Treatment Before, During, and After Pregnancy

To evaluate treatment patterns before, during, and after pregnancy in women with MS and a live birth, Dr. Houtchens and colleagues used a US administrative claims database to conduct a retrospective analysis of women ages 18 to 65 with MS, a claim indicative of a live birth, and one-year continuous eligibility before and after pregnancy in the IMS Health Real World Data Adjudicated Claims US database from January 1, 2006, to June 30, 2015. Disease-modifying drug treatment was evaluated during the year prior to pregnancy (at three-month intervals), the three trimesters of pregnancy, puerperium (six weeks post-pregnancy), and one year post pregnancy (seven to 12 weeks post pregnancy and three to six, six to nine, and nine to 12 months post pregnancy). The researchers evaluated the proportion of women exposed to disease-modifying drug treatment during the 12 time periods. Results were also stratified by the number of relapses women experienced in the year prior to pregnancy.

Of 190,475 women with MS, 2,158 met eligibility criteria. Mean age was 30.26. Most women had commercial health insurance (98%) and were from the Midwest (32%), South (30%), or Northeast (29%) regions of the US.

The proportion of women with MS and a live birth treated with any disease-modifying drug was 20.48% at nine to 12 months pre-pregnancy, 21.46% at six to nine months pre-pregnancy, 20.62% at three to six months pre-pregnancy, and 17.75% at three months pre-pregnancy. During pregnancy, the proportion of women treated with a disease-modifying drug decreased to 12.05% during the first trimester and 1.90% during the second trimester, and then increased slightly to 2.97% during the third trimester. The proportion of women treated with disease-modifying drugs increased to 8.34% during puerperium, 12.93% during seven to 12 weeks post partum, 21.97% during three to six months post partum, 24.47% during six to nine months post partum, and 25.49% during nine to 12 months post partum. The majority of women (81.9%) had received disease-modifying drug treatment by six to nine months post partum. The proportion of women with disease-modifying drug treatment before and after pregnancy increased numerically with the number of relapses experienced before pregnancy.

Treatment After a Live Birth

In a separate analysis using the same cohort, Dr. Houtchens and colleagues looked closer at the time to initiation of disease-modifying drug treatment after a live birth in women with MS. Of the 2,094 women included in this analysis, the proportion with a live birth initiating a disease-modifying drug treatment within one year was 28.46%, and the proportion with no disease-modifying treatment within one year was 71.54%.

For those initiating a disease-modifying treatment within one year, mean time from live birth to first treatment was 118.98 days, and median time to first treatment was 93.50 days. A total of 16.11% received a disease-modifying drug less than 30 days after live birth, approximately half initiated a treatment within 90 days (47.82%), and three-quarters initiated a disease-modifying drug within six months (75.5%). The proportion of patients initiating treatment within one year after live birth increased with higher numbers of pre-pregnancy relapses (zero relapses, n = 441, 24.53%; one relapse, n = 108, 50.94%; two relapses, n = 33, 54.10%; three or more relapses, n = 14, 60.87%). The mean number of days until disease-modifying drug initiation for those receiving treatment within one year who had zero pre-pregnancy relapses was 123.57 (median, 99); one relapse, 107.95 (median, 80); two relapses, 120.76 (median, 98); and three or more relapses, 55.57 (median, 49.5). Patients who received disease-modifying drug treatment one year pre-pregnancy were more likely to receive treatment within one year after delivery, compared with patients without exposure to treatment in the year before pregnancy (72.58% vs 12.44%).

This study was supported by EMD Serono.

Treatment Before, During, and After Pregnancy

To evaluate treatment patterns before, during, and after pregnancy in women with MS and a live birth, Dr. Houtchens and colleagues used a US administrative claims database to conduct a retrospective analysis of women ages 18 to 65 with MS, a claim indicative of a live birth, and one-year continuous eligibility before and after pregnancy in the IMS Health Real World Data Adjudicated Claims US database from January 1, 2006, to June 30, 2015. Disease-modifying drug treatment was evaluated during the year prior to pregnancy (at three-month intervals), the three trimesters of pregnancy, puerperium (six weeks post-pregnancy), and one year post pregnancy (seven to 12 weeks post pregnancy and three to six, six to nine, and nine to 12 months post pregnancy). The researchers evaluated the proportion of women exposed to disease-modifying drug treatment during the 12 time periods. Results were also stratified by the number of relapses women experienced in the year prior to pregnancy.

Of 190,475 women with MS, 2,158 met eligibility criteria. Mean age was 30.26. Most women had commercial health insurance (98%) and were from the Midwest (32%), South (30%), or Northeast (29%) regions of the US.

The proportion of women with MS and a live birth treated with any disease-modifying drug was 20.48% at nine to 12 months pre-pregnancy, 21.46% at six to nine months pre-pregnancy, 20.62% at three to six months pre-pregnancy, and 17.75% at three months pre-pregnancy. During pregnancy, the proportion of women treated with a disease-modifying drug decreased to 12.05% during the first trimester and 1.90% during the second trimester, and then increased slightly to 2.97% during the third trimester. The proportion of women treated with disease-modifying drugs increased to 8.34% during puerperium, 12.93% during seven to 12 weeks post partum, 21.97% during three to six months post partum, 24.47% during six to nine months post partum, and 25.49% during nine to 12 months post partum. The majority of women (81.9%) had received disease-modifying drug treatment by six to nine months post partum. The proportion of women with disease-modifying drug treatment before and after pregnancy increased numerically with the number of relapses experienced before pregnancy.

Treatment After a Live Birth

In a separate analysis using the same cohort, Dr. Houtchens and colleagues looked closer at the time to initiation of disease-modifying drug treatment after a live birth in women with MS. Of the 2,094 women included in this analysis, the proportion with a live birth initiating a disease-modifying drug treatment within one year was 28.46%, and the proportion with no disease-modifying treatment within one year was 71.54%.

For those initiating a disease-modifying treatment within one year, mean time from live birth to first treatment was 118.98 days, and median time to first treatment was 93.50 days. A total of 16.11% received a disease-modifying drug less than 30 days after live birth, approximately half initiated a treatment within 90 days (47.82%), and three-quarters initiated a disease-modifying drug within six months (75.5%). The proportion of patients initiating treatment within one year after live birth increased with higher numbers of pre-pregnancy relapses (zero relapses, n = 441, 24.53%; one relapse, n = 108, 50.94%; two relapses, n = 33, 54.10%; three or more relapses, n = 14, 60.87%). The mean number of days until disease-modifying drug initiation for those receiving treatment within one year who had zero pre-pregnancy relapses was 123.57 (median, 99); one relapse, 107.95 (median, 80); two relapses, 120.76 (median, 98); and three or more relapses, 55.57 (median, 49.5). Patients who received disease-modifying drug treatment one year pre-pregnancy were more likely to receive treatment within one year after delivery, compared with patients without exposure to treatment in the year before pregnancy (72.58% vs 12.44%).

This study was supported by EMD Serono.

Treatment Before, During, and After Pregnancy

To evaluate treatment patterns before, during, and after pregnancy in women with MS and a live birth, Dr. Houtchens and colleagues used a US administrative claims database to conduct a retrospective analysis of women ages 18 to 65 with MS, a claim indicative of a live birth, and one-year continuous eligibility before and after pregnancy in the IMS Health Real World Data Adjudicated Claims US database from January 1, 2006, to June 30, 2015. Disease-modifying drug treatment was evaluated during the year prior to pregnancy (at three-month intervals), the three trimesters of pregnancy, puerperium (six weeks post-pregnancy), and one year post pregnancy (seven to 12 weeks post pregnancy and three to six, six to nine, and nine to 12 months post pregnancy). The researchers evaluated the proportion of women exposed to disease-modifying drug treatment during the 12 time periods. Results were also stratified by the number of relapses women experienced in the year prior to pregnancy.

Of 190,475 women with MS, 2,158 met eligibility criteria. Mean age was 30.26. Most women had commercial health insurance (98%) and were from the Midwest (32%), South (30%), or Northeast (29%) regions of the US.

The proportion of women with MS and a live birth treated with any disease-modifying drug was 20.48% at nine to 12 months pre-pregnancy, 21.46% at six to nine months pre-pregnancy, 20.62% at three to six months pre-pregnancy, and 17.75% at three months pre-pregnancy. During pregnancy, the proportion of women treated with a disease-modifying drug decreased to 12.05% during the first trimester and 1.90% during the second trimester, and then increased slightly to 2.97% during the third trimester. The proportion of women treated with disease-modifying drugs increased to 8.34% during puerperium, 12.93% during seven to 12 weeks post partum, 21.97% during three to six months post partum, 24.47% during six to nine months post partum, and 25.49% during nine to 12 months post partum. The majority of women (81.9%) had received disease-modifying drug treatment by six to nine months post partum. The proportion of women with disease-modifying drug treatment before and after pregnancy increased numerically with the number of relapses experienced before pregnancy.

Treatment After a Live Birth

In a separate analysis using the same cohort, Dr. Houtchens and colleagues looked closer at the time to initiation of disease-modifying drug treatment after a live birth in women with MS. Of the 2,094 women included in this analysis, the proportion with a live birth initiating a disease-modifying drug treatment within one year was 28.46%, and the proportion with no disease-modifying treatment within one year was 71.54%.

For those initiating a disease-modifying treatment within one year, mean time from live birth to first treatment was 118.98 days, and median time to first treatment was 93.50 days. A total of 16.11% received a disease-modifying drug less than 30 days after live birth, approximately half initiated a treatment within 90 days (47.82%), and three-quarters initiated a disease-modifying drug within six months (75.5%). The proportion of patients initiating treatment within one year after live birth increased with higher numbers of pre-pregnancy relapses (zero relapses, n = 441, 24.53%; one relapse, n = 108, 50.94%; two relapses, n = 33, 54.10%; three or more relapses, n = 14, 60.87%). The mean number of days until disease-modifying drug initiation for those receiving treatment within one year who had zero pre-pregnancy relapses was 123.57 (median, 99); one relapse, 107.95 (median, 80); two relapses, 120.76 (median, 98); and three or more relapses, 55.57 (median, 49.5). Patients who received disease-modifying drug treatment one year pre-pregnancy were more likely to receive treatment within one year after delivery, compared with patients without exposure to treatment in the year before pregnancy (72.58% vs 12.44%).

This study was supported by EMD Serono.

Photo from Penn Medicine

CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.

“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”

She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.

The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.

CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.

Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.

“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”

The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.

Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.

Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.

All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.

ALL with EM involvement

The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.

They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.

Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.

The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.

Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.

Nine of the 10 patients achieved MRD-negative CR at day 28.

One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.

Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.

Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.

Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.

The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.

The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL. 

Photo from Penn Medicine

CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.

“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”

She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.

The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.

CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.

Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.

“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”

The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.

Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.

Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.

All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.

ALL with EM involvement

The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.

They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.

Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.

The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.

Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.

Nine of the 10 patients achieved MRD-negative CR at day 28.

One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.

Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.

Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.

Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.

The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.

The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL. 

Photo from Penn Medicine

CHICAGO—Outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) are dismal, with the probability of event-free survival ranging from 15% to 70% after a first relapse to 15% to 20% after a second relapse.

“So novel therapies are obviously urgently needed,” Mala Kiran Talekar, MD, of the Children's Hospital of Philadelphia in Pennsylvania, affirmed. “And herein comes the role of CAR T cells as a breakthrough therapy for relapsed/refractory pediatric ALL.”

She presented the outcome of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with non-CNS extramedullary (EM) relapse at the ASCO 2017 Annual meeting as abstract 10507.

The investigators had drawn the patient population for this analysis from 2 CAR studies, CTL019 and CTL119.

CTL019, which had already been completed, employed a murine CAR, and CTL119 is ongoing and uses a humanized CAR.

Of the 60 patients enrolled in CTL019, 56 (93%) achieved a complete response (CR) at day 28, and 100% had a CNS remission. Their 12-month overall survival (OS) was 79%.

“[K]eep in mind, when the study first started,” Dr Talekar said, “the patient population that had been referred to us was patients who had suffered a second or greater relapse or had been refractory to forms of treatment available to them, and the majority had been refractory to multiple therapies.”

The humanized CAR study, CTL119, is divided into 2 cohorts—one with CAR-naïve patients (n=22) and the other a CAR-retreatment arm (n=15) with patients who had received previous CAR therapy and relapsed.

Dr Talekar explained that the humanized CAR was made with the intention of decreasing rejection or loss of persistence of the T cells related to murine antigenicity.

Nine patients (60%) in the CAR-retreatment arm achieved a CR at day 28, and at 6 months, 78% experienced relapse-free survival (RFS) with a median follow-up of 12 months.

All of the CAR-naïve patients achieved CR at day 28, with 86% achieving RFS at 6 months, with a median follow-up of 10 months.

ALL with EM involvement

The investigators identified 10 pediatric patients treated in the murine (n=6) or humanized (n=4) trials who had received CAR therapy for isolated extramedullary disease or for combined bone marrow extramedullary (BM/EM) relapse of ALL.

They defined EM relapse as involvement of a non-CNS site confirmed by imaging with or without pathology within 12 months of CAR T-cell infusion. After infusion, patients had diagnostic imaging performed at 1, 3, 6, 9, and 12 months.

Of the 10 patients, 5 had active EM involvement at the time of infusion, 2 had isolated EM relapse—1 with parotid and multifocal bony lesions and 1 with testis and sinus lesions—and 5 had multiple sites of EM relapse.

The patients had 2 to 4 prior ALL relapses, 2 had prior local radiation to the EM site, and all 10 had received prior bone marrow transplants.

Three patients had an MLL rearrangement, 1 had hypodiploid ALL, and 1 had trisomy 21.

Nine of the 10 patients achieved MRD-negative CR at day 28.

One patient was not evaluable because his disease progressed within 2 weeks of CAR therapy in both the bone marrow and EM site. He died 6 weeks after the infusion.

Five patients evaluated by serial imaging had objective responses. Two had no evidence of EM disease by day 28, 2 had resolution by 3 months, and 1 had continued decrease in the size of her uterine mass at 3 and 6 months. She underwent hysterectomy at 8 months with no evidence of disease on pathology.

Four patients with a prior history of skin or testicular involvement had no evidence of disease by exam at day 28.

Three of the 9 patients relapsed with CD19+ disease. One had skin/medullary involvement and died at 38 months after CAR T-cell infusion. And 2 had medullary disease: 1 died at 17 months and 1 is alive at 28 months.

The remaining 6 patients are alive and well at a median follow-up of 10 months (range, 3 – 16 months) without recurrence of disease.

The investigators therefore concluded that single agent CAR T-cell immunotherapy can induce potent and durable response in patients with EM relapse of their ALL. 

Micrograph showing MDS

A 3-arm phase 2 study of azacitidine alone or in combination with lenalidomide or vorinostat in patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) has shown the combination therapies to have similar overall response rates (ORR) to azacitidine monotherapy. Based on these findings, investigators did not choose either combination arm for phase 3 testing of overall survival.

However, patients with CMML treated with the azacitidine-lenalidomide combination had twice the ORR compared with azacitidine monotherapy, they reported.

And patients with certain mutations, such as DNMT3A, BCOR, and NRAS, had higher overall response rates, although only those with the DNMT3A mutation were significant.

Mikkael A. Sekeres, MD, of the Cleveland Clinic in Cleveland, Ohio, and colleagues reported these findings in the Journal of Clinical Oncology on behalf of the North American Intergroup Study SWOG S117.

Doses of azacitidine were the same for monotherapy and combination arms: 75 mg/m²/day intravenously or subcutaneously on days 1 to 7 of a 28-day cycle.

Patients in the lenalidomide arm received 10 mg/day orally of that drug on days 1 to 21, and patients in the vorinostat arm received 300 mg twice daily orally on days 3 to 9.

Patient characteristics

Patients had MDS of IPSS Intermediate-2 or higher or bone marrow blasts 5% or greater. Patients with CMML had fewer than 20% blasts.

The investigators randomized 277 patients to receive either azacitidine alone (n=92), azacitidine plus lenalidomide (n=93), or azacitidine plus vorinostat (n=92).

 Patients were a median age of 70 years (range, 28 to 93). Eighty-five patients (31%) were female, 53 (19%) had CMML, and 18 (6%) had treatment-related MDS. More than half the patients were transfusion-dependent at baseline.

Baseline characteristics were similar across the 3 arms. The investigators noted that the baseline characteristics were also similar across the 90 centers participating in the study, whether they were an MDS Center of Excellence or a high-volume center.

Adverse events

 For the most part, therapy-related adverse events were similar across the arms.

Rates of grade 3 or higher febrile neutropenia and infection and infestations were similar for all 3 cohorts: 89% for azaciditine monotherapy, 91% for the lenalidomide combination, and 91% for the vorinostat combination.

However, the vorinostat arm had more grade 3 or higher gastrointestinal toxicities (14 patients, 15%) compared with the monotherapy arm (4 patients, 4%), P=0.02.

And patients receiving lenalidomide experienced more grade 3 or higher rash (14 patients, 16%) compared with patients receiving monotherapy (3 patients, 3%), P=0.005.

Patients in the combination arms stopped therapy at significantly higher rates than the monotherapy arm. Eight percent of patients receiving monotherapy stopped treatment compared with 20% in the lenalidomide arm and 21% in the vorinostat arm.

Patients in the combination arms also had more dose modifications not specified in the protocol than those in the monotherapy arm. Twenty-four percent receiving azacitidine monotherapy had non-protocol defined dose modifications, compared with 43% in the lenalidomide arm and 42% in the vorinostat arm.

Responses

The ORR for the entire study population was 38%.

Patients in the monotherapy arm had an ORR of 38%, those in the lenalidomide arm, 49%, and those in the vorinostate arm, 27%. Neither arm achieved significance compared with the monotherapy arm.

Patients who were treatment-naïve in the lenalidomide arm had a somewhat improved ORR compared with monotherapy, P=0.08.

The median duration of response for all cohorts was 15 months: 10 months for monotherapy, 14 months for lenalidomide, and 18 months for vorinostat.

Patients who were able to remain on therapy for 6 months or more in the lenalidomide arm achieved a higher ORR of 87% compared with monotherapy (62%, P=0.01). However, there was no difference in response duration with longer therapy.

The median overall survival (OS) was 17 months for all patients, 15 months for patients in the monotherapy group, 19 months for those in the lenalidomide arm, and 17 months for those in the vorinostat group.

CMML patients had similar OS across treatment arms, with the median not yet reached for patients in the monotherapy arm.

Subgroup responses

Patients with CMML in the lenalidomide arm had a significantly higher ORR than CMML patients in the monotherapy arm, 68% and 28%, respectively (P=0.02).

Median duration of response for CMML patients was 19 months, with no differences between the arms.

The investigators observed no differences in ORR for therapy-related MDS, IPSS subgroups, transfusion-dependent patients, or allogeneic transplant rates.

However, they noted ORR was better for patients with chromosome 5 abnormality regardless of treatment arm than for those without the abnormality (odds ratio, 2.17, P=0.008).

One hundred thirteen patients had mutational data available. They had a median number of 2 mutations (range, 0 to 7), with the most common being ASXL1 (n = 31), TET2 (n = 26), SRSF2 (n = 23), TP53 (n = 22), RUNX1 (n = 21), and U2AF1 (n = 19).

Patients with DNMT3A mutation had a significantly higher ORR than for patients without mutations, 67% and 34%, respectively P=0.025).

Patients with BCOR and NRAS mutations had numerically higher, but non-significant, ORR than non-mutated patients. Patients with BCOR mutation had a 57% ORR compared with 34% for non-mutated patients (P=0.23).  Patients with NRAS mutation had a 60% ORR compared with 36% for non-mutated patients (P=0.28).

Patients with mutations in TET2 (P = .046) and TP53 (P = .003) had a worse response duration than those without mutations.

Response duration was significantly better with fewer mutations. For 2 or more mutations, the hazard ration was 6.86 versus no mutations (P=0.01).

The investigators believed under-dosing may have compromised response and survival in the combination arms. They suggested that studies focused on the subgroups that seemed to benefit from the combinations should be conducted. 

Micrograph showing MDS

A 3-arm phase 2 study of azacitidine alone or in combination with lenalidomide or vorinostat in patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) has shown the combination therapies to have similar overall response rates (ORR) to azacitidine monotherapy. Based on these findings, investigators did not choose either combination arm for phase 3 testing of overall survival.

However, patients with CMML treated with the azacitidine-lenalidomide combination had twice the ORR compared with azacitidine monotherapy, they reported.

And patients with certain mutations, such as DNMT3A, BCOR, and NRAS, had higher overall response rates, although only those with the DNMT3A mutation were significant.

Mikkael A. Sekeres, MD, of the Cleveland Clinic in Cleveland, Ohio, and colleagues reported these findings in the Journal of Clinical Oncology on behalf of the North American Intergroup Study SWOG S117.

Doses of azacitidine were the same for monotherapy and combination arms: 75 mg/m²/day intravenously or subcutaneously on days 1 to 7 of a 28-day cycle.

Patients in the lenalidomide arm received 10 mg/day orally of that drug on days 1 to 21, and patients in the vorinostat arm received 300 mg twice daily orally on days 3 to 9.

Patient characteristics

Patients had MDS of IPSS Intermediate-2 or higher or bone marrow blasts 5% or greater. Patients with CMML had fewer than 20% blasts.

The investigators randomized 277 patients to receive either azacitidine alone (n=92), azacitidine plus lenalidomide (n=93), or azacitidine plus vorinostat (n=92).

 Patients were a median age of 70 years (range, 28 to 93). Eighty-five patients (31%) were female, 53 (19%) had CMML, and 18 (6%) had treatment-related MDS. More than half the patients were transfusion-dependent at baseline.

Baseline characteristics were similar across the 3 arms. The investigators noted that the baseline characteristics were also similar across the 90 centers participating in the study, whether they were an MDS Center of Excellence or a high-volume center.

Adverse events

 For the most part, therapy-related adverse events were similar across the arms.

Rates of grade 3 or higher febrile neutropenia and infection and infestations were similar for all 3 cohorts: 89% for azaciditine monotherapy, 91% for the lenalidomide combination, and 91% for the vorinostat combination.

However, the vorinostat arm had more grade 3 or higher gastrointestinal toxicities (14 patients, 15%) compared with the monotherapy arm (4 patients, 4%), P=0.02.

And patients receiving lenalidomide experienced more grade 3 or higher rash (14 patients, 16%) compared with patients receiving monotherapy (3 patients, 3%), P=0.005.

Patients in the combination arms stopped therapy at significantly higher rates than the monotherapy arm. Eight percent of patients receiving monotherapy stopped treatment compared with 20% in the lenalidomide arm and 21% in the vorinostat arm.

Patients in the combination arms also had more dose modifications not specified in the protocol than those in the monotherapy arm. Twenty-four percent receiving azacitidine monotherapy had non-protocol defined dose modifications, compared with 43% in the lenalidomide arm and 42% in the vorinostat arm.

Responses

The ORR for the entire study population was 38%.

Patients in the monotherapy arm had an ORR of 38%, those in the lenalidomide arm, 49%, and those in the vorinostate arm, 27%. Neither arm achieved significance compared with the monotherapy arm.

Patients who were treatment-naïve in the lenalidomide arm had a somewhat improved ORR compared with monotherapy, P=0.08.

The median duration of response for all cohorts was 15 months: 10 months for monotherapy, 14 months for lenalidomide, and 18 months for vorinostat.

Patients who were able to remain on therapy for 6 months or more in the lenalidomide arm achieved a higher ORR of 87% compared with monotherapy (62%, P=0.01). However, there was no difference in response duration with longer therapy.

The median overall survival (OS) was 17 months for all patients, 15 months for patients in the monotherapy group, 19 months for those in the lenalidomide arm, and 17 months for those in the vorinostat group.

CMML patients had similar OS across treatment arms, with the median not yet reached for patients in the monotherapy arm.

Subgroup responses

Patients with CMML in the lenalidomide arm had a significantly higher ORR than CMML patients in the monotherapy arm, 68% and 28%, respectively (P=0.02).

Median duration of response for CMML patients was 19 months, with no differences between the arms.

The investigators observed no differences in ORR for therapy-related MDS, IPSS subgroups, transfusion-dependent patients, or allogeneic transplant rates.

However, they noted ORR was better for patients with chromosome 5 abnormality regardless of treatment arm than for those without the abnormality (odds ratio, 2.17, P=0.008).

One hundred thirteen patients had mutational data available. They had a median number of 2 mutations (range, 0 to 7), with the most common being ASXL1 (n = 31), TET2 (n = 26), SRSF2 (n = 23), TP53 (n = 22), RUNX1 (n = 21), and U2AF1 (n = 19).

Patients with DNMT3A mutation had a significantly higher ORR than for patients without mutations, 67% and 34%, respectively P=0.025).

Patients with BCOR and NRAS mutations had numerically higher, but non-significant, ORR than non-mutated patients. Patients with BCOR mutation had a 57% ORR compared with 34% for non-mutated patients (P=0.23).  Patients with NRAS mutation had a 60% ORR compared with 36% for non-mutated patients (P=0.28).

Patients with mutations in TET2 (P = .046) and TP53 (P = .003) had a worse response duration than those without mutations.

Response duration was significantly better with fewer mutations. For 2 or more mutations, the hazard ration was 6.86 versus no mutations (P=0.01).

The investigators believed under-dosing may have compromised response and survival in the combination arms. They suggested that studies focused on the subgroups that seemed to benefit from the combinations should be conducted. 

Micrograph showing MDS

A 3-arm phase 2 study of azacitidine alone or in combination with lenalidomide or vorinostat in patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) has shown the combination therapies to have similar overall response rates (ORR) to azacitidine monotherapy. Based on these findings, investigators did not choose either combination arm for phase 3 testing of overall survival.

However, patients with CMML treated with the azacitidine-lenalidomide combination had twice the ORR compared with azacitidine monotherapy, they reported.

And patients with certain mutations, such as DNMT3A, BCOR, and NRAS, had higher overall response rates, although only those with the DNMT3A mutation were significant.

Mikkael A. Sekeres, MD, of the Cleveland Clinic in Cleveland, Ohio, and colleagues reported these findings in the Journal of Clinical Oncology on behalf of the North American Intergroup Study SWOG S117.

Doses of azacitidine were the same for monotherapy and combination arms: 75 mg/m²/day intravenously or subcutaneously on days 1 to 7 of a 28-day cycle.

Patients in the lenalidomide arm received 10 mg/day orally of that drug on days 1 to 21, and patients in the vorinostat arm received 300 mg twice daily orally on days 3 to 9.

Patient characteristics

Patients had MDS of IPSS Intermediate-2 or higher or bone marrow blasts 5% or greater. Patients with CMML had fewer than 20% blasts.

The investigators randomized 277 patients to receive either azacitidine alone (n=92), azacitidine plus lenalidomide (n=93), or azacitidine plus vorinostat (n=92).

 Patients were a median age of 70 years (range, 28 to 93). Eighty-five patients (31%) were female, 53 (19%) had CMML, and 18 (6%) had treatment-related MDS. More than half the patients were transfusion-dependent at baseline.

Baseline characteristics were similar across the 3 arms. The investigators noted that the baseline characteristics were also similar across the 90 centers participating in the study, whether they were an MDS Center of Excellence or a high-volume center.

Adverse events

 For the most part, therapy-related adverse events were similar across the arms.

Rates of grade 3 or higher febrile neutropenia and infection and infestations were similar for all 3 cohorts: 89% for azaciditine monotherapy, 91% for the lenalidomide combination, and 91% for the vorinostat combination.

However, the vorinostat arm had more grade 3 or higher gastrointestinal toxicities (14 patients, 15%) compared with the monotherapy arm (4 patients, 4%), P=0.02.

And patients receiving lenalidomide experienced more grade 3 or higher rash (14 patients, 16%) compared with patients receiving monotherapy (3 patients, 3%), P=0.005.

Patients in the combination arms stopped therapy at significantly higher rates than the monotherapy arm. Eight percent of patients receiving monotherapy stopped treatment compared with 20% in the lenalidomide arm and 21% in the vorinostat arm.

Patients in the combination arms also had more dose modifications not specified in the protocol than those in the monotherapy arm. Twenty-four percent receiving azacitidine monotherapy had non-protocol defined dose modifications, compared with 43% in the lenalidomide arm and 42% in the vorinostat arm.

Responses

The ORR for the entire study population was 38%.

Patients in the monotherapy arm had an ORR of 38%, those in the lenalidomide arm, 49%, and those in the vorinostate arm, 27%. Neither arm achieved significance compared with the monotherapy arm.

Patients who were treatment-naïve in the lenalidomide arm had a somewhat improved ORR compared with monotherapy, P=0.08.

The median duration of response for all cohorts was 15 months: 10 months for monotherapy, 14 months for lenalidomide, and 18 months for vorinostat.

Patients who were able to remain on therapy for 6 months or more in the lenalidomide arm achieved a higher ORR of 87% compared with monotherapy (62%, P=0.01). However, there was no difference in response duration with longer therapy.

The median overall survival (OS) was 17 months for all patients, 15 months for patients in the monotherapy group, 19 months for those in the lenalidomide arm, and 17 months for those in the vorinostat group.

CMML patients had similar OS across treatment arms, with the median not yet reached for patients in the monotherapy arm.

Subgroup responses

Patients with CMML in the lenalidomide arm had a significantly higher ORR than CMML patients in the monotherapy arm, 68% and 28%, respectively (P=0.02).

Median duration of response for CMML patients was 19 months, with no differences between the arms.

The investigators observed no differences in ORR for therapy-related MDS, IPSS subgroups, transfusion-dependent patients, or allogeneic transplant rates.

However, they noted ORR was better for patients with chromosome 5 abnormality regardless of treatment arm than for those without the abnormality (odds ratio, 2.17, P=0.008).

One hundred thirteen patients had mutational data available. They had a median number of 2 mutations (range, 0 to 7), with the most common being ASXL1 (n = 31), TET2 (n = 26), SRSF2 (n = 23), TP53 (n = 22), RUNX1 (n = 21), and U2AF1 (n = 19).

Patients with DNMT3A mutation had a significantly higher ORR than for patients without mutations, 67% and 34%, respectively P=0.025).

Patients with BCOR and NRAS mutations had numerically higher, but non-significant, ORR than non-mutated patients. Patients with BCOR mutation had a 57% ORR compared with 34% for non-mutated patients (P=0.23).  Patients with NRAS mutation had a 60% ORR compared with 36% for non-mutated patients (P=0.28).

Patients with mutations in TET2 (P = .046) and TP53 (P = .003) had a worse response duration than those without mutations.

Response duration was significantly better with fewer mutations. For 2 or more mutations, the hazard ration was 6.86 versus no mutations (P=0.01).

The investigators believed under-dosing may have compromised response and survival in the combination arms. They suggested that studies focused on the subgroups that seemed to benefit from the combinations should be conducted. 

Infants who slept in their own rooms by age 9 months slept significantly longer and better than those who continued sharing a room with their parents as recommended by the American Academy of Pediatrics, the authors of a prospective study of 279 mother-infant dyads reported June 5.

The findings “raise questions about the well-intended AAP recommendation that room-sharing should ideally occur for all infants until their first birthday,” wrote Ian M. Paul, MD, of Penn State University, Hershey, and his associates (Pediatrics. 2017 Jun 5. doi: 10.1542/peds.2017-0122). “Perhaps our most troubling finding was that room-sharing was associated with overnight transitions to bed-sharing, which is strongly discouraged by the AAP.”

Infants who slept in their own rooms by age 9 months slept significantly longer and better than those who continued sharing a room with their parents as recommended by the American Academy of Pediatrics, the authors of a prospective study of 279 mother-infant dyads reported June 5.

The findings “raise questions about the well-intended AAP recommendation that room-sharing should ideally occur for all infants until their first birthday,” wrote Ian M. Paul, MD, of Penn State University, Hershey, and his associates (Pediatrics. 2017 Jun 5. doi: 10.1542/peds.2017-0122). “Perhaps our most troubling finding was that room-sharing was associated with overnight transitions to bed-sharing, which is strongly discouraged by the AAP.”

Infants who slept in their own rooms by age 9 months slept significantly longer and better than those who continued sharing a room with their parents as recommended by the American Academy of Pediatrics, the authors of a prospective study of 279 mother-infant dyads reported June 5.

The findings “raise questions about the well-intended AAP recommendation that room-sharing should ideally occur for all infants until their first birthday,” wrote Ian M. Paul, MD, of Penn State University, Hershey, and his associates (Pediatrics. 2017 Jun 5. doi: 10.1542/peds.2017-0122). “Perhaps our most troubling finding was that room-sharing was associated with overnight transitions to bed-sharing, which is strongly discouraged by the AAP.”

The increasingly complex health care system in the United States relies heavily on quality improvement, interprofessional collaboration, patient outcomes, health policy legislation, and advocacy. While important, most of these factors are outside the scope of the traditional master’s-level education program—necessitating the development of methods to help advanced practice providers, including NPs and PAs, obtain additional skills. The solution of choice, for many professions, has been the introduction of the “professional doctorate” as a complementary alternative to the typical research-focused doctoral program, such as the PhD.

Traditional PhD curricula prepare individuals to perform research that is typically specialized and confined to their field of study.¹ While this research does produce new knowledge, it usually remains in the realm of academia and often does not address any specific “real-world” problem.² But to be recognized, compensated, and identified as a full professional in modern society, one must be equipped to address practical problems.

Analysis by Taylor and Maxwell and by Lee, Green, and Brennan has shown that, rather than theory, the workplace demands the application of knowledge geared toward daily professional duties.^3,4 They envisioned a doctorate-prepared practitioner who had less skill in pure research but who would be able to apply theory to everyday problems in the workplace.^4,5 Rather than devalue the contributions of classical PhD training, this model proposed the creation of a hybrid curriculum that would prepare individuals to use “applied research.”³ As the professional doctorate gained acceptance, it matured from the “first-generation” concept (which was quite similar to the PhD in structure) to “second-generation,” which is more focused on discipline and workplace realities.^3,5 In general, these professional doctorates can be earned in less time than a PhD and do not require original research.

Over the past two decades, more than 500 unique professional practice doctorate programs have emerged across the US, in fields ranging from nursing to bioethics. One of the most prominent is the Doctor of Nursing Practice (DNP), designed for RNs seeking a post-professional degree in nursing. In 2004, following three years of research by a task force, the American Association of Colleges of Nursing (AACN) endorsed the DNP, with the goal that it would become the minimum educational standard for advanced practice nurses by 2015.⁶ According to the AACN, there are 289 DNP programs in the US, with an additional 128 in development.⁶

The PA profession has lagged behind not only our NP colleagues, but also many other health professions, in the adoption of a discipline-specific, doctoral-level degree. Our counterparts in audiology, physical therapy, occupational therapy, and athletic training have been part of the exponential growth in second-generation health care doctorates.⁷ While these programs may differ in concept, they share several similarities: They do not require original research; they include a clinical component; and they promote knowledge in the context of the workplace.^5-8

In the past five years, PAs have started considering (or debating, depending on your perspective) a professional/clinical doctorate as the next step in our post-professional journey. It’s about time, when you consider that 16.8% of newly certified PAs intend to pursue additional education or clinical training, according to a recent report from the National Commission on Certification of Physician Assistants.⁹

There are already a few doctoral programs for PAs. Among the earliest clinically focused doctorate programs was the US Army/Air Force-Baylor DScPAS-EM program, designed to educate military PAs at the doctoral level upon completion of an 18-month emergency medicine residency.¹⁰ Lincoln Memorial University has a Doctor of Medical Science (DMS) program, comprised of one year of online advanced clinical medicine coursework and one year of online coursework focused on primary care, hospital medicine, emergency medicine, or education.¹¹ And Lynchburg College in Virginia has just launched a post-professional doctoral program for PAs; this DMS program includes a clinical fellowship, as well as coursework in leadership training, health care management and law, organizational behavior, disaster medicine, and global health.¹²

While not strictly created for PAs, the Doctor of Health Science programs at Nova Southeastern University and A.T. Still University have been educating PAs at the doctoral level for more than 10 years.^13,14 Later this year, A.T. Still University plans to introduce a post-professional Doctor of Physician Assistant Studies that will provide a pathway for PAs wishing to become leaders and scholar-practitioners, develop core leadership abilities, and/or enter PA education without the location-specific requirement of a clinical or academic residency.

When the push for professional practice doctorates started, pundits claimed they were just an attempt at a “cash grab” by universities looking to bolster their rosters (and their coffers). But advocates have long argued that these degrees provide practitioners with the knowledge and training required to offer advanced services in increasingly complex social and technologic environments.⁷ No less than The Institute of Medicine, The Joint Commission, and the Robert Wood Johnson Foundation have called for the reinvention of education programs to equip today’s health professionals with the highest level of scientific knowledge and practice expertise.

Why? First and foremost, to ensure quality patient outcomes. Beyond that, better prepared clinicians can help to address provider shortages. Those with doctorates can also serve as faculty, educating the next generation of health care providers. And practically speaking, for those seeking advanced education, holding a doctorate will create opportunities for increased decision-making and upward mobility in the workplace.

There is no question that our current health care environment is driven by the regulations and costs of the Affordable Care Act, as well as quality management systems and strategies. NPs and PAs are in a unique position to cost-effectively direct the care of, and advocate for, diverse patient populations. NPs and PAs who recognize this opportunity to serve need doctoral-level training tailored to this milieu.

Do you agree? Share your thoughts on professional doctorates with me at [email protected].

The increasingly complex health care system in the United States relies heavily on quality improvement, interprofessional collaboration, patient outcomes, health policy legislation, and advocacy. While important, most of these factors are outside the scope of the traditional master’s-level education program—necessitating the development of methods to help advanced practice providers, including NPs and PAs, obtain additional skills. The solution of choice, for many professions, has been the introduction of the “professional doctorate” as a complementary alternative to the typical research-focused doctoral program, such as the PhD.

Traditional PhD curricula prepare individuals to perform research that is typically specialized and confined to their field of study.¹ While this research does produce new knowledge, it usually remains in the realm of academia and often does not address any specific “real-world” problem.² But to be recognized, compensated, and identified as a full professional in modern society, one must be equipped to address practical problems.

Analysis by Taylor and Maxwell and by Lee, Green, and Brennan has shown that, rather than theory, the workplace demands the application of knowledge geared toward daily professional duties.^3,4 They envisioned a doctorate-prepared practitioner who had less skill in pure research but who would be able to apply theory to everyday problems in the workplace.^4,5 Rather than devalue the contributions of classical PhD training, this model proposed the creation of a hybrid curriculum that would prepare individuals to use “applied research.”³ As the professional doctorate gained acceptance, it matured from the “first-generation” concept (which was quite similar to the PhD in structure) to “second-generation,” which is more focused on discipline and workplace realities.^3,5 In general, these professional doctorates can be earned in less time than a PhD and do not require original research.

Over the past two decades, more than 500 unique professional practice doctorate programs have emerged across the US, in fields ranging from nursing to bioethics. One of the most prominent is the Doctor of Nursing Practice (DNP), designed for RNs seeking a post-professional degree in nursing. In 2004, following three years of research by a task force, the American Association of Colleges of Nursing (AACN) endorsed the DNP, with the goal that it would become the minimum educational standard for advanced practice nurses by 2015.⁶ According to the AACN, there are 289 DNP programs in the US, with an additional 128 in development.⁶

The PA profession has lagged behind not only our NP colleagues, but also many other health professions, in the adoption of a discipline-specific, doctoral-level degree. Our counterparts in audiology, physical therapy, occupational therapy, and athletic training have been part of the exponential growth in second-generation health care doctorates.⁷ While these programs may differ in concept, they share several similarities: They do not require original research; they include a clinical component; and they promote knowledge in the context of the workplace.^5-8

In the past five years, PAs have started considering (or debating, depending on your perspective) a professional/clinical doctorate as the next step in our post-professional journey. It’s about time, when you consider that 16.8% of newly certified PAs intend to pursue additional education or clinical training, according to a recent report from the National Commission on Certification of Physician Assistants.⁹

There are already a few doctoral programs for PAs. Among the earliest clinically focused doctorate programs was the US Army/Air Force-Baylor DScPAS-EM program, designed to educate military PAs at the doctoral level upon completion of an 18-month emergency medicine residency.¹⁰ Lincoln Memorial University has a Doctor of Medical Science (DMS) program, comprised of one year of online advanced clinical medicine coursework and one year of online coursework focused on primary care, hospital medicine, emergency medicine, or education.¹¹ And Lynchburg College in Virginia has just launched a post-professional doctoral program for PAs; this DMS program includes a clinical fellowship, as well as coursework in leadership training, health care management and law, organizational behavior, disaster medicine, and global health.¹²

While not strictly created for PAs, the Doctor of Health Science programs at Nova Southeastern University and A.T. Still University have been educating PAs at the doctoral level for more than 10 years.^13,14 Later this year, A.T. Still University plans to introduce a post-professional Doctor of Physician Assistant Studies that will provide a pathway for PAs wishing to become leaders and scholar-practitioners, develop core leadership abilities, and/or enter PA education without the location-specific requirement of a clinical or academic residency.

When the push for professional practice doctorates started, pundits claimed they were just an attempt at a “cash grab” by universities looking to bolster their rosters (and their coffers). But advocates have long argued that these degrees provide practitioners with the knowledge and training required to offer advanced services in increasingly complex social and technologic environments.⁷ No less than The Institute of Medicine, The Joint Commission, and the Robert Wood Johnson Foundation have called for the reinvention of education programs to equip today’s health professionals with the highest level of scientific knowledge and practice expertise.

Why? First and foremost, to ensure quality patient outcomes. Beyond that, better prepared clinicians can help to address provider shortages. Those with doctorates can also serve as faculty, educating the next generation of health care providers. And practically speaking, for those seeking advanced education, holding a doctorate will create opportunities for increased decision-making and upward mobility in the workplace.

There is no question that our current health care environment is driven by the regulations and costs of the Affordable Care Act, as well as quality management systems and strategies. NPs and PAs are in a unique position to cost-effectively direct the care of, and advocate for, diverse patient populations. NPs and PAs who recognize this opportunity to serve need doctoral-level training tailored to this milieu.

Do you agree? Share your thoughts on professional doctorates with me at [email protected].

The increasingly complex health care system in the United States relies heavily on quality improvement, interprofessional collaboration, patient outcomes, health policy legislation, and advocacy. While important, most of these factors are outside the scope of the traditional master’s-level education program—necessitating the development of methods to help advanced practice providers, including NPs and PAs, obtain additional skills. The solution of choice, for many professions, has been the introduction of the “professional doctorate” as a complementary alternative to the typical research-focused doctoral program, such as the PhD.

Traditional PhD curricula prepare individuals to perform research that is typically specialized and confined to their field of study.¹ While this research does produce new knowledge, it usually remains in the realm of academia and often does not address any specific “real-world” problem.² But to be recognized, compensated, and identified as a full professional in modern society, one must be equipped to address practical problems.

Analysis by Taylor and Maxwell and by Lee, Green, and Brennan has shown that, rather than theory, the workplace demands the application of knowledge geared toward daily professional duties.^3,4 They envisioned a doctorate-prepared practitioner who had less skill in pure research but who would be able to apply theory to everyday problems in the workplace.^4,5 Rather than devalue the contributions of classical PhD training, this model proposed the creation of a hybrid curriculum that would prepare individuals to use “applied research.”³ As the professional doctorate gained acceptance, it matured from the “first-generation” concept (which was quite similar to the PhD in structure) to “second-generation,” which is more focused on discipline and workplace realities.^3,5 In general, these professional doctorates can be earned in less time than a PhD and do not require original research.

Over the past two decades, more than 500 unique professional practice doctorate programs have emerged across the US, in fields ranging from nursing to bioethics. One of the most prominent is the Doctor of Nursing Practice (DNP), designed for RNs seeking a post-professional degree in nursing. In 2004, following three years of research by a task force, the American Association of Colleges of Nursing (AACN) endorsed the DNP, with the goal that it would become the minimum educational standard for advanced practice nurses by 2015.⁶ According to the AACN, there are 289 DNP programs in the US, with an additional 128 in development.⁶

The PA profession has lagged behind not only our NP colleagues, but also many other health professions, in the adoption of a discipline-specific, doctoral-level degree. Our counterparts in audiology, physical therapy, occupational therapy, and athletic training have been part of the exponential growth in second-generation health care doctorates.⁷ While these programs may differ in concept, they share several similarities: They do not require original research; they include a clinical component; and they promote knowledge in the context of the workplace.^5-8

In the past five years, PAs have started considering (or debating, depending on your perspective) a professional/clinical doctorate as the next step in our post-professional journey. It’s about time, when you consider that 16.8% of newly certified PAs intend to pursue additional education or clinical training, according to a recent report from the National Commission on Certification of Physician Assistants.⁹

There are already a few doctoral programs for PAs. Among the earliest clinically focused doctorate programs was the US Army/Air Force-Baylor DScPAS-EM program, designed to educate military PAs at the doctoral level upon completion of an 18-month emergency medicine residency.¹⁰ Lincoln Memorial University has a Doctor of Medical Science (DMS) program, comprised of one year of online advanced clinical medicine coursework and one year of online coursework focused on primary care, hospital medicine, emergency medicine, or education.¹¹ And Lynchburg College in Virginia has just launched a post-professional doctoral program for PAs; this DMS program includes a clinical fellowship, as well as coursework in leadership training, health care management and law, organizational behavior, disaster medicine, and global health.¹²

While not strictly created for PAs, the Doctor of Health Science programs at Nova Southeastern University and A.T. Still University have been educating PAs at the doctoral level for more than 10 years.^13,14 Later this year, A.T. Still University plans to introduce a post-professional Doctor of Physician Assistant Studies that will provide a pathway for PAs wishing to become leaders and scholar-practitioners, develop core leadership abilities, and/or enter PA education without the location-specific requirement of a clinical or academic residency.

When the push for professional practice doctorates started, pundits claimed they were just an attempt at a “cash grab” by universities looking to bolster their rosters (and their coffers). But advocates have long argued that these degrees provide practitioners with the knowledge and training required to offer advanced services in increasingly complex social and technologic environments.⁷ No less than The Institute of Medicine, The Joint Commission, and the Robert Wood Johnson Foundation have called for the reinvention of education programs to equip today’s health professionals with the highest level of scientific knowledge and practice expertise.

Why? First and foremost, to ensure quality patient outcomes. Beyond that, better prepared clinicians can help to address provider shortages. Those with doctorates can also serve as faculty, educating the next generation of health care providers. And practically speaking, for those seeking advanced education, holding a doctorate will create opportunities for increased decision-making and upward mobility in the workplace.

There is no question that our current health care environment is driven by the regulations and costs of the Affordable Care Act, as well as quality management systems and strategies. NPs and PAs are in a unique position to cost-effectively direct the care of, and advocate for, diverse patient populations. NPs and PAs who recognize this opportunity to serve need doctoral-level training tailored to this milieu.

Do you agree? Share your thoughts on professional doctorates with me at [email protected].

CHICAGO – An experimental liquid biopsy method plumbs the depths of the genome to detect a broad array of mutations in blood samples that closely correspond to variants in tumors.

The high-intensity method for detecting circulating free DNA (cfDNA) in plasma detected at least one significant genetic variant in samples from 89% of patients with advanced breast, lung, and prostate cancers.

If validated in further studies, the technique could inform more accurate drug selection in patients with refractory disease and eventually may form the basis for plasma-based assays to detect early-stage cancers, said Pedram Razavi, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Neil Osterweil/Frontline Medical News

Deep scanning

The high-intensity sequencing method scans for 508 genes in a 2 million base-pair swath of genome, performing 60,000 repeat reads on each genome region to improve the assay’s sensitivity, and deep sequencing allows for detection of rare “needle-in-a-haystack” variants.

Dr. Razavi and his colleagues examined prospectively collected blood and tissues from 161 patients, 124 of whom had samples sufficient for concordance studies.

The samples were collected within 6 weeks of a de novo cancer diagnosis or evidence of disease progression, before the initiation of therapy.

Both cfDNA and genomic data from white blood cells (WBCs) of each patient were sequenced with the aforementioned 508-gene panel covering a broad range of known cancer variants and mutations.

Tumor tissues were sequenced with MSK-IMPACT, a 410 gene assay, with blinding of results in regard to plasma and WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in breast cancer and non–small cell lung cancer (NSCLC).

As noted before, 89% of patients had at least one genetic variant detected in both the tumor and in plasma, including 97% of patients with metastatic breast cancer, 85% of those with NSCLC, and 84% of patients with metastatic prostate cancer.

The investigators identified 864 clonal or subclonal variants in tissue samples from all three of these cancers, and 627 of the variants also were found in plasma.

In addition, 76% of clinically actionable somatic mutations identified in tumors also were found in plasma, which suggests that the high-intensity sequencing technique may be able to identify tumor heterogeneity that is not always evident in single tumor biopsies, Dr. Razavi said.

Neil Osterweil/Frontline Medical News

‘A clear advance’

“The work by Dr. Razavi and colleagues is a clear advance in the field because it surveys for the first time a much broader panel of genes – 508 genes in this case – and it does it with much deeper sequencing, which means it can detect much rarer alterations,” commented ASCO expert John Heymach, MD, PhD, from the University of Texas MD Anderson Cancer Center in Houston.

The study “helps illuminate a path toward a day when we will be using circulating tumor DNA assays for early detection of cancer, and not just for selecting certain therapies,” he added.

“We’re a long way from utilizing liquid biopsy for detecting cancers; already though, we’re seeing some utility of circulating tumor DNA in the domain of identifying novel alterations as a means of segmentation clinical trials,” commented ASCO expert Sumanta Kumar Pal, MD, from City of Hope in Duarte, Calif.

Neil Osterweil/Frontline Medical News

CHICAGO – An experimental liquid biopsy method plumbs the depths of the genome to detect a broad array of mutations in blood samples that closely correspond to variants in tumors.

The high-intensity method for detecting circulating free DNA (cfDNA) in plasma detected at least one significant genetic variant in samples from 89% of patients with advanced breast, lung, and prostate cancers.

If validated in further studies, the technique could inform more accurate drug selection in patients with refractory disease and eventually may form the basis for plasma-based assays to detect early-stage cancers, said Pedram Razavi, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Neil Osterweil/Frontline Medical News

Deep scanning

The high-intensity sequencing method scans for 508 genes in a 2 million base-pair swath of genome, performing 60,000 repeat reads on each genome region to improve the assay’s sensitivity, and deep sequencing allows for detection of rare “needle-in-a-haystack” variants.

Dr. Razavi and his colleagues examined prospectively collected blood and tissues from 161 patients, 124 of whom had samples sufficient for concordance studies.

The samples were collected within 6 weeks of a de novo cancer diagnosis or evidence of disease progression, before the initiation of therapy.

Both cfDNA and genomic data from white blood cells (WBCs) of each patient were sequenced with the aforementioned 508-gene panel covering a broad range of known cancer variants and mutations.

Tumor tissues were sequenced with MSK-IMPACT, a 410 gene assay, with blinding of results in regard to plasma and WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in breast cancer and non–small cell lung cancer (NSCLC).

As noted before, 89% of patients had at least one genetic variant detected in both the tumor and in plasma, including 97% of patients with metastatic breast cancer, 85% of those with NSCLC, and 84% of patients with metastatic prostate cancer.

The investigators identified 864 clonal or subclonal variants in tissue samples from all three of these cancers, and 627 of the variants also were found in plasma.

In addition, 76% of clinically actionable somatic mutations identified in tumors also were found in plasma, which suggests that the high-intensity sequencing technique may be able to identify tumor heterogeneity that is not always evident in single tumor biopsies, Dr. Razavi said.

Neil Osterweil/Frontline Medical News

‘A clear advance’

“The work by Dr. Razavi and colleagues is a clear advance in the field because it surveys for the first time a much broader panel of genes – 508 genes in this case – and it does it with much deeper sequencing, which means it can detect much rarer alterations,” commented ASCO expert John Heymach, MD, PhD, from the University of Texas MD Anderson Cancer Center in Houston.

The study “helps illuminate a path toward a day when we will be using circulating tumor DNA assays for early detection of cancer, and not just for selecting certain therapies,” he added.

“We’re a long way from utilizing liquid biopsy for detecting cancers; already though, we’re seeing some utility of circulating tumor DNA in the domain of identifying novel alterations as a means of segmentation clinical trials,” commented ASCO expert Sumanta Kumar Pal, MD, from City of Hope in Duarte, Calif.

Neil Osterweil/Frontline Medical News

CHICAGO – An experimental liquid biopsy method plumbs the depths of the genome to detect a broad array of mutations in blood samples that closely correspond to variants in tumors.

The high-intensity method for detecting circulating free DNA (cfDNA) in plasma detected at least one significant genetic variant in samples from 89% of patients with advanced breast, lung, and prostate cancers.

If validated in further studies, the technique could inform more accurate drug selection in patients with refractory disease and eventually may form the basis for plasma-based assays to detect early-stage cancers, said Pedram Razavi, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Neil Osterweil/Frontline Medical News

Deep scanning

The high-intensity sequencing method scans for 508 genes in a 2 million base-pair swath of genome, performing 60,000 repeat reads on each genome region to improve the assay’s sensitivity, and deep sequencing allows for detection of rare “needle-in-a-haystack” variants.

Dr. Razavi and his colleagues examined prospectively collected blood and tissues from 161 patients, 124 of whom had samples sufficient for concordance studies.

The samples were collected within 6 weeks of a de novo cancer diagnosis or evidence of disease progression, before the initiation of therapy.

Both cfDNA and genomic data from white blood cells (WBCs) of each patient were sequenced with the aforementioned 508-gene panel covering a broad range of known cancer variants and mutations.

Tumor tissues were sequenced with MSK-IMPACT, a 410 gene assay, with blinding of results in regard to plasma and WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in breast cancer and non–small cell lung cancer (NSCLC).

As noted before, 89% of patients had at least one genetic variant detected in both the tumor and in plasma, including 97% of patients with metastatic breast cancer, 85% of those with NSCLC, and 84% of patients with metastatic prostate cancer.

The investigators identified 864 clonal or subclonal variants in tissue samples from all three of these cancers, and 627 of the variants also were found in plasma.

In addition, 76% of clinically actionable somatic mutations identified in tumors also were found in plasma, which suggests that the high-intensity sequencing technique may be able to identify tumor heterogeneity that is not always evident in single tumor biopsies, Dr. Razavi said.

Neil Osterweil/Frontline Medical News

‘A clear advance’

“The work by Dr. Razavi and colleagues is a clear advance in the field because it surveys for the first time a much broader panel of genes – 508 genes in this case – and it does it with much deeper sequencing, which means it can detect much rarer alterations,” commented ASCO expert John Heymach, MD, PhD, from the University of Texas MD Anderson Cancer Center in Houston.

The study “helps illuminate a path toward a day when we will be using circulating tumor DNA assays for early detection of cancer, and not just for selecting certain therapies,” he added.

“We’re a long way from utilizing liquid biopsy for detecting cancers; already though, we’re seeing some utility of circulating tumor DNA in the domain of identifying novel alterations as a means of segmentation clinical trials,” commented ASCO expert Sumanta Kumar Pal, MD, from City of Hope in Duarte, Calif.

Neil Osterweil/Frontline Medical News

New high-priced cancer treatments rarely demonstrate value, compared with the prices being charged for them.

Researchers examined clinical trial data for new treatments using scoring frameworks developed by both the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) that assess the value of cancer therapies by taking into consideration survival gains in relation to toxicity and quality. Findings were simultaneously published online June 2 in The Lancet Oncology (2017 June 2. doi: 10.1016/S1470-2045(17)30415-1) and presented at the annual meeting of the American Society of Clinical Oncology.

crazydiva/Thinkstock

[email protected]
 

New high-priced cancer treatments rarely demonstrate value, compared with the prices being charged for them.

Researchers examined clinical trial data for new treatments using scoring frameworks developed by both the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) that assess the value of cancer therapies by taking into consideration survival gains in relation to toxicity and quality. Findings were simultaneously published online June 2 in The Lancet Oncology (2017 June 2. doi: 10.1016/S1470-2045(17)30415-1) and presented at the annual meeting of the American Society of Clinical Oncology.

crazydiva/Thinkstock

[email protected]
 

New high-priced cancer treatments rarely demonstrate value, compared with the prices being charged for them.

Researchers examined clinical trial data for new treatments using scoring frameworks developed by both the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) that assess the value of cancer therapies by taking into consideration survival gains in relation to toxicity and quality. Findings were simultaneously published online June 2 in The Lancet Oncology (2017 June 2. doi: 10.1016/S1470-2045(17)30415-1) and presented at the annual meeting of the American Society of Clinical Oncology.

crazydiva/Thinkstock

[email protected]
 

CHICAGO – Compared with single-agent chemotherapy of the oncologist’s choice, the PARP inhibitor olaparib reduced the risk of progression or death by 42% in women with BRCA-related HER2-negative metastatic breast cancer, the OlympiAD trialists reported in a plenary session at the annual meeting of the American Society of Clinical Oncology.

Lead author Mark E. Robson, MD, of Memorial Sloan Kettering Cancer Center, New York, discussed findings of the randomized phase III trial, as well as strategies for building on the trial’s success and what the future holds for this class of agents in breast cancer.

Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives travel, accommodations, and/or expenses from AstraZeneca; receives honoraria from AstraZeneca; and receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro. The trial was funded by AstraZeneca.

CHICAGO – Compared with single-agent chemotherapy of the oncologist’s choice, the PARP inhibitor olaparib reduced the risk of progression or death by 42% in women with BRCA-related HER2-negative metastatic breast cancer, the OlympiAD trialists reported in a plenary session at the annual meeting of the American Society of Clinical Oncology.

Lead author Mark E. Robson, MD, of Memorial Sloan Kettering Cancer Center, New York, discussed findings of the randomized phase III trial, as well as strategies for building on the trial’s success and what the future holds for this class of agents in breast cancer.

Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives travel, accommodations, and/or expenses from AstraZeneca; receives honoraria from AstraZeneca; and receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro. The trial was funded by AstraZeneca.

CHICAGO – Compared with single-agent chemotherapy of the oncologist’s choice, the PARP inhibitor olaparib reduced the risk of progression or death by 42% in women with BRCA-related HER2-negative metastatic breast cancer, the OlympiAD trialists reported in a plenary session at the annual meeting of the American Society of Clinical Oncology.

Lead author Mark E. Robson, MD, of Memorial Sloan Kettering Cancer Center, New York, discussed findings of the randomized phase III trial, as well as strategies for building on the trial’s success and what the future holds for this class of agents in breast cancer.

Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives travel, accommodations, and/or expenses from AstraZeneca; receives honoraria from AstraZeneca; and receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro. The trial was funded by AstraZeneca.

CHICAGO – Adding abiraterone acetate plus prednisone to androgen deprivation therapy in hormone-naive high-risk prostate cancer patients significantly improves overall survival, according to “practice-changing” results from the phase III LATITUDE trial and the multiarm, multistage STAMPEDE trial.

In the double-blind, randomized, placebo-controlled LATITUDE trial, 597 patients with newly diagnosed high-risk metastatic prostate cancer who received 1,000 mg of abiraterone acetate daily plus 5 mg of prednisone daily in addition to androgen deprivation therapy experienced a 38% reduction in the risk of death and a 53% reduction in the risk of radiographic progression or death at a median follow-up of 30.4 months, compared with 602 such patients who received placebo and androgen deprivation, Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, Villejuif, France, reported at the annual meeting of the American Society of Clinical Oncology.

Significant improvements also were seen in the treatment vs. placebo group for all secondary endpoints, including time to prostate-specific-antigen progression (hazard ratio, 0.30), time to pain progression (HR, 0.70), time to next symptomatic skeletal event (HR, 0.70), time to chemotherapy (HR, 0.44), and time to subsequent prostate cancer therapy (HR, 0.42), Dr. Fizazi said.

He discussed the findings, including side effects, and ongoing and future studies, in a video interview.

[email protected]

CHICAGO – Adding abiraterone acetate plus prednisone to androgen deprivation therapy in hormone-naive high-risk prostate cancer patients significantly improves overall survival, according to “practice-changing” results from the phase III LATITUDE trial and the multiarm, multistage STAMPEDE trial.

In the double-blind, randomized, placebo-controlled LATITUDE trial, 597 patients with newly diagnosed high-risk metastatic prostate cancer who received 1,000 mg of abiraterone acetate daily plus 5 mg of prednisone daily in addition to androgen deprivation therapy experienced a 38% reduction in the risk of death and a 53% reduction in the risk of radiographic progression or death at a median follow-up of 30.4 months, compared with 602 such patients who received placebo and androgen deprivation, Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, Villejuif, France, reported at the annual meeting of the American Society of Clinical Oncology.

Significant improvements also were seen in the treatment vs. placebo group for all secondary endpoints, including time to prostate-specific-antigen progression (hazard ratio, 0.30), time to pain progression (HR, 0.70), time to next symptomatic skeletal event (HR, 0.70), time to chemotherapy (HR, 0.44), and time to subsequent prostate cancer therapy (HR, 0.42), Dr. Fizazi said.

He discussed the findings, including side effects, and ongoing and future studies, in a video interview.

[email protected]

CHICAGO – Adding abiraterone acetate plus prednisone to androgen deprivation therapy in hormone-naive high-risk prostate cancer patients significantly improves overall survival, according to “practice-changing” results from the phase III LATITUDE trial and the multiarm, multistage STAMPEDE trial.

In the double-blind, randomized, placebo-controlled LATITUDE trial, 597 patients with newly diagnosed high-risk metastatic prostate cancer who received 1,000 mg of abiraterone acetate daily plus 5 mg of prednisone daily in addition to androgen deprivation therapy experienced a 38% reduction in the risk of death and a 53% reduction in the risk of radiographic progression or death at a median follow-up of 30.4 months, compared with 602 such patients who received placebo and androgen deprivation, Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, Villejuif, France, reported at the annual meeting of the American Society of Clinical Oncology.

Significant improvements also were seen in the treatment vs. placebo group for all secondary endpoints, including time to prostate-specific-antigen progression (hazard ratio, 0.30), time to pain progression (HR, 0.70), time to next symptomatic skeletal event (HR, 0.70), time to chemotherapy (HR, 0.44), and time to subsequent prostate cancer therapy (HR, 0.42), Dr. Fizazi said.

He discussed the findings, including side effects, and ongoing and future studies, in a video interview.

[email protected]

CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.

As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.

For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).

Neil Osterweil/Frontline Medical News

STREAM

Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.

The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.

The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.

For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.

In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.

Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).

At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.

Neil Osterweil/Frontline Medical News

Recurrence fears assuaged

In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.

“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.

Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).

Neil Osterweil/Frontline Medical News

CALM

In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.

Neil Osterweil/Frontline Medical News

CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.

As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.

For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).

Neil Osterweil/Frontline Medical News

STREAM

Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.

The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.

The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.

For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.

In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.

Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).

At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.

Neil Osterweil/Frontline Medical News

Recurrence fears assuaged

In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.

“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.

Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).

Neil Osterweil/Frontline Medical News

CALM

In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.

Neil Osterweil/Frontline Medical News

CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.

As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.

For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).

Neil Osterweil/Frontline Medical News

STREAM

Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.

The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.

The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.

For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.

In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.

Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).

At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.

Neil Osterweil/Frontline Medical News

Recurrence fears assuaged

In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.

“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.

Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).

Neil Osterweil/Frontline Medical News

CALM

In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.

Neil Osterweil/Frontline Medical News