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Prognostic factors in stage 2B–3B cervical cancer in an era of chemoradiation
Abstracts / Gynecologic Oncology 127 (2012) S1–S34
Radiographic response of pelvic and para-aortic lymphadenopathy to a radiation boost in the definitive management of locally advanced cervical cancer D. Rash, Y. Lee, R. Valicenti, M. Mathai, J. Mayadev. Department of Radiation Oncology, University of California Davis, USA. Objectives: To evaluate the radiographic response by CT or PET/CT scan of suspicious pelvic and para-aortic lymph nodes in patients with locally advanced cervical cancer treated with concurrent chemoradiation. Methods: From 2007 to 2011, 68 patients were treated with chemoradiation for locally advanced cervical cancer, of which 40 patients had pelvic and para-aortic lymphadenopathy. For 18 patients, pre- and post-therapy CT scans with contrast and/or PET/ CT scans were available for review. Pretreatment lymph nodes with a short axis measurement ≥1 cm by CT scan or with an SUV N 3 by PET scan were considered pathologically involved. The total external beam radiation dose delivered to involved lymph nodes was recorded. Response to treatment was determined by the change in size of the lymph node by short axis and change in SUV activity. The patterns of failure, time to recurrence, overall survival, and diseasefree survival were determined. Results: 64 lymph nodes were identified as suspicious for metastatic involvement by pretreatment imaging characteristics. The external beam radiation dose delivered to these lymph nodes ranged from 0 to 60 Gy with a mean dose of 55 Gy. Pelvic lymph nodes were treated with a higher external beam dose than para-aortic lymph nodes (mean dose 55.3 Gy versus 51.7 Gy, respectively). There was no correlation between the dose delivered to the lymph node and the change in size of the lymph node along the short axis following treatment (R = 0.03). For lymph nodes that received ≤54 Gy the mean change in size was − 0.83 cm; for lymph nodes that received N54 Gy the mean change in size was − 0.96 cm (p = 0.53). There was no association between the dose delivered and the change in PET activity. 100% of lymph nodes demonstrated a response to delivered dose. 74% of lymph nodes demonstrated a complete resolution of abnormal SUV following chemoradiation with a mean radiation dose delivered of 51 Gy. Median follow up was 15 months. Local control at 1 year was 93%, disease free survival at 1year was 75.2% and overall survival at 2-years was 86%. 33% of patients developed distant metastases within 18 months of diagnosis. All patients that died developed distant metastases without pelvic failure. Conclusion: The likelihood of response to concurrent chemoradiation in macroscopically enlarged or PET-avid lymph nodes does not correlate with radiation boost dose escalation beyond 54 Gy.
doi:10.1016/j.ygyno.2012.07.008
Prognostic factors in stage 2B–3B cervical cancer in an era of chemoradiation E. Bishop, E. Nugent, C. Mathews, R. Farrell, L. Landrum, D. McMeekin. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The University of Oklahoma Health Science Center, Oklahoma City, OK, USA. Objectives: To identify the clinicopathologic factors associated with recurrence in stage IIB–IIIB cervical cancer treated with chemoradiation in order to define risk groups. Methods: A single institution database of 537 pts with cervical cancer from 1998 to 2010 was created. Patients with stage IIB–IIIB cervical cancer (n = 133 pts (25%)) treated with chemoradiation were identified. Clinicopathologic variables were collected and correlated
S3
with response rates, patterns of failure, progression free survival (PFS), and overall survival (OS). Univariate and multivariate analyses were conducted to identify the prognostic factors for PFS within subsets of patients. Kaplan–Meier survival curves were calculated and compared using log-rank tests. Results: A total of 133 pts had stage IIB (56%) to IIIB (39%) disease. All pts underwent biopsy and diagnostic imaging. The median age was 53 yrs, 82% had squamous histology, and 16% had adenocarcinoma. In addition, 52 pts (39%) underwent lymph node dissection (LND). Overall, 29/52 (56%) had positive nodes, with 27% para-aortic positivity and 56% pelvic positivity among those with LND. ChemoXRT was administered in 94%, XRT alone in 4%, and no treatment in 2%. Among those receiving treatment, 15% received extended field XRT. With a median f/u of 25 months, 43% of patients recurred and 36 month PFS was 55% for IIB and 35% for IIIB disease (p = 0.01). Median OS for IIB disease was 59 months while median OS for IIIB disease was 24 months (p = 0.002). Among patients who recurred, 31% recurred locally (vagina or pelvis), 18% recurred in the abdomen, and 22% had distant failures. For patients who underwent LND there was no difference in PFS between lymph node positive and lymph node negative patients (p = 0.87). In multivariate analysis, we did not identify significant associations between clinicopathologic factors (LVSI, grade, histology, and tumor size) and recurrence in this population. Conclusion: In stage IIB–IIIB cervical cancer managed in an era of chemoradiation, we were unable to use standard clinicopathologic variables to define risk groups. New prognostic models including tissue/serum biomarkers are needed to create risk models in this patient population. The finding that patients with surgically assessed positive nodes had similar outcomes to those with negative nodes is intriguing, and suggests that LND may play a role in IIB–IIIB disease.
doi:10.1016/j.ygyno.2012.07.009
Examining the role of extra peritoneal lymph node dissection and IMRT in women with cervical cancer E. Dickson, C. Evans, R. Isaksson Vogel, C. Shideman, K. Dusenbery, M. Geller. University of Minnesota, Minneapolis, MN, USA. Objectives: To determine the difference in disease free and overall survival of patients with cervical cancer treated with extra peritoneal lymph node dissection (EPLND) vs. intensity modulated radiation therapy (IMRT). Methods: A chart review was performed on all patients diagnosed with stage IB–IV cervical cancer who had a pre-treatment imaging study from November 2005 to September 2011. Patients were placed into groups according to treatment modality (EPLND ± EBRT vs. IMRT alone); clinical and demographic characteristics were compared. Outcomes of interest were overall survival (OS) and progression free survival (PFS) and comparisons were stratified on stage (low stages: stage IB and II disease; high stages: III and IV). Univariate and ageadjusted Cox proportional hazard models were performed. Odds ratios (OR) with 95% confidence intervals (CI) and p-values were reported. Results: Eighty-one patients were included; 31 in the IMRT group and 50 in the EPLND. The IMRT group had 14 with low stage disease (7 IB and 7 II) and 17 with high stage (12 III and 5 IV). In the EPLND group, 40 had low stage disease (31 IB, 9 II) and 10 had high stage disease (8 III, 2 IV). Women treated with IMRT had significantly higher stage (p = 0.0022) and grade disease (p = 0.0507) than patients treated with EPLND. Women with lower stage (IB/II) cervix cancer were significantly more likely to experience progression, recurrence or death when treated with IMRT compared to those who received
Radiographic response of pelvic and para-aortic lymphadenopathy to a radiation boost in the definitive management of locally advanced cervical cancer D. Rash, Y. Lee, R. Valicenti, M. Mathai, J. Mayadev. Department of Radiation Oncology, University of California Davis, USA. Objectives: To evaluate the radiographic response by CT or PET/CT scan of suspicious pelvic and para-aortic lymph nodes in patients with locally advanced cervical cancer treated with concurrent chemoradiation. Methods: From 2007 to 2011, 68 patients were treated with chemoradiation for locally advanced cervical cancer, of which 40 patients had pelvic and para-aortic lymphadenopathy. For 18 patients, pre- and post-therapy CT scans with contrast and/or PET/ CT scans were available for review. Pretreatment lymph nodes with a short axis measurement ≥1 cm by CT scan or with an SUV N 3 by PET scan were considered pathologically involved. The total external beam radiation dose delivered to involved lymph nodes was recorded. Response to treatment was determined by the change in size of the lymph node by short axis and change in SUV activity. The patterns of failure, time to recurrence, overall survival, and diseasefree survival were determined. Results: 64 lymph nodes were identified as suspicious for metastatic involvement by pretreatment imaging characteristics. The external beam radiation dose delivered to these lymph nodes ranged from 0 to 60 Gy with a mean dose of 55 Gy. Pelvic lymph nodes were treated with a higher external beam dose than para-aortic lymph nodes (mean dose 55.3 Gy versus 51.7 Gy, respectively). There was no correlation between the dose delivered to the lymph node and the change in size of the lymph node along the short axis following treatment (R = 0.03). For lymph nodes that received ≤54 Gy the mean change in size was − 0.83 cm; for lymph nodes that received N54 Gy the mean change in size was − 0.96 cm (p = 0.53). There was no association between the dose delivered and the change in PET activity. 100% of lymph nodes demonstrated a response to delivered dose. 74% of lymph nodes demonstrated a complete resolution of abnormal SUV following chemoradiation with a mean radiation dose delivered of 51 Gy. Median follow up was 15 months. Local control at 1 year was 93%, disease free survival at 1year was 75.2% and overall survival at 2-years was 86%. 33% of patients developed distant metastases within 18 months of diagnosis. All patients that died developed distant metastases without pelvic failure. Conclusion: The likelihood of response to concurrent chemoradiation in macroscopically enlarged or PET-avid lymph nodes does not correlate with radiation boost dose escalation beyond 54 Gy.
doi:10.1016/j.ygyno.2012.07.008
Prognostic factors in stage 2B–3B cervical cancer in an era of chemoradiation E. Bishop, E. Nugent, C. Mathews, R. Farrell, L. Landrum, D. McMeekin. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The University of Oklahoma Health Science Center, Oklahoma City, OK, USA. Objectives: To identify the clinicopathologic factors associated with recurrence in stage IIB–IIIB cervical cancer treated with chemoradiation in order to define risk groups. Methods: A single institution database of 537 pts with cervical cancer from 1998 to 2010 was created. Patients with stage IIB–IIIB cervical cancer (n = 133 pts (25%)) treated with chemoradiation were identified. Clinicopathologic variables were collected and correlated
S3
with response rates, patterns of failure, progression free survival (PFS), and overall survival (OS). Univariate and multivariate analyses were conducted to identify the prognostic factors for PFS within subsets of patients. Kaplan–Meier survival curves were calculated and compared using log-rank tests. Results: A total of 133 pts had stage IIB (56%) to IIIB (39%) disease. All pts underwent biopsy and diagnostic imaging. The median age was 53 yrs, 82% had squamous histology, and 16% had adenocarcinoma. In addition, 52 pts (39%) underwent lymph node dissection (LND). Overall, 29/52 (56%) had positive nodes, with 27% para-aortic positivity and 56% pelvic positivity among those with LND. ChemoXRT was administered in 94%, XRT alone in 4%, and no treatment in 2%. Among those receiving treatment, 15% received extended field XRT. With a median f/u of 25 months, 43% of patients recurred and 36 month PFS was 55% for IIB and 35% for IIIB disease (p = 0.01). Median OS for IIB disease was 59 months while median OS for IIIB disease was 24 months (p = 0.002). Among patients who recurred, 31% recurred locally (vagina or pelvis), 18% recurred in the abdomen, and 22% had distant failures. For patients who underwent LND there was no difference in PFS between lymph node positive and lymph node negative patients (p = 0.87). In multivariate analysis, we did not identify significant associations between clinicopathologic factors (LVSI, grade, histology, and tumor size) and recurrence in this population. Conclusion: In stage IIB–IIIB cervical cancer managed in an era of chemoradiation, we were unable to use standard clinicopathologic variables to define risk groups. New prognostic models including tissue/serum biomarkers are needed to create risk models in this patient population. The finding that patients with surgically assessed positive nodes had similar outcomes to those with negative nodes is intriguing, and suggests that LND may play a role in IIB–IIIB disease.
doi:10.1016/j.ygyno.2012.07.009
Examining the role of extra peritoneal lymph node dissection and IMRT in women with cervical cancer E. Dickson, C. Evans, R. Isaksson Vogel, C. Shideman, K. Dusenbery, M. Geller. University of Minnesota, Minneapolis, MN, USA. Objectives: To determine the difference in disease free and overall survival of patients with cervical cancer treated with extra peritoneal lymph node dissection (EPLND) vs. intensity modulated radiation therapy (IMRT). Methods: A chart review was performed on all patients diagnosed with stage IB–IV cervical cancer who had a pre-treatment imaging study from November 2005 to September 2011. Patients were placed into groups according to treatment modality (EPLND ± EBRT vs. IMRT alone); clinical and demographic characteristics were compared. Outcomes of interest were overall survival (OS) and progression free survival (PFS) and comparisons were stratified on stage (low stages: stage IB and II disease; high stages: III and IV). Univariate and ageadjusted Cox proportional hazard models were performed. Odds ratios (OR) with 95% confidence intervals (CI) and p-values were reported. Results: Eighty-one patients were included; 31 in the IMRT group and 50 in the EPLND. The IMRT group had 14 with low stage disease (7 IB and 7 II) and 17 with high stage (12 III and 5 IV). In the EPLND group, 40 had low stage disease (31 IB, 9 II) and 10 had high stage disease (8 III, 2 IV). Women treated with IMRT had significantly higher stage (p = 0.0022) and grade disease (p = 0.0507) than patients treated with EPLND. Women with lower stage (IB/II) cervix cancer were significantly more likely to experience progression, recurrence or death when treated with IMRT compared to those who received