what parts you have in order to figure out how they drive, right?” We want them to drive better.

Let me give you an example. Many men come to see me with complaints of erectile dysfunction. They refuse to take sildenafil and tadalafil (Viagra and Cialis), saying, “Oh my gosh, those are magic pills. I won’t be a man if take them.” We all know that doesn’t make any sense. I explain to them how their penis works: “Your penis is a muscle. The muscle does two things. It contracts and it relaxes, just like your bicep. It’s just that your penis muscle is smooth muscle, which means it responds to fight or flight. It’s on the autonomic nervous system.”

I explain that if the muscle of the penis is relaxed, it fills with blood and expands. It gets big and hard, and it traps the blood. But when the muscles of the penis are contracted, when they are tight, it squeezes out all the blood, like squeezing out a sponge. So the important thing to do if you want to have good erections is to get the muscles to relax. Relaxed muscle increases erections. I get them to understand that sildenafil and tadalafil are phosphodiesterase 5 inhibitors: smooth-muscle relaxants. Instead of saying, “I need to take Viagra or Cialis because I’m broken,” it’s, “Oh hey honey, I need to take my muscle relaxants because my muscles aren’t working the way that they used to.”

In the future, I’ll go into what happens in erectile dysfunction. We’ll go into what can happen with erectile dysfunction and the many reasons why it happens. It’s getting them to understand that if we get the muscles to relax, you will have better erections. This is how the penis works. It’s why the medicine works. The patients will actually try the therapy and they’ll feel so much better about it. They’ll say, “Oh my gosh, this makes so much sense.” They work on their mental muscles to get the muscles of the penis to relax. Understanding anatomy and physiology helps them understand the treatments, which leads to better outcomes.

How about the female side? If a woman comes to see me reporting that she can’t have an orgasm, part of it is education and understanding the anatomy and physiology. The clitoris and the penis are exactly the same thing. The head of the clitoris and the head of the penis are the same. The clitoris has legs that go all the way down to the butt bone. So everyone is sitting on their genitals right now. The butt bones connect to the bottom of the clitoris or the bottom of the penis. They each have legs called crura. When you get patients to understand where their anatomy is and how it functions, they will then understand how to maximize their quality of life.

The clitoris has smooth muscle just like the penis. When that smooth muscle relaxes, it gorges with blood. When you stimulate it, it can lead to orgasm for most people. But, wait a minute. The clitoris is not inside the vagina. It’s outside. It’s behind the labia majora. If you follow the labia minora up, you get to the head of the clitoris. If patients understand that, they then will understand that penetration is not the way the majority of people orgasm.

I love pictures. I show everyone pictures in my office. They help patients to understand why vibration or outside stimulation on the vulva will allow orgasm to happen. And so instead of patients coming in saying, “I’m broken, I can’t orgasm from penetration,” or, “Dr. Rubin, I’m broken because I can’t get erections,” getting them to understand the anatomy and physiology helps them understand the treatment.

As we go forward, I’ll talk more about anatomy and physiology and how to increase the sexual health of our patients. For now though, please stop calling them private parts. Please use your understanding of anatomy and physiology to educate your patients to have better sexual health and higher quality of life. You may be the only clinician to ever do so, and it will make their life so much better.

Dr. Rubin is an assistant clinical professor, department of urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Today, I’d like to talk about private parts. You know: the genitals, down there.

I hate all of that. I really wish that we can get to a place where we can talk about genitals and sexual health the same way we do about high blood pressure and diabetes. In fact, when a new patient comes in and they get a new diagnosis of diabetes, you spend time explaining to them how their pancreas works. I don’t remember all the details because I’m a urologist. But you explain the details of diabetes, how it works, why therapy is important, and how it’s very important for quality of life.

I would like us to take that same understanding of anatomy and physiology and use it to explain to patients how their sexual health works because when they understand it, they then have the tools to make it better. I say to patients, “You have to know what parts you have in order to figure out how they drive, right?” We want them to drive better.

Let me give you an example. Many men come to see me with complaints of erectile dysfunction. They refuse to take sildenafil and tadalafil (Viagra and Cialis), saying, “Oh my gosh, those are magic pills. I won’t be a man if take them.” We all know that doesn’t make any sense. I explain to them how their penis works: “Your penis is a muscle. The muscle does two things. It contracts and it relaxes, just like your bicep. It’s just that your penis muscle is smooth muscle, which means it responds to fight or flight. It’s on the autonomic nervous system.”

I explain that if the muscle of the penis is relaxed, it fills with blood and expands. It gets big and hard, and it traps the blood. But when the muscles of the penis are contracted, when they are tight, it squeezes out all the blood, like squeezing out a sponge. So the important thing to do if you want to have good erections is to get the muscles to relax. Relaxed muscle increases erections. I get them to understand that sildenafil and tadalafil are phosphodiesterase 5 inhibitors: smooth-muscle relaxants. Instead of saying, “I need to take Viagra or Cialis because I’m broken,” it’s, “Oh hey honey, I need to take my muscle relaxants because my muscles aren’t working the way that they used to.”

In the future, I’ll go into what happens in erectile dysfunction. We’ll go into what can happen with erectile dysfunction and the many reasons why it happens. It’s getting them to understand that if we get the muscles to relax, you will have better erections. This is how the penis works. It’s why the medicine works. The patients will actually try the therapy and they’ll feel so much better about it. They’ll say, “Oh my gosh, this makes so much sense.” They work on their mental muscles to get the muscles of the penis to relax. Understanding anatomy and physiology helps them understand the treatments, which leads to better outcomes.

How about the female side? If a woman comes to see me reporting that she can’t have an orgasm, part of it is education and understanding the anatomy and physiology. The clitoris and the penis are exactly the same thing. The head of the clitoris and the head of the penis are the same. The clitoris has legs that go all the way down to the butt bone. So everyone is sitting on their genitals right now. The butt bones connect to the bottom of the clitoris or the bottom of the penis. They each have legs called crura. When you get patients to understand where their anatomy is and how it functions, they will then understand how to maximize their quality of life.

The clitoris has smooth muscle just like the penis. When that smooth muscle relaxes, it gorges with blood. When you stimulate it, it can lead to orgasm for most people. But, wait a minute. The clitoris is not inside the vagina. It’s outside. It’s behind the labia majora. If you follow the labia minora up, you get to the head of the clitoris. If patients understand that, they then will understand that penetration is not the way the majority of people orgasm.

I love pictures. I show everyone pictures in my office. They help patients to understand why vibration or outside stimulation on the vulva will allow orgasm to happen. And so instead of patients coming in saying, “I’m broken, I can’t orgasm from penetration,” or, “Dr. Rubin, I’m broken because I can’t get erections,” getting them to understand the anatomy and physiology helps them understand the treatment.

As we go forward, I’ll talk more about anatomy and physiology and how to increase the sexual health of our patients. For now though, please stop calling them private parts. Please use your understanding of anatomy and physiology to educate your patients to have better sexual health and higher quality of life. You may be the only clinician to ever do so, and it will make their life so much better.

Dr. Rubin is an assistant clinical professor, department of urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Today, I’d like to talk about private parts. You know: the genitals, down there.

I hate all of that. I really wish that we can get to a place where we can talk about genitals and sexual health the same way we do about high blood pressure and diabetes. In fact, when a new patient comes in and they get a new diagnosis of diabetes, you spend time explaining to them how their pancreas works. I don’t remember all the details because I’m a urologist. But you explain the details of diabetes, how it works, why therapy is important, and how it’s very important for quality of life.

I would like us to take that same understanding of anatomy and physiology and use it to explain to patients how their sexual health works because when they understand it, they then have the tools to make it better. I say to patients, “You have to know what parts you have in order to figure out how they drive, right?” We want them to drive better.

Let me give you an example. Many men come to see me with complaints of erectile dysfunction. They refuse to take sildenafil and tadalafil (Viagra and Cialis), saying, “Oh my gosh, those are magic pills. I won’t be a man if take them.” We all know that doesn’t make any sense. I explain to them how their penis works: “Your penis is a muscle. The muscle does two things. It contracts and it relaxes, just like your bicep. It’s just that your penis muscle is smooth muscle, which means it responds to fight or flight. It’s on the autonomic nervous system.”

I explain that if the muscle of the penis is relaxed, it fills with blood and expands. It gets big and hard, and it traps the blood. But when the muscles of the penis are contracted, when they are tight, it squeezes out all the blood, like squeezing out a sponge. So the important thing to do if you want to have good erections is to get the muscles to relax. Relaxed muscle increases erections. I get them to understand that sildenafil and tadalafil are phosphodiesterase 5 inhibitors: smooth-muscle relaxants. Instead of saying, “I need to take Viagra or Cialis because I’m broken,” it’s, “Oh hey honey, I need to take my muscle relaxants because my muscles aren’t working the way that they used to.”

In the future, I’ll go into what happens in erectile dysfunction. We’ll go into what can happen with erectile dysfunction and the many reasons why it happens. It’s getting them to understand that if we get the muscles to relax, you will have better erections. This is how the penis works. It’s why the medicine works. The patients will actually try the therapy and they’ll feel so much better about it. They’ll say, “Oh my gosh, this makes so much sense.” They work on their mental muscles to get the muscles of the penis to relax. Understanding anatomy and physiology helps them understand the treatments, which leads to better outcomes.

How about the female side? If a woman comes to see me reporting that she can’t have an orgasm, part of it is education and understanding the anatomy and physiology. The clitoris and the penis are exactly the same thing. The head of the clitoris and the head of the penis are the same. The clitoris has legs that go all the way down to the butt bone. So everyone is sitting on their genitals right now. The butt bones connect to the bottom of the clitoris or the bottom of the penis. They each have legs called crura. When you get patients to understand where their anatomy is and how it functions, they will then understand how to maximize their quality of life.

The clitoris has smooth muscle just like the penis. When that smooth muscle relaxes, it gorges with blood. When you stimulate it, it can lead to orgasm for most people. But, wait a minute. The clitoris is not inside the vagina. It’s outside. It’s behind the labia majora. If you follow the labia minora up, you get to the head of the clitoris. If patients understand that, they then will understand that penetration is not the way the majority of people orgasm.

I love pictures. I show everyone pictures in my office. They help patients to understand why vibration or outside stimulation on the vulva will allow orgasm to happen. And so instead of patients coming in saying, “I’m broken, I can’t orgasm from penetration,” or, “Dr. Rubin, I’m broken because I can’t get erections,” getting them to understand the anatomy and physiology helps them understand the treatment.

As we go forward, I’ll talk more about anatomy and physiology and how to increase the sexual health of our patients. For now though, please stop calling them private parts. Please use your understanding of anatomy and physiology to educate your patients to have better sexual health and higher quality of life. You may be the only clinician to ever do so, and it will make their life so much better.

Dr. Rubin is an assistant clinical professor, department of urology, at Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article first appeared on Medscape.com.

More time spent on social media spent in ways defined as problematic was significantly associated with increased depressive symptoms during pregnancy, based on data from more than 600 individuals.

Depressive symptoms among pregnant women have risen in recent years, but the potential impact of social media use on depression in pregnancy has not been well studied, wrote Lotte Muskens, a PhD candidate at Tilburg (the Netherlands) University and colleagues.

In a study published in the Journal of Affective Disorders, the researchers surveyed 697 pregnant women aged 19-42 years who were part of a larger longitudinal prospective study (the Brabant Study) in the Netherlands. The mean age of the participants was 31 years; 96% were employed, 99% had a partner, and 71% had a bachelor’s degree or higher. Depressive symptoms were assessed at 12, 20, and 28 weeks of pregnancy using the Dutch version of the 10-item Edinburgh Depression Scale (EDS).

SonerCdem/Thinkstock

The researchers categorized the participants into trajectories of depressive symptoms during pregnancy, with 489 identified as low stable (mean EDS scores 2.8-3.0), 183 as intermediate stable (mean EDS scores 8.4-8.8), and 25 as high stable (mean EDS scores 15.1-16.9).

Problematic SMU was identified using the six-item Bergen Social Media Addiction Scale (BSMAS) at 12 weeks of pregnancy; scores ranged from 6 to 30, with higher scores representing more problematic SMU.

The mean BSMAS scores were 9.0, 10.7, and 12.6 for the low-stable, intermediate-stable, and high-stable depression groups, respectively.

Data on social media use (SMU) were collected at 12 weeks of pregnancy. Social media was defined as common platforms including Facebook, Instagram, LinkedIn, Pinterest, Twitter, and YouTube.

SMU was defined in terms of intensity, measured by time and frequency. Time was measured by asking participants to list how many hours per day they used social media on a scale of 1 (no use of social media) to 9 (7 or more hours per day). Frequency was measured by asking how often participants visited the various social media platforms, on a scale of 1 (no use of social media) to 7 (five or more visits per day). Overall, the participants averaged 1.6 hours per day and 19.5 visits per week on SMU.

Increased time and frequency of SMU was significantly associated with increased odds of being in the high-stable group, compared with the low-stable group in an adjusted analysis (odds ratios, 1.51 and 1.05, respectively; P = .017 and P = .019, respectively).

In addition, problematic SMU (as defined by higher BSMAS scores) remained significantly associated with increased odds of belonging to the intermediate-stable or high-stable classes in an adjusted analysis (odds ratios, 1.17 and 1.31; P < .001 for both).

“While our results suggest that SMU can have negative consequences for pregnant women’s mental wellbeing, it is important to note that SMU during pregnancy may also be helpful for some pregnant women,” as many women, especially first-time mothers, find information and support through social media, the researchers wrote in their discussion.

The findings were limited by several factors, including the variation in group sizes for depressive symptoms, reliance on self-reports, and the collection of data during the COVID-19 pandemic, which may have affected the results, the researchers noted.

However, the results were strengthened by the large sample size and longitudinal design that allowed measurement of trajectories. More research is needed to determine causal relationships, but the data indicate an association between higher levels of depression during pregnancy and more intense and problematic SMU use, and health care providers should discuss SMU in addition to other risk factors for depression in pregnant women, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

More time spent on social media spent in ways defined as problematic was significantly associated with increased depressive symptoms during pregnancy, based on data from more than 600 individuals.

Depressive symptoms among pregnant women have risen in recent years, but the potential impact of social media use on depression in pregnancy has not been well studied, wrote Lotte Muskens, a PhD candidate at Tilburg (the Netherlands) University and colleagues.

In a study published in the Journal of Affective Disorders, the researchers surveyed 697 pregnant women aged 19-42 years who were part of a larger longitudinal prospective study (the Brabant Study) in the Netherlands. The mean age of the participants was 31 years; 96% were employed, 99% had a partner, and 71% had a bachelor’s degree or higher. Depressive symptoms were assessed at 12, 20, and 28 weeks of pregnancy using the Dutch version of the 10-item Edinburgh Depression Scale (EDS).

SonerCdem/Thinkstock

The researchers categorized the participants into trajectories of depressive symptoms during pregnancy, with 489 identified as low stable (mean EDS scores 2.8-3.0), 183 as intermediate stable (mean EDS scores 8.4-8.8), and 25 as high stable (mean EDS scores 15.1-16.9).

Problematic SMU was identified using the six-item Bergen Social Media Addiction Scale (BSMAS) at 12 weeks of pregnancy; scores ranged from 6 to 30, with higher scores representing more problematic SMU.

The mean BSMAS scores were 9.0, 10.7, and 12.6 for the low-stable, intermediate-stable, and high-stable depression groups, respectively.

Data on social media use (SMU) were collected at 12 weeks of pregnancy. Social media was defined as common platforms including Facebook, Instagram, LinkedIn, Pinterest, Twitter, and YouTube.

SMU was defined in terms of intensity, measured by time and frequency. Time was measured by asking participants to list how many hours per day they used social media on a scale of 1 (no use of social media) to 9 (7 or more hours per day). Frequency was measured by asking how often participants visited the various social media platforms, on a scale of 1 (no use of social media) to 7 (five or more visits per day). Overall, the participants averaged 1.6 hours per day and 19.5 visits per week on SMU.

Increased time and frequency of SMU was significantly associated with increased odds of being in the high-stable group, compared with the low-stable group in an adjusted analysis (odds ratios, 1.51 and 1.05, respectively; P = .017 and P = .019, respectively).

In addition, problematic SMU (as defined by higher BSMAS scores) remained significantly associated with increased odds of belonging to the intermediate-stable or high-stable classes in an adjusted analysis (odds ratios, 1.17 and 1.31; P < .001 for both).

“While our results suggest that SMU can have negative consequences for pregnant women’s mental wellbeing, it is important to note that SMU during pregnancy may also be helpful for some pregnant women,” as many women, especially first-time mothers, find information and support through social media, the researchers wrote in their discussion.

The findings were limited by several factors, including the variation in group sizes for depressive symptoms, reliance on self-reports, and the collection of data during the COVID-19 pandemic, which may have affected the results, the researchers noted.

However, the results were strengthened by the large sample size and longitudinal design that allowed measurement of trajectories. More research is needed to determine causal relationships, but the data indicate an association between higher levels of depression during pregnancy and more intense and problematic SMU use, and health care providers should discuss SMU in addition to other risk factors for depression in pregnant women, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

More time spent on social media spent in ways defined as problematic was significantly associated with increased depressive symptoms during pregnancy, based on data from more than 600 individuals.

Depressive symptoms among pregnant women have risen in recent years, but the potential impact of social media use on depression in pregnancy has not been well studied, wrote Lotte Muskens, a PhD candidate at Tilburg (the Netherlands) University and colleagues.

In a study published in the Journal of Affective Disorders, the researchers surveyed 697 pregnant women aged 19-42 years who were part of a larger longitudinal prospective study (the Brabant Study) in the Netherlands. The mean age of the participants was 31 years; 96% were employed, 99% had a partner, and 71% had a bachelor’s degree or higher. Depressive symptoms were assessed at 12, 20, and 28 weeks of pregnancy using the Dutch version of the 10-item Edinburgh Depression Scale (EDS).

SonerCdem/Thinkstock

The researchers categorized the participants into trajectories of depressive symptoms during pregnancy, with 489 identified as low stable (mean EDS scores 2.8-3.0), 183 as intermediate stable (mean EDS scores 8.4-8.8), and 25 as high stable (mean EDS scores 15.1-16.9).

Problematic SMU was identified using the six-item Bergen Social Media Addiction Scale (BSMAS) at 12 weeks of pregnancy; scores ranged from 6 to 30, with higher scores representing more problematic SMU.

The mean BSMAS scores were 9.0, 10.7, and 12.6 for the low-stable, intermediate-stable, and high-stable depression groups, respectively.

Data on social media use (SMU) were collected at 12 weeks of pregnancy. Social media was defined as common platforms including Facebook, Instagram, LinkedIn, Pinterest, Twitter, and YouTube.

SMU was defined in terms of intensity, measured by time and frequency. Time was measured by asking participants to list how many hours per day they used social media on a scale of 1 (no use of social media) to 9 (7 or more hours per day). Frequency was measured by asking how often participants visited the various social media platforms, on a scale of 1 (no use of social media) to 7 (five or more visits per day). Overall, the participants averaged 1.6 hours per day and 19.5 visits per week on SMU.

Increased time and frequency of SMU was significantly associated with increased odds of being in the high-stable group, compared with the low-stable group in an adjusted analysis (odds ratios, 1.51 and 1.05, respectively; P = .017 and P = .019, respectively).

In addition, problematic SMU (as defined by higher BSMAS scores) remained significantly associated with increased odds of belonging to the intermediate-stable or high-stable classes in an adjusted analysis (odds ratios, 1.17 and 1.31; P < .001 for both).

“While our results suggest that SMU can have negative consequences for pregnant women’s mental wellbeing, it is important to note that SMU during pregnancy may also be helpful for some pregnant women,” as many women, especially first-time mothers, find information and support through social media, the researchers wrote in their discussion.

The findings were limited by several factors, including the variation in group sizes for depressive symptoms, reliance on self-reports, and the collection of data during the COVID-19 pandemic, which may have affected the results, the researchers noted.

However, the results were strengthened by the large sample size and longitudinal design that allowed measurement of trajectories. More research is needed to determine causal relationships, but the data indicate an association between higher levels of depression during pregnancy and more intense and problematic SMU use, and health care providers should discuss SMU in addition to other risk factors for depression in pregnant women, the researchers concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

A version of this article first appeared on Medscape.com.

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

A version of this article first appeared on Medscape.com.

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

A version of this article first appeared on Medscape.com.

David Nichols, PhD, a leading expert in the field of psychedelic research and the founding president of the Heffter Research Institute, often answers the question, “What is a psychedelic?” by saying, “The scientific definition I always use is that they are substances that produce changes in thought, mood, and affect, which only occur during dreaming or religious exaltation.”^1,2 However, this definition does not account for the experiences of naturally occurring psychoses, such as those seen in schizophrenia.

Lasha Khetsuriani

The phenomenology of psychotic experiences between drug-induced and naturally occurring psychoses differs, and the use of psychedelics does not necessarily replicate or simulate the symptoms of schizophrenia. For example, drug induced hallucinations are often described as more intense and vivid, while those associated with schizophrenia are described as more persistent and distressing.³

An altered state of consciousness is a hallmark of a psychedelic trip, but not a characteristic of schizophrenia. Patients with schizophrenia who have used psychedelics typically report that their experiences under the influence of these drugs are distinct from their usual experiences with the condition. Additionally, according to many experts, the underlying neurobiological mechanisms are different, with psychedelics affecting serotonin receptors and schizophrenia thought to be linked more to dopamine dysregulation, among other factors.

However, there are some instances of naturally occurring psychoses that are difficult to distinguish from the experiences reported by those who take psychedelics. This article explores the similarities between psychedelic experiences induced by serotonergic psychedelics, 5-HT2A agonists, such as LSD, psilocybin, and mescaline, and a rare psychiatric disorder known as the “oneiroid state.”
 

Origins and definitions

The term “oneiroia” is derived from the Greek words for “sleep” and “similar,” referring to the dreamlike character of the condition. It is widely acknowledged that psychedelics can temporarily induce dreamlike states,⁴ but this article focuses specifically on the naturally occurring, endogenous dreamlike state.

Oneiroid state was first described by German psychiatrist Wilhelm Mayer-Gross in the early 20th century and was once well-known among European psychiatrists. Some classified it as a part of schizophrenia, others saw it as an unusual manifestation of affective disorder, and still others considered it an atypical psychosis. Nevertheless, this phenomenon has received limited attention in American psychiatric journals.

The key characteristic of this condition is a distinctive state of consciousness marked by vivid and florid hallucinations, and a succession of constantly shifting dreamlike or surrealistic visuals and imagery often similar to mystical or cosmic experiences. Self-awareness and orientation in time and place are often disturbed, and delusions are experienced within this altered state.⁵

To gain a better understanding of the oneiroid state, it may be helpful to turn to European or other schools of psychiatry with a history of studying this phenomenon, as American psychiatry has limited knowledge in this area.

As described in the “Handbook of Psychiatry” by Russian psychiatrist A.V. Snezhnevsky, published in 1983, oneiroid state, also known as oneiroid syndrome, is a dreamlike and imaginative state characterized by a bizarre combination of reality and vivid phantasmagoric imaginations.⁶ In this state, individuals are completely detached from their surroundings and experience a change in self-awareness, often displaying either a lack of movement or senseless excitement.

Patients often experience the oneiroid state as active participants, as if they are in a movie theater, not only watching the story, but also being part of it, reacting to it with either “external immobility” or senseless excitement, completely detached from their surroundings. This is similar to the portrayal of the emotions of the characters in Steven Spielberg’s film “Ready Player One.”

The entry in Dr. Snezhnevsky’s “Handbook” states: “Some patients in Oneiroid State experience travels to other worlds, such as interacting with inhabitants on Mars, collecting gems on the moon, exploring invisible cities, participating in conspiracies and insurrections, fighting with pirates, chasing The Flying Dutchman, wandering through ancient Rome, and even visiting heaven or hell. At times, the patient’s imagination reaches a state of mystical contemplation.”⁶

In contrast to delirium, which never impairs self-awareness, oneiroid state is marked by drastic changes in the sense of self. The memory of the subjective experience during the oneiroia is much more vivid and consistent than in delirium. Patients who have experienced the oneiroid state often have complete recall of their experience, as if they have just woken up from a dream.

It was commonly thought that oneiroid state was part of the group of functional psychoses, rather than organic psychoses, and was not considered to be a result of mind-altering psychedelics. It was not considered a manifestation of epilepsy either. Oneiroid state could last for weeks or even months, making it unlikely to be related to an epileptic seizure. Furthermore, EEG results did not show any seizurelike activity during the state.

An excellent case study on oneiroid state was published in Israel in 2000. The authors described two patients who experienced the oneiroid state for several days or even weeks.⁷ One of the patients reported that during the illness, he experienced himself aboard a spaceship as a cosmonaut, heading for a different universe. On another occasion, the patient perceived himself as a person living 2,000 years ago and being guilty of Christ’s death.

The second patient reported that everything around her appeared “like in the movies,” and she saw others as characters from comic strips. Both patients alternated between catatonic excitement and sluggishness and would sometimes come back to reality for a few minutes to respond to questions. Physical exams, laboratory tests, neurological tests, and a brain scan were all normal in both cases.
 

Conclusions

As mentioned earlier, oneiroid state is not widely discussed in American psychiatric journals and is now considered a rare condition globally, despite being a common occurrence in the past century. A diagnosis similar to oneiroid state, known as bouffée délirante, is still in use in some French-speaking countries, with a noticeable decline in frequency.^2,8 The widespread acceptance of international classification systems such as the ICD-10, which does not recognize the diagnosis, is likely one of the reasons for this decline.

However, the decrease in the prevalence of the oneiroid state is not unique, as other forms of mental illness, such as the catatonic subtype of schizophrenia, are also becoming less prevalent. The cause of this decline is uncertain. Could changes in the way mental disorders affect 5HT2A receptors be a contributing factor?

In conclusion, as the field of psychedelic research experiences a resurgence, this little-known manifestation of mental illness, oneiroid state, may be worth reexamining.

With the expected approval and regulation of psilocybin and MDMA by the FDA, and classical psychedelics widely regarded as nonaddictive and safer than other recreational drugs, the phenomenological similarity between the naturally occurring impaired consciousness of the oneiroid state and the altered states of consciousness brought about by entheogenic substances should be seen as a possibility for enhanced understanding, rather than as a cause for concern.

Dr. Khetsuriani is a supervising psychiatrist at the Bronx Psychiatric Center in Bronx, N.Y., and has a private psychiatric practice located in Manhattan, N.Y.

References

1. Nichols DE. Keynote address, 39th Telluride Mushroom Festival, Aug. 15-18, 2019. https://www.youtube.com/watch?v=RlDCM5JQzRk.

2. Nichols DE. Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478.

3. Leptourgos P et al. Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison. Schizophr Bull. 2020 Dec 1;46(6):1396-1408. doi: 10.1093/schbul/sbaa117.

4. Kraehenmann R. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications. Curr Neuropharmacol. 2017;15(7):1032-42. doi: 10.2174/1573413713666170619092629.

5. Henri EY et al. “Acute Delusional Psychosis” in Hirsch SR and Shepherd M, eds. Themes and variations in European psychiatry: An anthology. Charlottesville: University Press of Virginia, 1974.

6. Snezhnevsky A, ed. Handbook of Psychiatry. Moscow: Meditsina, 1983.

7. Kaptsan A et al. Oneiroid syndrome: A concept of use for Western psychiatry. Isr J Psychiatry Relat Sci. 2000;37(4):278-85.

8. https://en.wikipedia.org/wiki/Bouff%C3%A9e_d%C3%A9lirante.

David Nichols, PhD, a leading expert in the field of psychedelic research and the founding president of the Heffter Research Institute, often answers the question, “What is a psychedelic?” by saying, “The scientific definition I always use is that they are substances that produce changes in thought, mood, and affect, which only occur during dreaming or religious exaltation.”^1,2 However, this definition does not account for the experiences of naturally occurring psychoses, such as those seen in schizophrenia.

Lasha Khetsuriani

The phenomenology of psychotic experiences between drug-induced and naturally occurring psychoses differs, and the use of psychedelics does not necessarily replicate or simulate the symptoms of schizophrenia. For example, drug induced hallucinations are often described as more intense and vivid, while those associated with schizophrenia are described as more persistent and distressing.³

An altered state of consciousness is a hallmark of a psychedelic trip, but not a characteristic of schizophrenia. Patients with schizophrenia who have used psychedelics typically report that their experiences under the influence of these drugs are distinct from their usual experiences with the condition. Additionally, according to many experts, the underlying neurobiological mechanisms are different, with psychedelics affecting serotonin receptors and schizophrenia thought to be linked more to dopamine dysregulation, among other factors.

However, there are some instances of naturally occurring psychoses that are difficult to distinguish from the experiences reported by those who take psychedelics. This article explores the similarities between psychedelic experiences induced by serotonergic psychedelics, 5-HT2A agonists, such as LSD, psilocybin, and mescaline, and a rare psychiatric disorder known as the “oneiroid state.”
 

Origins and definitions

The term “oneiroia” is derived from the Greek words for “sleep” and “similar,” referring to the dreamlike character of the condition. It is widely acknowledged that psychedelics can temporarily induce dreamlike states,⁴ but this article focuses specifically on the naturally occurring, endogenous dreamlike state.

Oneiroid state was first described by German psychiatrist Wilhelm Mayer-Gross in the early 20th century and was once well-known among European psychiatrists. Some classified it as a part of schizophrenia, others saw it as an unusual manifestation of affective disorder, and still others considered it an atypical psychosis. Nevertheless, this phenomenon has received limited attention in American psychiatric journals.

The key characteristic of this condition is a distinctive state of consciousness marked by vivid and florid hallucinations, and a succession of constantly shifting dreamlike or surrealistic visuals and imagery often similar to mystical or cosmic experiences. Self-awareness and orientation in time and place are often disturbed, and delusions are experienced within this altered state.⁵

To gain a better understanding of the oneiroid state, it may be helpful to turn to European or other schools of psychiatry with a history of studying this phenomenon, as American psychiatry has limited knowledge in this area.

As described in the “Handbook of Psychiatry” by Russian psychiatrist A.V. Snezhnevsky, published in 1983, oneiroid state, also known as oneiroid syndrome, is a dreamlike and imaginative state characterized by a bizarre combination of reality and vivid phantasmagoric imaginations.⁶ In this state, individuals are completely detached from their surroundings and experience a change in self-awareness, often displaying either a lack of movement or senseless excitement.

Patients often experience the oneiroid state as active participants, as if they are in a movie theater, not only watching the story, but also being part of it, reacting to it with either “external immobility” or senseless excitement, completely detached from their surroundings. This is similar to the portrayal of the emotions of the characters in Steven Spielberg’s film “Ready Player One.”

The entry in Dr. Snezhnevsky’s “Handbook” states: “Some patients in Oneiroid State experience travels to other worlds, such as interacting with inhabitants on Mars, collecting gems on the moon, exploring invisible cities, participating in conspiracies and insurrections, fighting with pirates, chasing The Flying Dutchman, wandering through ancient Rome, and even visiting heaven or hell. At times, the patient’s imagination reaches a state of mystical contemplation.”⁶

In contrast to delirium, which never impairs self-awareness, oneiroid state is marked by drastic changes in the sense of self. The memory of the subjective experience during the oneiroia is much more vivid and consistent than in delirium. Patients who have experienced the oneiroid state often have complete recall of their experience, as if they have just woken up from a dream.

It was commonly thought that oneiroid state was part of the group of functional psychoses, rather than organic psychoses, and was not considered to be a result of mind-altering psychedelics. It was not considered a manifestation of epilepsy either. Oneiroid state could last for weeks or even months, making it unlikely to be related to an epileptic seizure. Furthermore, EEG results did not show any seizurelike activity during the state.

An excellent case study on oneiroid state was published in Israel in 2000. The authors described two patients who experienced the oneiroid state for several days or even weeks.⁷ One of the patients reported that during the illness, he experienced himself aboard a spaceship as a cosmonaut, heading for a different universe. On another occasion, the patient perceived himself as a person living 2,000 years ago and being guilty of Christ’s death.

The second patient reported that everything around her appeared “like in the movies,” and she saw others as characters from comic strips. Both patients alternated between catatonic excitement and sluggishness and would sometimes come back to reality for a few minutes to respond to questions. Physical exams, laboratory tests, neurological tests, and a brain scan were all normal in both cases.
 

Conclusions

As mentioned earlier, oneiroid state is not widely discussed in American psychiatric journals and is now considered a rare condition globally, despite being a common occurrence in the past century. A diagnosis similar to oneiroid state, known as bouffée délirante, is still in use in some French-speaking countries, with a noticeable decline in frequency.^2,8 The widespread acceptance of international classification systems such as the ICD-10, which does not recognize the diagnosis, is likely one of the reasons for this decline.

However, the decrease in the prevalence of the oneiroid state is not unique, as other forms of mental illness, such as the catatonic subtype of schizophrenia, are also becoming less prevalent. The cause of this decline is uncertain. Could changes in the way mental disorders affect 5HT2A receptors be a contributing factor?

In conclusion, as the field of psychedelic research experiences a resurgence, this little-known manifestation of mental illness, oneiroid state, may be worth reexamining.

With the expected approval and regulation of psilocybin and MDMA by the FDA, and classical psychedelics widely regarded as nonaddictive and safer than other recreational drugs, the phenomenological similarity between the naturally occurring impaired consciousness of the oneiroid state and the altered states of consciousness brought about by entheogenic substances should be seen as a possibility for enhanced understanding, rather than as a cause for concern.

Dr. Khetsuriani is a supervising psychiatrist at the Bronx Psychiatric Center in Bronx, N.Y., and has a private psychiatric practice located in Manhattan, N.Y.

References

1. Nichols DE. Keynote address, 39th Telluride Mushroom Festival, Aug. 15-18, 2019. https://www.youtube.com/watch?v=RlDCM5JQzRk.

2. Nichols DE. Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478.

3. Leptourgos P et al. Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison. Schizophr Bull. 2020 Dec 1;46(6):1396-1408. doi: 10.1093/schbul/sbaa117.

4. Kraehenmann R. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications. Curr Neuropharmacol. 2017;15(7):1032-42. doi: 10.2174/1573413713666170619092629.

5. Henri EY et al. “Acute Delusional Psychosis” in Hirsch SR and Shepherd M, eds. Themes and variations in European psychiatry: An anthology. Charlottesville: University Press of Virginia, 1974.

6. Snezhnevsky A, ed. Handbook of Psychiatry. Moscow: Meditsina, 1983.

7. Kaptsan A et al. Oneiroid syndrome: A concept of use for Western psychiatry. Isr J Psychiatry Relat Sci. 2000;37(4):278-85.

8. https://en.wikipedia.org/wiki/Bouff%C3%A9e_d%C3%A9lirante.

David Nichols, PhD, a leading expert in the field of psychedelic research and the founding president of the Heffter Research Institute, often answers the question, “What is a psychedelic?” by saying, “The scientific definition I always use is that they are substances that produce changes in thought, mood, and affect, which only occur during dreaming or religious exaltation.”^1,2 However, this definition does not account for the experiences of naturally occurring psychoses, such as those seen in schizophrenia.

Lasha Khetsuriani

The phenomenology of psychotic experiences between drug-induced and naturally occurring psychoses differs, and the use of psychedelics does not necessarily replicate or simulate the symptoms of schizophrenia. For example, drug induced hallucinations are often described as more intense and vivid, while those associated with schizophrenia are described as more persistent and distressing.³

An altered state of consciousness is a hallmark of a psychedelic trip, but not a characteristic of schizophrenia. Patients with schizophrenia who have used psychedelics typically report that their experiences under the influence of these drugs are distinct from their usual experiences with the condition. Additionally, according to many experts, the underlying neurobiological mechanisms are different, with psychedelics affecting serotonin receptors and schizophrenia thought to be linked more to dopamine dysregulation, among other factors.

However, there are some instances of naturally occurring psychoses that are difficult to distinguish from the experiences reported by those who take psychedelics. This article explores the similarities between psychedelic experiences induced by serotonergic psychedelics, 5-HT2A agonists, such as LSD, psilocybin, and mescaline, and a rare psychiatric disorder known as the “oneiroid state.”
 

Origins and definitions

The term “oneiroia” is derived from the Greek words for “sleep” and “similar,” referring to the dreamlike character of the condition. It is widely acknowledged that psychedelics can temporarily induce dreamlike states,⁴ but this article focuses specifically on the naturally occurring, endogenous dreamlike state.

Oneiroid state was first described by German psychiatrist Wilhelm Mayer-Gross in the early 20th century and was once well-known among European psychiatrists. Some classified it as a part of schizophrenia, others saw it as an unusual manifestation of affective disorder, and still others considered it an atypical psychosis. Nevertheless, this phenomenon has received limited attention in American psychiatric journals.

The key characteristic of this condition is a distinctive state of consciousness marked by vivid and florid hallucinations, and a succession of constantly shifting dreamlike or surrealistic visuals and imagery often similar to mystical or cosmic experiences. Self-awareness and orientation in time and place are often disturbed, and delusions are experienced within this altered state.⁵

To gain a better understanding of the oneiroid state, it may be helpful to turn to European or other schools of psychiatry with a history of studying this phenomenon, as American psychiatry has limited knowledge in this area.

As described in the “Handbook of Psychiatry” by Russian psychiatrist A.V. Snezhnevsky, published in 1983, oneiroid state, also known as oneiroid syndrome, is a dreamlike and imaginative state characterized by a bizarre combination of reality and vivid phantasmagoric imaginations.⁶ In this state, individuals are completely detached from their surroundings and experience a change in self-awareness, often displaying either a lack of movement or senseless excitement.

Patients often experience the oneiroid state as active participants, as if they are in a movie theater, not only watching the story, but also being part of it, reacting to it with either “external immobility” or senseless excitement, completely detached from their surroundings. This is similar to the portrayal of the emotions of the characters in Steven Spielberg’s film “Ready Player One.”

The entry in Dr. Snezhnevsky’s “Handbook” states: “Some patients in Oneiroid State experience travels to other worlds, such as interacting with inhabitants on Mars, collecting gems on the moon, exploring invisible cities, participating in conspiracies and insurrections, fighting with pirates, chasing The Flying Dutchman, wandering through ancient Rome, and even visiting heaven or hell. At times, the patient’s imagination reaches a state of mystical contemplation.”⁶

In contrast to delirium, which never impairs self-awareness, oneiroid state is marked by drastic changes in the sense of self. The memory of the subjective experience during the oneiroia is much more vivid and consistent than in delirium. Patients who have experienced the oneiroid state often have complete recall of their experience, as if they have just woken up from a dream.

It was commonly thought that oneiroid state was part of the group of functional psychoses, rather than organic psychoses, and was not considered to be a result of mind-altering psychedelics. It was not considered a manifestation of epilepsy either. Oneiroid state could last for weeks or even months, making it unlikely to be related to an epileptic seizure. Furthermore, EEG results did not show any seizurelike activity during the state.

An excellent case study on oneiroid state was published in Israel in 2000. The authors described two patients who experienced the oneiroid state for several days or even weeks.⁷ One of the patients reported that during the illness, he experienced himself aboard a spaceship as a cosmonaut, heading for a different universe. On another occasion, the patient perceived himself as a person living 2,000 years ago and being guilty of Christ’s death.

The second patient reported that everything around her appeared “like in the movies,” and she saw others as characters from comic strips. Both patients alternated between catatonic excitement and sluggishness and would sometimes come back to reality for a few minutes to respond to questions. Physical exams, laboratory tests, neurological tests, and a brain scan were all normal in both cases.
 

Conclusions

As mentioned earlier, oneiroid state is not widely discussed in American psychiatric journals and is now considered a rare condition globally, despite being a common occurrence in the past century. A diagnosis similar to oneiroid state, known as bouffée délirante, is still in use in some French-speaking countries, with a noticeable decline in frequency.^2,8 The widespread acceptance of international classification systems such as the ICD-10, which does not recognize the diagnosis, is likely one of the reasons for this decline.

However, the decrease in the prevalence of the oneiroid state is not unique, as other forms of mental illness, such as the catatonic subtype of schizophrenia, are also becoming less prevalent. The cause of this decline is uncertain. Could changes in the way mental disorders affect 5HT2A receptors be a contributing factor?

In conclusion, as the field of psychedelic research experiences a resurgence, this little-known manifestation of mental illness, oneiroid state, may be worth reexamining.

With the expected approval and regulation of psilocybin and MDMA by the FDA, and classical psychedelics widely regarded as nonaddictive and safer than other recreational drugs, the phenomenological similarity between the naturally occurring impaired consciousness of the oneiroid state and the altered states of consciousness brought about by entheogenic substances should be seen as a possibility for enhanced understanding, rather than as a cause for concern.

Dr. Khetsuriani is a supervising psychiatrist at the Bronx Psychiatric Center in Bronx, N.Y., and has a private psychiatric practice located in Manhattan, N.Y.

References

1. Nichols DE. Keynote address, 39th Telluride Mushroom Festival, Aug. 15-18, 2019. https://www.youtube.com/watch?v=RlDCM5JQzRk.

2. Nichols DE. Psychedelics. Pharmacol Rev. 2016 Apr;68(2):264-355. doi: 10.1124/pr.115.011478.

3. Leptourgos P et al. Hallucinations Under Psychedelics and in the Schizophrenia Spectrum: An Interdisciplinary and Multiscale Comparison. Schizophr Bull. 2020 Dec 1;46(6):1396-1408. doi: 10.1093/schbul/sbaa117.

4. Kraehenmann R. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications. Curr Neuropharmacol. 2017;15(7):1032-42. doi: 10.2174/1573413713666170619092629.

5. Henri EY et al. “Acute Delusional Psychosis” in Hirsch SR and Shepherd M, eds. Themes and variations in European psychiatry: An anthology. Charlottesville: University Press of Virginia, 1974.

6. Snezhnevsky A, ed. Handbook of Psychiatry. Moscow: Meditsina, 1983.

7. Kaptsan A et al. Oneiroid syndrome: A concept of use for Western psychiatry. Isr J Psychiatry Relat Sci. 2000;37(4):278-85.

8. https://en.wikipedia.org/wiki/Bouff%C3%A9e_d%C3%A9lirante.