IMRT Fails to Aid Survival in Cervical Ca Patients

GÖTEBORG, SWEDEN—Eliminating nodal disease in cervical cancer patients with positive pelvic and para-aortic positive lymph nodes failed to improve survival in a prospective 24-patient phase II study.

The results were presented at the annual meeting of the European Society for Therapeutic Radiology and Oncology.

Investigators at the Mallinckrodt Institute of Radiology in St. Louis used positron-emission tomography (PET) to guide 60 Gy of intensity-modulated radiation therapy (IMRT) to pelvic and para-aortic lymph nodes where metastases had been detected by PET with fluorodeoxyglucose (FDG).

Three months after radiotherapy, 21 patients were screened again by FDG-PET, a timetable the lead investigator, Dr. Perry W. Grigsby, had previously reported to be predictive of survival (JAMA 2007;298:2289-95). Nineteen patients (90%) had negative lymph nodes at this point, suggesting radiotherapy had been successful.

Six of the 19 patients—nearly a third—already had new metastases in other locations, however. By 40 months, nearly all had progressed. Cause-specific survival at that point was about 50%, said Dr. Grigsby, professor of radiation oncology, nuclear medicine, and gynecologic oncology at Washington University, St. Louis.

“Some of these patients have been treated for their recurrences, and will live a few months longer,” he observed.

The 5-year survival rate for cervical cancer with positive lymph nodes is only about 30%, according to Dr. Grigsby. Efforts to deliver more radiotherapy to positive lymph nodes have so far resulted in high toxicity with no improvement in survival.

For the current study, patients had to have positive nodes with no other sites of metastases when enrolled. Half of the 24 patients had stage IIIb disease; nine had stage IIb disease, and three cases were stage Ib2. The majority, 20 patients, had squamous cell histology; 2 patients had adenocarcinoma, and 1 each were classified with clear cell or small cell cervical cancer.

The protocol delivered a clinical target volume-nodal of 50 Gy over 30 fractions to the pelvis and para-aortic lymph node regions, along with a molecular target volume-nodal of 60 Gy directed at the FDG-PET-positive lymph nodes in these areas. In addition, the women were treated with six cycles of brachytherapy (6.5-Gy high dose rate) and weekly cisplatin (40 mg/m

The median treatment time was reported as 53 days, with a median follow-up of 22 months.

Acute toxicity was high, with 58% of patients having grade 3 adverse events, 33% with grade 4, and one patient dying of a chemotherapy-related adverse event. Late toxicity occurred in 13% of patients: two with small bowel obstructions and one with proctitis.

The results show that delivering 60 Gy of PET-guided IMRT to pelvic and para-aortic lymph nodes along with concurrent chemotherapy is feasible and eliminates nodal disease in most patients, Dr. Grigsby said.

Nonetheless, he found survival remains poor due to development of distant metastases.

“These patients are at exceptionally high risk of dying from metastatic disease, and we need to search out improved systemic agents in order to cure this patient population,” he concluded.

Dr. Grigsby stated that he had no conflicts of interest to disclose.

Positive lymph nodes are shown in green on the FDG-PET scan.

In one dose-distribution plan, the blue areas receive 50 Gy of radiation and the positive lymph nodes (orange) receive 60 Gy. Images courtesy Dr. Perry W. Grigsby

GÖTEBORG, SWEDEN—Eliminating nodal disease in cervical cancer patients with positive pelvic and para-aortic positive lymph nodes failed to improve survival in a prospective 24-patient phase II study.

The results were presented at the annual meeting of the European Society for Therapeutic Radiology and Oncology.

Investigators at the Mallinckrodt Institute of Radiology in St. Louis used positron-emission tomography (PET) to guide 60 Gy of intensity-modulated radiation therapy (IMRT) to pelvic and para-aortic lymph nodes where metastases had been detected by PET with fluorodeoxyglucose (FDG).

Three months after radiotherapy, 21 patients were screened again by FDG-PET, a timetable the lead investigator, Dr. Perry W. Grigsby, had previously reported to be predictive of survival (JAMA 2007;298:2289-95). Nineteen patients (90%) had negative lymph nodes at this point, suggesting radiotherapy had been successful.

Six of the 19 patients—nearly a third—already had new metastases in other locations, however. By 40 months, nearly all had progressed. Cause-specific survival at that point was about 50%, said Dr. Grigsby, professor of radiation oncology, nuclear medicine, and gynecologic oncology at Washington University, St. Louis.

“Some of these patients have been treated for their recurrences, and will live a few months longer,” he observed.

The 5-year survival rate for cervical cancer with positive lymph nodes is only about 30%, according to Dr. Grigsby. Efforts to deliver more radiotherapy to positive lymph nodes have so far resulted in high toxicity with no improvement in survival.

For the current study, patients had to have positive nodes with no other sites of metastases when enrolled. Half of the 24 patients had stage IIIb disease; nine had stage IIb disease, and three cases were stage Ib2. The majority, 20 patients, had squamous cell histology; 2 patients had adenocarcinoma, and 1 each were classified with clear cell or small cell cervical cancer.

The protocol delivered a clinical target volume-nodal of 50 Gy over 30 fractions to the pelvis and para-aortic lymph node regions, along with a molecular target volume-nodal of 60 Gy directed at the FDG-PET-positive lymph nodes in these areas. In addition, the women were treated with six cycles of brachytherapy (6.5-Gy high dose rate) and weekly cisplatin (40 mg/m

The median treatment time was reported as 53 days, with a median follow-up of 22 months.

Acute toxicity was high, with 58% of patients having grade 3 adverse events, 33% with grade 4, and one patient dying of a chemotherapy-related adverse event. Late toxicity occurred in 13% of patients: two with small bowel obstructions and one with proctitis.

The results show that delivering 60 Gy of PET-guided IMRT to pelvic and para-aortic lymph nodes along with concurrent chemotherapy is feasible and eliminates nodal disease in most patients, Dr. Grigsby said.

Nonetheless, he found survival remains poor due to development of distant metastases.

“These patients are at exceptionally high risk of dying from metastatic disease, and we need to search out improved systemic agents in order to cure this patient population,” he concluded.

Dr. Grigsby stated that he had no conflicts of interest to disclose.

Positive lymph nodes are shown in green on the FDG-PET scan.

In one dose-distribution plan, the blue areas receive 50 Gy of radiation and the positive lymph nodes (orange) receive 60 Gy. Images courtesy Dr. Perry W. Grigsby

GÖTEBORG, SWEDEN—Eliminating nodal disease in cervical cancer patients with positive pelvic and para-aortic positive lymph nodes failed to improve survival in a prospective 24-patient phase II study.

The results were presented at the annual meeting of the European Society for Therapeutic Radiology and Oncology.

Investigators at the Mallinckrodt Institute of Radiology in St. Louis used positron-emission tomography (PET) to guide 60 Gy of intensity-modulated radiation therapy (IMRT) to pelvic and para-aortic lymph nodes where metastases had been detected by PET with fluorodeoxyglucose (FDG).

Three months after radiotherapy, 21 patients were screened again by FDG-PET, a timetable the lead investigator, Dr. Perry W. Grigsby, had previously reported to be predictive of survival (JAMA 2007;298:2289-95). Nineteen patients (90%) had negative lymph nodes at this point, suggesting radiotherapy had been successful.

Six of the 19 patients—nearly a third—already had new metastases in other locations, however. By 40 months, nearly all had progressed. Cause-specific survival at that point was about 50%, said Dr. Grigsby, professor of radiation oncology, nuclear medicine, and gynecologic oncology at Washington University, St. Louis.

“Some of these patients have been treated for their recurrences, and will live a few months longer,” he observed.

The 5-year survival rate for cervical cancer with positive lymph nodes is only about 30%, according to Dr. Grigsby. Efforts to deliver more radiotherapy to positive lymph nodes have so far resulted in high toxicity with no improvement in survival.

For the current study, patients had to have positive nodes with no other sites of metastases when enrolled. Half of the 24 patients had stage IIIb disease; nine had stage IIb disease, and three cases were stage Ib2. The majority, 20 patients, had squamous cell histology; 2 patients had adenocarcinoma, and 1 each were classified with clear cell or small cell cervical cancer.

The protocol delivered a clinical target volume-nodal of 50 Gy over 30 fractions to the pelvis and para-aortic lymph node regions, along with a molecular target volume-nodal of 60 Gy directed at the FDG-PET-positive lymph nodes in these areas. In addition, the women were treated with six cycles of brachytherapy (6.5-Gy high dose rate) and weekly cisplatin (40 mg/m

The median treatment time was reported as 53 days, with a median follow-up of 22 months.

Acute toxicity was high, with 58% of patients having grade 3 adverse events, 33% with grade 4, and one patient dying of a chemotherapy-related adverse event. Late toxicity occurred in 13% of patients: two with small bowel obstructions and one with proctitis.

The results show that delivering 60 Gy of PET-guided IMRT to pelvic and para-aortic lymph nodes along with concurrent chemotherapy is feasible and eliminates nodal disease in most patients, Dr. Grigsby said.

Nonetheless, he found survival remains poor due to development of distant metastases.

“These patients are at exceptionally high risk of dying from metastatic disease, and we need to search out improved systemic agents in order to cure this patient population,” he concluded.

Dr. Grigsby stated that he had no conflicts of interest to disclose.

Positive lymph nodes are shown in green on the FDG-PET scan.

In one dose-distribution plan, the blue areas receive 50 Gy of radiation and the positive lymph nodes (orange) receive 60 Gy. Images courtesy Dr. Perry W. Grigsby