Roxanne Nelson

ORLANDO – Active surveillance prior to initiating targeted therapy could be an option for some patients with metastatic renal cell carcinoma (mRCC), according to new findings.

“Active surveillance does not affect the efficacy of subsequent therapies,” said lead study author Davide Bimbatti, MD, of the Azienda Ospedaliera Universitaria Integrata, University of Verona (Italy). “In selected patients, active surveillance allows us to delay the start of systemic treatment, and patients in active surveillance rarely have a worsening of prognostic class,” he said in a press briefing held at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Targeted therapies can improve survival in mRCC but treatment is not curative and associated toxicities can interfere with quality of life and force patients to discontinue treatment. Active surveillance delays the use of systemic therapy and associated toxicities, and is a feasible strategy for patients with indolent disease.

However, the effect of active surveillance on tumor burden and prognosis have not been investigated.

To address this issue, Dr. Bimbatti and his colleagues conducted a retrospective study and evaluated the effect of active surveillance on overall survival and postsurveillance overall survival, progression-free survival, and tumor burden (a measure of the number of sites and tumor size).

The study cohort included 48 patients with mRCC who underwent active surveillance during 2007-2016 and changes in the International mRCC Database Consortium (IMDC) prognostic class and tumor burden were analyzed for associations with these endpoints.

At baseline, 69% of patients had a favorable prognostic IMDC class, 25% were at an intermediate class, and 6% had a poor class designation. The main sites of metastases were lung (56%), lymph nodes (25%), pancreas (14%), adrenal gland (8%), CNS (8%), and bone (6%).

At a median follow-up of 37.3 months, 79.2% of patients were still alive and, at a median surveillance duration of 16.7 months, 71% of patients had begun a targeted therapy. There were a total of 17 deaths (33%).

Median progression-free survival was 16.6 months and median postsurveillance overall survival was 39.1 months.

During active surveillance, only four patients transitioned from good to intermediate IMDC prognostic class. IMDC classes overall maintained their prognostic value during active surveillance, Dr. Bimbatti said. IMDC class was also the only factor that was associated with time on surveillance.

At baseline, tumor burden was in one site for 65% of patients, two sites in 31%, and three or more sites for 4%, but during active surveillance, changes occurred in one site in 35% of patients, two in 48%, and more than two in 17%.

A change in tumor burden (greater than or equal to 2.2 times the original burden), however, was related to poorer postsurveillance survival (hazard ratio,1.23; P less than .01), but not with overall survival (HR, 1.0; P less than .05).

Conversely, any increase in metastatic sites was associated with both significantly worse postsurveillance and overall survival (HR = 2.6, P = 0.04; and HR = 3.3, P less than 0.01).

Commenting on the study, Primo N. Lara Jr., MD, of the University of California, Davis, Comprehensive Cancer Center explained that active surveillance “remains a reasonable option for highly selected patients.”

“[The investigators] provide reassuring data that active surveillance does not alter the IMDC risk grouping,” he said, and that the results of this study overall, were similar to those of prior research.

There were some limitations to the study, in that it was retrospective and conducted at a single institution. “It also failed to account for psychosocial issues such as anxiety during the active surveillance phase,” he said.

Critical questions also remain, Dr. Lara added, such as what are the validated selection criteria for patients entering active surveillance or what is the threshold of tumor burden to warrant active surveillance discontinuation.

The funding source was not disclosed. Dr. Bimbatti and his coauthors have no disclosures. Dr. Lara reports financial ties to multiple pharmaceutical companies.

ORLANDO – Active surveillance prior to initiating targeted therapy could be an option for some patients with metastatic renal cell carcinoma (mRCC), according to new findings.

“Active surveillance does not affect the efficacy of subsequent therapies,” said lead study author Davide Bimbatti, MD, of the Azienda Ospedaliera Universitaria Integrata, University of Verona (Italy). “In selected patients, active surveillance allows us to delay the start of systemic treatment, and patients in active surveillance rarely have a worsening of prognostic class,” he said in a press briefing held at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Targeted therapies can improve survival in mRCC but treatment is not curative and associated toxicities can interfere with quality of life and force patients to discontinue treatment. Active surveillance delays the use of systemic therapy and associated toxicities, and is a feasible strategy for patients with indolent disease.

However, the effect of active surveillance on tumor burden and prognosis have not been investigated.

To address this issue, Dr. Bimbatti and his colleagues conducted a retrospective study and evaluated the effect of active surveillance on overall survival and postsurveillance overall survival, progression-free survival, and tumor burden (a measure of the number of sites and tumor size).

The study cohort included 48 patients with mRCC who underwent active surveillance during 2007-2016 and changes in the International mRCC Database Consortium (IMDC) prognostic class and tumor burden were analyzed for associations with these endpoints.

At baseline, 69% of patients had a favorable prognostic IMDC class, 25% were at an intermediate class, and 6% had a poor class designation. The main sites of metastases were lung (56%), lymph nodes (25%), pancreas (14%), adrenal gland (8%), CNS (8%), and bone (6%).

At a median follow-up of 37.3 months, 79.2% of patients were still alive and, at a median surveillance duration of 16.7 months, 71% of patients had begun a targeted therapy. There were a total of 17 deaths (33%).

Median progression-free survival was 16.6 months and median postsurveillance overall survival was 39.1 months.

During active surveillance, only four patients transitioned from good to intermediate IMDC prognostic class. IMDC classes overall maintained their prognostic value during active surveillance, Dr. Bimbatti said. IMDC class was also the only factor that was associated with time on surveillance.

At baseline, tumor burden was in one site for 65% of patients, two sites in 31%, and three or more sites for 4%, but during active surveillance, changes occurred in one site in 35% of patients, two in 48%, and more than two in 17%.

A change in tumor burden (greater than or equal to 2.2 times the original burden), however, was related to poorer postsurveillance survival (hazard ratio,1.23; P less than .01), but not with overall survival (HR, 1.0; P less than .05).

Conversely, any increase in metastatic sites was associated with both significantly worse postsurveillance and overall survival (HR = 2.6, P = 0.04; and HR = 3.3, P less than 0.01).

Commenting on the study, Primo N. Lara Jr., MD, of the University of California, Davis, Comprehensive Cancer Center explained that active surveillance “remains a reasonable option for highly selected patients.”

“[The investigators] provide reassuring data that active surveillance does not alter the IMDC risk grouping,” he said, and that the results of this study overall, were similar to those of prior research.

There were some limitations to the study, in that it was retrospective and conducted at a single institution. “It also failed to account for psychosocial issues such as anxiety during the active surveillance phase,” he said.

Critical questions also remain, Dr. Lara added, such as what are the validated selection criteria for patients entering active surveillance or what is the threshold of tumor burden to warrant active surveillance discontinuation.

The funding source was not disclosed. Dr. Bimbatti and his coauthors have no disclosures. Dr. Lara reports financial ties to multiple pharmaceutical companies.

ORLANDO – Active surveillance prior to initiating targeted therapy could be an option for some patients with metastatic renal cell carcinoma (mRCC), according to new findings.

“Active surveillance does not affect the efficacy of subsequent therapies,” said lead study author Davide Bimbatti, MD, of the Azienda Ospedaliera Universitaria Integrata, University of Verona (Italy). “In selected patients, active surveillance allows us to delay the start of systemic treatment, and patients in active surveillance rarely have a worsening of prognostic class,” he said in a press briefing held at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Targeted therapies can improve survival in mRCC but treatment is not curative and associated toxicities can interfere with quality of life and force patients to discontinue treatment. Active surveillance delays the use of systemic therapy and associated toxicities, and is a feasible strategy for patients with indolent disease.

However, the effect of active surveillance on tumor burden and prognosis have not been investigated.

To address this issue, Dr. Bimbatti and his colleagues conducted a retrospective study and evaluated the effect of active surveillance on overall survival and postsurveillance overall survival, progression-free survival, and tumor burden (a measure of the number of sites and tumor size).

The study cohort included 48 patients with mRCC who underwent active surveillance during 2007-2016 and changes in the International mRCC Database Consortium (IMDC) prognostic class and tumor burden were analyzed for associations with these endpoints.

At baseline, 69% of patients had a favorable prognostic IMDC class, 25% were at an intermediate class, and 6% had a poor class designation. The main sites of metastases were lung (56%), lymph nodes (25%), pancreas (14%), adrenal gland (8%), CNS (8%), and bone (6%).

At a median follow-up of 37.3 months, 79.2% of patients were still alive and, at a median surveillance duration of 16.7 months, 71% of patients had begun a targeted therapy. There were a total of 17 deaths (33%).

Median progression-free survival was 16.6 months and median postsurveillance overall survival was 39.1 months.

During active surveillance, only four patients transitioned from good to intermediate IMDC prognostic class. IMDC classes overall maintained their prognostic value during active surveillance, Dr. Bimbatti said. IMDC class was also the only factor that was associated with time on surveillance.

At baseline, tumor burden was in one site for 65% of patients, two sites in 31%, and three or more sites for 4%, but during active surveillance, changes occurred in one site in 35% of patients, two in 48%, and more than two in 17%.

A change in tumor burden (greater than or equal to 2.2 times the original burden), however, was related to poorer postsurveillance survival (hazard ratio,1.23; P less than .01), but not with overall survival (HR, 1.0; P less than .05).

Conversely, any increase in metastatic sites was associated with both significantly worse postsurveillance and overall survival (HR = 2.6, P = 0.04; and HR = 3.3, P less than 0.01).

Commenting on the study, Primo N. Lara Jr., MD, of the University of California, Davis, Comprehensive Cancer Center explained that active surveillance “remains a reasonable option for highly selected patients.”

“[The investigators] provide reassuring data that active surveillance does not alter the IMDC risk grouping,” he said, and that the results of this study overall, were similar to those of prior research.

There were some limitations to the study, in that it was retrospective and conducted at a single institution. “It also failed to account for psychosocial issues such as anxiety during the active surveillance phase,” he said.

Critical questions also remain, Dr. Lara added, such as what are the validated selection criteria for patients entering active surveillance or what is the threshold of tumor burden to warrant active surveillance discontinuation.

The funding source was not disclosed. Dr. Bimbatti and his coauthors have no disclosures. Dr. Lara reports financial ties to multiple pharmaceutical companies.

Orlando – The updated results of a large phase III trial support the use of chemoradiation with 5-fluorouracil (5-FU) and mitomycin C (MMC) and confirm that this treatment regimen should be a standard of care for muscle-invasive bladder cancer (MIBC).

When comparing patients who received radiation therapy with those who received chemoradiation, there was a robust improvement in bladder cancer specific survival for the latter when adjusted for known prognostic factors (hazard ratio, 0.73; P = .043).

There was also a borderline significant improvement in metastasis-free survival (HR, 0.78) and a significant reduction in the need for salvage cystectomy in the patients treated with chemoradiation (2-year rate, chemoradiotherapy11% vs. radiation therapy:17%, HR, 0.54; P = .03).

There were no statistically significant differences between groups when it came to overall survival, but, even though overall survival did not reach significance, at 2 years, there was a hint of separation of the curves, explained study author Emma Hall, MD, from the Institute of Cancer Research, London at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

One of the treatment arms received a reduced rate of radiation therapy to see if that would decrease toxicity. “The radiation therapy volume modification that we used did not reduce toxicity, but there is no evidence of an increase in local failure rate, suggesting it is safe to pursue clinical trials of volume sparing radiation therapy using newer technology adaptive delivery techniques,” said Dr. Hall.

The initial findings of the BC2001 study showed that adding chemotherapy (5-FU + MMC) to radiotherapy significantly improved rates of MIBC locoregional control but that reduced high-dose volume versus standard radiotherapy did not significantly reduce late side effects.

This study was a clinical trial set up to test two different questions in the treatment of MIBC, as an alternative to cystectomy. “We wanted to see if adding synchronous chemotherapy to radiotherapy would improve locoregional recurrence control and if reducing the radiation dose to uninvolved bladder would reduce toxicity and not impact local regional recurrence control,” according to Dr. Hall.

Under the 2 x 2 partial factorial design, 458 patients were randomized to radiation therapy (n = 178) or chemoradiation (n = 182) and/or to standard radiation therapy (n = 108) or reduced high-dose volume radiation therapy (n = 111).

The primary endpoint was locoregional control, and secondary endpoints included overall survival, bladder-cancer specific survival, metastasis-free survival, and salvage cystectomy rates.

The initial patients received radiation therapy instead of chemoradiation, and there was a robust improvement in bladder cancer–specific survival when adjusted for known prognostic factors (HR, 0.73; P = .043).

The analysis, presented in 2012, showed a reduction of about one-third of locoregional recurrence. The local control rates were 54% in the radiotherapy-alone arm and 67% in the chemoradiotherapy arm.

There was no significant difference in overall survival at that time.

For the radiotherapy comparison, the rate of late toxicity was low, and much lower than was anticipated, at the outset of the trial, and there was no difference in treatment groups, said Dr. Hall.

In an updated analysis, with a median of 10 years of follow-up, 70% of the patients were now deceased. “These represent robust data, and it is unlikely we will see any changes to the data,” she noted.

The findings presented now had an additional 4 years of follow-up, and while there were additional late events, the results were basically the same.

The rate of local control now showed a 40% reduction in the risk of recurrence and 5-year local control rates of 49% in the radiotherapy arm and 63% in the chemoradiotherapy arm.

“With 10 years follow up, an improvement in locoregional control and a reduced salvage cystectomy rate is confirmed with chemoradiotherapy,” Dr. Hall concluded, “and, taken together with the good quality of life data we have, this is important for this group.”

In a discussion of the paper, Dr. Jonathan Rosenberg, MD, from Memorial Sloan Kettering Cancer Center in New York, agrees with the conclusion that the data continue to support the use of chemoradiotherapy and that 5-FU + MMC is a good option.

He noted that 5-FU + MMC is a standard of care regardless of cisplatin eligibility, but he cannot draw conclusions on dose volume. “There are also other options for chemosensitization,” he said, but it is also import to determine the best way to select patients who will derive the most benefit from chemoradiation.

“There is a high need for robust predictive biomarkers, and we need novel approaches to move beyond chemotherapy,” he said.

The study was supported by Cancer Research UK. Dr Hall has received research funding from Accuray, AstraZeneca, Aventis, and Bayer. Several co-authors also have disclosed relationships with industry. Dr. Rosenberg has disclosed multiple relationships with industry.

Orlando – The updated results of a large phase III trial support the use of chemoradiation with 5-fluorouracil (5-FU) and mitomycin C (MMC) and confirm that this treatment regimen should be a standard of care for muscle-invasive bladder cancer (MIBC).

When comparing patients who received radiation therapy with those who received chemoradiation, there was a robust improvement in bladder cancer specific survival for the latter when adjusted for known prognostic factors (hazard ratio, 0.73; P = .043).

There was also a borderline significant improvement in metastasis-free survival (HR, 0.78) and a significant reduction in the need for salvage cystectomy in the patients treated with chemoradiation (2-year rate, chemoradiotherapy11% vs. radiation therapy:17%, HR, 0.54; P = .03).

There were no statistically significant differences between groups when it came to overall survival, but, even though overall survival did not reach significance, at 2 years, there was a hint of separation of the curves, explained study author Emma Hall, MD, from the Institute of Cancer Research, London at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

One of the treatment arms received a reduced rate of radiation therapy to see if that would decrease toxicity. “The radiation therapy volume modification that we used did not reduce toxicity, but there is no evidence of an increase in local failure rate, suggesting it is safe to pursue clinical trials of volume sparing radiation therapy using newer technology adaptive delivery techniques,” said Dr. Hall.

The initial findings of the BC2001 study showed that adding chemotherapy (5-FU + MMC) to radiotherapy significantly improved rates of MIBC locoregional control but that reduced high-dose volume versus standard radiotherapy did not significantly reduce late side effects.

This study was a clinical trial set up to test two different questions in the treatment of MIBC, as an alternative to cystectomy. “We wanted to see if adding synchronous chemotherapy to radiotherapy would improve locoregional recurrence control and if reducing the radiation dose to uninvolved bladder would reduce toxicity and not impact local regional recurrence control,” according to Dr. Hall.

Under the 2 x 2 partial factorial design, 458 patients were randomized to radiation therapy (n = 178) or chemoradiation (n = 182) and/or to standard radiation therapy (n = 108) or reduced high-dose volume radiation therapy (n = 111).

The primary endpoint was locoregional control, and secondary endpoints included overall survival, bladder-cancer specific survival, metastasis-free survival, and salvage cystectomy rates.

The initial patients received radiation therapy instead of chemoradiation, and there was a robust improvement in bladder cancer–specific survival when adjusted for known prognostic factors (HR, 0.73; P = .043).

The analysis, presented in 2012, showed a reduction of about one-third of locoregional recurrence. The local control rates were 54% in the radiotherapy-alone arm and 67% in the chemoradiotherapy arm.

There was no significant difference in overall survival at that time.

For the radiotherapy comparison, the rate of late toxicity was low, and much lower than was anticipated, at the outset of the trial, and there was no difference in treatment groups, said Dr. Hall.

In an updated analysis, with a median of 10 years of follow-up, 70% of the patients were now deceased. “These represent robust data, and it is unlikely we will see any changes to the data,” she noted.

The findings presented now had an additional 4 years of follow-up, and while there were additional late events, the results were basically the same.

The rate of local control now showed a 40% reduction in the risk of recurrence and 5-year local control rates of 49% in the radiotherapy arm and 63% in the chemoradiotherapy arm.

“With 10 years follow up, an improvement in locoregional control and a reduced salvage cystectomy rate is confirmed with chemoradiotherapy,” Dr. Hall concluded, “and, taken together with the good quality of life data we have, this is important for this group.”

In a discussion of the paper, Dr. Jonathan Rosenberg, MD, from Memorial Sloan Kettering Cancer Center in New York, agrees with the conclusion that the data continue to support the use of chemoradiotherapy and that 5-FU + MMC is a good option.

He noted that 5-FU + MMC is a standard of care regardless of cisplatin eligibility, but he cannot draw conclusions on dose volume. “There are also other options for chemosensitization,” he said, but it is also import to determine the best way to select patients who will derive the most benefit from chemoradiation.

“There is a high need for robust predictive biomarkers, and we need novel approaches to move beyond chemotherapy,” he said.

The study was supported by Cancer Research UK. Dr Hall has received research funding from Accuray, AstraZeneca, Aventis, and Bayer. Several co-authors also have disclosed relationships with industry. Dr. Rosenberg has disclosed multiple relationships with industry.

Orlando – The updated results of a large phase III trial support the use of chemoradiation with 5-fluorouracil (5-FU) and mitomycin C (MMC) and confirm that this treatment regimen should be a standard of care for muscle-invasive bladder cancer (MIBC).

When comparing patients who received radiation therapy with those who received chemoradiation, there was a robust improvement in bladder cancer specific survival for the latter when adjusted for known prognostic factors (hazard ratio, 0.73; P = .043).

There was also a borderline significant improvement in metastasis-free survival (HR, 0.78) and a significant reduction in the need for salvage cystectomy in the patients treated with chemoradiation (2-year rate, chemoradiotherapy11% vs. radiation therapy:17%, HR, 0.54; P = .03).

There were no statistically significant differences between groups when it came to overall survival, but, even though overall survival did not reach significance, at 2 years, there was a hint of separation of the curves, explained study author Emma Hall, MD, from the Institute of Cancer Research, London at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

One of the treatment arms received a reduced rate of radiation therapy to see if that would decrease toxicity. “The radiation therapy volume modification that we used did not reduce toxicity, but there is no evidence of an increase in local failure rate, suggesting it is safe to pursue clinical trials of volume sparing radiation therapy using newer technology adaptive delivery techniques,” said Dr. Hall.

The initial findings of the BC2001 study showed that adding chemotherapy (5-FU + MMC) to radiotherapy significantly improved rates of MIBC locoregional control but that reduced high-dose volume versus standard radiotherapy did not significantly reduce late side effects.

This study was a clinical trial set up to test two different questions in the treatment of MIBC, as an alternative to cystectomy. “We wanted to see if adding synchronous chemotherapy to radiotherapy would improve locoregional recurrence control and if reducing the radiation dose to uninvolved bladder would reduce toxicity and not impact local regional recurrence control,” according to Dr. Hall.

Under the 2 x 2 partial factorial design, 458 patients were randomized to radiation therapy (n = 178) or chemoradiation (n = 182) and/or to standard radiation therapy (n = 108) or reduced high-dose volume radiation therapy (n = 111).

The primary endpoint was locoregional control, and secondary endpoints included overall survival, bladder-cancer specific survival, metastasis-free survival, and salvage cystectomy rates.

The initial patients received radiation therapy instead of chemoradiation, and there was a robust improvement in bladder cancer–specific survival when adjusted for known prognostic factors (HR, 0.73; P = .043).

The analysis, presented in 2012, showed a reduction of about one-third of locoregional recurrence. The local control rates were 54% in the radiotherapy-alone arm and 67% in the chemoradiotherapy arm.

There was no significant difference in overall survival at that time.

For the radiotherapy comparison, the rate of late toxicity was low, and much lower than was anticipated, at the outset of the trial, and there was no difference in treatment groups, said Dr. Hall.

In an updated analysis, with a median of 10 years of follow-up, 70% of the patients were now deceased. “These represent robust data, and it is unlikely we will see any changes to the data,” she noted.

The findings presented now had an additional 4 years of follow-up, and while there were additional late events, the results were basically the same.

The rate of local control now showed a 40% reduction in the risk of recurrence and 5-year local control rates of 49% in the radiotherapy arm and 63% in the chemoradiotherapy arm.

“With 10 years follow up, an improvement in locoregional control and a reduced salvage cystectomy rate is confirmed with chemoradiotherapy,” Dr. Hall concluded, “and, taken together with the good quality of life data we have, this is important for this group.”

In a discussion of the paper, Dr. Jonathan Rosenberg, MD, from Memorial Sloan Kettering Cancer Center in New York, agrees with the conclusion that the data continue to support the use of chemoradiotherapy and that 5-FU + MMC is a good option.

He noted that 5-FU + MMC is a standard of care regardless of cisplatin eligibility, but he cannot draw conclusions on dose volume. “There are also other options for chemosensitization,” he said, but it is also import to determine the best way to select patients who will derive the most benefit from chemoradiation.

“There is a high need for robust predictive biomarkers, and we need novel approaches to move beyond chemotherapy,” he said.

The study was supported by Cancer Research UK. Dr Hall has received research funding from Accuray, AstraZeneca, Aventis, and Bayer. Several co-authors also have disclosed relationships with industry. Dr. Rosenberg has disclosed multiple relationships with industry.

A new large study has identified 78 significantly mutated genes (SMGs) and has enlarged the genetic landscape of prostate cancer. In addition, 37 genes that were not previously reported as SMGs in prostate cancer and 23 that were not previously identified as recurrently altered in cancer, were identified.

“Through aggregation and uniform genomic analysis, we refined the map of somatic mutations in prostate cancer and identified cancer genes and pathways not previously associated with this disease,” said lead author Dr. Joshua Armenia, of the Memorial Sloan Kettering Cancer Center, New York.

“Our findings may inform patient stratification and translational investigation,” Dr. Armenia said in a press briefing held in 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

SilverV/thinkstockphotos

[email protected]

A new large study has identified 78 significantly mutated genes (SMGs) and has enlarged the genetic landscape of prostate cancer. In addition, 37 genes that were not previously reported as SMGs in prostate cancer and 23 that were not previously identified as recurrently altered in cancer, were identified.

“Through aggregation and uniform genomic analysis, we refined the map of somatic mutations in prostate cancer and identified cancer genes and pathways not previously associated with this disease,” said lead author Dr. Joshua Armenia, of the Memorial Sloan Kettering Cancer Center, New York.

“Our findings may inform patient stratification and translational investigation,” Dr. Armenia said in a press briefing held in 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

SilverV/thinkstockphotos

[email protected]

A new large study has identified 78 significantly mutated genes (SMGs) and has enlarged the genetic landscape of prostate cancer. In addition, 37 genes that were not previously reported as SMGs in prostate cancer and 23 that were not previously identified as recurrently altered in cancer, were identified.

“Through aggregation and uniform genomic analysis, we refined the map of somatic mutations in prostate cancer and identified cancer genes and pathways not previously associated with this disease,” said lead author Dr. Joshua Armenia, of the Memorial Sloan Kettering Cancer Center, New York.

“Our findings may inform patient stratification and translational investigation,” Dr. Armenia said in a press briefing held in 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

SilverV/thinkstockphotos

[email protected]

ORLANDO – A large analysis has identified 65 novel prostate cancer susceptibility loci, including an early-onset locus, and captured an additional 6% of the familial relevant risk for prostate cancer.

In the Oncoarray stratified analysis, the researchers detected two single nucleotide polymorphisms (SNPs) that were associated with early-onset prostate cancer, defined as disease occurring in men younger than 55 years, and four that were associated with both aggressive and indolent disease.

roobcio/Thinkstock

ORLANDO – A large analysis has identified 65 novel prostate cancer susceptibility loci, including an early-onset locus, and captured an additional 6% of the familial relevant risk for prostate cancer.

In the Oncoarray stratified analysis, the researchers detected two single nucleotide polymorphisms (SNPs) that were associated with early-onset prostate cancer, defined as disease occurring in men younger than 55 years, and four that were associated with both aggressive and indolent disease.

roobcio/Thinkstock

ORLANDO – A large analysis has identified 65 novel prostate cancer susceptibility loci, including an early-onset locus, and captured an additional 6% of the familial relevant risk for prostate cancer.

In the Oncoarray stratified analysis, the researchers detected two single nucleotide polymorphisms (SNPs) that were associated with early-onset prostate cancer, defined as disease occurring in men younger than 55 years, and four that were associated with both aggressive and indolent disease.

roobcio/Thinkstock

Inpatient palliative care can help maintain quality of life (QoL) in patients undergoing hematopoietic stem cell transplantation (HCT), based on the results of a randomized clinical trial to assess the effect of inpatient palliative care on patient and caregiver-reported outcomes while hospitalized for HCT and for 3 months after transplantation.

During the 2-week period following their transplants, patients who received inpatient palliative care experienced a 14.72-point decrease in QoL, compared with a 21.54-point decrease in QoL for those assigned to standard transplant care alone. The difference was statistically significant (JAMA. 2016;316[20]:2094-2103. doi:10.1001/jama.2016.16786).

In addition to the QoL results, Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston, and coauthors, noted that “exploratory secondary outcomes also showed that patients in the palliative care group benefited, with less increase in their depression symptoms, lower anxiety symptoms, and less increase in symptom burden compared with those receiving standard transplant care.

“Thus, palliative care may help to lessen the decline in QoL experienced by patients during hospitalization for HCT, which has long been perceived as a natural aspect of the transplantation process.”

The study cohort comprised 160 adults with hematologic malignancies undergoing autologous/allogeneic HCT, and 94 caregivers.

A total of 81 patients were assigned to the intervention, and were seen by palliative care clinicians at least twice a week while they were hospitalized. The palliative care intervention focused on managing both physical and psychological symptoms, and those who were assigned to the standard care arm (n = 79) could also request to be seen by the palliative care team.

Quality of life was measured based on mean FACT-BMT score. In the palliative care group, the FACT-BMT score was 110.26 at hospitalization and 95.46 at 2 weeks after transplant (mean change, −14.72). For the standard care group, FACT-BMT score was 106.83 at hospitalization and 85.42 at 2 weeks after transplant (mean change, −21.54) The −6.82 difference between the group groups was statistically significant (95% CI, −13.48 to −0.16; P = .045).

When looking at secondary outcomes, those in the intervention group had lower mean depression scores at 2 weeks based on the HADS-D measure. For the intervention group, the mean baseline score was 3.95 and the mean week 2 score was 6.39. For the control group, the baseline score was 4.94 and the week 2 score was 8.86. The difference between the groups was 1.49 (95% CI, 0.20-2.78; P = .02). Depression scores remained lower in the intervention group at 3 months.

The intervention group also reported a decrease in anxiety symptoms, but the control group reported an increase in anxiety symptoms from baseline to week 2 on the HADS-A measure. The mean difference in score between the two groups was 1.92; (95% CI, 0.83-3.01; P less than .001). However, there was no significant difference between the two groups at 3 months after transplant.

The study was supported by the National Palliative Care Research Foundation and grant K24 CA 181253 from the National Cancer Institute. Dr. El-Jawahri reported no disclosures.

Inpatient palliative care can help maintain quality of life (QoL) in patients undergoing hematopoietic stem cell transplantation (HCT), based on the results of a randomized clinical trial to assess the effect of inpatient palliative care on patient and caregiver-reported outcomes while hospitalized for HCT and for 3 months after transplantation.

During the 2-week period following their transplants, patients who received inpatient palliative care experienced a 14.72-point decrease in QoL, compared with a 21.54-point decrease in QoL for those assigned to standard transplant care alone. The difference was statistically significant (JAMA. 2016;316[20]:2094-2103. doi:10.1001/jama.2016.16786).

In addition to the QoL results, Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston, and coauthors, noted that “exploratory secondary outcomes also showed that patients in the palliative care group benefited, with less increase in their depression symptoms, lower anxiety symptoms, and less increase in symptom burden compared with those receiving standard transplant care.

“Thus, palliative care may help to lessen the decline in QoL experienced by patients during hospitalization for HCT, which has long been perceived as a natural aspect of the transplantation process.”

The study cohort comprised 160 adults with hematologic malignancies undergoing autologous/allogeneic HCT, and 94 caregivers.

A total of 81 patients were assigned to the intervention, and were seen by palliative care clinicians at least twice a week while they were hospitalized. The palliative care intervention focused on managing both physical and psychological symptoms, and those who were assigned to the standard care arm (n = 79) could also request to be seen by the palliative care team.

Quality of life was measured based on mean FACT-BMT score. In the palliative care group, the FACT-BMT score was 110.26 at hospitalization and 95.46 at 2 weeks after transplant (mean change, −14.72). For the standard care group, FACT-BMT score was 106.83 at hospitalization and 85.42 at 2 weeks after transplant (mean change, −21.54) The −6.82 difference between the group groups was statistically significant (95% CI, −13.48 to −0.16; P = .045).

When looking at secondary outcomes, those in the intervention group had lower mean depression scores at 2 weeks based on the HADS-D measure. For the intervention group, the mean baseline score was 3.95 and the mean week 2 score was 6.39. For the control group, the baseline score was 4.94 and the week 2 score was 8.86. The difference between the groups was 1.49 (95% CI, 0.20-2.78; P = .02). Depression scores remained lower in the intervention group at 3 months.

The intervention group also reported a decrease in anxiety symptoms, but the control group reported an increase in anxiety symptoms from baseline to week 2 on the HADS-A measure. The mean difference in score between the two groups was 1.92; (95% CI, 0.83-3.01; P less than .001). However, there was no significant difference between the two groups at 3 months after transplant.

The study was supported by the National Palliative Care Research Foundation and grant K24 CA 181253 from the National Cancer Institute. Dr. El-Jawahri reported no disclosures.

Inpatient palliative care can help maintain quality of life (QoL) in patients undergoing hematopoietic stem cell transplantation (HCT), based on the results of a randomized clinical trial to assess the effect of inpatient palliative care on patient and caregiver-reported outcomes while hospitalized for HCT and for 3 months after transplantation.

During the 2-week period following their transplants, patients who received inpatient palliative care experienced a 14.72-point decrease in QoL, compared with a 21.54-point decrease in QoL for those assigned to standard transplant care alone. The difference was statistically significant (JAMA. 2016;316[20]:2094-2103. doi:10.1001/jama.2016.16786).

In addition to the QoL results, Areej El-Jawahri, MD, of Massachusetts General Hospital in Boston, and coauthors, noted that “exploratory secondary outcomes also showed that patients in the palliative care group benefited, with less increase in their depression symptoms, lower anxiety symptoms, and less increase in symptom burden compared with those receiving standard transplant care.

“Thus, palliative care may help to lessen the decline in QoL experienced by patients during hospitalization for HCT, which has long been perceived as a natural aspect of the transplantation process.”

The study cohort comprised 160 adults with hematologic malignancies undergoing autologous/allogeneic HCT, and 94 caregivers.

A total of 81 patients were assigned to the intervention, and were seen by palliative care clinicians at least twice a week while they were hospitalized. The palliative care intervention focused on managing both physical and psychological symptoms, and those who were assigned to the standard care arm (n = 79) could also request to be seen by the palliative care team.

Quality of life was measured based on mean FACT-BMT score. In the palliative care group, the FACT-BMT score was 110.26 at hospitalization and 95.46 at 2 weeks after transplant (mean change, −14.72). For the standard care group, FACT-BMT score was 106.83 at hospitalization and 85.42 at 2 weeks after transplant (mean change, −21.54) The −6.82 difference between the group groups was statistically significant (95% CI, −13.48 to −0.16; P = .045).

When looking at secondary outcomes, those in the intervention group had lower mean depression scores at 2 weeks based on the HADS-D measure. For the intervention group, the mean baseline score was 3.95 and the mean week 2 score was 6.39. For the control group, the baseline score was 4.94 and the week 2 score was 8.86. The difference between the groups was 1.49 (95% CI, 0.20-2.78; P = .02). Depression scores remained lower in the intervention group at 3 months.

The intervention group also reported a decrease in anxiety symptoms, but the control group reported an increase in anxiety symptoms from baseline to week 2 on the HADS-A measure. The mean difference in score between the two groups was 1.92; (95% CI, 0.83-3.01; P less than .001). However, there was no significant difference between the two groups at 3 months after transplant.

The study was supported by the National Palliative Care Research Foundation and grant K24 CA 181253 from the National Cancer Institute. Dr. El-Jawahri reported no disclosures.

Single-agent therapy with decitabine elicited favorable responses in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) who had cytogenetic abnormalities associated with an unfavorable risk profile, a study showed.

Even though the responses were not long lasting, the overall survival rates were similar to those of AML patients who had an intermediate-risk cytogenetic profile and who had received the same treatment regimen.

Adult AML patients with karyotypes associated with unfavorable risk and older patients with AML (aged 60 or older) generally have poor outcomes, with a median survival in the range of 1 year. Those with AML and TP53 mutations tend to be older (median age, 61-67 years), and nearly all patients have karyotypes associated with unfavorable risk. These patients have particularly dismal outcomes, with median survival in the range of 4-6 months, if they receive cytotoxic chemotherapy.

In their study, John S Welch, MD, of Washington University, St Louis, and his colleagues evaluated somatic mutations and their relationships to clinical responses in 84 adult patients with AML or MDS who received treatment with decitabine as monotherapy.

Decitabine was administered at a dose of 20 mg/m² of body surface area per day for 10 consecutive days in monthly cycles. An extension cohort that included 32 additional patients also were treated with decitabine but in different protocols.

Of the entire cohort of 116 patients, 15 patients (13%) achieved a complete remission, and 38 patients had bone marrow blast clearance with less than 5% blasts (complete remission with incomplete count recovery or morphologic complete remission). The overall response rate was 46%. In addition, 9 patients (8%), achieved a partial response, stable disease was observed in 23 patients (20%), and progressive disease was seen in 19 patients (16%).

Clinical responses were strongly correlated with karyotypes associated with unfavorable risk and the presence of TP53 mutations. Bone marrow blast clearance (complete remission, complete remission with incomplete count recovery, or morphologic complete remission) occurred in 29 of 43 patients with karyotypes associated with unfavorable risk (67%), compared with 24 of 71 patients with karyotypes associated with intermediate or favorable risk (34%). The same pattern was observed in all patients with TP53 mutations (100%) versus 32 of 78 patients with wildtype TP53 mutations (41%).

“Additional studies will be required to determine whether these differences in survival are truly due to improved responses associated with decitabine or whether conventional chemotherapy with an anthracycline and cytarabine actually decreases the rate of survival among patients with unfavorable-risk cytogenetic profiles,” wrote Dr. Welch and his colleagues.

The study was supported by the Specialized Program of Research Excellence in AML of the National Cancer Institute and the Genomics of AML Program Project. Dr. Welch had no disclosures, and several of his coauthors reported relationships with industry.

Single-agent therapy with decitabine elicited favorable responses in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) who had cytogenetic abnormalities associated with an unfavorable risk profile, a study showed.

Even though the responses were not long lasting, the overall survival rates were similar to those of AML patients who had an intermediate-risk cytogenetic profile and who had received the same treatment regimen.

Adult AML patients with karyotypes associated with unfavorable risk and older patients with AML (aged 60 or older) generally have poor outcomes, with a median survival in the range of 1 year. Those with AML and TP53 mutations tend to be older (median age, 61-67 years), and nearly all patients have karyotypes associated with unfavorable risk. These patients have particularly dismal outcomes, with median survival in the range of 4-6 months, if they receive cytotoxic chemotherapy.

In their study, John S Welch, MD, of Washington University, St Louis, and his colleagues evaluated somatic mutations and their relationships to clinical responses in 84 adult patients with AML or MDS who received treatment with decitabine as monotherapy.

Decitabine was administered at a dose of 20 mg/m² of body surface area per day for 10 consecutive days in monthly cycles. An extension cohort that included 32 additional patients also were treated with decitabine but in different protocols.

Of the entire cohort of 116 patients, 15 patients (13%) achieved a complete remission, and 38 patients had bone marrow blast clearance with less than 5% blasts (complete remission with incomplete count recovery or morphologic complete remission). The overall response rate was 46%. In addition, 9 patients (8%), achieved a partial response, stable disease was observed in 23 patients (20%), and progressive disease was seen in 19 patients (16%).

Clinical responses were strongly correlated with karyotypes associated with unfavorable risk and the presence of TP53 mutations. Bone marrow blast clearance (complete remission, complete remission with incomplete count recovery, or morphologic complete remission) occurred in 29 of 43 patients with karyotypes associated with unfavorable risk (67%), compared with 24 of 71 patients with karyotypes associated with intermediate or favorable risk (34%). The same pattern was observed in all patients with TP53 mutations (100%) versus 32 of 78 patients with wildtype TP53 mutations (41%).

“Additional studies will be required to determine whether these differences in survival are truly due to improved responses associated with decitabine or whether conventional chemotherapy with an anthracycline and cytarabine actually decreases the rate of survival among patients with unfavorable-risk cytogenetic profiles,” wrote Dr. Welch and his colleagues.

The study was supported by the Specialized Program of Research Excellence in AML of the National Cancer Institute and the Genomics of AML Program Project. Dr. Welch had no disclosures, and several of his coauthors reported relationships with industry.

Single-agent therapy with decitabine elicited favorable responses in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) who had cytogenetic abnormalities associated with an unfavorable risk profile, a study showed.

Even though the responses were not long lasting, the overall survival rates were similar to those of AML patients who had an intermediate-risk cytogenetic profile and who had received the same treatment regimen.

Adult AML patients with karyotypes associated with unfavorable risk and older patients with AML (aged 60 or older) generally have poor outcomes, with a median survival in the range of 1 year. Those with AML and TP53 mutations tend to be older (median age, 61-67 years), and nearly all patients have karyotypes associated with unfavorable risk. These patients have particularly dismal outcomes, with median survival in the range of 4-6 months, if they receive cytotoxic chemotherapy.

In their study, John S Welch, MD, of Washington University, St Louis, and his colleagues evaluated somatic mutations and their relationships to clinical responses in 84 adult patients with AML or MDS who received treatment with decitabine as monotherapy.

Decitabine was administered at a dose of 20 mg/m² of body surface area per day for 10 consecutive days in monthly cycles. An extension cohort that included 32 additional patients also were treated with decitabine but in different protocols.

Of the entire cohort of 116 patients, 15 patients (13%) achieved a complete remission, and 38 patients had bone marrow blast clearance with less than 5% blasts (complete remission with incomplete count recovery or morphologic complete remission). The overall response rate was 46%. In addition, 9 patients (8%), achieved a partial response, stable disease was observed in 23 patients (20%), and progressive disease was seen in 19 patients (16%).

Clinical responses were strongly correlated with karyotypes associated with unfavorable risk and the presence of TP53 mutations. Bone marrow blast clearance (complete remission, complete remission with incomplete count recovery, or morphologic complete remission) occurred in 29 of 43 patients with karyotypes associated with unfavorable risk (67%), compared with 24 of 71 patients with karyotypes associated with intermediate or favorable risk (34%). The same pattern was observed in all patients with TP53 mutations (100%) versus 32 of 78 patients with wildtype TP53 mutations (41%).

“Additional studies will be required to determine whether these differences in survival are truly due to improved responses associated with decitabine or whether conventional chemotherapy with an anthracycline and cytarabine actually decreases the rate of survival among patients with unfavorable-risk cytogenetic profiles,” wrote Dr. Welch and his colleagues.

The study was supported by the Specialized Program of Research Excellence in AML of the National Cancer Institute and the Genomics of AML Program Project. Dr. Welch had no disclosures, and several of his coauthors reported relationships with industry.

Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.

The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.

But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.

This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).

DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.

The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.

The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.

The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.

Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).

Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.

After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).

Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.

“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.

Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.

The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.

But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.

This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).

DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.

The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.

The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.

The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.

Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).

Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.

After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).

Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.

“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.

Patients with double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) have inferior outcomes after undergoing autologous stem cell transplantation (ASCT), according to a new study published in the Journal of Clinical Oncology.

The worst outcomes were observed in patients with concurrent DELs and DHLs, and this “supports the concept that the double-hit/double-expressor biology appears to render DLBCL resistant to and less likely to be cured by chemotherapy,” write Alex Herrera, MD, an oncologist at the City of Hope, Duarte, Calif., and his colleagues.

But that said, a significant proportion of patients with relapsed/refractory DEL did experience durable remissions following ASCT, particularly those with isolated DEL without DHL.

This suggests that “the presence of DEL alone should not be considered a contraindication to ASCT,” the authors wrote (J Clin Oncol. 2016 Oct. 24. doi: 10.1200/JCO.2016.68.2740).

DHLs and DELs are subtypes of diffuse large B-cell lymphoma (DLBCL), and while they are associated with poor outcomes after standard chemoimmunotherapy, data remain limited as to outcomes of patients with relapsed or refractory disease who undergo ASCT.

The retrospective multicenter study included 117 patients with chemotherapy-sensitive relapsed/refractory DLBCL who underwent ASCT and had archival tumor material available. DEL with MYC/BCL2 coexpression was observed in 52 patients (44%) while 15 patients expressed MYC-R (13%), of whom 12 (10%) had DHL.

The median follow-up time was 45 months for survivors, and the 4-year progression-free survival (PFS) and overall survival (OS) were 54% for the entire cohort.

The 4-year PFS and OS in patients with DHL was worse as compared to those without DHL; 28% vs. 57% (P = .013), and 25% vs. 66% (P less than .001), respectively.

Those with DHL had poorer PFS (28%) and OS (25%), compared with patients with DEL but not DHL (PFS, 53% and OS, 61%) as well as patients with neither DEL nor DHL (PFS, 60% and OS, 70%; three-way P value for PFS, P = .013; OS, P = .002).

Patients with concurrent DEL and DHL had the poorest outcome, with a 4-year PFS of 0%.

After researchers adjusted for clinical characteristics, the only factors that remained significantly associated with PFS were DEL (hazard ratio, 1.8; P = .035) and DHL (HR, 2.9; P = .009). Factors that were significantly associated with OS were DHL (HR, 3.4; P = .004) and remission status at ASCT (HR for partial response, 2.4; P = .007).

Overall, patients with DHL were less likely to achieve a complete response following salvage therapy, and those with DEL and patients with DHL had a shorter time to relapse after induction therapy.

“Although some patients with relapsed/refractory DHL had long-term remission after ASCT (isolated DHL without DEL), the low survival rate in this group argues that alternative transplantation strategies, including allogeneic hematopoietic stem cell transplantation or peri-ASCT relapse prevention strategies should be studied,” they concluded.

Cancer survivors who underwent hematopoietic cell transplantation (HCT) face a greater risk for hospitalizations and mortality, compared with survivors who did not have HCT.

New findings show that disparities in infectious and respiratory complications were marked between the two groups, but differences in circulatory disease, mental health diagnoses, and second cancers were insignificant.

“Clinicians who care for long-term survivors of HCT should be aware of comprehensive surveillance guidelines available for this high-risk population,” wrote Eric J. Chow, MD, of the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.68.8457).

There have only been a few comprehensive analyses that have compared HCT with non-HCT cancer survivors. Thus, the authors noted that it is unclear if HCT survivors are at a greater risk of late complications, compared with other cancer survivors.

To address this issue, Dr. Chow and his team matched 2-year cancer survivors who had undergone HCT (n = 1,792; 52% allogeneic and 90% hematologic malignancies) to non-HCT 2-year cancer survivors, using a state cancer registry (n = 5,455), and the general population (n = 16,340), using driver’s license files.

The investigators found that the 10-year cumulative incidence of any hospitalization or death related to all major organ-system outcomes was significantly different (P less than .05) between the HCT survivors and general population.

Patients with a history of HCT had a 30.6% cumulative incidence of infectious complications (difference vs. non-HCT: 8.7%) and a 26.8% incidence of any respiratory complications (difference vs. non-HCT: 6.9%), the investigators reported.

In contrast, the 10-year cumulative incidences of nervous system, circulatory, and genitourinary complications; mental health outcomes; and the development of new cancers did not differ between the HCT and non-HCT groups.

The incidence of pregnancy-related hospitalization among women of childbearing age was lower in the HCT group, compared with non-HCT patients (group difference, 24.4%).

At the 2-year endpoint, Dr. Chow and his associates noted that certain risks were “notably higher” in patients who had undergone HCT, including primary infections (hazard ratio, 1.4), respiratory complications (HR, 1.3), and death from any cause (HR, 1.1).

A significantly greater hospitalization rate also was observed in the HCT group versus the non-HCT group (280 episodes per 1,000 person-years vs. 173 episodes per 1,000 person years; P less than .001).

“Future work to identify more specific risk factors associated with late infections and respiratory complications may help to further refine these guidelines and identify new prevention strategies,” the authors concluded.

The study was funded by grants from the National Institutes of Health. Dr. Chow had no disclosures and several coauthors report relationships with industry.

Cancer survivors who underwent hematopoietic cell transplantation (HCT) face a greater risk for hospitalizations and mortality, compared with survivors who did not have HCT.

New findings show that disparities in infectious and respiratory complications were marked between the two groups, but differences in circulatory disease, mental health diagnoses, and second cancers were insignificant.

“Clinicians who care for long-term survivors of HCT should be aware of comprehensive surveillance guidelines available for this high-risk population,” wrote Eric J. Chow, MD, of the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.68.8457).

There have only been a few comprehensive analyses that have compared HCT with non-HCT cancer survivors. Thus, the authors noted that it is unclear if HCT survivors are at a greater risk of late complications, compared with other cancer survivors.

To address this issue, Dr. Chow and his team matched 2-year cancer survivors who had undergone HCT (n = 1,792; 52% allogeneic and 90% hematologic malignancies) to non-HCT 2-year cancer survivors, using a state cancer registry (n = 5,455), and the general population (n = 16,340), using driver’s license files.

The investigators found that the 10-year cumulative incidence of any hospitalization or death related to all major organ-system outcomes was significantly different (P less than .05) between the HCT survivors and general population.

Patients with a history of HCT had a 30.6% cumulative incidence of infectious complications (difference vs. non-HCT: 8.7%) and a 26.8% incidence of any respiratory complications (difference vs. non-HCT: 6.9%), the investigators reported.

In contrast, the 10-year cumulative incidences of nervous system, circulatory, and genitourinary complications; mental health outcomes; and the development of new cancers did not differ between the HCT and non-HCT groups.

The incidence of pregnancy-related hospitalization among women of childbearing age was lower in the HCT group, compared with non-HCT patients (group difference, 24.4%).

At the 2-year endpoint, Dr. Chow and his associates noted that certain risks were “notably higher” in patients who had undergone HCT, including primary infections (hazard ratio, 1.4), respiratory complications (HR, 1.3), and death from any cause (HR, 1.1).

A significantly greater hospitalization rate also was observed in the HCT group versus the non-HCT group (280 episodes per 1,000 person-years vs. 173 episodes per 1,000 person years; P less than .001).

“Future work to identify more specific risk factors associated with late infections and respiratory complications may help to further refine these guidelines and identify new prevention strategies,” the authors concluded.

The study was funded by grants from the National Institutes of Health. Dr. Chow had no disclosures and several coauthors report relationships with industry.

Cancer survivors who underwent hematopoietic cell transplantation (HCT) face a greater risk for hospitalizations and mortality, compared with survivors who did not have HCT.

New findings show that disparities in infectious and respiratory complications were marked between the two groups, but differences in circulatory disease, mental health diagnoses, and second cancers were insignificant.

“Clinicians who care for long-term survivors of HCT should be aware of comprehensive surveillance guidelines available for this high-risk population,” wrote Eric J. Chow, MD, of the Fred Hutchinson Cancer Research Center, Seattle, and his colleagues (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.68.8457).

There have only been a few comprehensive analyses that have compared HCT with non-HCT cancer survivors. Thus, the authors noted that it is unclear if HCT survivors are at a greater risk of late complications, compared with other cancer survivors.

To address this issue, Dr. Chow and his team matched 2-year cancer survivors who had undergone HCT (n = 1,792; 52% allogeneic and 90% hematologic malignancies) to non-HCT 2-year cancer survivors, using a state cancer registry (n = 5,455), and the general population (n = 16,340), using driver’s license files.

The investigators found that the 10-year cumulative incidence of any hospitalization or death related to all major organ-system outcomes was significantly different (P less than .05) between the HCT survivors and general population.

Patients with a history of HCT had a 30.6% cumulative incidence of infectious complications (difference vs. non-HCT: 8.7%) and a 26.8% incidence of any respiratory complications (difference vs. non-HCT: 6.9%), the investigators reported.

In contrast, the 10-year cumulative incidences of nervous system, circulatory, and genitourinary complications; mental health outcomes; and the development of new cancers did not differ between the HCT and non-HCT groups.

The incidence of pregnancy-related hospitalization among women of childbearing age was lower in the HCT group, compared with non-HCT patients (group difference, 24.4%).

At the 2-year endpoint, Dr. Chow and his associates noted that certain risks were “notably higher” in patients who had undergone HCT, including primary infections (hazard ratio, 1.4), respiratory complications (HR, 1.3), and death from any cause (HR, 1.1).

A significantly greater hospitalization rate also was observed in the HCT group versus the non-HCT group (280 episodes per 1,000 person-years vs. 173 episodes per 1,000 person years; P less than .001).

“Future work to identify more specific risk factors associated with late infections and respiratory complications may help to further refine these guidelines and identify new prevention strategies,” the authors concluded.

The study was funded by grants from the National Institutes of Health. Dr. Chow had no disclosures and several coauthors report relationships with industry.

Treatment with androgen deprivation therapy (ADT) was not associated with an increased risk of dementia in a large, population-based study, according to investigators.

Previous studies have demonstrated that low testosterone levels are associated with cognitive impairment and Alzheimer’s disease, but the association between ADT and cognitive impairment remains controversial, with conflicting results being reported.

In the current large population-based study, compared with nonuse, treatment with ADT did not increase the risk of dementia (incidence, 7.4 vs. 4.4 per 1,000 person years, adjusted hazard ratio, 1.02; 95%CI, 0.87-1.19), reported Farzin Khosrow-Khavar, PhD, of McGill University, Montreal, and colleagues.

“Consistent with our findings, a recent meta-analysis found that although patients treated with ADT performed worse on visuomotor tasks in comparison with control subjects or their own baseline assessments, there were no significant differences in cognitive domains that are pertinent to dementia including performance on attention/working memory, executive function, language, verbal memory, visual memory, and visuospatial ability” they wrote (J Clin Oncol. 2016 Nov. 21 doi: 10.1200/JCO.2016.69.6203).

In a smaller study of 9,272 patients, recently published in JAMA Oncology, prostate cancer patients treated with ADT were more than twice as likely as were those who were not to develop dementia.

For the current study, investigators identified a cohort of 30,903 men who were newly diagnosed with nonmetastatic prostate cancer between April 1, 1988, and April 30, 2015, using the United Kingdom’s Clinical Practice Research Datalink. The patients were then observed until April 30, 2016.

Within this cohort, 799 patients were newly diagnosed with dementia, which extrapolated to a crude incidence of 6.0 per 1,000 person-years. During the follow-up period, 17,994 patients (58.2%) were treated with ADT, and the median duration of use was 2.3 years.

Men who were using ADT tended to be older and were more likely to have ever used tobacco products, and they were also more likely to have had higher prostate-specific antigen levels and a higher prevalence of comorbidities, compared with nonusers.

In the primary analysis, ADT use was not associated with an overall higher risk of developing dementia (adjusted HR, 1.02; 95% CI, 0.87-1.19).

In secondary analyses, the risk did not vary with cumulative duration of use. Findings were similar when the risk was assessed by the type of ADT used for treatment, and when the association was evaluated with Alzheimer’s disease (adjusted HR, 1.11; 95% CI, 0.85-1.44) versus other types of dementia (adjusted HR, 0.97; 95% CI, 0.80-1.18).

The authors noted that additional studies in different settings are needed to confirm these new findings.

The study was supported by a foundation grant from the Canadian Institutes of Health Research. The authors declared that there were no conflicts of interest.

Treatment with androgen deprivation therapy (ADT) was not associated with an increased risk of dementia in a large, population-based study, according to investigators.

Previous studies have demonstrated that low testosterone levels are associated with cognitive impairment and Alzheimer’s disease, but the association between ADT and cognitive impairment remains controversial, with conflicting results being reported.

In the current large population-based study, compared with nonuse, treatment with ADT did not increase the risk of dementia (incidence, 7.4 vs. 4.4 per 1,000 person years, adjusted hazard ratio, 1.02; 95%CI, 0.87-1.19), reported Farzin Khosrow-Khavar, PhD, of McGill University, Montreal, and colleagues.

“Consistent with our findings, a recent meta-analysis found that although patients treated with ADT performed worse on visuomotor tasks in comparison with control subjects or their own baseline assessments, there were no significant differences in cognitive domains that are pertinent to dementia including performance on attention/working memory, executive function, language, verbal memory, visual memory, and visuospatial ability” they wrote (J Clin Oncol. 2016 Nov. 21 doi: 10.1200/JCO.2016.69.6203).

In a smaller study of 9,272 patients, recently published in JAMA Oncology, prostate cancer patients treated with ADT were more than twice as likely as were those who were not to develop dementia.

For the current study, investigators identified a cohort of 30,903 men who were newly diagnosed with nonmetastatic prostate cancer between April 1, 1988, and April 30, 2015, using the United Kingdom’s Clinical Practice Research Datalink. The patients were then observed until April 30, 2016.

Within this cohort, 799 patients were newly diagnosed with dementia, which extrapolated to a crude incidence of 6.0 per 1,000 person-years. During the follow-up period, 17,994 patients (58.2%) were treated with ADT, and the median duration of use was 2.3 years.

Men who were using ADT tended to be older and were more likely to have ever used tobacco products, and they were also more likely to have had higher prostate-specific antigen levels and a higher prevalence of comorbidities, compared with nonusers.

In the primary analysis, ADT use was not associated with an overall higher risk of developing dementia (adjusted HR, 1.02; 95% CI, 0.87-1.19).

In secondary analyses, the risk did not vary with cumulative duration of use. Findings were similar when the risk was assessed by the type of ADT used for treatment, and when the association was evaluated with Alzheimer’s disease (adjusted HR, 1.11; 95% CI, 0.85-1.44) versus other types of dementia (adjusted HR, 0.97; 95% CI, 0.80-1.18).

The authors noted that additional studies in different settings are needed to confirm these new findings.

The study was supported by a foundation grant from the Canadian Institutes of Health Research. The authors declared that there were no conflicts of interest.

Treatment with androgen deprivation therapy (ADT) was not associated with an increased risk of dementia in a large, population-based study, according to investigators.

Previous studies have demonstrated that low testosterone levels are associated with cognitive impairment and Alzheimer’s disease, but the association between ADT and cognitive impairment remains controversial, with conflicting results being reported.

In the current large population-based study, compared with nonuse, treatment with ADT did not increase the risk of dementia (incidence, 7.4 vs. 4.4 per 1,000 person years, adjusted hazard ratio, 1.02; 95%CI, 0.87-1.19), reported Farzin Khosrow-Khavar, PhD, of McGill University, Montreal, and colleagues.

“Consistent with our findings, a recent meta-analysis found that although patients treated with ADT performed worse on visuomotor tasks in comparison with control subjects or their own baseline assessments, there were no significant differences in cognitive domains that are pertinent to dementia including performance on attention/working memory, executive function, language, verbal memory, visual memory, and visuospatial ability” they wrote (J Clin Oncol. 2016 Nov. 21 doi: 10.1200/JCO.2016.69.6203).

In a smaller study of 9,272 patients, recently published in JAMA Oncology, prostate cancer patients treated with ADT were more than twice as likely as were those who were not to develop dementia.

For the current study, investigators identified a cohort of 30,903 men who were newly diagnosed with nonmetastatic prostate cancer between April 1, 1988, and April 30, 2015, using the United Kingdom’s Clinical Practice Research Datalink. The patients were then observed until April 30, 2016.

Within this cohort, 799 patients were newly diagnosed with dementia, which extrapolated to a crude incidence of 6.0 per 1,000 person-years. During the follow-up period, 17,994 patients (58.2%) were treated with ADT, and the median duration of use was 2.3 years.

Men who were using ADT tended to be older and were more likely to have ever used tobacco products, and they were also more likely to have had higher prostate-specific antigen levels and a higher prevalence of comorbidities, compared with nonusers.

In the primary analysis, ADT use was not associated with an overall higher risk of developing dementia (adjusted HR, 1.02; 95% CI, 0.87-1.19).

In secondary analyses, the risk did not vary with cumulative duration of use. Findings were similar when the risk was assessed by the type of ADT used for treatment, and when the association was evaluated with Alzheimer’s disease (adjusted HR, 1.11; 95% CI, 0.85-1.44) versus other types of dementia (adjusted HR, 0.97; 95% CI, 0.80-1.18).

The authors noted that additional studies in different settings are needed to confirm these new findings.

The study was supported by a foundation grant from the Canadian Institutes of Health Research. The authors declared that there were no conflicts of interest.

A novel panel of DNA methylation markers may aid in predicting survival outcomes in metastatic breast cancer (MBC), according to new findings.

Using a new quantitative assay known as cMethDNA, researchers found that a high cumulative methylation index (CMI) level, as measured with a six-gene panel after beginning a new treatment, was consistently associated with both progression-free survival and overall survival, as well as progressive disease.

Even though these results are encouraging, however, its clinical application is still unknown, they noted.

Bruce Jancin/Frontline Medical News

A novel panel of DNA methylation markers may aid in predicting survival outcomes in metastatic breast cancer (MBC), according to new findings.

Using a new quantitative assay known as cMethDNA, researchers found that a high cumulative methylation index (CMI) level, as measured with a six-gene panel after beginning a new treatment, was consistently associated with both progression-free survival and overall survival, as well as progressive disease.

Even though these results are encouraging, however, its clinical application is still unknown, they noted.

Bruce Jancin/Frontline Medical News

A novel panel of DNA methylation markers may aid in predicting survival outcomes in metastatic breast cancer (MBC), according to new findings.

Using a new quantitative assay known as cMethDNA, researchers found that a high cumulative methylation index (CMI) level, as measured with a six-gene panel after beginning a new treatment, was consistently associated with both progression-free survival and overall survival, as well as progressive disease.

Even though these results are encouraging, however, its clinical application is still unknown, they noted.

Bruce Jancin/Frontline Medical News