Hodgkin Lymphoma

PET scanner

Photo by Jens Maus

LUGANO—Results of the RATHL trial indicate that bleomycin can be omitted from ABVD therapy following a negative interim FDG-PET scan in patients with Hodgkin lymphoma.

Progression-free survival (PFS) and overall survival (OS) were the same at 3 years for patients who were PET-negative after 2 cycles of ABVD and then continued therapy with or without bleomycin.

These results were presented at the 13th International Conference on Malignant Lymphoma (13-ICML).

Investigators based the RATHL study on the principles that it’s desirable to de-escalate treatment in the best responders to avoid late toxicity and that PET scans after 2 cycles of ABVD are highly predictive.

The team enrolled 1214 patients from 6 countries, 861 of whom were in the UK. Patients received a PET scan at staging, 2 cycles of ABVD, and then a second PET scan (PET2).

If patients were negative after PET2, they were randomized to receive 4 more cycles of ABVD or AVD and no radiotherapy.

If they were positive after PET2, patients received 4 cycles of BEACOPP-14 or 3 cycles of escalated BEACOPP. These patients then received a third PET scan, and the positive patients went on to receive radiotherapy or a salvage regimen.

The PET3-negative patients received 2 more cycles of BEACOPP-14 or one of escalated BEACOPP without radiotherapy.

Peter W. Johnson, MD, of the University of Southampton in the UK, presented the results of these treatment regimens during the plenary session of 13-ICML as abstract 008.

Patient characteristics

Patients were a median age of 33 (range, 18-79), and 55% were male. They had disease stages of II (41%), III (31%), or IV (28%).

Seventy-four percent of patients had a performance status of 0. Almost half (49%) had an IPS score of 2 to 3, and 18% had an IPS score of 4 or more. Thirty-two percent had bulky disease.

Investigators followed the patients for a median of 34.7 months (range, 1 day to 68.2 months).

Results after PET2

Seventy-seven patients were missing a second PET scan, mostly due to PET protocol violations of having to use the same scanner for the baseline and second scan and the same acquisition time.

“We were very strict on our quality control,” Dr Johnson said, “because we wished to make sure this was reproducible data.”

So the results after 2 cycles of ABVD treatment were based on 1137 patients.

PET-negative patients

More than 80% of patients were PET-negative after 2 cycles. Four hundred and sixty-nine patients were randomized to receive ABVD and 466 to AVD.

The groups were well-balanced in terms of median age, performance status, stage, B symptoms, bulky disease, and IPS score.

There was a significant excess of neutropenic fever (P=0.032) and infection (P=0.040) in those patients continuing on ABVD compared to AVD. And any hematologic toxicity was highly significantly different between the 2 arms (P<0.001).

“So we have demonstrated that continuing with bleomycin beyond cycle 2 is accompanied by significantly more toxicity,” Dr Johnson said.

Ninety-eight percent of patients in both cohorts received at least 6 cycles of therapy post-randomization.

At a median follow-up of 36.3 months, 65% of patients in the ABVD arm and 69% in the AVD arm achieved a complete remission (CR) or unconfirmed CR (CRu).

Fourteen patients died in each of the arms. Seven patients died of their disease in the AVD arm, compared with 1 in the ABVD arm. Slightly more patients died from toxicity in the ABVD arm.

The primary endpoint of PFS showed very little difference between the 2 arms. The 3-year PFS in the intent-to-treat analysis was 85.4% for patients in the ABVD arm and 84.4% for those in the AVD arm.

The investigators observed that the PFS of 85% was somewhat lower than the 95% PFS observed in the literature. So they looked at the association between baseline factors and PFS after negative PET2.

“And what stands out from this is that if you have high-stage disease at presentation, there is a slightly higher chance of treatment failure following a negative PET scan,” Dr Johnson said. “And you can see the trend here, from early stage disease up to advanced-stage disease, the PET scan becomes a less reliable indicator of result.”

The investigators also conducted a subgroup analysis of the PET2-negative patients and found there was no difference in outcome between treatment arms in patients with more advanced disease, with bulky disease, with a high IPS score, or according to the PET score.

“So we have not succeeded in finding any subgroup where it appears to be beneficial to continue bleomycin,” Dr Johnson said.

The OS rate was also the same between the 2 arms, at 97%.

PET2-positive patients

One hundred and seventy-four patients who were positive after the second PET scan received either BEACOPP for 14 days or escalated BEACOPP.

The percentage of patients who experienced grade 3-4 toxicities was largely similar between the 2 regimens, although the patients receiving escalated BEACOPP had more neutropenia (P=0.057), thrombocytopenia (P=0.001), and neutropenic fever (P=0.08).

In terms of efficacy, two-thirds of patients became PET-negative by the third PET scan, and 48% of patients achieved a CR or CRu.

Twenty-one patients died, 8 due to Hodgkin lymphoma.

The PFS was 66.0% in the BEACOPP-14 group and 71.1% in the escalated-BEACOPP group. The 3-year OS was 89.6% in the BEACOPP-14 group and 82.8% in the escalated-BEACOPP group.

For the entire group of 1214 patients, the 3-year PFS was 82.5%, and the OS was 95.4%.

Based on these results, the investigators concluded that it is safe to omit bleomycin and consolidation radiotherapy from subsequent ABVD therapy after a negative interim PET scan. And doing so reduces toxicity, especially dyspnea, thromboembolism, and neutropenic fever.

“[B]y using more selective chemotherapy and much less radiotherapy than we have previously used in our studies, where we’re giving less than 3% of patients consolidation radiotherapy, the results appear to be favorable and an improvement over what we have seen previously,” Dr Johnson said.

Details on lung toxicity in this study were presented separately at 13-ICML as abstract 041.

PET scanner

Photo by Jens Maus

LUGANO—Results of the RATHL trial indicate that bleomycin can be omitted from ABVD therapy following a negative interim FDG-PET scan in patients with Hodgkin lymphoma.

Progression-free survival (PFS) and overall survival (OS) were the same at 3 years for patients who were PET-negative after 2 cycles of ABVD and then continued therapy with or without bleomycin.

These results were presented at the 13th International Conference on Malignant Lymphoma (13-ICML).

Investigators based the RATHL study on the principles that it’s desirable to de-escalate treatment in the best responders to avoid late toxicity and that PET scans after 2 cycles of ABVD are highly predictive.

The team enrolled 1214 patients from 6 countries, 861 of whom were in the UK. Patients received a PET scan at staging, 2 cycles of ABVD, and then a second PET scan (PET2).

If patients were negative after PET2, they were randomized to receive 4 more cycles of ABVD or AVD and no radiotherapy.

If they were positive after PET2, patients received 4 cycles of BEACOPP-14 or 3 cycles of escalated BEACOPP. These patients then received a third PET scan, and the positive patients went on to receive radiotherapy or a salvage regimen.

The PET3-negative patients received 2 more cycles of BEACOPP-14 or one of escalated BEACOPP without radiotherapy.

Peter W. Johnson, MD, of the University of Southampton in the UK, presented the results of these treatment regimens during the plenary session of 13-ICML as abstract 008.

Patient characteristics

Patients were a median age of 33 (range, 18-79), and 55% were male. They had disease stages of II (41%), III (31%), or IV (28%).

Seventy-four percent of patients had a performance status of 0. Almost half (49%) had an IPS score of 2 to 3, and 18% had an IPS score of 4 or more. Thirty-two percent had bulky disease.

Investigators followed the patients for a median of 34.7 months (range, 1 day to 68.2 months).

Results after PET2

Seventy-seven patients were missing a second PET scan, mostly due to PET protocol violations of having to use the same scanner for the baseline and second scan and the same acquisition time.

“We were very strict on our quality control,” Dr Johnson said, “because we wished to make sure this was reproducible data.”

So the results after 2 cycles of ABVD treatment were based on 1137 patients.

PET-negative patients

More than 80% of patients were PET-negative after 2 cycles. Four hundred and sixty-nine patients were randomized to receive ABVD and 466 to AVD.

The groups were well-balanced in terms of median age, performance status, stage, B symptoms, bulky disease, and IPS score.

There was a significant excess of neutropenic fever (P=0.032) and infection (P=0.040) in those patients continuing on ABVD compared to AVD. And any hematologic toxicity was highly significantly different between the 2 arms (P<0.001).

“So we have demonstrated that continuing with bleomycin beyond cycle 2 is accompanied by significantly more toxicity,” Dr Johnson said.

Ninety-eight percent of patients in both cohorts received at least 6 cycles of therapy post-randomization.

At a median follow-up of 36.3 months, 65% of patients in the ABVD arm and 69% in the AVD arm achieved a complete remission (CR) or unconfirmed CR (CRu).

Fourteen patients died in each of the arms. Seven patients died of their disease in the AVD arm, compared with 1 in the ABVD arm. Slightly more patients died from toxicity in the ABVD arm.

The primary endpoint of PFS showed very little difference between the 2 arms. The 3-year PFS in the intent-to-treat analysis was 85.4% for patients in the ABVD arm and 84.4% for those in the AVD arm.

The investigators observed that the PFS of 85% was somewhat lower than the 95% PFS observed in the literature. So they looked at the association between baseline factors and PFS after negative PET2.

“And what stands out from this is that if you have high-stage disease at presentation, there is a slightly higher chance of treatment failure following a negative PET scan,” Dr Johnson said. “And you can see the trend here, from early stage disease up to advanced-stage disease, the PET scan becomes a less reliable indicator of result.”

The investigators also conducted a subgroup analysis of the PET2-negative patients and found there was no difference in outcome between treatment arms in patients with more advanced disease, with bulky disease, with a high IPS score, or according to the PET score.

“So we have not succeeded in finding any subgroup where it appears to be beneficial to continue bleomycin,” Dr Johnson said.

The OS rate was also the same between the 2 arms, at 97%.

PET2-positive patients

One hundred and seventy-four patients who were positive after the second PET scan received either BEACOPP for 14 days or escalated BEACOPP.

The percentage of patients who experienced grade 3-4 toxicities was largely similar between the 2 regimens, although the patients receiving escalated BEACOPP had more neutropenia (P=0.057), thrombocytopenia (P=0.001), and neutropenic fever (P=0.08).

In terms of efficacy, two-thirds of patients became PET-negative by the third PET scan, and 48% of patients achieved a CR or CRu.

Twenty-one patients died, 8 due to Hodgkin lymphoma.

The PFS was 66.0% in the BEACOPP-14 group and 71.1% in the escalated-BEACOPP group. The 3-year OS was 89.6% in the BEACOPP-14 group and 82.8% in the escalated-BEACOPP group.

For the entire group of 1214 patients, the 3-year PFS was 82.5%, and the OS was 95.4%.

Based on these results, the investigators concluded that it is safe to omit bleomycin and consolidation radiotherapy from subsequent ABVD therapy after a negative interim PET scan. And doing so reduces toxicity, especially dyspnea, thromboembolism, and neutropenic fever.

“[B]y using more selective chemotherapy and much less radiotherapy than we have previously used in our studies, where we’re giving less than 3% of patients consolidation radiotherapy, the results appear to be favorable and an improvement over what we have seen previously,” Dr Johnson said.

Details on lung toxicity in this study were presented separately at 13-ICML as abstract 041.

PET scanner

Photo by Jens Maus

LUGANO—Results of the RATHL trial indicate that bleomycin can be omitted from ABVD therapy following a negative interim FDG-PET scan in patients with Hodgkin lymphoma.

Progression-free survival (PFS) and overall survival (OS) were the same at 3 years for patients who were PET-negative after 2 cycles of ABVD and then continued therapy with or without bleomycin.

These results were presented at the 13th International Conference on Malignant Lymphoma (13-ICML).

Investigators based the RATHL study on the principles that it’s desirable to de-escalate treatment in the best responders to avoid late toxicity and that PET scans after 2 cycles of ABVD are highly predictive.

The team enrolled 1214 patients from 6 countries, 861 of whom were in the UK. Patients received a PET scan at staging, 2 cycles of ABVD, and then a second PET scan (PET2).

If patients were negative after PET2, they were randomized to receive 4 more cycles of ABVD or AVD and no radiotherapy.

If they were positive after PET2, patients received 4 cycles of BEACOPP-14 or 3 cycles of escalated BEACOPP. These patients then received a third PET scan, and the positive patients went on to receive radiotherapy or a salvage regimen.

The PET3-negative patients received 2 more cycles of BEACOPP-14 or one of escalated BEACOPP without radiotherapy.

Peter W. Johnson, MD, of the University of Southampton in the UK, presented the results of these treatment regimens during the plenary session of 13-ICML as abstract 008.

Patient characteristics

Patients were a median age of 33 (range, 18-79), and 55% were male. They had disease stages of II (41%), III (31%), or IV (28%).

Seventy-four percent of patients had a performance status of 0. Almost half (49%) had an IPS score of 2 to 3, and 18% had an IPS score of 4 or more. Thirty-two percent had bulky disease.

Investigators followed the patients for a median of 34.7 months (range, 1 day to 68.2 months).

Results after PET2

Seventy-seven patients were missing a second PET scan, mostly due to PET protocol violations of having to use the same scanner for the baseline and second scan and the same acquisition time.

“We were very strict on our quality control,” Dr Johnson said, “because we wished to make sure this was reproducible data.”

So the results after 2 cycles of ABVD treatment were based on 1137 patients.

PET-negative patients

More than 80% of patients were PET-negative after 2 cycles. Four hundred and sixty-nine patients were randomized to receive ABVD and 466 to AVD.

The groups were well-balanced in terms of median age, performance status, stage, B symptoms, bulky disease, and IPS score.

There was a significant excess of neutropenic fever (P=0.032) and infection (P=0.040) in those patients continuing on ABVD compared to AVD. And any hematologic toxicity was highly significantly different between the 2 arms (P<0.001).

“So we have demonstrated that continuing with bleomycin beyond cycle 2 is accompanied by significantly more toxicity,” Dr Johnson said.

Ninety-eight percent of patients in both cohorts received at least 6 cycles of therapy post-randomization.

At a median follow-up of 36.3 months, 65% of patients in the ABVD arm and 69% in the AVD arm achieved a complete remission (CR) or unconfirmed CR (CRu).

Fourteen patients died in each of the arms. Seven patients died of their disease in the AVD arm, compared with 1 in the ABVD arm. Slightly more patients died from toxicity in the ABVD arm.

The primary endpoint of PFS showed very little difference between the 2 arms. The 3-year PFS in the intent-to-treat analysis was 85.4% for patients in the ABVD arm and 84.4% for those in the AVD arm.

The investigators observed that the PFS of 85% was somewhat lower than the 95% PFS observed in the literature. So they looked at the association between baseline factors and PFS after negative PET2.

“And what stands out from this is that if you have high-stage disease at presentation, there is a slightly higher chance of treatment failure following a negative PET scan,” Dr Johnson said. “And you can see the trend here, from early stage disease up to advanced-stage disease, the PET scan becomes a less reliable indicator of result.”

The investigators also conducted a subgroup analysis of the PET2-negative patients and found there was no difference in outcome between treatment arms in patients with more advanced disease, with bulky disease, with a high IPS score, or according to the PET score.

“So we have not succeeded in finding any subgroup where it appears to be beneficial to continue bleomycin,” Dr Johnson said.

The OS rate was also the same between the 2 arms, at 97%.

PET2-positive patients

One hundred and seventy-four patients who were positive after the second PET scan received either BEACOPP for 14 days or escalated BEACOPP.

The percentage of patients who experienced grade 3-4 toxicities was largely similar between the 2 regimens, although the patients receiving escalated BEACOPP had more neutropenia (P=0.057), thrombocytopenia (P=0.001), and neutropenic fever (P=0.08).

In terms of efficacy, two-thirds of patients became PET-negative by the third PET scan, and 48% of patients achieved a CR or CRu.

Twenty-one patients died, 8 due to Hodgkin lymphoma.

The PFS was 66.0% in the BEACOPP-14 group and 71.1% in the escalated-BEACOPP group. The 3-year OS was 89.6% in the BEACOPP-14 group and 82.8% in the escalated-BEACOPP group.

For the entire group of 1214 patients, the 3-year PFS was 82.5%, and the OS was 95.4%.

Based on these results, the investigators concluded that it is safe to omit bleomycin and consolidation radiotherapy from subsequent ABVD therapy after a negative interim PET scan. And doing so reduces toxicity, especially dyspnea, thromboembolism, and neutropenic fever.

“[B]y using more selective chemotherapy and much less radiotherapy than we have previously used in our studies, where we’re giving less than 3% of patients consolidation radiotherapy, the results appear to be favorable and an improvement over what we have seen previously,” Dr Johnson said.

Details on lung toxicity in this study were presented separately at 13-ICML as abstract 041.

 

 

Blood samples

Photo by Graham Colm

 

GLASGOW—A non-invasive prenatal test (NIPT) used to identify chromosomal fetal disorders can detect maternal cancers before symptoms appear, a new study has shown.

Testing revealed chromosomal abnormalities in 3 women that bore a resemblance to abnormalities observed in cancers. And additional testing confirmed the women had cancer—Hodgkin lymphoma (HL), follicular lymphoma (FL), and ovarian carcinoma.

This research was presented at the European Human Genetics Conference 2015 and published simultaneously in JAMA Oncology.

Nathalie Brison, PhD, of University Hospitals Leuven in Belgium, and her colleagues conducted this research with the goal of improving the NIPT test. They wanted to overcome some of the technical problems that can cause the test to produce false-negative or false-positive results.

“Even though it is very reliable, we believed that we could make it even better, and, in doing so, we could also find other chromosomal abnormalities apart from the traditional trisomy syndromes—Down’s [trisomy 21], Edward’s [trisomy 18], and Patau [trisomy 13],” Dr Brison said.

“Using the new, adapted test in over 6000 pregnancies, and looking at other chromosomes, we identified 3 different genomic abnormalities in 3 women that could not be linked to either the maternal or fetal genomic profile. We realized that the abnormalities bore a resemblance to those found in cancer and referred the women to the oncology unit.”

Further examination, including whole-body MRI scanning and pathological and genetic investigations, revealed the presence of 3 different early stage cancers in the women: ovarian carcinoma, FL, and HL.

The researchers said that, without NIPT, these cancers likely would not have been detected until the women developed symptoms.

“Considering the bad prognosis of some cancers when detected later, and given that we know that it is both possible and safe to treat the disease during pregnancy, this is an important added advantage of NIPT,” said study author Joris Vermeesch, PhD, also of University Hospitals Leuven.

“During pregnancy, cancer-related symptoms may well be masked. Fatigue, nausea, abdominal pain, and vaginal blood loss are easily interpretable as a normal part of being pregnant. NIPT offers an opportunity for the accurate screening of high-risk women for cancer, allowing us to overcome the challenge of early diagnosis in pregnant women.”

Two of the 3 women diagnosed with cancer were treated. The woman with ovarian cancer was treated after delivery.

The woman with HL was treated during pregnancy and ultimately gave birth to a healthy girl. The woman with FL has indolent disease and may not require treatment for years, according to the researchers.

Follow-up investigations in the treated women showed that NIPT had the additional advantage of allowing for treatment monitoring. The researchers were able to see that chromosomal profiles became normal during and after chemotherapy.

Because NIPT involves looking at chromosomes other than 13, 18, and 21, the women taking part in this study were informed about the possibility of incidental findings.

“However, our study feeds into the ethical debate about whether or not to report incidental findings to patients and also has implications for the current political discussions concerning reimbursement and funding of NIPT by national healthcare systems,” Dr Vermeesch said.

The results also suggest that NIPT might enable the detection of pre-symptomatic cancers in the general population.

“We now know that it is possible to offer the accurate detection of chromosomally imbalanced cancers to the general population via minimally invasive screening methods,” Dr Brison said. “The normalization of the NIPT profile in these patients following treatment indicates that we can also measure response to treatment as early as after the first administration of chemotherapy.”

“Of course, larger-scale studies will be required to validate these results further, but we are confident that we have made an important step towards the possibility of wide-scale, effective, non-invasive cancer screening capable of detecting disease at an early stage.”

 

 

Blood samples

Photo by Graham Colm

 

GLASGOW—A non-invasive prenatal test (NIPT) used to identify chromosomal fetal disorders can detect maternal cancers before symptoms appear, a new study has shown.

Testing revealed chromosomal abnormalities in 3 women that bore a resemblance to abnormalities observed in cancers. And additional testing confirmed the women had cancer—Hodgkin lymphoma (HL), follicular lymphoma (FL), and ovarian carcinoma.

This research was presented at the European Human Genetics Conference 2015 and published simultaneously in JAMA Oncology.

Nathalie Brison, PhD, of University Hospitals Leuven in Belgium, and her colleagues conducted this research with the goal of improving the NIPT test. They wanted to overcome some of the technical problems that can cause the test to produce false-negative or false-positive results.

“Even though it is very reliable, we believed that we could make it even better, and, in doing so, we could also find other chromosomal abnormalities apart from the traditional trisomy syndromes—Down’s [trisomy 21], Edward’s [trisomy 18], and Patau [trisomy 13],” Dr Brison said.

“Using the new, adapted test in over 6000 pregnancies, and looking at other chromosomes, we identified 3 different genomic abnormalities in 3 women that could not be linked to either the maternal or fetal genomic profile. We realized that the abnormalities bore a resemblance to those found in cancer and referred the women to the oncology unit.”

Further examination, including whole-body MRI scanning and pathological and genetic investigations, revealed the presence of 3 different early stage cancers in the women: ovarian carcinoma, FL, and HL.

The researchers said that, without NIPT, these cancers likely would not have been detected until the women developed symptoms.

“Considering the bad prognosis of some cancers when detected later, and given that we know that it is both possible and safe to treat the disease during pregnancy, this is an important added advantage of NIPT,” said study author Joris Vermeesch, PhD, also of University Hospitals Leuven.

“During pregnancy, cancer-related symptoms may well be masked. Fatigue, nausea, abdominal pain, and vaginal blood loss are easily interpretable as a normal part of being pregnant. NIPT offers an opportunity for the accurate screening of high-risk women for cancer, allowing us to overcome the challenge of early diagnosis in pregnant women.”

Two of the 3 women diagnosed with cancer were treated. The woman with ovarian cancer was treated after delivery.

The woman with HL was treated during pregnancy and ultimately gave birth to a healthy girl. The woman with FL has indolent disease and may not require treatment for years, according to the researchers.

Follow-up investigations in the treated women showed that NIPT had the additional advantage of allowing for treatment monitoring. The researchers were able to see that chromosomal profiles became normal during and after chemotherapy.

Because NIPT involves looking at chromosomes other than 13, 18, and 21, the women taking part in this study were informed about the possibility of incidental findings.

“However, our study feeds into the ethical debate about whether or not to report incidental findings to patients and also has implications for the current political discussions concerning reimbursement and funding of NIPT by national healthcare systems,” Dr Vermeesch said.

The results also suggest that NIPT might enable the detection of pre-symptomatic cancers in the general population.

“We now know that it is possible to offer the accurate detection of chromosomally imbalanced cancers to the general population via minimally invasive screening methods,” Dr Brison said. “The normalization of the NIPT profile in these patients following treatment indicates that we can also measure response to treatment as early as after the first administration of chemotherapy.”

“Of course, larger-scale studies will be required to validate these results further, but we are confident that we have made an important step towards the possibility of wide-scale, effective, non-invasive cancer screening capable of detecting disease at an early stage.”

 

 

Blood samples

Photo by Graham Colm

 

GLASGOW—A non-invasive prenatal test (NIPT) used to identify chromosomal fetal disorders can detect maternal cancers before symptoms appear, a new study has shown.

Testing revealed chromosomal abnormalities in 3 women that bore a resemblance to abnormalities observed in cancers. And additional testing confirmed the women had cancer—Hodgkin lymphoma (HL), follicular lymphoma (FL), and ovarian carcinoma.

This research was presented at the European Human Genetics Conference 2015 and published simultaneously in JAMA Oncology.

Nathalie Brison, PhD, of University Hospitals Leuven in Belgium, and her colleagues conducted this research with the goal of improving the NIPT test. They wanted to overcome some of the technical problems that can cause the test to produce false-negative or false-positive results.

“Even though it is very reliable, we believed that we could make it even better, and, in doing so, we could also find other chromosomal abnormalities apart from the traditional trisomy syndromes—Down’s [trisomy 21], Edward’s [trisomy 18], and Patau [trisomy 13],” Dr Brison said.

“Using the new, adapted test in over 6000 pregnancies, and looking at other chromosomes, we identified 3 different genomic abnormalities in 3 women that could not be linked to either the maternal or fetal genomic profile. We realized that the abnormalities bore a resemblance to those found in cancer and referred the women to the oncology unit.”

Further examination, including whole-body MRI scanning and pathological and genetic investigations, revealed the presence of 3 different early stage cancers in the women: ovarian carcinoma, FL, and HL.

The researchers said that, without NIPT, these cancers likely would not have been detected until the women developed symptoms.

“Considering the bad prognosis of some cancers when detected later, and given that we know that it is both possible and safe to treat the disease during pregnancy, this is an important added advantage of NIPT,” said study author Joris Vermeesch, PhD, also of University Hospitals Leuven.

“During pregnancy, cancer-related symptoms may well be masked. Fatigue, nausea, abdominal pain, and vaginal blood loss are easily interpretable as a normal part of being pregnant. NIPT offers an opportunity for the accurate screening of high-risk women for cancer, allowing us to overcome the challenge of early diagnosis in pregnant women.”

Two of the 3 women diagnosed with cancer were treated. The woman with ovarian cancer was treated after delivery.

The woman with HL was treated during pregnancy and ultimately gave birth to a healthy girl. The woman with FL has indolent disease and may not require treatment for years, according to the researchers.

Follow-up investigations in the treated women showed that NIPT had the additional advantage of allowing for treatment monitoring. The researchers were able to see that chromosomal profiles became normal during and after chemotherapy.

Because NIPT involves looking at chromosomes other than 13, 18, and 21, the women taking part in this study were informed about the possibility of incidental findings.

“However, our study feeds into the ethical debate about whether or not to report incidental findings to patients and also has implications for the current political discussions concerning reimbursement and funding of NIPT by national healthcare systems,” Dr Vermeesch said.

The results also suggest that NIPT might enable the detection of pre-symptomatic cancers in the general population.

“We now know that it is possible to offer the accurate detection of chromosomally imbalanced cancers to the general population via minimally invasive screening methods,” Dr Brison said. “The normalization of the NIPT profile in these patients following treatment indicates that we can also measure response to treatment as early as after the first administration of chemotherapy.”

“Of course, larger-scale studies will be required to validate these results further, but we are confident that we have made an important step towards the possibility of wide-scale, effective, non-invasive cancer screening capable of detecting disease at an early stage.”

Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

Doctor and patient

Photo courtesy of NIH

In trying to estimate the global cancer burden, researchers found that cases of Hodgkin lymphoma (HL) have decreased worldwide over the last 2 decades.

The team studied 28 cancer types in 188 countries, and HL was the only malignancy whose incidence decreased from 1990 to 2013.

And the number of HL deaths in 2013 was comparatively low. When the researchers ranked cancers according to the number of global deaths, HL was 26th on the list of 28.

The researchers disclosed these results in JAMA Oncology.

The team collected data from cancer registries, vital records, verbal autopsy reports, and other sources to estimate the global cancer burden.

The data suggested that, in 2013, there were 14.9 million new cancer cases and 8.2 million cancer deaths worldwide. The proportion of cancer deaths as part of all deaths increased from 12% in 1990 to 15% in 2013.

The most common malignancy in men was prostate cancer, with 1.4 million cases in 2013. For women, it was breast cancer, with 1.8 million cases in 2013.

Tracheal, bronchus, and lung cancers were the leading cause of cancer death in men and women, with 1.6 million deaths in 2013.

Hematologic malignancies

Globally, the age-standardized incidence of HL per 100,000 people decreased by 34% during the time period studied. Cases of HL fell from about 103,000 in 1990 to 93,000 in 2013.

When the researchers ranked cancer types according to the number of global deaths in 2013, HL came in 26th. There were about 24,000 HL deaths in 2013—14,000 among men and 10,000 among women.

Non-Hodgkin lymphoma (NHL) came in 11th for global cancer deaths in 2013. There were about 226,000 NHL deaths—133,000 among men and 92,000 among women.

In addition, the incidence of NHL more than doubled from 1990 to 2013, rising from about 227,000 to 465,000. According to 2013 data, 1 in 103 men and 1 in 151 women developed NHL between birth and 79 years of age.

The researchers observed an increase in cases of multiple myeloma (MM) as well, from about 63,000 in 1990 to 117,000 in 2013.

In 2013, there were about 79,000 MM deaths—42,000 among men and 37,000 among women. MM ranked 19th on the list of global cancer deaths in 2013.

Leukemia ranked 9th on the list. There were about 265,000 leukemia deaths in 2013—149,000 among men and 116,000 among women.

Cases of leukemia increased from 297,000 in 1990 to 414,000 in 2013. According to 2013 data, 1 in 127 men and 1 in 203 women developed leukemia between birth and 79 years of age.

This research shows that cancer remains a major threat to people’s health around the world, said study author Christina Fitzmaurice, MD, of the University of Washington in Seattle.

“Cancer prevention, screening, and treatment programs are costly,” she noted, “and it is very important for countries to know which cancers cause the highest disease burden in order to allocate scarce resources appropriately.”

Micrograph showing HL

LONDON—Results of a small, phase 1 trial suggest CD30-directed chimeric antigen receptor (CAR) T-cell therapy is feasible in patients with aggressive Hodgkin lymphoma (HL).

The trial included 7 patients with relapsed or refractory HL.

Five of the patients achieved stable disease or better after infusions of CAR T cells, and the researchers said treatment-related adverse events were manageable.

William (Wei) Cao, PhD, of Cellular Biomedicine Group, presented these results at the 10th Annual World Stem Cells & Regenerative Medicine Congress.

The research was funded by Cellular Biomedicine Group, the company developing the CAR T-cell therapy (known as CBM-C30.1), as well as by grants from the National Natural Science Foundation of China and the National Basic Science and Development Program of China.

The trial included 7 patients with progressive HL. Two patients had stage III disease, and 5 had stage IV. The patients had a median of 16 prior treatments (range, 8-24) and limited prognosis (several months to less than 2-year survival) with currently available therapies.

The patients received escalating doses of autologous T cells transduced with a CD30-directed CAR moiety for 3 to 5 days, following a conditioning regimen. The researchers measured the level of CAR transgenes in peripheral blood and biopsied tumor tissues by quantitative PCR.

Two patients achieved a partial response to CAR T-cell therapy, and 3 attained stable disease. So the therapy resulted in an overall disease control rate of 71.4% (5/7) and an objective response rate of 28.6% (2/7).

Stable disease lasted 2 months in 2 of the patients and more than 3.5 months in the third patient. Partial response lasted more than 2 months in 1 patient and more than 3.5 months in the other.

Dr Cao said adverse events consisted largely of fever and were manageable with medical intervention. One patient experienced 5-day self-limiting arthralgia, myalgia, and dual knee swelling 2 weeks after cell infusion. There were no delayed or severe adverse events.

“We are very encouraged by the efficacy and toxicity profile of our CAR-T CD30 technology,” Dr Cao said, “given that the [patients] were diagnosed with stage III and IV Hodgkin’s lymphoma.”

Micrograph showing HL

LONDON—Results of a small, phase 1 trial suggest CD30-directed chimeric antigen receptor (CAR) T-cell therapy is feasible in patients with aggressive Hodgkin lymphoma (HL).

The trial included 7 patients with relapsed or refractory HL.

Five of the patients achieved stable disease or better after infusions of CAR T cells, and the researchers said treatment-related adverse events were manageable.

William (Wei) Cao, PhD, of Cellular Biomedicine Group, presented these results at the 10th Annual World Stem Cells & Regenerative Medicine Congress.

The research was funded by Cellular Biomedicine Group, the company developing the CAR T-cell therapy (known as CBM-C30.1), as well as by grants from the National Natural Science Foundation of China and the National Basic Science and Development Program of China.

The trial included 7 patients with progressive HL. Two patients had stage III disease, and 5 had stage IV. The patients had a median of 16 prior treatments (range, 8-24) and limited prognosis (several months to less than 2-year survival) with currently available therapies.

The patients received escalating doses of autologous T cells transduced with a CD30-directed CAR moiety for 3 to 5 days, following a conditioning regimen. The researchers measured the level of CAR transgenes in peripheral blood and biopsied tumor tissues by quantitative PCR.

Two patients achieved a partial response to CAR T-cell therapy, and 3 attained stable disease. So the therapy resulted in an overall disease control rate of 71.4% (5/7) and an objective response rate of 28.6% (2/7).

Stable disease lasted 2 months in 2 of the patients and more than 3.5 months in the third patient. Partial response lasted more than 2 months in 1 patient and more than 3.5 months in the other.

Dr Cao said adverse events consisted largely of fever and were manageable with medical intervention. One patient experienced 5-day self-limiting arthralgia, myalgia, and dual knee swelling 2 weeks after cell infusion. There were no delayed or severe adverse events.

“We are very encouraged by the efficacy and toxicity profile of our CAR-T CD30 technology,” Dr Cao said, “given that the [patients] were diagnosed with stage III and IV Hodgkin’s lymphoma.”

Micrograph showing HL

LONDON—Results of a small, phase 1 trial suggest CD30-directed chimeric antigen receptor (CAR) T-cell therapy is feasible in patients with aggressive Hodgkin lymphoma (HL).

The trial included 7 patients with relapsed or refractory HL.

Five of the patients achieved stable disease or better after infusions of CAR T cells, and the researchers said treatment-related adverse events were manageable.

William (Wei) Cao, PhD, of Cellular Biomedicine Group, presented these results at the 10th Annual World Stem Cells & Regenerative Medicine Congress.

The research was funded by Cellular Biomedicine Group, the company developing the CAR T-cell therapy (known as CBM-C30.1), as well as by grants from the National Natural Science Foundation of China and the National Basic Science and Development Program of China.

The trial included 7 patients with progressive HL. Two patients had stage III disease, and 5 had stage IV. The patients had a median of 16 prior treatments (range, 8-24) and limited prognosis (several months to less than 2-year survival) with currently available therapies.

The patients received escalating doses of autologous T cells transduced with a CD30-directed CAR moiety for 3 to 5 days, following a conditioning regimen. The researchers measured the level of CAR transgenes in peripheral blood and biopsied tumor tissues by quantitative PCR.

Two patients achieved a partial response to CAR T-cell therapy, and 3 attained stable disease. So the therapy resulted in an overall disease control rate of 71.4% (5/7) and an objective response rate of 28.6% (2/7).

Stable disease lasted 2 months in 2 of the patients and more than 3.5 months in the third patient. Partial response lasted more than 2 months in 1 patient and more than 3.5 months in the other.

Dr Cao said adverse events consisted largely of fever and were manageable with medical intervention. One patient experienced 5-day self-limiting arthralgia, myalgia, and dual knee swelling 2 weeks after cell infusion. There were no delayed or severe adverse events.

“We are very encouraged by the efficacy and toxicity profile of our CAR-T CD30 technology,” Dr Cao said, “given that the [patients] were diagnosed with stage III and IV Hodgkin’s lymphoma.”

Doctor examines patient

Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.

These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.

Both studies were published in the British Journal of General Practice.

“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.

“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”

The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.

The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).

In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.

The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).

Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.

Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.

Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.

“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”

Doctor examines patient

Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.

These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.

Both studies were published in the British Journal of General Practice.

“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.

“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”

The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.

The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).

In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.

The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).

Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.

Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.

Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.

“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”

Doctor examines patient

Results from two new studies indicate that lymphadenopathy and head and neck masses are associated with a higher risk of lymphoma than we thought.

These two factors proved to be the strongest predictors of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

So unless these symptoms can be explained, general practitioners should refer affected patients to specialists as quickly as possible, study investigators said.

Both studies were published in the British Journal of General Practice.

“Cancer guidelines are based on the most robust evidence, and, up to now, this has been missing,” said Willie Hamilton, MD, of the University of Exeter Medical School in the UK.

“Our research has revealed the importance of persistent, swollen lymph glands, particularly in the neck, as part of cancer. Of course, swollen glands are common with throat infections, but in cancer, they are usually larger and painless. It’s been known for a long time that this could represent cancer. This study shows that the risk is higher than previously thought.”

The first study was a large-scale assessment of symptoms that are markers of NHL. Researchers assessed 4362 NHL patients (≥ 40 years of age) and 19,468 controls.

The 5 symptoms associated with the highest risk of developing NHL were lymphadenopathy (odds ratio [OR]=263), head and neck mass not described as lymphadenopathy (OR=49), other mass (OR=12), weight loss (OR=3.2), and abdominal pain (OR=2.5).

In the second study, investigators assessed 283 HL patients (≥ 40 years of age) and 1237 control subjects.

The team found that 6 features were independently associated with HL—lymphadenopathy (OR=280), head and neck mass not described as lymphadenopathy (OR=260), other mass (OR=12), thrombocytosis (OR=6.0), raised inflammatory markers (OR=5.2), and low full blood count (OR=2.8).

Combining the results of both studies, the investigators found that, for subjects older than 60 years of age, lymphadenopathy had a positive-predictive value of 18.6% for either NHL or HL. The positive-predictive value was 4.6% for head and neck mass and 1.1% for a mass elsewhere.

Therefore, the team said patients in this age group who present with lymphadenopathy or a head and neck mass should be referred to a specialist, unless there is a clear alternative explanation.

Referral is particularly urgent if either symptom has been present for 6 weeks or more, according to the investigators. They said that no blood test or other symptoms change that.

“Early diagnosis is vital to reducing cancer deaths,” said Liz Shephard, PhD, of the University of Exeter Medical School. “We now hope that this research will feed into guidelines to help GPs refer earlier and potentially to save lives.”

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

 

 

AACR Annual Meeting 2015

 

PHILADELPHIA—A retrospective study has revealed factors that appear to influence a person’s susceptibility to Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and other malignancies.

Study investigators looked at patients diagnosed with WM or LPL over a 20-year period and found about a 50% excess of second primary cancers in this population.

The patients had a significantly increased risk of multiple hematologic and solid tumor malignancies, and a few of these malignancies had shared susceptibility factors with WM/LPL.

The investigators believe that identifying these factors may prove useful for determining genetic susceptibility to WM/LPL.

Mary L. McMaster, MD, of the National Cancer Institute in Bethesda, Maryland, and her colleagues presented these findings at the AACR Annual Meeting 2015 (abstract 3709).

The team used data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SSER) database to evaluate the risk of subsequent primary cancer in 3825 patients diagnosed with WM (n=2163) or LPL (n=1662) from 1992 to 2011. The patients’ median age was 70, most of them were male (n=2221), and most were white (n=3153).

Dr McMaster said she and her colleagues looked at both WM and LPL in this study because SEER does not include information about immunoglobulin subtype, which makes it difficult to identify all WM cases with absolute certainty.

“[D]epending on what information a pathologist has when they review a bone marrow biopsy, for example, they may or may not know whether there’s IgM present,” Dr McMaster said. “So you may have a diagnosis of LPL and not have the information required to make the diagnosis of WM. For that reason, we combined both entities for this study.”

Dr McMaster and her colleagues calculated the observed-to-expected standardized incidence ratios (SIRs) for invasive cancers. After adjusting for multiple comparisons, the team found that survivors of WM/LPL had a significantly increased risk of developing a second primary malignancy (SIR=1.49).

This increased risk was seen for males and females and persisted throughout follow-up. The risk was higher for patients younger than 65 years of age (SIR=1.95).

Hematologic malignancies

WM/LPL survivors had a significantly increased risk of several hematologic malignancies. The SIR was 4.09 for all hematologic malignancies, 4.29 for lymphomas, and 3.16 for leukemias.

Dr McMaster pointed out that several lymphoma subtypes can have lymphoplasmacytic differentiation, the most common being marginal zone lymphoma. And this could potentially result in misclassification.

“So we actually ran the study with and without marginal zone lymphoma and saw no difference in the results,” she said. “So we don’t think misclassification accounts for the majority of what we’re seeing.”

The investigators found that WM/LPL survivors had the highest risk of developing Burkitt lymphoma (SIR=13.45), followed by Hodgkin lymphoma (SIR=9.80), T-cell non-Hodgkin lymphoma (SIR=6.62), mantle cell lymphoma (SIR=5.37), diffuse large B-cell lymphoma (DLBCL, SIR=4.76), multiple myeloma (SIR=4.40), any non-Hodgkin lymphoma (SIR=4.08), and acute myeloid leukemia (AML, SIR=3.27).

“Waldenström’s is known to transform, on occasion, to DLBCL,” Dr McMaster said. “So that may well account for the excess of DLBCL that we see in this population.”

She also noted that, prior to the early 2000s, WM was typically treated with alkylating agents. And alkylating agents have been linked to an increased risk of AML.

In this population, the risk of AML peaked 5 to 10 years after WM/LPL diagnosis and was only present in patients treated prior to 2002. This suggests the AML observed in this study was likely treatment-related.

Dr McMaster and her colleagues also found that WM/LPL survivors did not have a significantly increased risk of developing acute lymphocytic leukemia (SIR=0), hairy cell leukemia (SIR=0), chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR=0.97), or follicular lymphoma (SIR=2.25).

Solid tumors

WM/LPL survivors did have a significantly increased risk of certain solid tumor malignancies. The overall SIR for solid tumors was 1.21.

The risk was significant for non-epithelial skin cancers (SIR=5.15), thyroid cancers (SIR=3.13), melanoma (SIR=1.72), and cancers of the lung and bronchus (SIR=1.44) or respiratory system (SIR=1.42).

“Melanoma has an immunological basis, as does Waldenström’s, so we think there may be some shared etiology there,” Dr McMaster said.

She also noted that a strong risk factor for thyroid cancer, particularly papillary thyroid cancer, is a history of autoimmune thyroid disease.

“Autoimmune disease of any sort is a risk factor for Waldenström’s macroglobulinemia,” she said. “So again, we think there might be a basis for shared susceptibility there.”

Dr McMaster said this research suggests that multiple primary cancers may occur in a single individual because of shared genetic susceptibility, shared environmental exposures, treatment effects, or chance. She believes future research will show that both genetic and environmental factors contribute to WM.

Investigators are currently conducting whole-exome sequencing studies and genome-wide association studies in patients with familial and spontaneous WM, with the hopes of identifying genes that contribute to WM susceptibility.

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

PET scan of the body

Image by Jens Langner

Performing PET scans immediately after chemotherapy may reveal which Hodgkin lymphoma (HL) patients need radiotherapy (RT).

A study published in NEJM showed similar rates of progression-free survival in HL patients who werePET-negative after chemotherapy, whether they received subsequent RT or not.

However, the investigators said longer follow-up is needed to determine if eliminating RT in PET-negative patients will lead to fewer late effects and improved overall survival.

The 602 patients who agreed to take part in this trial, known as RAPID, had a PET scan performed after chemotherapy. Patients who tested positive received RT.

Those who tested negative were divided into 2 groups. One group of 211 patients received no further treatment, and the other group of 209 patients had the standard RT.

At a median of 60 months of follow-up, the proportion of patients who were alive and disease-free was 94.6% in the RT group and 90.8% in the group that hadn’t received further treatment.

Eight patients in the RT group progressed, and 8 died (3 with disease progression, 1 of whom died from HL). Five of the deaths occurred in patients who did not ultimately receive RT.

In the untreated group, 20 patients progressed, and 4 patients died (2 with disease progression and none from HL).

“This research is an important step forward,” said study author John Radford, of The University of Manchester and The Christie NHS Foundation Trust in the UK.

“The results of RAPID show that, in early stage Hodgkin lymphoma, radiotherapy after initial chemotherapy marginally reduces the recurrence rate, but this is bought at the expense of exposing to radiation all patients with negative PET findings, most of whom are already cured.”

PET scan of the body

Image by Jens Langner

Performing PET scans immediately after chemotherapy may reveal which Hodgkin lymphoma (HL) patients need radiotherapy (RT).

A study published in NEJM showed similar rates of progression-free survival in HL patients who werePET-negative after chemotherapy, whether they received subsequent RT or not.

However, the investigators said longer follow-up is needed to determine if eliminating RT in PET-negative patients will lead to fewer late effects and improved overall survival.

The 602 patients who agreed to take part in this trial, known as RAPID, had a PET scan performed after chemotherapy. Patients who tested positive received RT.

Those who tested negative were divided into 2 groups. One group of 211 patients received no further treatment, and the other group of 209 patients had the standard RT.

At a median of 60 months of follow-up, the proportion of patients who were alive and disease-free was 94.6% in the RT group and 90.8% in the group that hadn’t received further treatment.

Eight patients in the RT group progressed, and 8 died (3 with disease progression, 1 of whom died from HL). Five of the deaths occurred in patients who did not ultimately receive RT.

In the untreated group, 20 patients progressed, and 4 patients died (2 with disease progression and none from HL).

“This research is an important step forward,” said study author John Radford, of The University of Manchester and The Christie NHS Foundation Trust in the UK.

“The results of RAPID show that, in early stage Hodgkin lymphoma, radiotherapy after initial chemotherapy marginally reduces the recurrence rate, but this is bought at the expense of exposing to radiation all patients with negative PET findings, most of whom are already cured.”

PET scan of the body

Image by Jens Langner

Performing PET scans immediately after chemotherapy may reveal which Hodgkin lymphoma (HL) patients need radiotherapy (RT).

A study published in NEJM showed similar rates of progression-free survival in HL patients who werePET-negative after chemotherapy, whether they received subsequent RT or not.

However, the investigators said longer follow-up is needed to determine if eliminating RT in PET-negative patients will lead to fewer late effects and improved overall survival.

The 602 patients who agreed to take part in this trial, known as RAPID, had a PET scan performed after chemotherapy. Patients who tested positive received RT.

Those who tested negative were divided into 2 groups. One group of 211 patients received no further treatment, and the other group of 209 patients had the standard RT.

At a median of 60 months of follow-up, the proportion of patients who were alive and disease-free was 94.6% in the RT group and 90.8% in the group that hadn’t received further treatment.

Eight patients in the RT group progressed, and 8 died (3 with disease progression, 1 of whom died from HL). Five of the deaths occurred in patients who did not ultimately receive RT.

In the untreated group, 20 patients progressed, and 4 patients died (2 with disease progression and none from HL).

“This research is an important step forward,” said study author John Radford, of The University of Manchester and The Christie NHS Foundation Trust in the UK.

“The results of RAPID show that, in early stage Hodgkin lymphoma, radiotherapy after initial chemotherapy marginally reduces the recurrence rate, but this is bought at the expense of exposing to radiation all patients with negative PET findings, most of whom are already cured.”

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.