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Phase II Consolidation Chemotherapy With Ifosfamide and Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Cervix Uteri
I. J. Radiation Oncology d Biology d Physics
S452
2503
Volume 81, Number 2, Supplement, 2011
Post-therapy Positron Emission Tomography may Obviate the Need for Conventional Follow-up in Patients Receiving Chemoradiation for Advanced Cervical Cancer
S. Siva, A. Herschtal, J. Thomas, D. Bernshaw, S. Gill, R. Hicks, K. Narayan Peter MacCallum Cancer Centre, East Melbourne, Australia Purpose/Objective(s): A study was undertaken to investigate the detection of relapse and survival outcomes in patients with advanced cervical cancer treated with curative intent chemoradiotherapy, and evaluated with a post-therapy 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Materials/Methods: Between January 2002 and June 2007, 105 consecutive patients were prospectively enrolled into a registry study designed to assess outcomes of chemoradiotherapy. A FDG-PET scan was performed between 3 and 12 months post-treatment (median of 4.9 months) at clinician discretion. Tumor response was graded as complete metabolic response, partial metabolic response, or progressive metabolic disease. Results: The median follow-up was 36 months. At post-therapy FDG-PET, 73 patients had a complete metabolic response (70%), 10 patients had a partial metabolic response (9%), and 22 patients had progressive metabolic disease (21%). Cancer specific survival at 3 years was 81% in all patients, and 98% for those with a complete metabolic response. Overall survival at 3 years was 77% in all patients, and 95% for those with a complete metabolic response. On multivariate analysis, complete metabolic response (P \.0001) and pretreatment tumor volume (P = .041) were strong predictors for overall survival. The number of involved lymph nodes (P \.005) and International Federation of Gynecology and Obstetrics stage (P = .04) were predictive of relapse-free survival. Patients with complete metabolic response had a distant failure rate 36-fold less than those with partial metabolic response (P \.0001). After complete metabolic response, only 1 patient (1.6%) relapsed without symptoms and was detected through routine physical examination. This patient was successfully salvaged and had no further evidence of disease. In total, 18 patients relapsed at a single site, and 13 underwent salvage therapies, with a 3-year survival of 67%. Conclusions: The presence of a complete metabolic response at post-therapy FDG-PET is a powerful predictor for survival after chemoradiation. The very low rate of recurrence in patients with a complete metabolic response justifies a conservative follow-up approach for these patients, because relapse is usually symptomatic and is not detected by routine clinical review. Author Disclosure: S. Siva: None. A. Herschtal: None. J. Thomas: None. D. Bernshaw: None. S. Gill: None. R. Hicks: None. K. Narayan: None.
2504
Phase II Consolidation Chemotherapy With Ifosfamide and Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Cervix Uteri
P. Mahasittiwat, N. Ieumwananonthachai, J. Setakornnukul, N. Soontornpong, S. Udompunturak, P. Pattaranutraporn Department of Radiology, Division of Radiation Oncology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Purpose/Objective(s): The role of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced cervical carcinoma is controversial. This study was to evaluate the efficacy and toxicity of consolidation chemotherapy with ifosfamide and cisplatin in locally advanced squamous cell carcinoma of the cervix uteri. Materials/Methods: The prospective study was performed between October 2005 and November 2006 in Siriraj Hospital, Mahidol University, Thailand based on IRB approval. Pretreatment evaluation included physical examination, punch biopsies, cystoscopy, abdominal CT, CXR and blood chemistry. Patients received concurrent cisplatin (40 mg/m2) weekly with radiotherapy plus 3 cycles of adjuvant cisplatin (75 mg/m2) and ifosfamide (5000 mg/m2). Radiotherapy was composed of external RT and 4 fractions of HDR intracavitary brachytherapy with 80 - 85 Gy of point A dose. Treatment response (RECIST criteria) was evaluated by clinical, abdominal CT and cervical biopsies. Survival analysis was calculated by Kaplan- Meier method. Results: Nineteen patients with stage IIB (21%) and IIIB (79%) were enrolled in this study. The median of age was 47 years (range, 34 - 60). Eighteen patients (94.7%) had complete response and one patient (5%) had partial response. Nine patients (47.4%) received 3 cycles of adjuvant chemotherapy. Fifteen patients (78.9%) had acute grade 3 - 4 hematologic toxicities. Other acute grade 3 toxicities were 4 nausea, 3 vomiting, 2 electrolyte imbalance, 2 fatigue and 2 diarrhea. No patient died from acute toxicity. At last follow up time, 13 patients were alive with no disease. Four patients have died of progression of disease and 2 patients have died of other causes. The median follow up time was 56.4 months (range, 14.8 - 65.9). The 4 year survival rate and 4 year progression free survival rate was 78.9% and 78.3%, respectively. The 4 year cause-specific survival rate was 83.9%. None of the patients had any late grade . 3 toxicity. Conclusions: Consolidation chemotherapy with ifosfamide and cisplatin in locally advanced squamous cell carcinoma of the cervix uteri showed interesting results. A randomized control trial with additional concomitant medication such as a hematopoietic growth factor could be considered to prove benefit. Author Disclosure: P. Mahasittiwat: B. Research Grant; Medication support by Baxter Oncology. N. Ieumwananonthachai: None. J. Setakornnukul: None. N. Soontornpong: None. S. Udompunturak: None. P. Pattaranutraporn: None.
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Outcomes For Cervical Cancer Patients Treated With Extended Field Intensity Modulated Radiation Therapy And Concurrent Cisplatin
L. Jensen1, M. D. Hasselle2, B. S. Rose1, S. K. Nath1, Y. Hasan2, C. M. Yashar1, A. J. Mundt1, L. K. Mell1 1
University of California San Diego, La Jolla, CA, 2University of Chicago, Chicago, IL
Purpose/Objective(s): Extended field radiotherapy for cervical cancer is limited by high rates of toxicity and poor outcomes. Intensity modulated extended field radiation therapy (EF-IMRT) may reduce toxicity and permit more intensive systemic therapy. Here we report outcomes and toxicity for cervical cancer patients treated with EF-IMRT. Materials/Methods: Twenty-one patients treated with EF-IMRT and concurrent weekly cisplatin from 2003 - 2010 were included. Overall survival (OS) and disease free survival (DFS) were estimated using the Kaplan-Meier method. Time to locoregional failure (LRF) was defined as time to first evidence of disease recurrence in the pelvis or para-aortic region. LRF, distant
S452
2503
Volume 81, Number 2, Supplement, 2011
Post-therapy Positron Emission Tomography may Obviate the Need for Conventional Follow-up in Patients Receiving Chemoradiation for Advanced Cervical Cancer
S. Siva, A. Herschtal, J. Thomas, D. Bernshaw, S. Gill, R. Hicks, K. Narayan Peter MacCallum Cancer Centre, East Melbourne, Australia Purpose/Objective(s): A study was undertaken to investigate the detection of relapse and survival outcomes in patients with advanced cervical cancer treated with curative intent chemoradiotherapy, and evaluated with a post-therapy 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Materials/Methods: Between January 2002 and June 2007, 105 consecutive patients were prospectively enrolled into a registry study designed to assess outcomes of chemoradiotherapy. A FDG-PET scan was performed between 3 and 12 months post-treatment (median of 4.9 months) at clinician discretion. Tumor response was graded as complete metabolic response, partial metabolic response, or progressive metabolic disease. Results: The median follow-up was 36 months. At post-therapy FDG-PET, 73 patients had a complete metabolic response (70%), 10 patients had a partial metabolic response (9%), and 22 patients had progressive metabolic disease (21%). Cancer specific survival at 3 years was 81% in all patients, and 98% for those with a complete metabolic response. Overall survival at 3 years was 77% in all patients, and 95% for those with a complete metabolic response. On multivariate analysis, complete metabolic response (P \.0001) and pretreatment tumor volume (P = .041) were strong predictors for overall survival. The number of involved lymph nodes (P \.005) and International Federation of Gynecology and Obstetrics stage (P = .04) were predictive of relapse-free survival. Patients with complete metabolic response had a distant failure rate 36-fold less than those with partial metabolic response (P \.0001). After complete metabolic response, only 1 patient (1.6%) relapsed without symptoms and was detected through routine physical examination. This patient was successfully salvaged and had no further evidence of disease. In total, 18 patients relapsed at a single site, and 13 underwent salvage therapies, with a 3-year survival of 67%. Conclusions: The presence of a complete metabolic response at post-therapy FDG-PET is a powerful predictor for survival after chemoradiation. The very low rate of recurrence in patients with a complete metabolic response justifies a conservative follow-up approach for these patients, because relapse is usually symptomatic and is not detected by routine clinical review. Author Disclosure: S. Siva: None. A. Herschtal: None. J. Thomas: None. D. Bernshaw: None. S. Gill: None. R. Hicks: None. K. Narayan: None.
2504
Phase II Consolidation Chemotherapy With Ifosfamide and Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Cervix Uteri
P. Mahasittiwat, N. Ieumwananonthachai, J. Setakornnukul, N. Soontornpong, S. Udompunturak, P. Pattaranutraporn Department of Radiology, Division of Radiation Oncology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Purpose/Objective(s): The role of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced cervical carcinoma is controversial. This study was to evaluate the efficacy and toxicity of consolidation chemotherapy with ifosfamide and cisplatin in locally advanced squamous cell carcinoma of the cervix uteri. Materials/Methods: The prospective study was performed between October 2005 and November 2006 in Siriraj Hospital, Mahidol University, Thailand based on IRB approval. Pretreatment evaluation included physical examination, punch biopsies, cystoscopy, abdominal CT, CXR and blood chemistry. Patients received concurrent cisplatin (40 mg/m2) weekly with radiotherapy plus 3 cycles of adjuvant cisplatin (75 mg/m2) and ifosfamide (5000 mg/m2). Radiotherapy was composed of external RT and 4 fractions of HDR intracavitary brachytherapy with 80 - 85 Gy of point A dose. Treatment response (RECIST criteria) was evaluated by clinical, abdominal CT and cervical biopsies. Survival analysis was calculated by Kaplan- Meier method. Results: Nineteen patients with stage IIB (21%) and IIIB (79%) were enrolled in this study. The median of age was 47 years (range, 34 - 60). Eighteen patients (94.7%) had complete response and one patient (5%) had partial response. Nine patients (47.4%) received 3 cycles of adjuvant chemotherapy. Fifteen patients (78.9%) had acute grade 3 - 4 hematologic toxicities. Other acute grade 3 toxicities were 4 nausea, 3 vomiting, 2 electrolyte imbalance, 2 fatigue and 2 diarrhea. No patient died from acute toxicity. At last follow up time, 13 patients were alive with no disease. Four patients have died of progression of disease and 2 patients have died of other causes. The median follow up time was 56.4 months (range, 14.8 - 65.9). The 4 year survival rate and 4 year progression free survival rate was 78.9% and 78.3%, respectively. The 4 year cause-specific survival rate was 83.9%. None of the patients had any late grade . 3 toxicity. Conclusions: Consolidation chemotherapy with ifosfamide and cisplatin in locally advanced squamous cell carcinoma of the cervix uteri showed interesting results. A randomized control trial with additional concomitant medication such as a hematopoietic growth factor could be considered to prove benefit. Author Disclosure: P. Mahasittiwat: B. Research Grant; Medication support by Baxter Oncology. N. Ieumwananonthachai: None. J. Setakornnukul: None. N. Soontornpong: None. S. Udompunturak: None. P. Pattaranutraporn: None.
2505
Outcomes For Cervical Cancer Patients Treated With Extended Field Intensity Modulated Radiation Therapy And Concurrent Cisplatin
L. Jensen1, M. D. Hasselle2, B. S. Rose1, S. K. Nath1, Y. Hasan2, C. M. Yashar1, A. J. Mundt1, L. K. Mell1 1
University of California San Diego, La Jolla, CA, 2University of Chicago, Chicago, IL
Purpose/Objective(s): Extended field radiotherapy for cervical cancer is limited by high rates of toxicity and poor outcomes. Intensity modulated extended field radiation therapy (EF-IMRT) may reduce toxicity and permit more intensive systemic therapy. Here we report outcomes and toxicity for cervical cancer patients treated with EF-IMRT. Materials/Methods: Twenty-one patients treated with EF-IMRT and concurrent weekly cisplatin from 2003 - 2010 were included. Overall survival (OS) and disease free survival (DFS) were estimated using the Kaplan-Meier method. Time to locoregional failure (LRF) was defined as time to first evidence of disease recurrence in the pelvis or para-aortic region. LRF, distant