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Outcome and pattern of failure in pathological stage I-II papillary serous carcinoma of the endometrium: implications for adjuvant radiation therapy
Proceedings of the 44th Annual ASTRO Meeting
Conclusions: The amount of small bowel spared from high dose radiation with IMRT decreases markedly with relatively small increases in the margins used to determine the initial target volume. This finding emphasizes the importance of accurate definition of target volumes and the need for highly accurate methods to position the pelvis. Even when similar margins are used to design the PTV, IMRT tends to produce less sparing of normal tissues in obese patients. This finding combined with the poorer setup reproducibility in such patients suggests that they would achieve less benefit from IMRT treatment than thinner patients.
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Outcome and Pattern of Failure in Pathological Stage I-II Papillary Serous Carcinoma of the Endometrium: Implications for Adjuvant Radiation Therapy
N. Mehta, A.J. Mundt Department of Radiation and Cellular Oncology, University of Chciago, Chicago, IL Purpose/Objective: Papillary serous (PS) carcinoma of the endometrium is known to have a poor prognosis with a high rate of recurrence. Most patients present with advanced stage (FIGO stage III-IV) tumors and there is little information on outcome and optimal treatment of women with early stage disease. Patients with early stage disease are often grouped with advanced disease patients and treated with whole abdomen radiation therapy (WART) ⫹/- chemotherapy in prior studies. Furthermore, most studies that have analyzed early stage disease have grouped PS with clear cell histology. As a result, the optimal management of these patients remains less defined. The purpose of this study is to evaluate the outcome and patterns of failure in women with pathological stage I-II PS carcinoma and discuss the implications for adjuvant radiation therapy (RT). Materials/Methods: Between 1990 and 2001, 868 endometrial carcinoma patients underwent primary surgery at our institution. Sixty-eight had papillary serous histologies, among which 23 (2.7%) had pathological stage I-II disease. All underwent TAH-BSO and assessment of peritoneal cytology. None received preoperative RT. Pelvic and para-aortic lymph node sampling were preformed in 12 and 8 patients, respectively. FIGO stages were: 3 IA, 8 IB, 6 IC, 5 IIA, and 1 IIB. The depth of myometrial invasion included: 3 none, 10 ⱕ1/2, and 10 ⬎1/2. Cervical involvement was present in 6 patients. Adjuvant therapies included: 9 none, 10 RT (6 whole pelvic, 1 vaginal brachytherapy, 3 whole pelvic ⫹ vaginal brachytherapy), 4 chemotherapy (3 alone and 1 following whole pelvic RT), and 1 hormonal therapy alone. No patient received WART or para-aortic RT. Median follow-up was 38.7 months (range, 3-109 months). Results: The 5-year actuarial disease-free (DFS) and cause-specific (CSS) survivals for the entire group were 44% and 73.6%, respectively. Age, stage, and depth of myometrial invasion were not correlated with disease relapse. The overall failure rate was 35% (8/23). Five patients (22%) failed in the pelvis of which four relapsed in the vagina alone. There were no pelvic failures in patients treated with adjuvant RT. The 5-year actuarial pelvic recurrence rate was 27.5% and was 42.5% among the 13 women who did not receive RT compared with 0% among the 10 who did receive RT (p⫽0.06). Of note, patients treated with adjuvant RT had higher stage disease (p⫽0.02). Only 2 patients (8.7%) failed in the abdomen and both had a simultaneous distant recurrence. None had an isolated abdominal failure. The overall distant failure rate was 22% (5/23) and 4 of the failures occurred in patients who did not receive chemotherapy. Conclusions: Pathological stage I-II papillary serous carcinomas comprise a small percentage of patients with endometrial cancer. Although these women have organ-confined disease, recurrence is common particularly in the pelvis and distant sites. However, pelvic failure was effectively reduced by adjuvant pelvic RT. Unlike traditionally thought, abdominal recurrence was rare in our patients despite not delivering WART. The high rate of distant failure supports the use of chemotherapy. Our results suggest that the optimal approach to these patients is pelvic RT plus chemotherapy.
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Long Term Outcome of Adjuvant Whole Abdominopelvic Irradiation for Patients with Stage I/II Endometrial Cancer Harboring Poor Histological Subtypes including Serous-Papillary/Clear Cell
D. Krauss1, A. Martinez1, S. Weiner2, J. Stromberg1, C. Mitchell1, J. Jennings2, P. Chen1, A. Sherman2, D. Brabbins1 1 Dept. of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 2Dept. of Gynecological Oncology, William Beaumont Hospital, Royal Oak, MI Purpose/Objective: Endometrial cancer patients with serous-papillary and/or clear cell histology have a poor prognosis with low survival rates. The same poor outcome has been seen for those patients with endometrioid histology with both high grade and deep myometrial invasion. In an effort to improve the poor outcome of these patients, a trial of whole abdominal irradiation with a para-aortic, diaphragmatic, pelvic and vaginal boost (WAPI) was initiated in 1982. The purpose of this analysis was to evaluate the long-term results of treatment with adjuvant WAPI in patients at increased risk for abdominopelvic recurrence with specific attention to those individuals with stage I-II disease with serous papillary (S/P) and clear cell (C/C). Materials/Methods: In a prospective, nonrandomized trial, 45 patients with stage I-II endometrial cancer were identified who were felt to be at increased risk for intraabdominal or pelvic recurrence between 1/82 and 4/2000. The mean age at diagnosis was 64.3 yrs. All patients were surgically staged and treated. Thirty-three patients (73) were 1998 FIGO stage I and the remaining 12 (27%) stage II. Of the 45 patients 34 (76%) had either serous papillary (S/P) or clear cell (C/C histology). All patients with ⱕ 50% myometrial invasion possessed either a P/S or C/C histology. All adenocarcinoma patients (11) had both high grade lesions and deep myometrial invasion. Results: Mean follow-up for the entire group was 5.3 years (range 0.3-14.7). The 5-year overall survival (OS), disease-free survival (DFS) and cause specific survival (CSS) for all patients were 70%, 60% and 88% respectively. The table depicts the 5-year survival rates with the corresponding p-values (log-rank) from the Kaplan-Meyer analysis. No statistical differences were noted by histological subtypes. A total of 9 patients (20%) experienced recurrence with the first site of failure being extra-abominal lymph nodes (33%), lung (22%), abdomen/pelvis (11%), vagina (11%) and other (22%). 56% of recurrences occurred in those patients with S/P or C/C and 44% in those with adenocarcinoma p⫽0.638). Multivariate analysis (age,stage, grade, histology, extent of myometrial invasion, peritoneal cytology, and/or lymph node status as negative versus not done) demonstrated only age (p⫽0.036) to be of prognostic significance with respect to overall survival. No factors demonstrated prognostic significance in terms of either CSS or DFS. The majority of patients experience either acute grade I-2 GI toxicity or hematologic toxicity. Chronic toxicity was much less frequent although 14% experience grade 3 GI and 2% experienced grade 3 renal toxicities.
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Conclusions: The amount of small bowel spared from high dose radiation with IMRT decreases markedly with relatively small increases in the margins used to determine the initial target volume. This finding emphasizes the importance of accurate definition of target volumes and the need for highly accurate methods to position the pelvis. Even when similar margins are used to design the PTV, IMRT tends to produce less sparing of normal tissues in obese patients. This finding combined with the poorer setup reproducibility in such patients suggests that they would achieve less benefit from IMRT treatment than thinner patients.
69
Outcome and Pattern of Failure in Pathological Stage I-II Papillary Serous Carcinoma of the Endometrium: Implications for Adjuvant Radiation Therapy
N. Mehta, A.J. Mundt Department of Radiation and Cellular Oncology, University of Chciago, Chicago, IL Purpose/Objective: Papillary serous (PS) carcinoma of the endometrium is known to have a poor prognosis with a high rate of recurrence. Most patients present with advanced stage (FIGO stage III-IV) tumors and there is little information on outcome and optimal treatment of women with early stage disease. Patients with early stage disease are often grouped with advanced disease patients and treated with whole abdomen radiation therapy (WART) ⫹/- chemotherapy in prior studies. Furthermore, most studies that have analyzed early stage disease have grouped PS with clear cell histology. As a result, the optimal management of these patients remains less defined. The purpose of this study is to evaluate the outcome and patterns of failure in women with pathological stage I-II PS carcinoma and discuss the implications for adjuvant radiation therapy (RT). Materials/Methods: Between 1990 and 2001, 868 endometrial carcinoma patients underwent primary surgery at our institution. Sixty-eight had papillary serous histologies, among which 23 (2.7%) had pathological stage I-II disease. All underwent TAH-BSO and assessment of peritoneal cytology. None received preoperative RT. Pelvic and para-aortic lymph node sampling were preformed in 12 and 8 patients, respectively. FIGO stages were: 3 IA, 8 IB, 6 IC, 5 IIA, and 1 IIB. The depth of myometrial invasion included: 3 none, 10 ⱕ1/2, and 10 ⬎1/2. Cervical involvement was present in 6 patients. Adjuvant therapies included: 9 none, 10 RT (6 whole pelvic, 1 vaginal brachytherapy, 3 whole pelvic ⫹ vaginal brachytherapy), 4 chemotherapy (3 alone and 1 following whole pelvic RT), and 1 hormonal therapy alone. No patient received WART or para-aortic RT. Median follow-up was 38.7 months (range, 3-109 months). Results: The 5-year actuarial disease-free (DFS) and cause-specific (CSS) survivals for the entire group were 44% and 73.6%, respectively. Age, stage, and depth of myometrial invasion were not correlated with disease relapse. The overall failure rate was 35% (8/23). Five patients (22%) failed in the pelvis of which four relapsed in the vagina alone. There were no pelvic failures in patients treated with adjuvant RT. The 5-year actuarial pelvic recurrence rate was 27.5% and was 42.5% among the 13 women who did not receive RT compared with 0% among the 10 who did receive RT (p⫽0.06). Of note, patients treated with adjuvant RT had higher stage disease (p⫽0.02). Only 2 patients (8.7%) failed in the abdomen and both had a simultaneous distant recurrence. None had an isolated abdominal failure. The overall distant failure rate was 22% (5/23) and 4 of the failures occurred in patients who did not receive chemotherapy. Conclusions: Pathological stage I-II papillary serous carcinomas comprise a small percentage of patients with endometrial cancer. Although these women have organ-confined disease, recurrence is common particularly in the pelvis and distant sites. However, pelvic failure was effectively reduced by adjuvant pelvic RT. Unlike traditionally thought, abdominal recurrence was rare in our patients despite not delivering WART. The high rate of distant failure supports the use of chemotherapy. Our results suggest that the optimal approach to these patients is pelvic RT plus chemotherapy.
70
Long Term Outcome of Adjuvant Whole Abdominopelvic Irradiation for Patients with Stage I/II Endometrial Cancer Harboring Poor Histological Subtypes including Serous-Papillary/Clear Cell
D. Krauss1, A. Martinez1, S. Weiner2, J. Stromberg1, C. Mitchell1, J. Jennings2, P. Chen1, A. Sherman2, D. Brabbins1 1 Dept. of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, 2Dept. of Gynecological Oncology, William Beaumont Hospital, Royal Oak, MI Purpose/Objective: Endometrial cancer patients with serous-papillary and/or clear cell histology have a poor prognosis with low survival rates. The same poor outcome has been seen for those patients with endometrioid histology with both high grade and deep myometrial invasion. In an effort to improve the poor outcome of these patients, a trial of whole abdominal irradiation with a para-aortic, diaphragmatic, pelvic and vaginal boost (WAPI) was initiated in 1982. The purpose of this analysis was to evaluate the long-term results of treatment with adjuvant WAPI in patients at increased risk for abdominopelvic recurrence with specific attention to those individuals with stage I-II disease with serous papillary (S/P) and clear cell (C/C). Materials/Methods: In a prospective, nonrandomized trial, 45 patients with stage I-II endometrial cancer were identified who were felt to be at increased risk for intraabdominal or pelvic recurrence between 1/82 and 4/2000. The mean age at diagnosis was 64.3 yrs. All patients were surgically staged and treated. Thirty-three patients (73) were 1998 FIGO stage I and the remaining 12 (27%) stage II. Of the 45 patients 34 (76%) had either serous papillary (S/P) or clear cell (C/C histology). All patients with ⱕ 50% myometrial invasion possessed either a P/S or C/C histology. All adenocarcinoma patients (11) had both high grade lesions and deep myometrial invasion. Results: Mean follow-up for the entire group was 5.3 years (range 0.3-14.7). The 5-year overall survival (OS), disease-free survival (DFS) and cause specific survival (CSS) for all patients were 70%, 60% and 88% respectively. The table depicts the 5-year survival rates with the corresponding p-values (log-rank) from the Kaplan-Meyer analysis. No statistical differences were noted by histological subtypes. A total of 9 patients (20%) experienced recurrence with the first site of failure being extra-abominal lymph nodes (33%), lung (22%), abdomen/pelvis (11%), vagina (11%) and other (22%). 56% of recurrences occurred in those patients with S/P or C/C and 44% in those with adenocarcinoma p⫽0.638). Multivariate analysis (age,stage, grade, histology, extent of myometrial invasion, peritoneal cytology, and/or lymph node status as negative versus not done) demonstrated only age (p⫽0.036) to be of prognostic significance with respect to overall survival. No factors demonstrated prognostic significance in terms of either CSS or DFS. The majority of patients experience either acute grade I-2 GI toxicity or hematologic toxicity. Chronic toxicity was much less frequent although 14% experience grade 3 GI and 2% experienced grade 3 renal toxicities.
43