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Pulmonary metastasectomy may be useful for soft-tissue sarcoma spread
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The findings that surgery for pulmonary metastases achieves “relatively good median survival” that Dr. Chudgar and coauthors reported are “especially impressive when considering that more than 25% of these patients with metastatic cancer had five or more pulmonary lesions,” said Mark F. Berry, MD, MHS, of Stanford University in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:117-8).
Dr. Berry also said, however, that surgeons still must consider these results cautiously for several reasons. One, the study is retrospective and uncontrolled. Two, the study does not address whether the researchers selected healthy patients “with favorable disease characteristics” for pulmonary metastasectomy. “The sobering reality is that most patients still had recurrence relatively soon after complete pulmonary resection,” Dr. Berry said.
The study does support the current practice of pulmonary metastasectomy, which many patients may prefer for its invasive nature, compared with systemic chemotherapy treatment, he said. “Overall, surgeons can use this study to aid patient selection [and] to support the clinical decision to pursue resection of soft-tissue sarcoma pulmonary metastases for patients judged to be appropriate surgical candidates,” Dr. Berry concluded.
Dr. Berry had reported no financial disclosures.
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
The rate of soft-tissue sarcoma has nearly doubled over the past two decades, and up to 50% of patients with tissue sarcoma develop lung metastasis. A single-center study of 539 patients who had treatment for soft-tissue sarcoma has revealed disease and treatment characteristics that may aid patient selection and help predict overall and disease-free survival after diagnosis and treatment.
“Histologic subtype and size of the primary tumor were significantly associated with overall survival,” said lead author Neel P. Chudgar, MD, and his coauthors in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2017;154:319-30).
“Patients who underwent pulmonary metastasectomy [PM] for pleomorphic sarcoma/malignant fibrous histocytoma had the shortest median overall survival (23.6 months), whereas those who underwent PM for leiomyosarcoma had a median overall survival of 42 months,” he said.
The study subjects had pulmonary metastasectomies at Memorial Sloan Kettering Cancer Center, New York, during September 1991–June 2014. The median overall survival was 33.2 months, and median disease-free survival was 6.8 months for the entire cohort.
Among the disease characteristics associated with a lower hazard ratio of death shown by multivariable analyses were leiomyosarcoma histologic subtype (HR, 0.57), primary tumor size of 10 cm or less (HR, 1.00 vs. HR, 1.37 for those greater than 10 cm), increasing time from primary tumor resection to development of metastases (HR, 0.4 at less than 24 months vs. 1.0 at less than 6 months), solitary lung metastasis (HR, 1.0 vs. 1.8 for one year or more), and minimally invasive resection (HR, 0.71), all of which were statistically significant differences. Disease-free interval of more than one year and one pulmonary metastasis were significantly associated with lower hazard of disease recurrence.
Of patients, 70% had pulmonary metastasectomy as their primary treatment. The remainder had induction chemotherapy. In addition, 71% had open procedures over the 23-year study period, but minimally invasive operations became more common with time, increasing more than fourfold from the first half of the study period, vs. the last. They accounted for more than half of all procedures in the last five years of the study.
With regard to tumor type, fibrosarcoma was associated with longest median overall survival (65.2 months). Dr. Chudgar and his colleagues noted that 43% of these patients had low-grade primary tumors. Patients with low-grade tumors of all types had a median overall survival of 71.8 months, vs. 30.8 months for those with high-grade tumors.
“Our results indicate that therapeutic-intent pulmonary metastasectomy for soft-tissue sarcoma can be associated with prolonged survival,” Dr. Chudgar and his coauthors said. “The median survivals in our study are comparable with those in previous studies.” However, their analysis went beyond previous studies because they identified positive prognostic factors.
Dr. Chudgar and his coauthors acknowledge that various studies have drawn conflicting conclusions about the validity of histologic subtype as a prognostic factor, but their study differs from previous studies because it is a single-center cohort, “which increases the power to potentially identify significant differences, and we focused on soft-tissue sarcoma exclusively to enhance the homogeneity of the study population.”
Nonetheless, the researchers noted some limitations of their study, namely their collective analysis of the various soft-tissue sarcoma subtypes and the lack of a control group. Soft tissue sarcoma, because of its heterogeneous nature, challenges the adoption of precision medicine for this cancer type, but, until clinicians better understand the underlying mechanism of metastasis in these tumor types, Dr. Chudgar and his coauthors said, pulmonary metastasectomy “remains the best available treatment for soft tissue sarcoma pulmonary metastases.”
Dr. Chudgar and his coauthors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Characteristics that determine survival in patients with sarcomatous pulmonary metastases are tumor subtype and size, number of and time to metastases, and minimally invasive surgery.
Major finding: Patients with leiomyosarcoma histologic subtype tumor had a hazard ratio of 0.57 (P = .001), and those with a primary tumor size of 10 cm or less had an HR of 1, vs. an HR of 1.37 for those greater than 10 cm (P = .006)
Data source: A single-institution study of 539 patients who had pulmonary mastectomy for metastatic soft tissue sarcoma from September 1991 to June 2014.
Disclosures: Dr. Chudgar and his coauthors had no financial relationships to disclose.
Temporary tissue expanders optimize radiotherapy after mastectomy
LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.
The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.
“The shape and volume of the reconstruction” – and the need to avoid damaging the new breast – “got in the way of putting radiation where we wanted it to be. We ended up having bad radiotherapy plans, patients not getting skin-sparing mastectomies, and high probabilities of radiation complications to the reconstruction,” said investigator Eric Strom, MD, professor of radiation oncology at MD Anderson.
Radiologists and plastic and oncologic surgeons collaborated to try tissue expanders instead. “We wanted the advantage of skin-sparing mastectomy without the disadvantages” of immediate reconstruction, Dr. Strom said at the American Society of Breast Surgeons annual meeting.
With the new approach, “radiotherapy is superior. We don’t have to compromise our plans. I can put radiation everywhere it needs to be, without frying the heart” and almost completely avoiding the lungs, he said.
The 5-year rates of locoregional control, disease-free survival, and overall survival were 99.2%, 86.1%, and 92.4%, respectively, which “is extraordinary” in patients with stage 2-3 breast cancer, and likely due at least in part to optimal radiotherapy, he said.
Tissue expanders also keep the skin envelope open so it’s able to receive a graft at final reconstruction; abdominal skin doesn’t have to brought up to recreate the breast.
“This approach lessens negative interactions between breast reconstruction and [radiotherapy] and offers patients what they most desire: a high probability of freedom from cancer and optimal final aesthetic outcome,” said Zeina Ayoub, MD, a radiation oncology fellow at Anderson who presented the findings.
The median age of the women was 44 years, and almost all were node positive. Radiation was delivered to the chest wall and regional lymphatics, including the internal mammary chain.
Fifty women (13.0%) required explantation after radiation but before reconstruction, most commonly because of cellulitis; even so, more than half went on to final reconstruction.
Abdominal autologous reconstruction was the most common type, followed by latissimus dorsi–based reconstruction, and exchange of the tissue expander with an implant.
Dr. Ayoub and Dr. Strom had no relevant disclosures.
LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.
The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.
“The shape and volume of the reconstruction” – and the need to avoid damaging the new breast – “got in the way of putting radiation where we wanted it to be. We ended up having bad radiotherapy plans, patients not getting skin-sparing mastectomies, and high probabilities of radiation complications to the reconstruction,” said investigator Eric Strom, MD, professor of radiation oncology at MD Anderson.
Radiologists and plastic and oncologic surgeons collaborated to try tissue expanders instead. “We wanted the advantage of skin-sparing mastectomy without the disadvantages” of immediate reconstruction, Dr. Strom said at the American Society of Breast Surgeons annual meeting.
With the new approach, “radiotherapy is superior. We don’t have to compromise our plans. I can put radiation everywhere it needs to be, without frying the heart” and almost completely avoiding the lungs, he said.
The 5-year rates of locoregional control, disease-free survival, and overall survival were 99.2%, 86.1%, and 92.4%, respectively, which “is extraordinary” in patients with stage 2-3 breast cancer, and likely due at least in part to optimal radiotherapy, he said.
Tissue expanders also keep the skin envelope open so it’s able to receive a graft at final reconstruction; abdominal skin doesn’t have to brought up to recreate the breast.
“This approach lessens negative interactions between breast reconstruction and [radiotherapy] and offers patients what they most desire: a high probability of freedom from cancer and optimal final aesthetic outcome,” said Zeina Ayoub, MD, a radiation oncology fellow at Anderson who presented the findings.
The median age of the women was 44 years, and almost all were node positive. Radiation was delivered to the chest wall and regional lymphatics, including the internal mammary chain.
Fifty women (13.0%) required explantation after radiation but before reconstruction, most commonly because of cellulitis; even so, more than half went on to final reconstruction.
Abdominal autologous reconstruction was the most common type, followed by latissimus dorsi–based reconstruction, and exchange of the tissue expander with an implant.
Dr. Ayoub and Dr. Strom had no relevant disclosures.
LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.
The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.
“The shape and volume of the reconstruction” – and the need to avoid damaging the new breast – “got in the way of putting radiation where we wanted it to be. We ended up having bad radiotherapy plans, patients not getting skin-sparing mastectomies, and high probabilities of radiation complications to the reconstruction,” said investigator Eric Strom, MD, professor of radiation oncology at MD Anderson.
Radiologists and plastic and oncologic surgeons collaborated to try tissue expanders instead. “We wanted the advantage of skin-sparing mastectomy without the disadvantages” of immediate reconstruction, Dr. Strom said at the American Society of Breast Surgeons annual meeting.
With the new approach, “radiotherapy is superior. We don’t have to compromise our plans. I can put radiation everywhere it needs to be, without frying the heart” and almost completely avoiding the lungs, he said.
The 5-year rates of locoregional control, disease-free survival, and overall survival were 99.2%, 86.1%, and 92.4%, respectively, which “is extraordinary” in patients with stage 2-3 breast cancer, and likely due at least in part to optimal radiotherapy, he said.
Tissue expanders also keep the skin envelope open so it’s able to receive a graft at final reconstruction; abdominal skin doesn’t have to brought up to recreate the breast.
“This approach lessens negative interactions between breast reconstruction and [radiotherapy] and offers patients what they most desire: a high probability of freedom from cancer and optimal final aesthetic outcome,” said Zeina Ayoub, MD, a radiation oncology fellow at Anderson who presented the findings.
The median age of the women was 44 years, and almost all were node positive. Radiation was delivered to the chest wall and regional lymphatics, including the internal mammary chain.
Fifty women (13.0%) required explantation after radiation but before reconstruction, most commonly because of cellulitis; even so, more than half went on to final reconstruction.
Abdominal autologous reconstruction was the most common type, followed by latissimus dorsi–based reconstruction, and exchange of the tissue expander with an implant.
Dr. Ayoub and Dr. Strom had no relevant disclosures.
AT ASBS 2017
Key clinical point:
Major finding: The 5-year rates of locoregional control, disease-free survival, and overall survival were 99.2%, 86.1%, and 92.4%, respectively, likely due at least in part to optimal radiotherapy.
Data source: Review of 384 patients.
Disclosures: The investigators said they had no relevant disclosures.
Major bleeding deaths may outweigh VTE risk in older cancer patients
MADRID – Look before you leap into anticoagulation therapy for older cancer patients, results from a Canadian cohort study suggest.
Among patients 65 and older with cancer and a venous thromboembolic event (VTE) within 6 months of the cancer diagnosis, the 7-day mortality rate from VTE was 0.5%, compared with an 11% rate of death from a major bleeding episode, reported Alejandro Lazo-Langner MD, MSc from Western University in London, Canada.
If their findings are confirmed in further studies, “it would actually change what we do in terms of the treatment of thrombosis,” he said.
Risks for both VTE and for bleeding are known to be higher among patients with cancer than in the general population. Although a previously published systematic review suggested that mortality rates from recurrent VTE and major bleeding events were similar in the first 6 months of anticoagulation therapy, those results were limited by the heterogeneity of designs in the various studies included in the review, and by differences in outcome measures and the types of populations included, Dr. Lazo-Langner said.
To get a better idea of the case fatality rates of VTE recurrence and major bleeding and the case fatality rate ratio for each, the authors conducted a retrospective population-based cohort study in the Province of Ontario using de-identified linked administrative health care databases.
They assembled a cohort of patients 65 years of age and older who had a VTE event within 6 months of an initial cancer diagnosis. Recurrent VTE and major bleeding events were assessed within 180 days of the index date.
They found that from 2004 through 2014 there were 6,967 VTEs in cancer patients over 65 years of age (mean age 75) that were treated with an anticoagulant, either low-molecular-weight heparin (LMWH), LMWH plus warfarin, warfarin alone, or rivaroxaban (Xarelto).
Six months after the index VTE events, 235 patients (3%) had experienced a major bleeding event, and 1,184 (17%) had a recurrent VTE.
Within 7 days of the outcome event the mortality rate due to major bleeding was 11%, compared with 0.5% for recurrent VTEs. This translated into a mortality rate ratio for major bleeding vs. VTE of 21.8
Elizabeth Macintyre, MD, from the Hôpital Necker-Enfants Malades and University of Paris, France, who was not involved in the study, said in an interview that the results indicate that clinicians should not automatically assume that anticoagulation is a good idea for every older cancer patient.
“We now need to consider whether we should be reducing the time of anticoagulation, but that obviously depends on all sorts of other risk factors, so it has to be an individual patient decision. But the message is clearly don’t just anticoagulate to avoid the risk of thrombosis, and do in bear in mind that the other side of the coin could be just as serious,” she said.
The study was supported by the Institute for Clinical Evaluative Sciences, funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Lazo-Langner and Dr. Macintyre reported having no conflicts of interest to disclose.
MADRID – Look before you leap into anticoagulation therapy for older cancer patients, results from a Canadian cohort study suggest.
Among patients 65 and older with cancer and a venous thromboembolic event (VTE) within 6 months of the cancer diagnosis, the 7-day mortality rate from VTE was 0.5%, compared with an 11% rate of death from a major bleeding episode, reported Alejandro Lazo-Langner MD, MSc from Western University in London, Canada.
If their findings are confirmed in further studies, “it would actually change what we do in terms of the treatment of thrombosis,” he said.
Risks for both VTE and for bleeding are known to be higher among patients with cancer than in the general population. Although a previously published systematic review suggested that mortality rates from recurrent VTE and major bleeding events were similar in the first 6 months of anticoagulation therapy, those results were limited by the heterogeneity of designs in the various studies included in the review, and by differences in outcome measures and the types of populations included, Dr. Lazo-Langner said.
To get a better idea of the case fatality rates of VTE recurrence and major bleeding and the case fatality rate ratio for each, the authors conducted a retrospective population-based cohort study in the Province of Ontario using de-identified linked administrative health care databases.
They assembled a cohort of patients 65 years of age and older who had a VTE event within 6 months of an initial cancer diagnosis. Recurrent VTE and major bleeding events were assessed within 180 days of the index date.
They found that from 2004 through 2014 there were 6,967 VTEs in cancer patients over 65 years of age (mean age 75) that were treated with an anticoagulant, either low-molecular-weight heparin (LMWH), LMWH plus warfarin, warfarin alone, or rivaroxaban (Xarelto).
Six months after the index VTE events, 235 patients (3%) had experienced a major bleeding event, and 1,184 (17%) had a recurrent VTE.
Within 7 days of the outcome event the mortality rate due to major bleeding was 11%, compared with 0.5% for recurrent VTEs. This translated into a mortality rate ratio for major bleeding vs. VTE of 21.8
Elizabeth Macintyre, MD, from the Hôpital Necker-Enfants Malades and University of Paris, France, who was not involved in the study, said in an interview that the results indicate that clinicians should not automatically assume that anticoagulation is a good idea for every older cancer patient.
“We now need to consider whether we should be reducing the time of anticoagulation, but that obviously depends on all sorts of other risk factors, so it has to be an individual patient decision. But the message is clearly don’t just anticoagulate to avoid the risk of thrombosis, and do in bear in mind that the other side of the coin could be just as serious,” she said.
The study was supported by the Institute for Clinical Evaluative Sciences, funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Lazo-Langner and Dr. Macintyre reported having no conflicts of interest to disclose.
MADRID – Look before you leap into anticoagulation therapy for older cancer patients, results from a Canadian cohort study suggest.
Among patients 65 and older with cancer and a venous thromboembolic event (VTE) within 6 months of the cancer diagnosis, the 7-day mortality rate from VTE was 0.5%, compared with an 11% rate of death from a major bleeding episode, reported Alejandro Lazo-Langner MD, MSc from Western University in London, Canada.
If their findings are confirmed in further studies, “it would actually change what we do in terms of the treatment of thrombosis,” he said.
Risks for both VTE and for bleeding are known to be higher among patients with cancer than in the general population. Although a previously published systematic review suggested that mortality rates from recurrent VTE and major bleeding events were similar in the first 6 months of anticoagulation therapy, those results were limited by the heterogeneity of designs in the various studies included in the review, and by differences in outcome measures and the types of populations included, Dr. Lazo-Langner said.
To get a better idea of the case fatality rates of VTE recurrence and major bleeding and the case fatality rate ratio for each, the authors conducted a retrospective population-based cohort study in the Province of Ontario using de-identified linked administrative health care databases.
They assembled a cohort of patients 65 years of age and older who had a VTE event within 6 months of an initial cancer diagnosis. Recurrent VTE and major bleeding events were assessed within 180 days of the index date.
They found that from 2004 through 2014 there were 6,967 VTEs in cancer patients over 65 years of age (mean age 75) that were treated with an anticoagulant, either low-molecular-weight heparin (LMWH), LMWH plus warfarin, warfarin alone, or rivaroxaban (Xarelto).
Six months after the index VTE events, 235 patients (3%) had experienced a major bleeding event, and 1,184 (17%) had a recurrent VTE.
Within 7 days of the outcome event the mortality rate due to major bleeding was 11%, compared with 0.5% for recurrent VTEs. This translated into a mortality rate ratio for major bleeding vs. VTE of 21.8
Elizabeth Macintyre, MD, from the Hôpital Necker-Enfants Malades and University of Paris, France, who was not involved in the study, said in an interview that the results indicate that clinicians should not automatically assume that anticoagulation is a good idea for every older cancer patient.
“We now need to consider whether we should be reducing the time of anticoagulation, but that obviously depends on all sorts of other risk factors, so it has to be an individual patient decision. But the message is clearly don’t just anticoagulate to avoid the risk of thrombosis, and do in bear in mind that the other side of the coin could be just as serious,” she said.
The study was supported by the Institute for Clinical Evaluative Sciences, funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Lazo-Langner and Dr. Macintyre reported having no conflicts of interest to disclose.
AT EHA 2017
Key clinical point: In cancer patients older than 65, the risk of major bleeding from anticoagulants may outweigh the risk of venous thromboembolism.
Major finding: 7-day mortality rates were 11% for major bleeding vs 0.5% for recurrent VTE.
Data source: Retrospective cohort study of 6,967 cancer patients age 65 and older from Ontario, Canada.
Disclosures: The study was supported by the Institute for Clinical Evaluative Sciences, funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Lazo-Langner and Dr. Macintyre reported having no conflicts of interest to disclose.
DESKTOP III: Secondary surgery for recurrent OC improves PFS, TFST
CHICAGO – Secondary cytoreductive surgery resulted in a clinically meaningful increase in progression-free survival and time to first subsequent therapy in a phase III study of carefully selected women with ovarian cancer who experienced their first relapse after a platin-free interval of 6 months.
These interim findings from the randomized international DESKTOP III trial suggest that until final overall survival data are available to more definitively define the role of secondary cytoreductive surgery in this setting, it should at least be considered as an option in patients who are good candidates based on a positive AGO Study Group score, defined as an ECOG performance status score of 0, ascites of 500 mL or less, and complete resection at initial surgery, Andreas du Bois, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The median progression-free survival (PFS) in 204 women who met this criteria and who were randomized to undergo surgery followed by chemotherapy was 19.6 months, compared with 14 months in 203 women who were randomized to receive only second-line chemotherapy (hazard ratio, 0.66), said Dr. du Bois of AGO and Kliniken Essen-Mitte, Essen, Germany.
“Even more important ... only complete resection makes a difference ... and that adds a median 7.2 months PFS with a hazard ratio of 0.56, which is highly significant. Fortunately that translates into time to first subsequent treatment, which is a more patient-oriented outcome,” he said.
The time to third-line therapy was prolonged by a highly statistically significant median of 7.1 month (hazard ratio, 0.6).
“What was the trade-off for these benefits? The patients did not pay for it with excessive mortality,” he said, explaining that no significant differences were seen between the groups in terms of mortality at 30, 60, 90, or 180 days, and that no excessive toxicity or treatment burden was seen in either group.
Median age of the patients was 60 years; they were enrolled at 80 centers in 12 countries between 2010 and 2015. The platin-free interval exceeded 12 months in 75% and 76% of patient in the surgery and control arms, respectively.
Chemotherapy regimens in both the treatment and control arms were selected according to institutional standards, although platinum-based combination therapy was strongly recommended; 87% and 88% in the groups, respectively, received a platinum-containing second-line therapy.
Macroscopic complete resection was achieved in 72.5% of patients in the surgery arm, which was the rate predicted by the AGO scores.
“We know that the surgery and chemotherapy are the cornerstones of ovarian cancer therapy ... however, surgery in recurrent ovarian cancer has not been based on high-level evidence,” Dr. du Bois said. “So far there are only retrospective series suggesting that there might be a benefit or not.”
The German AGO group and the Gynecologic Oncology Group (GOG) in the United States thus initiated clinical trials to evaluate its role in recurrent ovarian cancer, including the DESKTOP series, he explained, noting that the AGO score was developed through these trials as a way to identify good surgical candidates based on preoperative factors.
It was confirmed in a prospective study that the score, which selects about 50% of all patients with platinum-sensitive recurrent ovarian cancer, could predict successful surgery, he added.
In the current study, the data with respect to overall survival – the primary study endpoint – have not reached maturity, but at 2 years it was 83%.
However, the findings of a meaningful benefit in progression-free survival and time to first subsequent treatment (advantages of 5.6 and 7.1 months, respectively) in secondary cytoreductive surgery patients is at least comparable with all phase III trials in second-line therapy for platinum-sensitive recurrent ovarian cancer so far, he said.
“In fact, it’s the most positive trial ever reported in this population,” he added, noted that he was referring to therapy trials, not maintenance trials.
Further, the fact that the surgery benefit was exclusive to patients with complete resection indicates the importance of selecting both the right center with capability of achieving complete resection in most patients, and the right patients, as identified by the AGO score.
“Hopefully, further follow-up will show that this benefit translates into overall survival,” he concluded, noting that overall survival will be evaluated after extended follow-up when 244 overall survival events are observed.
Dr. Du Bois reported serving as a consultant or adviser for AstraZeneca, Mundipharma, Pfizer, Pharmamar, and Roche/Genentech.
The findings from DESKTOP III complement those from prior retrospective studies, but one key difference is the emphasis on the importance of complete resection, abstract discussant Ritu Salani, MD, said at the meeting.
“I no longer believe that optimal resection is good enough in this patient population,” she said.
In fact, given that 67 patients in the study were not completely resected, it is important to look at whether there are any identifying factors that could help prevent surgery in these patients, and whether there are any minimally invasive or less invasive approaches, such as scoping and scoring these patients, to determine who really is completely resectable, she said.
Other studies of cytoreductive surgery, including GOG 213 and the Dutch SOCceR trial, are ongoing, and the primary endpoint of DESKTOP III is overall survival, she noted.
“We look forward to these data maturing.”
Dr. Salani is with the Ohio State University, Columbus. She has received honoraria from Clovis Oncology and Lynparza, and has served in a consulting or advisory role for Genentech/Roche.
The findings from DESKTOP III complement those from prior retrospective studies, but one key difference is the emphasis on the importance of complete resection, abstract discussant Ritu Salani, MD, said at the meeting.
“I no longer believe that optimal resection is good enough in this patient population,” she said.
In fact, given that 67 patients in the study were not completely resected, it is important to look at whether there are any identifying factors that could help prevent surgery in these patients, and whether there are any minimally invasive or less invasive approaches, such as scoping and scoring these patients, to determine who really is completely resectable, she said.
Other studies of cytoreductive surgery, including GOG 213 and the Dutch SOCceR trial, are ongoing, and the primary endpoint of DESKTOP III is overall survival, she noted.
“We look forward to these data maturing.”
Dr. Salani is with the Ohio State University, Columbus. She has received honoraria from Clovis Oncology and Lynparza, and has served in a consulting or advisory role for Genentech/Roche.
The findings from DESKTOP III complement those from prior retrospective studies, but one key difference is the emphasis on the importance of complete resection, abstract discussant Ritu Salani, MD, said at the meeting.
“I no longer believe that optimal resection is good enough in this patient population,” she said.
In fact, given that 67 patients in the study were not completely resected, it is important to look at whether there are any identifying factors that could help prevent surgery in these patients, and whether there are any minimally invasive or less invasive approaches, such as scoping and scoring these patients, to determine who really is completely resectable, she said.
Other studies of cytoreductive surgery, including GOG 213 and the Dutch SOCceR trial, are ongoing, and the primary endpoint of DESKTOP III is overall survival, she noted.
“We look forward to these data maturing.”
Dr. Salani is with the Ohio State University, Columbus. She has received honoraria from Clovis Oncology and Lynparza, and has served in a consulting or advisory role for Genentech/Roche.
CHICAGO – Secondary cytoreductive surgery resulted in a clinically meaningful increase in progression-free survival and time to first subsequent therapy in a phase III study of carefully selected women with ovarian cancer who experienced their first relapse after a platin-free interval of 6 months.
These interim findings from the randomized international DESKTOP III trial suggest that until final overall survival data are available to more definitively define the role of secondary cytoreductive surgery in this setting, it should at least be considered as an option in patients who are good candidates based on a positive AGO Study Group score, defined as an ECOG performance status score of 0, ascites of 500 mL or less, and complete resection at initial surgery, Andreas du Bois, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The median progression-free survival (PFS) in 204 women who met this criteria and who were randomized to undergo surgery followed by chemotherapy was 19.6 months, compared with 14 months in 203 women who were randomized to receive only second-line chemotherapy (hazard ratio, 0.66), said Dr. du Bois of AGO and Kliniken Essen-Mitte, Essen, Germany.
“Even more important ... only complete resection makes a difference ... and that adds a median 7.2 months PFS with a hazard ratio of 0.56, which is highly significant. Fortunately that translates into time to first subsequent treatment, which is a more patient-oriented outcome,” he said.
The time to third-line therapy was prolonged by a highly statistically significant median of 7.1 month (hazard ratio, 0.6).
“What was the trade-off for these benefits? The patients did not pay for it with excessive mortality,” he said, explaining that no significant differences were seen between the groups in terms of mortality at 30, 60, 90, or 180 days, and that no excessive toxicity or treatment burden was seen in either group.
Median age of the patients was 60 years; they were enrolled at 80 centers in 12 countries between 2010 and 2015. The platin-free interval exceeded 12 months in 75% and 76% of patient in the surgery and control arms, respectively.
Chemotherapy regimens in both the treatment and control arms were selected according to institutional standards, although platinum-based combination therapy was strongly recommended; 87% and 88% in the groups, respectively, received a platinum-containing second-line therapy.
Macroscopic complete resection was achieved in 72.5% of patients in the surgery arm, which was the rate predicted by the AGO scores.
“We know that the surgery and chemotherapy are the cornerstones of ovarian cancer therapy ... however, surgery in recurrent ovarian cancer has not been based on high-level evidence,” Dr. du Bois said. “So far there are only retrospective series suggesting that there might be a benefit or not.”
The German AGO group and the Gynecologic Oncology Group (GOG) in the United States thus initiated clinical trials to evaluate its role in recurrent ovarian cancer, including the DESKTOP series, he explained, noting that the AGO score was developed through these trials as a way to identify good surgical candidates based on preoperative factors.
It was confirmed in a prospective study that the score, which selects about 50% of all patients with platinum-sensitive recurrent ovarian cancer, could predict successful surgery, he added.
In the current study, the data with respect to overall survival – the primary study endpoint – have not reached maturity, but at 2 years it was 83%.
However, the findings of a meaningful benefit in progression-free survival and time to first subsequent treatment (advantages of 5.6 and 7.1 months, respectively) in secondary cytoreductive surgery patients is at least comparable with all phase III trials in second-line therapy for platinum-sensitive recurrent ovarian cancer so far, he said.
“In fact, it’s the most positive trial ever reported in this population,” he added, noted that he was referring to therapy trials, not maintenance trials.
Further, the fact that the surgery benefit was exclusive to patients with complete resection indicates the importance of selecting both the right center with capability of achieving complete resection in most patients, and the right patients, as identified by the AGO score.
“Hopefully, further follow-up will show that this benefit translates into overall survival,” he concluded, noting that overall survival will be evaluated after extended follow-up when 244 overall survival events are observed.
Dr. Du Bois reported serving as a consultant or adviser for AstraZeneca, Mundipharma, Pfizer, Pharmamar, and Roche/Genentech.
CHICAGO – Secondary cytoreductive surgery resulted in a clinically meaningful increase in progression-free survival and time to first subsequent therapy in a phase III study of carefully selected women with ovarian cancer who experienced their first relapse after a platin-free interval of 6 months.
These interim findings from the randomized international DESKTOP III trial suggest that until final overall survival data are available to more definitively define the role of secondary cytoreductive surgery in this setting, it should at least be considered as an option in patients who are good candidates based on a positive AGO Study Group score, defined as an ECOG performance status score of 0, ascites of 500 mL or less, and complete resection at initial surgery, Andreas du Bois, MD, reported at the annual meeting of the American Society of Clinical Oncology.
The median progression-free survival (PFS) in 204 women who met this criteria and who were randomized to undergo surgery followed by chemotherapy was 19.6 months, compared with 14 months in 203 women who were randomized to receive only second-line chemotherapy (hazard ratio, 0.66), said Dr. du Bois of AGO and Kliniken Essen-Mitte, Essen, Germany.
“Even more important ... only complete resection makes a difference ... and that adds a median 7.2 months PFS with a hazard ratio of 0.56, which is highly significant. Fortunately that translates into time to first subsequent treatment, which is a more patient-oriented outcome,” he said.
The time to third-line therapy was prolonged by a highly statistically significant median of 7.1 month (hazard ratio, 0.6).
“What was the trade-off for these benefits? The patients did not pay for it with excessive mortality,” he said, explaining that no significant differences were seen between the groups in terms of mortality at 30, 60, 90, or 180 days, and that no excessive toxicity or treatment burden was seen in either group.
Median age of the patients was 60 years; they were enrolled at 80 centers in 12 countries between 2010 and 2015. The platin-free interval exceeded 12 months in 75% and 76% of patient in the surgery and control arms, respectively.
Chemotherapy regimens in both the treatment and control arms were selected according to institutional standards, although platinum-based combination therapy was strongly recommended; 87% and 88% in the groups, respectively, received a platinum-containing second-line therapy.
Macroscopic complete resection was achieved in 72.5% of patients in the surgery arm, which was the rate predicted by the AGO scores.
“We know that the surgery and chemotherapy are the cornerstones of ovarian cancer therapy ... however, surgery in recurrent ovarian cancer has not been based on high-level evidence,” Dr. du Bois said. “So far there are only retrospective series suggesting that there might be a benefit or not.”
The German AGO group and the Gynecologic Oncology Group (GOG) in the United States thus initiated clinical trials to evaluate its role in recurrent ovarian cancer, including the DESKTOP series, he explained, noting that the AGO score was developed through these trials as a way to identify good surgical candidates based on preoperative factors.
It was confirmed in a prospective study that the score, which selects about 50% of all patients with platinum-sensitive recurrent ovarian cancer, could predict successful surgery, he added.
In the current study, the data with respect to overall survival – the primary study endpoint – have not reached maturity, but at 2 years it was 83%.
However, the findings of a meaningful benefit in progression-free survival and time to first subsequent treatment (advantages of 5.6 and 7.1 months, respectively) in secondary cytoreductive surgery patients is at least comparable with all phase III trials in second-line therapy for platinum-sensitive recurrent ovarian cancer so far, he said.
“In fact, it’s the most positive trial ever reported in this population,” he added, noted that he was referring to therapy trials, not maintenance trials.
Further, the fact that the surgery benefit was exclusive to patients with complete resection indicates the importance of selecting both the right center with capability of achieving complete resection in most patients, and the right patients, as identified by the AGO score.
“Hopefully, further follow-up will show that this benefit translates into overall survival,” he concluded, noting that overall survival will be evaluated after extended follow-up when 244 overall survival events are observed.
Dr. Du Bois reported serving as a consultant or adviser for AstraZeneca, Mundipharma, Pfizer, Pharmamar, and Roche/Genentech.
At THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Median progression-free survival was 19.6 vs. 14 months in the surgery vs. second-line chemotherapy-only arm.
Data source: The randomized phase III DESKTOP III study of 407 patients.
Disclosures: Dr. du Bois reported serving as a consultant or adviser for AstraZeneca, Mundipharma, Pfizer, Pharmamar, and Roche/Genentech.
VIDEO: Wedge resection offers higher survival for NSCLC
BOSTON – High quality wedge resection results in higher survival for patients with early stage non–small cell lung cancer when compared with stereotactic body radiation therapy, according to new research.
The analysis, reported at the annual meeting of the American Association for Thoracic Surgery, evaluated the treatment of 7,337 patients in the National Cancer Database with clinical T1-T2, N0, M0 non–small cell lung cancer who were treated with either wedge resection or stereotactic body radiation therapy from 2005 to 2012.
In this video, Varun Puri, MD, of Washington University, St. Louis, discusses the study and the significance of the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @legal_med
BOSTON – High quality wedge resection results in higher survival for patients with early stage non–small cell lung cancer when compared with stereotactic body radiation therapy, according to new research.
The analysis, reported at the annual meeting of the American Association for Thoracic Surgery, evaluated the treatment of 7,337 patients in the National Cancer Database with clinical T1-T2, N0, M0 non–small cell lung cancer who were treated with either wedge resection or stereotactic body radiation therapy from 2005 to 2012.
In this video, Varun Puri, MD, of Washington University, St. Louis, discusses the study and the significance of the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @legal_med
BOSTON – High quality wedge resection results in higher survival for patients with early stage non–small cell lung cancer when compared with stereotactic body radiation therapy, according to new research.
The analysis, reported at the annual meeting of the American Association for Thoracic Surgery, evaluated the treatment of 7,337 patients in the National Cancer Database with clinical T1-T2, N0, M0 non–small cell lung cancer who were treated with either wedge resection or stereotactic body radiation therapy from 2005 to 2012.
In this video, Varun Puri, MD, of Washington University, St. Louis, discusses the study and the significance of the findings.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @legal_med
AT THE AATS ANNUAL MEETING
Intraoperative radiation looks good for DCIS
LAS VEGAS – Intraoperative radiation therapy (IORT) is effective in patients with ductal carcinoma in situ (DCIS), and bilateral digital mammography and breast MRI effectively predicted which patients would be most suited for the procedure, according to a nonrandomized study.
The TARGIT-A trial showed that IORT was noninferior to external beam radiation therapy in women with early-stage breast cancer (Lancet. 2014 Feb 15;383:603-13), but the technique hasn’t been tested in DCIS patients.
The researchers conducted a prospective, nonrandomized study of DCIS in women who underwent core biopsy between February 2012 and July 2016 at Virginia Mason Medical Center. Those who elected breast conserving therapy were assessed for IORT using bilateral digital mammography and contrast enhanced MRI.
For criteria, the researchers selected patients over age 44 years with unifocal DCIS and a lesion size of up to 3.0 cm. Physicians recommended additional therapy when the pathology report revealed DCIS larger than 3 cm and/or margins of up to 2 mm.
Of the 57 patients initially enrolled, 7 were found to have invasive disease and were excluded. Another eight patients were excluded because of margins, tumor size, or multifocal disease, and were recommended for additional treatment.
The remaining 42 patients with DCIS were treated with IORT. At a mean follow-up time of 32 months, the researchers observed no local recurrences, and no Radiation Therapy Oncology Group grade 3 or 4 complications were reported.
Hyperpigmentation occurred more often in the IORT group, at 40% (17 of 42 patients), than in the additional treatment group, at 13% (1 of 8), a nonsignificant difference. The hyperpigmentation tended to be minimal and focused on the surgical scar. There were no differences between the groups with respect to superficial wound separation, infection, seroma, fat necrosis, transient radiation dermatitis, or rib fracture.
“Our conclusions are that are selection criteria with mammography and MRI are effective in identifying patients who are appropriate for IORT, and importantly, at 32 months follow-up, no patients had recurrences, so we’re not negatively impacting oncological outcome,” said Dr. Carlson.
The fact that eight patients were recommended for additional treatment based on margins, a disease span greater than 3 cm, or multifocal disease “is actually quite heartening because it implies that the mammogram and the MRI are quite effective at identifying patients that met our criteria,” said Dr. Carlson.
The study is small and had no control group, but Dr. Carlson is confident of the results. “We didn’t do a randomized trial because we believed strongly that IORT will be effective in these patients with good cosmesis. When you compare it to local recurrence rates in the TARGIT-A trial, we’re still doing quite well, so to some extent that can be used as a baseline benchmark,” she said.
LAS VEGAS – Intraoperative radiation therapy (IORT) is effective in patients with ductal carcinoma in situ (DCIS), and bilateral digital mammography and breast MRI effectively predicted which patients would be most suited for the procedure, according to a nonrandomized study.
The TARGIT-A trial showed that IORT was noninferior to external beam radiation therapy in women with early-stage breast cancer (Lancet. 2014 Feb 15;383:603-13), but the technique hasn’t been tested in DCIS patients.
The researchers conducted a prospective, nonrandomized study of DCIS in women who underwent core biopsy between February 2012 and July 2016 at Virginia Mason Medical Center. Those who elected breast conserving therapy were assessed for IORT using bilateral digital mammography and contrast enhanced MRI.
For criteria, the researchers selected patients over age 44 years with unifocal DCIS and a lesion size of up to 3.0 cm. Physicians recommended additional therapy when the pathology report revealed DCIS larger than 3 cm and/or margins of up to 2 mm.
Of the 57 patients initially enrolled, 7 were found to have invasive disease and were excluded. Another eight patients were excluded because of margins, tumor size, or multifocal disease, and were recommended for additional treatment.
The remaining 42 patients with DCIS were treated with IORT. At a mean follow-up time of 32 months, the researchers observed no local recurrences, and no Radiation Therapy Oncology Group grade 3 or 4 complications were reported.
Hyperpigmentation occurred more often in the IORT group, at 40% (17 of 42 patients), than in the additional treatment group, at 13% (1 of 8), a nonsignificant difference. The hyperpigmentation tended to be minimal and focused on the surgical scar. There were no differences between the groups with respect to superficial wound separation, infection, seroma, fat necrosis, transient radiation dermatitis, or rib fracture.
“Our conclusions are that are selection criteria with mammography and MRI are effective in identifying patients who are appropriate for IORT, and importantly, at 32 months follow-up, no patients had recurrences, so we’re not negatively impacting oncological outcome,” said Dr. Carlson.
The fact that eight patients were recommended for additional treatment based on margins, a disease span greater than 3 cm, or multifocal disease “is actually quite heartening because it implies that the mammogram and the MRI are quite effective at identifying patients that met our criteria,” said Dr. Carlson.
The study is small and had no control group, but Dr. Carlson is confident of the results. “We didn’t do a randomized trial because we believed strongly that IORT will be effective in these patients with good cosmesis. When you compare it to local recurrence rates in the TARGIT-A trial, we’re still doing quite well, so to some extent that can be used as a baseline benchmark,” she said.
LAS VEGAS – Intraoperative radiation therapy (IORT) is effective in patients with ductal carcinoma in situ (DCIS), and bilateral digital mammography and breast MRI effectively predicted which patients would be most suited for the procedure, according to a nonrandomized study.
The TARGIT-A trial showed that IORT was noninferior to external beam radiation therapy in women with early-stage breast cancer (Lancet. 2014 Feb 15;383:603-13), but the technique hasn’t been tested in DCIS patients.
The researchers conducted a prospective, nonrandomized study of DCIS in women who underwent core biopsy between February 2012 and July 2016 at Virginia Mason Medical Center. Those who elected breast conserving therapy were assessed for IORT using bilateral digital mammography and contrast enhanced MRI.
For criteria, the researchers selected patients over age 44 years with unifocal DCIS and a lesion size of up to 3.0 cm. Physicians recommended additional therapy when the pathology report revealed DCIS larger than 3 cm and/or margins of up to 2 mm.
Of the 57 patients initially enrolled, 7 were found to have invasive disease and were excluded. Another eight patients were excluded because of margins, tumor size, or multifocal disease, and were recommended for additional treatment.
The remaining 42 patients with DCIS were treated with IORT. At a mean follow-up time of 32 months, the researchers observed no local recurrences, and no Radiation Therapy Oncology Group grade 3 or 4 complications were reported.
Hyperpigmentation occurred more often in the IORT group, at 40% (17 of 42 patients), than in the additional treatment group, at 13% (1 of 8), a nonsignificant difference. The hyperpigmentation tended to be minimal and focused on the surgical scar. There were no differences between the groups with respect to superficial wound separation, infection, seroma, fat necrosis, transient radiation dermatitis, or rib fracture.
“Our conclusions are that are selection criteria with mammography and MRI are effective in identifying patients who are appropriate for IORT, and importantly, at 32 months follow-up, no patients had recurrences, so we’re not negatively impacting oncological outcome,” said Dr. Carlson.
The fact that eight patients were recommended for additional treatment based on margins, a disease span greater than 3 cm, or multifocal disease “is actually quite heartening because it implies that the mammogram and the MRI are quite effective at identifying patients that met our criteria,” said Dr. Carlson.
The study is small and had no control group, but Dr. Carlson is confident of the results. “We didn’t do a randomized trial because we believed strongly that IORT will be effective in these patients with good cosmesis. When you compare it to local recurrence rates in the TARGIT-A trial, we’re still doing quite well, so to some extent that can be used as a baseline benchmark,” she said.
AT ASBS 2017
Key clinical point: Intraoperative radiation appears safe and effective, and is more convenient than postoperative radiation.
Major finding: There were no ductal carcinoma in situ recurrences at a median 32 months’ follow-up.
Data source: Uncontrolled, prospective study of 42 patients.
Disclosures: The study was funded by the National Institutes of Health. Dr. Carlson reported having no financial disclosures.
Positive node risk defined for elderly breast cancer patients
LAS VEGAS – In women aged 70 years or older with hormone receptor–positive invasive breast cancer, their tumor size, grade, and histology – but not human epidermal growth factor receptor–2 status – predicted nodal positivity, according to a retrospective analysis.
Investigators at the Mayo Clinic, Rochester, Minn., reviewed 52,532 women in the National Cancer Database from 2010 to 2013 who were at least 70 years old with hormone receptor–positive invasive breast cancer and clinically node negative disease, who had axillary surgery performed. Two-thirds of the cohort was used to identify risk factors, and the remaining third to validate them. About 16% in both groups had cancer in their axillary lymph nodes.
On multivariate analysis, higher clinical T stage, higher grade, and invasive lobular and invasive mammary histology were all associated with positive nodes. Although significant on univariate analysis, age (P = .57) and HER2 status (P = .32) fell out on multivariate analysis.
Nodal positivity was more than five times as likely with clinical T2 tumors, compared with T1a tumors, and far less likely for patients with invasive mucinous carcinoma than for those with invasive ductal carcinoma.
The team expects to release a nomogram for general use in clinical practice to predict the risk of positive nodes for various combinations of tumor size, grade, and histology in older women. When the model predicted a less than 10% chance of node positive disease, the actual rate in the validation set was around 5.5%. When it predicted a 30%-39% chance, the actual rate was 32.6%. The area under the receiver operating characteristic curve was 0.7 in both the development and validation sets, indicating good discrimination.
The work grew out of an effort to implement the Society of Surgical Oncologists’ recommendation not to do routine sentinel node biopsies in clinically node negative, hormone receptor–positive invasive breast cancer in women over the age of 70 years, a recommendation the group made as part of its contribution to the Choosing Wisely campaign.
“After the guideline was released, we were sitting in the clinic thinking how to apply it to our patients,” lead investigator Jessemae Welsh, MD, a surgeon at the Mayo Clinic, said at the American Society of Breast Surgeons annual meeting.
The problem is that nodal positivity is important to know for other aspects of care, including regional nodal irradiation and duration of systemic hormone therapy, and axillary lymph node staging might still be indicated if older women are truly at high risk. “We [wanted] to develop a multivariate model that gives a precise estimate of nodal risk,” to help “patients and surgeons to decide together based on an individual risk” how best to proceed. Also, a prediction of low risk “can help reassure patients that they will do well without axillary surgery,” she said.
Mayo’s nomogram is unique in that it focuses specifically on women 70 years and older. Development of previous nomograms incorporated older women, but did not focus on them specifically, Dr. Welsh said.
Dr. Welsh said she had no relevant disclosures.
[email protected]
LAS VEGAS – In women aged 70 years or older with hormone receptor–positive invasive breast cancer, their tumor size, grade, and histology – but not human epidermal growth factor receptor–2 status – predicted nodal positivity, according to a retrospective analysis.
Investigators at the Mayo Clinic, Rochester, Minn., reviewed 52,532 women in the National Cancer Database from 2010 to 2013 who were at least 70 years old with hormone receptor–positive invasive breast cancer and clinically node negative disease, who had axillary surgery performed. Two-thirds of the cohort was used to identify risk factors, and the remaining third to validate them. About 16% in both groups had cancer in their axillary lymph nodes.
On multivariate analysis, higher clinical T stage, higher grade, and invasive lobular and invasive mammary histology were all associated with positive nodes. Although significant on univariate analysis, age (P = .57) and HER2 status (P = .32) fell out on multivariate analysis.
Nodal positivity was more than five times as likely with clinical T2 tumors, compared with T1a tumors, and far less likely for patients with invasive mucinous carcinoma than for those with invasive ductal carcinoma.
The team expects to release a nomogram for general use in clinical practice to predict the risk of positive nodes for various combinations of tumor size, grade, and histology in older women. When the model predicted a less than 10% chance of node positive disease, the actual rate in the validation set was around 5.5%. When it predicted a 30%-39% chance, the actual rate was 32.6%. The area under the receiver operating characteristic curve was 0.7 in both the development and validation sets, indicating good discrimination.
The work grew out of an effort to implement the Society of Surgical Oncologists’ recommendation not to do routine sentinel node biopsies in clinically node negative, hormone receptor–positive invasive breast cancer in women over the age of 70 years, a recommendation the group made as part of its contribution to the Choosing Wisely campaign.
“After the guideline was released, we were sitting in the clinic thinking how to apply it to our patients,” lead investigator Jessemae Welsh, MD, a surgeon at the Mayo Clinic, said at the American Society of Breast Surgeons annual meeting.
The problem is that nodal positivity is important to know for other aspects of care, including regional nodal irradiation and duration of systemic hormone therapy, and axillary lymph node staging might still be indicated if older women are truly at high risk. “We [wanted] to develop a multivariate model that gives a precise estimate of nodal risk,” to help “patients and surgeons to decide together based on an individual risk” how best to proceed. Also, a prediction of low risk “can help reassure patients that they will do well without axillary surgery,” she said.
Mayo’s nomogram is unique in that it focuses specifically on women 70 years and older. Development of previous nomograms incorporated older women, but did not focus on them specifically, Dr. Welsh said.
Dr. Welsh said she had no relevant disclosures.
[email protected]
LAS VEGAS – In women aged 70 years or older with hormone receptor–positive invasive breast cancer, their tumor size, grade, and histology – but not human epidermal growth factor receptor–2 status – predicted nodal positivity, according to a retrospective analysis.
Investigators at the Mayo Clinic, Rochester, Minn., reviewed 52,532 women in the National Cancer Database from 2010 to 2013 who were at least 70 years old with hormone receptor–positive invasive breast cancer and clinically node negative disease, who had axillary surgery performed. Two-thirds of the cohort was used to identify risk factors, and the remaining third to validate them. About 16% in both groups had cancer in their axillary lymph nodes.
On multivariate analysis, higher clinical T stage, higher grade, and invasive lobular and invasive mammary histology were all associated with positive nodes. Although significant on univariate analysis, age (P = .57) and HER2 status (P = .32) fell out on multivariate analysis.
Nodal positivity was more than five times as likely with clinical T2 tumors, compared with T1a tumors, and far less likely for patients with invasive mucinous carcinoma than for those with invasive ductal carcinoma.
The team expects to release a nomogram for general use in clinical practice to predict the risk of positive nodes for various combinations of tumor size, grade, and histology in older women. When the model predicted a less than 10% chance of node positive disease, the actual rate in the validation set was around 5.5%. When it predicted a 30%-39% chance, the actual rate was 32.6%. The area under the receiver operating characteristic curve was 0.7 in both the development and validation sets, indicating good discrimination.
The work grew out of an effort to implement the Society of Surgical Oncologists’ recommendation not to do routine sentinel node biopsies in clinically node negative, hormone receptor–positive invasive breast cancer in women over the age of 70 years, a recommendation the group made as part of its contribution to the Choosing Wisely campaign.
“After the guideline was released, we were sitting in the clinic thinking how to apply it to our patients,” lead investigator Jessemae Welsh, MD, a surgeon at the Mayo Clinic, said at the American Society of Breast Surgeons annual meeting.
The problem is that nodal positivity is important to know for other aspects of care, including regional nodal irradiation and duration of systemic hormone therapy, and axillary lymph node staging might still be indicated if older women are truly at high risk. “We [wanted] to develop a multivariate model that gives a precise estimate of nodal risk,” to help “patients and surgeons to decide together based on an individual risk” how best to proceed. Also, a prediction of low risk “can help reassure patients that they will do well without axillary surgery,” she said.
Mayo’s nomogram is unique in that it focuses specifically on women 70 years and older. Development of previous nomograms incorporated older women, but did not focus on them specifically, Dr. Welsh said.
Dr. Welsh said she had no relevant disclosures.
[email protected]
AT ASBS 2017
Key clinical point:
Major finding: On multivariate analysis, higher clinical T stage, higher grade, and invasive lobular and invasive mammary histology were all associated with positive nodes.
Data source: An analysis of data from 52,532 women in the National Cancer Database during 2010-2013.
Disclosures: The lead investigator had no disclosures.
Forgo axillary dissection for single suspicious node on ultrasound
LAS VEGAS – About half of breast cancer patients without palpable lymphadenopathy but with preoperative ultrasound-guided, biopsy-proven axillary lymph node metastases have N1 disease, according to a review of 129 women.
Among the 30 women with a primary tumor 2 cm or smaller and only one abnormal lymph node on axillary ultrasound, 22 (73%) had metastases limited to the one lymph node, suggesting that such patients “may undergo ... sentinel lymph node biopsy” instead of a complete axillary lymph node dissection (ALND), the investigators concluded.
The problem that has come up in clinical practice is that axillary ultrasound is now a routine part of breast cancer workup, but the original trial didn’t address ultrasound, said senior investigator Rubie Sue Jackson, MD, at the annual meeting of the American Society of Breast Surgeons. As a result, “surgeons don’t know what to do with an ultrasound-detected suspicious node. I think a lot of surgeons, if they detect a positive lymph node by ultrasound, even if it’s nonpalpable, would not consider the patient a candidate for sentinel lymph node biopsy. Our data suggest that many of these patients are being overtreated if they have an upfront axillary lymph node dissection,” she said.
The 129 women had 1-3 suspicious, nonpalpable nodes on ultrasound that turned out to have metastatic disease on needle biopsy. They all had subsequent ALNDs.
On final pathology, 67 women (52%) had only one metastatic node. For those women, a sentinel lymph node biopsy was likely all that they required. “They probably did not benefit from having an ALND,” said Dr. Jackson, a breast surgeon at the Anne Arundel Medical Center in Annapolis, Md. The other 62 women (48%) had N2-3 disease.
A primary tumor sized 2 cm or smaller (P = .012); nonlobular histology (P = .013), and having only one suspicious nonpalpable node on ultrasound (P = .008) were all associated with NI disease. Of the women who met the criteria, only eight (27%) had N 2-3 disease (P = .007).
“Patients meeting the three criteria are particularly unlikely to have three or more positive sentinel lymph nodes” and require subsequent ALND. “You don’t need to do a complete axillary lymph node dissection upfront, as long as they are getting a lumpectomy and whole breast radiation,” Dr. Jackson said.
These days at Anne Arundel, “we do the axillary ultrasound, we biopsy the lymph node if it looks suspicious, but we don’t feel forced to do an ALND. If a patient has tumor biology that’s likely to be highly responsive, we do upfront chemotherapy. If they have luminal tumor biology that’s not going to be very responsive to neoadjuvant therapy,” with one or two suspicious nodes, “and they are planning to get breast conserving therapy, I would do a sentinel lymph node biopsy and x-ray the specimen to make sure that I’ve retrieved the clip,” she said.
Dr. Jackson didn’t have any disclosures, and there was no industry funding for the work.
[email protected]
LAS VEGAS – About half of breast cancer patients without palpable lymphadenopathy but with preoperative ultrasound-guided, biopsy-proven axillary lymph node metastases have N1 disease, according to a review of 129 women.
Among the 30 women with a primary tumor 2 cm or smaller and only one abnormal lymph node on axillary ultrasound, 22 (73%) had metastases limited to the one lymph node, suggesting that such patients “may undergo ... sentinel lymph node biopsy” instead of a complete axillary lymph node dissection (ALND), the investigators concluded.
The problem that has come up in clinical practice is that axillary ultrasound is now a routine part of breast cancer workup, but the original trial didn’t address ultrasound, said senior investigator Rubie Sue Jackson, MD, at the annual meeting of the American Society of Breast Surgeons. As a result, “surgeons don’t know what to do with an ultrasound-detected suspicious node. I think a lot of surgeons, if they detect a positive lymph node by ultrasound, even if it’s nonpalpable, would not consider the patient a candidate for sentinel lymph node biopsy. Our data suggest that many of these patients are being overtreated if they have an upfront axillary lymph node dissection,” she said.
The 129 women had 1-3 suspicious, nonpalpable nodes on ultrasound that turned out to have metastatic disease on needle biopsy. They all had subsequent ALNDs.
On final pathology, 67 women (52%) had only one metastatic node. For those women, a sentinel lymph node biopsy was likely all that they required. “They probably did not benefit from having an ALND,” said Dr. Jackson, a breast surgeon at the Anne Arundel Medical Center in Annapolis, Md. The other 62 women (48%) had N2-3 disease.
A primary tumor sized 2 cm or smaller (P = .012); nonlobular histology (P = .013), and having only one suspicious nonpalpable node on ultrasound (P = .008) were all associated with NI disease. Of the women who met the criteria, only eight (27%) had N 2-3 disease (P = .007).
“Patients meeting the three criteria are particularly unlikely to have three or more positive sentinel lymph nodes” and require subsequent ALND. “You don’t need to do a complete axillary lymph node dissection upfront, as long as they are getting a lumpectomy and whole breast radiation,” Dr. Jackson said.
These days at Anne Arundel, “we do the axillary ultrasound, we biopsy the lymph node if it looks suspicious, but we don’t feel forced to do an ALND. If a patient has tumor biology that’s likely to be highly responsive, we do upfront chemotherapy. If they have luminal tumor biology that’s not going to be very responsive to neoadjuvant therapy,” with one or two suspicious nodes, “and they are planning to get breast conserving therapy, I would do a sentinel lymph node biopsy and x-ray the specimen to make sure that I’ve retrieved the clip,” she said.
Dr. Jackson didn’t have any disclosures, and there was no industry funding for the work.
[email protected]
LAS VEGAS – About half of breast cancer patients without palpable lymphadenopathy but with preoperative ultrasound-guided, biopsy-proven axillary lymph node metastases have N1 disease, according to a review of 129 women.
Among the 30 women with a primary tumor 2 cm or smaller and only one abnormal lymph node on axillary ultrasound, 22 (73%) had metastases limited to the one lymph node, suggesting that such patients “may undergo ... sentinel lymph node biopsy” instead of a complete axillary lymph node dissection (ALND), the investigators concluded.
The problem that has come up in clinical practice is that axillary ultrasound is now a routine part of breast cancer workup, but the original trial didn’t address ultrasound, said senior investigator Rubie Sue Jackson, MD, at the annual meeting of the American Society of Breast Surgeons. As a result, “surgeons don’t know what to do with an ultrasound-detected suspicious node. I think a lot of surgeons, if they detect a positive lymph node by ultrasound, even if it’s nonpalpable, would not consider the patient a candidate for sentinel lymph node biopsy. Our data suggest that many of these patients are being overtreated if they have an upfront axillary lymph node dissection,” she said.
The 129 women had 1-3 suspicious, nonpalpable nodes on ultrasound that turned out to have metastatic disease on needle biopsy. They all had subsequent ALNDs.
On final pathology, 67 women (52%) had only one metastatic node. For those women, a sentinel lymph node biopsy was likely all that they required. “They probably did not benefit from having an ALND,” said Dr. Jackson, a breast surgeon at the Anne Arundel Medical Center in Annapolis, Md. The other 62 women (48%) had N2-3 disease.
A primary tumor sized 2 cm or smaller (P = .012); nonlobular histology (P = .013), and having only one suspicious nonpalpable node on ultrasound (P = .008) were all associated with NI disease. Of the women who met the criteria, only eight (27%) had N 2-3 disease (P = .007).
“Patients meeting the three criteria are particularly unlikely to have three or more positive sentinel lymph nodes” and require subsequent ALND. “You don’t need to do a complete axillary lymph node dissection upfront, as long as they are getting a lumpectomy and whole breast radiation,” Dr. Jackson said.
These days at Anne Arundel, “we do the axillary ultrasound, we biopsy the lymph node if it looks suspicious, but we don’t feel forced to do an ALND. If a patient has tumor biology that’s likely to be highly responsive, we do upfront chemotherapy. If they have luminal tumor biology that’s not going to be very responsive to neoadjuvant therapy,” with one or two suspicious nodes, “and they are planning to get breast conserving therapy, I would do a sentinel lymph node biopsy and x-ray the specimen to make sure that I’ve retrieved the clip,” she said.
Dr. Jackson didn’t have any disclosures, and there was no industry funding for the work.
[email protected]
AT ASBS 2017
Key clinical point:
Major finding: Among the 30 women with tumors 2 cm or smaller, and only one abnormal lymph node on axillary ultrasound, 22 (73%) had metastasis limited to the one lymph node.
Data source: A review of 129 women with breast cancer.
Disclosures: There was no industry funding, and the senior investigator had no disclosures.
Omitting ALND in some breast cancer patients may be the right choice
PHILADELPHIA – The safety of sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) has been established for patients with cT1-2N0 cancer that are found to have one or two metastatic sentinel lymph nodes who undergo breast conservation therapy, but questions regarding the role of regional radiation have persisted.
This issue is addressed by the results of a large, prospective, 5+ year study at Memorial Sloan Kettering Cancer Center which confirmed the safety of omitting axillary lymph node dissection and suggested that regional radiation provides minimal benefit.
Dr. Morrow explained that, in August 2010, the breast surgery service at MSKCC adopted the guidelines that arose from the American College of Surgeons Oncology Group’s multicenter Z0011 trial and abandoned routine use of ALND in eligible patients. The goal of the study, she reported, was to determine how frequently axillary dissection was avoided in a consecutive, otherwise unselected, series of patients and to determine the incidence of local regional recurrence after SLNB alone in a population treated with known radiotherapy fields.
Eligible subjects had T1 or T2 node-negative breast cancer, were undergoing breast-conserving surgery with planned whole-breast irradiation, and were found to have hematoxylin-eosin-detected sentinel node metastases. Patients receiving neoadjuvant chemotherapy or requiring conversion to mastectomy, or those in whom partial breast irradiation or no radiotherapy was planned, were ineligible. Axillary imaging was not used in select patients. Criteria for axillary dissection were metastases in three or more sentinel nodes or the presence of matted nodes identified intraoperatively. The researchers did not use the MSKCC nomogram to predict the likelihood of non–sentinel node metastases.
Median patient age was 58 years and median tumor size 1.7 cm. With regard to tumor pathology, 87% had infiltrating ductal tumors, 94% had grade 2 or 3 disease, and the most common subtype was HR+, HER2– disease in 84%. “In this node-positive cohort of patients, 98% received adjuvant systemic therapy, most commonly both chemotherapy and endocrine therapy (received by 65%), and 93% completed radiotherapy,” Dr. Morrow said.
In the entire patient cohort, 84% (663) were treated with SLNB alone, Dr. Morrow said. Among the 130 patients requiring ALND, 68% (88) had metastases in three or more nodes, 26% (34) were found to have had matted nodes intraoperatively, and 6% (8) were eligible for SLNB alone but opted for ALND or had it recommended by their surgeon. “All of these occurred early in our experience, and this has not been repeated since,” Dr. Morrow said.
Among the SLNB-only patients, the 5-year event-free survival was 93%. “There were no isolated axillary recurrences,” Dr. Morrow said. The study reported four combined breast and axillary recurrences, three in nonradiated patients, and four combined nodal and distant recurrences, only one of which involved the axillary nodes. “The median time to any nodal recurrence was 25 months,” Dr. Morrow added. Among 484 patients who had 1 year or more of follow-up, 58% (280) received conventional supine breast tangents, 21% were treated prone – “meaning their axilla received essentially no radiotherapy,” Dr. Morrow said – and 21% had node field irradiation.
“If we compare patient characteristics based on radiotherapy fields treated, it’s clear that the patients who received nodal irradiation were a higher-risk group,” Dr. Morrow said. While all three groups had a median of one positive sentinel node, that “skewed towards two” in the nodal irradiation group, she said. This group also had higher rates of lymphovascular invasion (72% vs. 56% and 49% in the supine and prone groups, respectively) and extracapsular extension (41% vs. 31% and 25%).
The rates of nodal relapse were not statistically significant among the three groups: 1% in the prone group, 1.4% in the supine group, and 0% in the node irradiation group.
“Factors associated with a higher risk of distant metastases, such as young patient age, estrogen receptor negativity, or HER2 over-expression, were not associated with the need for axillary dissection and should not be used as priority selection criteria,” Dr. Morrow said. “Nodal recurrence was uncommon in the absence of routine nodal radiation therapy, and no isolated nodal failures were observed.
In his comments, Armando Giuliano, MD, of Cedars Sinai Medical Center in Los Angeles, principal investigator of the Z0011 trial, said the MSKCC study “extends and informs” the Z0011 findings. He noted that the prone treatment group in the MSKCC trial had a low rate of axillary recurrence. “Can you speculate how such excellent results are achieved without resection or irradiation?” he asked Dr. Morrow. “To me it appears that nodal irradiation provides very little benefit to this selected group of patients.”
The patients in the prone group were in the lowest-risk category of the study, Dr. Morrow said, but the fact that not all nodal disease becomes clinically evident, even in patients who do not receive radiotherapy or systemic therapy, along with the high use of systemic therapy in this group, may explain the low rates of axillary recurrence. “What I think we still need to find out, though, is whether or not failure to irradiate the nodes at all is in any way associated with decreased survival, as would be suggested in the MA.20 trial,” she said. “I think we will find that out from ongoing trials looking at no axillary dissection in mastectomy patients.”
Dr. Morrow and Dr. Giuliano reported no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, Pennsylvania, is to be published in Annals of Surgery pending editorial review.
PHILADELPHIA – The safety of sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) has been established for patients with cT1-2N0 cancer that are found to have one or two metastatic sentinel lymph nodes who undergo breast conservation therapy, but questions regarding the role of regional radiation have persisted.
This issue is addressed by the results of a large, prospective, 5+ year study at Memorial Sloan Kettering Cancer Center which confirmed the safety of omitting axillary lymph node dissection and suggested that regional radiation provides minimal benefit.
Dr. Morrow explained that, in August 2010, the breast surgery service at MSKCC adopted the guidelines that arose from the American College of Surgeons Oncology Group’s multicenter Z0011 trial and abandoned routine use of ALND in eligible patients. The goal of the study, she reported, was to determine how frequently axillary dissection was avoided in a consecutive, otherwise unselected, series of patients and to determine the incidence of local regional recurrence after SLNB alone in a population treated with known radiotherapy fields.
Eligible subjects had T1 or T2 node-negative breast cancer, were undergoing breast-conserving surgery with planned whole-breast irradiation, and were found to have hematoxylin-eosin-detected sentinel node metastases. Patients receiving neoadjuvant chemotherapy or requiring conversion to mastectomy, or those in whom partial breast irradiation or no radiotherapy was planned, were ineligible. Axillary imaging was not used in select patients. Criteria for axillary dissection were metastases in three or more sentinel nodes or the presence of matted nodes identified intraoperatively. The researchers did not use the MSKCC nomogram to predict the likelihood of non–sentinel node metastases.
Median patient age was 58 years and median tumor size 1.7 cm. With regard to tumor pathology, 87% had infiltrating ductal tumors, 94% had grade 2 or 3 disease, and the most common subtype was HR+, HER2– disease in 84%. “In this node-positive cohort of patients, 98% received adjuvant systemic therapy, most commonly both chemotherapy and endocrine therapy (received by 65%), and 93% completed radiotherapy,” Dr. Morrow said.
In the entire patient cohort, 84% (663) were treated with SLNB alone, Dr. Morrow said. Among the 130 patients requiring ALND, 68% (88) had metastases in three or more nodes, 26% (34) were found to have had matted nodes intraoperatively, and 6% (8) were eligible for SLNB alone but opted for ALND or had it recommended by their surgeon. “All of these occurred early in our experience, and this has not been repeated since,” Dr. Morrow said.
Among the SLNB-only patients, the 5-year event-free survival was 93%. “There were no isolated axillary recurrences,” Dr. Morrow said. The study reported four combined breast and axillary recurrences, three in nonradiated patients, and four combined nodal and distant recurrences, only one of which involved the axillary nodes. “The median time to any nodal recurrence was 25 months,” Dr. Morrow added. Among 484 patients who had 1 year or more of follow-up, 58% (280) received conventional supine breast tangents, 21% were treated prone – “meaning their axilla received essentially no radiotherapy,” Dr. Morrow said – and 21% had node field irradiation.
“If we compare patient characteristics based on radiotherapy fields treated, it’s clear that the patients who received nodal irradiation were a higher-risk group,” Dr. Morrow said. While all three groups had a median of one positive sentinel node, that “skewed towards two” in the nodal irradiation group, she said. This group also had higher rates of lymphovascular invasion (72% vs. 56% and 49% in the supine and prone groups, respectively) and extracapsular extension (41% vs. 31% and 25%).
The rates of nodal relapse were not statistically significant among the three groups: 1% in the prone group, 1.4% in the supine group, and 0% in the node irradiation group.
“Factors associated with a higher risk of distant metastases, such as young patient age, estrogen receptor negativity, or HER2 over-expression, were not associated with the need for axillary dissection and should not be used as priority selection criteria,” Dr. Morrow said. “Nodal recurrence was uncommon in the absence of routine nodal radiation therapy, and no isolated nodal failures were observed.
In his comments, Armando Giuliano, MD, of Cedars Sinai Medical Center in Los Angeles, principal investigator of the Z0011 trial, said the MSKCC study “extends and informs” the Z0011 findings. He noted that the prone treatment group in the MSKCC trial had a low rate of axillary recurrence. “Can you speculate how such excellent results are achieved without resection or irradiation?” he asked Dr. Morrow. “To me it appears that nodal irradiation provides very little benefit to this selected group of patients.”
The patients in the prone group were in the lowest-risk category of the study, Dr. Morrow said, but the fact that not all nodal disease becomes clinically evident, even in patients who do not receive radiotherapy or systemic therapy, along with the high use of systemic therapy in this group, may explain the low rates of axillary recurrence. “What I think we still need to find out, though, is whether or not failure to irradiate the nodes at all is in any way associated with decreased survival, as would be suggested in the MA.20 trial,” she said. “I think we will find that out from ongoing trials looking at no axillary dissection in mastectomy patients.”
Dr. Morrow and Dr. Giuliano reported no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, Pennsylvania, is to be published in Annals of Surgery pending editorial review.
PHILADELPHIA – The safety of sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) has been established for patients with cT1-2N0 cancer that are found to have one or two metastatic sentinel lymph nodes who undergo breast conservation therapy, but questions regarding the role of regional radiation have persisted.
This issue is addressed by the results of a large, prospective, 5+ year study at Memorial Sloan Kettering Cancer Center which confirmed the safety of omitting axillary lymph node dissection and suggested that regional radiation provides minimal benefit.
Dr. Morrow explained that, in August 2010, the breast surgery service at MSKCC adopted the guidelines that arose from the American College of Surgeons Oncology Group’s multicenter Z0011 trial and abandoned routine use of ALND in eligible patients. The goal of the study, she reported, was to determine how frequently axillary dissection was avoided in a consecutive, otherwise unselected, series of patients and to determine the incidence of local regional recurrence after SLNB alone in a population treated with known radiotherapy fields.
Eligible subjects had T1 or T2 node-negative breast cancer, were undergoing breast-conserving surgery with planned whole-breast irradiation, and were found to have hematoxylin-eosin-detected sentinel node metastases. Patients receiving neoadjuvant chemotherapy or requiring conversion to mastectomy, or those in whom partial breast irradiation or no radiotherapy was planned, were ineligible. Axillary imaging was not used in select patients. Criteria for axillary dissection were metastases in three or more sentinel nodes or the presence of matted nodes identified intraoperatively. The researchers did not use the MSKCC nomogram to predict the likelihood of non–sentinel node metastases.
Median patient age was 58 years and median tumor size 1.7 cm. With regard to tumor pathology, 87% had infiltrating ductal tumors, 94% had grade 2 or 3 disease, and the most common subtype was HR+, HER2– disease in 84%. “In this node-positive cohort of patients, 98% received adjuvant systemic therapy, most commonly both chemotherapy and endocrine therapy (received by 65%), and 93% completed radiotherapy,” Dr. Morrow said.
In the entire patient cohort, 84% (663) were treated with SLNB alone, Dr. Morrow said. Among the 130 patients requiring ALND, 68% (88) had metastases in three or more nodes, 26% (34) were found to have had matted nodes intraoperatively, and 6% (8) were eligible for SLNB alone but opted for ALND or had it recommended by their surgeon. “All of these occurred early in our experience, and this has not been repeated since,” Dr. Morrow said.
Among the SLNB-only patients, the 5-year event-free survival was 93%. “There were no isolated axillary recurrences,” Dr. Morrow said. The study reported four combined breast and axillary recurrences, three in nonradiated patients, and four combined nodal and distant recurrences, only one of which involved the axillary nodes. “The median time to any nodal recurrence was 25 months,” Dr. Morrow added. Among 484 patients who had 1 year or more of follow-up, 58% (280) received conventional supine breast tangents, 21% were treated prone – “meaning their axilla received essentially no radiotherapy,” Dr. Morrow said – and 21% had node field irradiation.
“If we compare patient characteristics based on radiotherapy fields treated, it’s clear that the patients who received nodal irradiation were a higher-risk group,” Dr. Morrow said. While all three groups had a median of one positive sentinel node, that “skewed towards two” in the nodal irradiation group, she said. This group also had higher rates of lymphovascular invasion (72% vs. 56% and 49% in the supine and prone groups, respectively) and extracapsular extension (41% vs. 31% and 25%).
The rates of nodal relapse were not statistically significant among the three groups: 1% in the prone group, 1.4% in the supine group, and 0% in the node irradiation group.
“Factors associated with a higher risk of distant metastases, such as young patient age, estrogen receptor negativity, or HER2 over-expression, were not associated with the need for axillary dissection and should not be used as priority selection criteria,” Dr. Morrow said. “Nodal recurrence was uncommon in the absence of routine nodal radiation therapy, and no isolated nodal failures were observed.
In his comments, Armando Giuliano, MD, of Cedars Sinai Medical Center in Los Angeles, principal investigator of the Z0011 trial, said the MSKCC study “extends and informs” the Z0011 findings. He noted that the prone treatment group in the MSKCC trial had a low rate of axillary recurrence. “Can you speculate how such excellent results are achieved without resection or irradiation?” he asked Dr. Morrow. “To me it appears that nodal irradiation provides very little benefit to this selected group of patients.”
The patients in the prone group were in the lowest-risk category of the study, Dr. Morrow said, but the fact that not all nodal disease becomes clinically evident, even in patients who do not receive radiotherapy or systemic therapy, along with the high use of systemic therapy in this group, may explain the low rates of axillary recurrence. “What I think we still need to find out, though, is whether or not failure to irradiate the nodes at all is in any way associated with decreased survival, as would be suggested in the MA.20 trial,” she said. “I think we will find that out from ongoing trials looking at no axillary dissection in mastectomy patients.”
Dr. Morrow and Dr. Giuliano reported no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, Pennsylvania, is to be published in Annals of Surgery pending editorial review.
AT THE ANNUAL ASA MEETING
BILCAP: adjuvant capecitabine boosts overall survival of biliary tract cancers
Patients who have undergone complete resection of biliary tract cancers live longer if they receive the oral chemotherapy agent capecitabine instead of simple observation, according to findings of the phase III randomized controlled BILCAP trial.
“The only curative treatment [for these cancers] is surgical resection, but even in that circumstance, most patients will ultimately succumb to the disease,” lead study author John N. Primrose, MD, professor of surgery at the University of Southampton (England), said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Results of the trial showed that compared with observation, capecitabine prolonged survival by a nonsignificant 15 months in the intention-to-treat population but by a significant 17 months in the per-protocol population. The drug had modest toxicity consistent with past experience and little impact on quality of life.
“On this basis, we believe that capecitabine should now become the standard of care for patients following curative resection of biliary tract cancer,” Dr. Primrose maintained.
The trial took place in a U.K. population, noted ASCO President Daniel F. Hayes, MD, clinical director of the breast oncology program and Stuart B. Padnos Professor in Breast Cancer Research at the University of Michigan Comprehensive Cancer Center in Ann Arbor.
“This is a cancer that is much more common in Asia than it is in the western world, and I think that will be one of the questions that will be raised, as to whether these [results] apply to patients from Asia with the same cancer,” he said. “Otherwise, this is an impressive study, an enormous amount of work, and a very important finding.”
Study coauthor John A. Bridgewater, PhD, a professor at University College Hospital in London, said that he was not concerned that the trial missed its primary endpoint.
“It would of course have been much nicer if it had been significant, but I don’t think there is any doubt that there is a genuine effect here,” he maintained, agreeing that capecitabine should be standard of care going forward.
Other chemotherapies have made their way into similar adjuvant trials since BILCAP began, including the combination of cisplatin and gemcitabine being tested in the randomized ACTICCA-1 trial, Dr. Bridgewater acknowledged. “We’ve been discussing the possible permutations if BILCAP turned out to be positive with [those investigators], and that study, cisplatin-gemcitabine compared to surveillance, will now be modified to cisplatin-gemcitabine versus capecitabine. We came to that agreement some time ago.”
The BILCAP investigators are undertaking biomarker analyses of patients’ tumors. “The genotype of a bile duct cancer that will do well with fluoropyrimidine [such as capecitabine] is unknown, and that is exactly what we’ll be looking at when we look at the material. That surely will be one of the most important questions,” he said.
At present, there is no evidence to suggest that biliary tract cancers arising in Asian populations, which are mainly due to chronic infection with liver flukes, will differ in their response to capecitabine, according to Dr. Bridgewater.
“Certainly, you’ll be able to see in the clinical subgroup analyses, the long and the short of it is that it’s actually very difficult to distinguish, certainly on clinical grounds, any group that benefits more than other groups,” he said. “So the short answer is, there shouldn’t be any difference. But do we really know? Not yet.”
Study details
Patients enrolled in BILCAP had macroscopically completely resected cholangiocarcinoma or gallbladder cancer (including liver and pancreatic resection, as appropriate). They were randomized evenly to eight cycles of capecitabine (Xeloda) at a conventional dose or observation (Capecitabine is approved by the Food and Drug Administration for treatment of breast and colorectal cancers).
With more than 80% of patients having at least 3 years of follow-up, median overall survival in the intention-to-treat population – the trial’s primary endpoint – was 51 months with capecitabine and 36 months with observation (hazard ratio [HR], 0.81; P = .097), Dr. Primrose reported. The benefit became significant in a sensitivity analysis that adjusted for prognostic factors (HR, 0.70; P = .007).
In addition, median overall survival in the per-protocol population was significantly longer with capecitabine, at 53 months, than with observation, at 36 months (HR, 0.75; P = .028).
Median recurrence-free survival in the intention-to-treat population was 25 months for the capecitabine group and 18 months for the observation group.
“The toxicity associated with chemotherapy was relatively modest and in fact very similar to what has been observed in other studies,” Dr. Primrose said. The predominant grade 3 or 4 toxicity seen with capecitabine was plantar-palmar erythema, which occurred in 20.7% of patients who received the drug. There were no capecitabine-related deaths.
“Our quality of life analysis showed that there was very little difference in quality of life related to chemotherapy over those who did not have chemotherapy,” he added.
Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.
Patients who have undergone complete resection of biliary tract cancers live longer if they receive the oral chemotherapy agent capecitabine instead of simple observation, according to findings of the phase III randomized controlled BILCAP trial.
“The only curative treatment [for these cancers] is surgical resection, but even in that circumstance, most patients will ultimately succumb to the disease,” lead study author John N. Primrose, MD, professor of surgery at the University of Southampton (England), said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Results of the trial showed that compared with observation, capecitabine prolonged survival by a nonsignificant 15 months in the intention-to-treat population but by a significant 17 months in the per-protocol population. The drug had modest toxicity consistent with past experience and little impact on quality of life.
“On this basis, we believe that capecitabine should now become the standard of care for patients following curative resection of biliary tract cancer,” Dr. Primrose maintained.
The trial took place in a U.K. population, noted ASCO President Daniel F. Hayes, MD, clinical director of the breast oncology program and Stuart B. Padnos Professor in Breast Cancer Research at the University of Michigan Comprehensive Cancer Center in Ann Arbor.
“This is a cancer that is much more common in Asia than it is in the western world, and I think that will be one of the questions that will be raised, as to whether these [results] apply to patients from Asia with the same cancer,” he said. “Otherwise, this is an impressive study, an enormous amount of work, and a very important finding.”
Study coauthor John A. Bridgewater, PhD, a professor at University College Hospital in London, said that he was not concerned that the trial missed its primary endpoint.
“It would of course have been much nicer if it had been significant, but I don’t think there is any doubt that there is a genuine effect here,” he maintained, agreeing that capecitabine should be standard of care going forward.
Other chemotherapies have made their way into similar adjuvant trials since BILCAP began, including the combination of cisplatin and gemcitabine being tested in the randomized ACTICCA-1 trial, Dr. Bridgewater acknowledged. “We’ve been discussing the possible permutations if BILCAP turned out to be positive with [those investigators], and that study, cisplatin-gemcitabine compared to surveillance, will now be modified to cisplatin-gemcitabine versus capecitabine. We came to that agreement some time ago.”
The BILCAP investigators are undertaking biomarker analyses of patients’ tumors. “The genotype of a bile duct cancer that will do well with fluoropyrimidine [such as capecitabine] is unknown, and that is exactly what we’ll be looking at when we look at the material. That surely will be one of the most important questions,” he said.
At present, there is no evidence to suggest that biliary tract cancers arising in Asian populations, which are mainly due to chronic infection with liver flukes, will differ in their response to capecitabine, according to Dr. Bridgewater.
“Certainly, you’ll be able to see in the clinical subgroup analyses, the long and the short of it is that it’s actually very difficult to distinguish, certainly on clinical grounds, any group that benefits more than other groups,” he said. “So the short answer is, there shouldn’t be any difference. But do we really know? Not yet.”
Study details
Patients enrolled in BILCAP had macroscopically completely resected cholangiocarcinoma or gallbladder cancer (including liver and pancreatic resection, as appropriate). They were randomized evenly to eight cycles of capecitabine (Xeloda) at a conventional dose or observation (Capecitabine is approved by the Food and Drug Administration for treatment of breast and colorectal cancers).
With more than 80% of patients having at least 3 years of follow-up, median overall survival in the intention-to-treat population – the trial’s primary endpoint – was 51 months with capecitabine and 36 months with observation (hazard ratio [HR], 0.81; P = .097), Dr. Primrose reported. The benefit became significant in a sensitivity analysis that adjusted for prognostic factors (HR, 0.70; P = .007).
In addition, median overall survival in the per-protocol population was significantly longer with capecitabine, at 53 months, than with observation, at 36 months (HR, 0.75; P = .028).
Median recurrence-free survival in the intention-to-treat population was 25 months for the capecitabine group and 18 months for the observation group.
“The toxicity associated with chemotherapy was relatively modest and in fact very similar to what has been observed in other studies,” Dr. Primrose said. The predominant grade 3 or 4 toxicity seen with capecitabine was plantar-palmar erythema, which occurred in 20.7% of patients who received the drug. There were no capecitabine-related deaths.
“Our quality of life analysis showed that there was very little difference in quality of life related to chemotherapy over those who did not have chemotherapy,” he added.
Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.
Patients who have undergone complete resection of biliary tract cancers live longer if they receive the oral chemotherapy agent capecitabine instead of simple observation, according to findings of the phase III randomized controlled BILCAP trial.
“The only curative treatment [for these cancers] is surgical resection, but even in that circumstance, most patients will ultimately succumb to the disease,” lead study author John N. Primrose, MD, professor of surgery at the University of Southampton (England), said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Results of the trial showed that compared with observation, capecitabine prolonged survival by a nonsignificant 15 months in the intention-to-treat population but by a significant 17 months in the per-protocol population. The drug had modest toxicity consistent with past experience and little impact on quality of life.
“On this basis, we believe that capecitabine should now become the standard of care for patients following curative resection of biliary tract cancer,” Dr. Primrose maintained.
The trial took place in a U.K. population, noted ASCO President Daniel F. Hayes, MD, clinical director of the breast oncology program and Stuart B. Padnos Professor in Breast Cancer Research at the University of Michigan Comprehensive Cancer Center in Ann Arbor.
“This is a cancer that is much more common in Asia than it is in the western world, and I think that will be one of the questions that will be raised, as to whether these [results] apply to patients from Asia with the same cancer,” he said. “Otherwise, this is an impressive study, an enormous amount of work, and a very important finding.”
Study coauthor John A. Bridgewater, PhD, a professor at University College Hospital in London, said that he was not concerned that the trial missed its primary endpoint.
“It would of course have been much nicer if it had been significant, but I don’t think there is any doubt that there is a genuine effect here,” he maintained, agreeing that capecitabine should be standard of care going forward.
Other chemotherapies have made their way into similar adjuvant trials since BILCAP began, including the combination of cisplatin and gemcitabine being tested in the randomized ACTICCA-1 trial, Dr. Bridgewater acknowledged. “We’ve been discussing the possible permutations if BILCAP turned out to be positive with [those investigators], and that study, cisplatin-gemcitabine compared to surveillance, will now be modified to cisplatin-gemcitabine versus capecitabine. We came to that agreement some time ago.”
The BILCAP investigators are undertaking biomarker analyses of patients’ tumors. “The genotype of a bile duct cancer that will do well with fluoropyrimidine [such as capecitabine] is unknown, and that is exactly what we’ll be looking at when we look at the material. That surely will be one of the most important questions,” he said.
At present, there is no evidence to suggest that biliary tract cancers arising in Asian populations, which are mainly due to chronic infection with liver flukes, will differ in their response to capecitabine, according to Dr. Bridgewater.
“Certainly, you’ll be able to see in the clinical subgroup analyses, the long and the short of it is that it’s actually very difficult to distinguish, certainly on clinical grounds, any group that benefits more than other groups,” he said. “So the short answer is, there shouldn’t be any difference. But do we really know? Not yet.”
Study details
Patients enrolled in BILCAP had macroscopically completely resected cholangiocarcinoma or gallbladder cancer (including liver and pancreatic resection, as appropriate). They were randomized evenly to eight cycles of capecitabine (Xeloda) at a conventional dose or observation (Capecitabine is approved by the Food and Drug Administration for treatment of breast and colorectal cancers).
With more than 80% of patients having at least 3 years of follow-up, median overall survival in the intention-to-treat population – the trial’s primary endpoint – was 51 months with capecitabine and 36 months with observation (hazard ratio [HR], 0.81; P = .097), Dr. Primrose reported. The benefit became significant in a sensitivity analysis that adjusted for prognostic factors (HR, 0.70; P = .007).
In addition, median overall survival in the per-protocol population was significantly longer with capecitabine, at 53 months, than with observation, at 36 months (HR, 0.75; P = .028).
Median recurrence-free survival in the intention-to-treat population was 25 months for the capecitabine group and 18 months for the observation group.
“The toxicity associated with chemotherapy was relatively modest and in fact very similar to what has been observed in other studies,” Dr. Primrose said. The predominant grade 3 or 4 toxicity seen with capecitabine was plantar-palmar erythema, which occurred in 20.7% of patients who received the drug. There were no capecitabine-related deaths.
“Our quality of life analysis showed that there was very little difference in quality of life related to chemotherapy over those who did not have chemotherapy,” he added.
Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Compared with observation, capecitabine prolonged median overall survival by 15 months in the intention-to-treat population (P = .097) and by 17 months in the per-protocol population (P = .028).
Data source: BILCAP, a phase III randomized controlled trial among 447 patients who had undergone complete resection of biliary tract cancers.
Disclosures: Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.