A.M. Quick

Primary radiation therapy for medically inoperable patients with clinical stage I and II endometrial carcinoma

OBJECTIVE To determine the outcomes associated with primary radiation therapy for medically inoperable, clinical stage I and II, endometrial adenocarcinoma (EAC). METHODS A multi-institution, retrospective chart review from January 1997 to January 2009 was performed. Overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS) and time to progression (TTP) were assessed using the Kaplan-Meier method. Disease-specific survival was analyzed using a competing risks approach. RESULTS Seventy-four patients were evaluable. The median age and BMI were 65 years (range 36-92 years) and 46 kg/m(2) (range 23-111 kg/m(2)), respectively. 85.1% had severe systemic disease, most frequently cardiopulmonary risk and morbid obesity. With a mean follow-up of 31 months, 13 patients (17.6%) experienced a recurrence. The median PFS and OS were 43.5 months and 47.2 months, respectively. Overall, 35 women died, including 4 women who died of unknown cause. Of the remaining 31 women, 7 patients (9.5%) died of disease, while 24 died of other causes (32.4%). The hazard ratio comparing the risk of death due to other causes to the risk of death due to disease was 3.4 (95% CI 1.4-9.4, p=0.003). Among patients who are alive three years after diagnosis, 14% recurred and the conditional recurrence estimate did not exceed 16%. CONCLUSIONS Primary radiation therapy for clinical stage I and II EAC is a feasible option for medically inoperable patients and provides disease control, with fewer than 16% of surviving patients experiencing recurrence.

Abstract P3-12-01: Locoregional failure rates do not vary by breast cancer subtype after mastectomy in a modern cohort of patients with T1-2 tumors with 1-3 pathologically involved lymph nodes

Purpose/Objective(s): A recent meta-analysis of 22 randomized trials accrued between 1964-86 demonstrated significantly higher rates of locoregional failure (LRF), total failure (TF) and breast-cancer mortality in women with 1-3 positive (+) axillary lymph nodes (ALN) who did not receive radiotherapy after mastectomy (mast.). Given the improvements in diagnostic and therapeutic approaches, the challenge today is whether breast cancer patients with T1-T2 tumors with 1-3+ ALN have similar substantial risk that routinely warrants the delivery of post mastectomy radiotherapy (PMRT). We further set out to explore whether the risk of failure varies by breast cancer subtype. Materials/Methods: We reviewed patients with pathologic T1-2N1 breast cancer treated with initial mast. and adjuvant systemic therapy (ST) from 2000-2013. The primary endpoint was LRF, defined as a recurrence in either the ipsilateral chestwall or regional lympatics (axillary, internal mammary, or supraclavicular nodes). Secondary endpoints include rates of TF (LRF or distant metastases), disease-free survival (DFS, failure or death), and overall survival (OS). Patients were classified into 3 basic subtypes: hormone receptor positive/HER2 negative (HR+), HER2 positive (HER2+), and triple negative (TN). Survival analysis was performed using the Kaplan-Meier method. The log-rank test was used to compare survival between groups. Results : We identified 550 eligible patients from our prospectively maintained cancer registry. Median follow-up was 5 years. Baseline characteristics included median age 53 yrs, 61% pathologic T2, 39% grade 3, 48% with lymphovascular invasion. Subtypes included 72% HR+ (n=393), 16% HER2+ (n=89), 12% TN (n=66) and 0.4% unknown (n=2). Treatment included chemotherapy in 78% (n=428), PMRT in 15% (n=82), and anti-endocrine therapy in 70% (n=385). A median of 18 ALN (range, 1-68) were removed, 10% (N=55) had sentinel-lymph node biopsy only, and 17%(N=95) had micrometastases (N1mic) only. A total of 296 pts had 1+ node, 165 pts 2+ nodes and 89 pts 3+ nodes. The 5 yr LRF rate for the entire cohort was 3.9% and patients with 1+, 2+, and 3+ nodes had 5 yr LRF of 2.6%, 4.7% and 6.4%, respectively (p=0.79). The 5 yr LRF for HR+, HER2+ and TN was 3.9%, 1.5%, and 6.6%, respectively (p=0.39). When stratified by 1+, 2+ or 3+ nodes, the 5 yr LRF for HR+ vs. HER2+ vs. TN were 2.4%, 6.8%, and 0% vs. 5.8%, 15.4%, and 0% vs. 5.7%, 0%, and 4.8%, p=0.43. The 5 yr TF, DFS, and OS rates for HR+, HER2+ and TN were 90.5% vs. 88.5%. vs. 83.6% (p=0.76); 84.9% vs. 82.6% vs. 79.2% (p=0.85); and 91.4% vs. 86.2% vs. 81.3% (p=0.83). Conclusions : In a cohort of patients with T1-2N1 breast cancer treated with modern therapy, we found low rates of LRF which did not vary amongst HR+, HER2+ and TN patients. In particular, HR+ patients with 1+ LN had extremely low rates of LRF Given these low recurrence rates, caution should be given in routinely recommending PMRT for every woman with 1-3+ ALN after mast. and adjuvant ST. Citation Format: Bazan JG, Majithia L, Quick AM, Terando AM, Agnese D, Mrozek E, Farrar W, White JR. Locoregional failure rates do not vary by breast cancer subtype after mastectomy in a modern cohort of patients with T1-2 tumors with 1-3 pathologically involved lymph nodes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-01.

Rates of unacceptable variation (UV) of normal tissue constraints in patients undergoing chest wall/breast and regional nodal irradiation (RNI) in a routine clinical practice.

67 Background: TheNSABP B51/RTOG 1304 clinical trial defines dose-volume constraints for targets/normal tissue receiving RNI. We sought to evaluate UV rate in normal tissue based on the NSABP B51/RTOG 1304 protocol in patients receiving chestwall/breast (CW/B) and RNI in daily practice. METHODS Treatment records of CW/B+RNI patients from 2/2012-5/2015 were studied for: CW or B radiotherapy (RT), RT type (intensity modulated [IMRT] or 3D conformal [3DCRT]), internal mammary node (IMN) inclusion, primary site boost, and nodal boost. No case is enrolled on B51/1304. Dose volume histogram (DVH) was analyzed for the rate of ≥ 1 UV for the following normal tissue constraints: Heart mean dose ≤ 5 Gy; ipsilateral lung (IL): V20 ≤ 35%, V10 ≤ 60%, V5 ≤ 70%; contralateral lung (CL) V5 ≤ 15%; contralateral breast (CB) V4.1 ≤ 5%. Logistic regression is used to test the association between UV and key variables. RESULTS 203 consecutive cases received CW/B+RNI (105 left, 98 right). RT was to CW in 170 (84%), B in 33 (16%), primary site boost 133 (66%), and IMN 170 (84%). 38 (19%) received IMRT and 14 (6.9%) had a nodal boost. 46 patients (22.6%) had ≥ 1 UV. 19 patients (9.4%) had ≥ 2 UV, all in IMRT patients. 2 patients (1.0%) had a heart UV at 5.2 Gy and 5.6 Gy. The most common UV was CB (n = 32, 15.7%) and IL V5 (n = 22, 10.8%). Higher UV rates are associated with use of IMRT (vs. 3DCRT): 86.8% vs. 7.9%, OR = 77.2 (95% CI 25.7-231.4, p < 0.0001); IMN irradiation: OR = 11.5 (95% CI 1.5-86.8, p = 0.02); and use of nodal boost: OR = 7.4 (95% CI 2.3-23.4, p = 0.001). The most common UVs in IMRT cases are CB (n = 27, 71%), IL V5 (n = 19, 50%), CL V5 (n = 14, 37%) and for 3DCRT are IL V20 (n = 5, 3%), CB (n = 5, 3%) and IL V5 (n = 3, 1.8%). On multivariate analysis, use of IMRT (OR = 64.7, 95% CI 20.8-201.5, p < 0.001) and use of nodal boost (OR = 5.5, 95% CI 1.1-27.1, p = 0.04) but not IMN irradiation (OR = 2.7, 95% CI 0.3-22.0, p = 0.35) were independently associated with higher UV rate. CONCLUSIONS The rate of UV per B51/1304 criteria with 3DCRT in routine clinical practice is low (7.9%). Women treated with IMRT had a significantly higher overall UV rate and clinicians should be aware of this as they initiate treatment planning for RNI.

Locoregional failure rates after mastectomy for breast cancer patients with T1-2 tumors and axillary nodal microscopic metastases.

64 Background: The indications for postmastectomy radiotherapy (PMRT) are expanding to include patients 1-3 axillary nodal metastases (ALN). Improvements in diagnostic evaluation have led to increasing numbers of breast cancer (BC) patients who are found to have microscopic nodal metastases (N1mic). The challenge today is whether these BC patients have risk that warrants the routine delivery of PMRT. METHODS We reviewed patients with pathologic T1-2N1 BC treated with initial mastectomy (mast) and adjuvant systemic therapy (ST) from 2000-2013. The primary endpoint was locoregional failure (LRF), defined as a recurrence in either the ipsilateral chestwall or regional lymphatics (axillary, internal mammary, or supraclavicular). Secondary endpoints were disease-free survival (DFS, failure or death) and overall survival (OS). The log-rank test was used to compare survival between groups. RESULTS We identified 550 eligible patients from our prospectively maintained cancer registry with 5 year median follow-up. 95 patients (17%) had N1mic disease. Baseline characteristics include: median age 53 yrs, 61% pathologic T2, 39% grade 3, 72% hormone receptor positive, 16% HER2+, 12% triple-negative. Treatment included chemotherapy in 78% (n = 428), PMRT in 15% (n = 82), and anti-endocrine therapy in 70% (n = 385). A median of 18 ALN (range, 1-68) were removed. Among the patients with N1mic disease, 81 had 1+ node, 13 had 2+ nodes, and 1 had 3+ nodes. The 5 yr LRF was 0% for patients with N1mic disease vs. 4.6% in those macro metastases (p = 0.84). The 5 yr LRF rate for the entire cohort was 3.9%; patients with 1+, 2+, and 3+ nodes had 5 yr LRF of 2.6%, 4.7% and 6.4%, respectively (p = 0.79). Patients with N1mic disease had a trend towards improved DFS (91.6% vs. 82.3%, p = 0.07) and significantly improved OS (96.9% vs. 87.6%, p = 0.03) compared to patients with macrometastases. CONCLUSIONS In a cohort of patients with T1-2,N1 BC treated with modern therapy, we found overall low rates of LRF. Patients with N1mic disease had no LRF events and improved OS compared to patients with macrometastases. These findings support that PMRT should not be routinely recommended for N1mic BC patients with T1-2 tumors.

Abstract 3726: Sexual function following surgery with or without intracavitary vaginal brachytherapy for early stage endometrial carcinoma

Objective: The purpose of this research study is to describe the effects of intracavitary vaginal brachytherapy (IVB) on sexual function and quality of life of women with early stage endometrial cancer. Methods: 156 women, ages 20-75, with FIGO stage I to II endometrial cancer from 2002-2007 treated with surgery alone or surgery and IVB were identified and mailed questionnaires. Quality of life and sexual function were measured using the previously validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, the Cervix Cancer module, and the Sexual function-Vaginal changes Questionnaire. Pertinent data from prior surgery and radiation treatments were abstracted. Fisher9s exact tests were used to evaluate the association of the variables. Results: In total, 87 surveys (56%) were returned. 70 patients completed the survey, 17 in the IVB arm and 53 in the surgery alone arm. In general, the overall quality of life was excellent in both treatment arms, with few patients reporting anxiety, depression, pain, or limitations of activities of daily living. However, 12% of patients treated with IVB (2/17) reported difficulty controlling their bowels compared to 8% of surgery alone patients (4/53) (p=0.037) and 30% (5/ 17) vs. 13% (7/ 53) reported edema in one or both legs (p=0.040). 55% of respondents had not been sexually active in the previous month (11/17, 65% IVB and 27/52, 52 % surgery) (p=0.6). Of sexually active patients (45%, N=31), 43% of IVB (3/7) and 42% (11/26) of surgery alone patients complained of vagina dryness during sexual activity (p=0.935) and 29% (2/7) vs. 20 % (5/25) felt their vagina was short (p=0.635). While 29% in both cohorts reported vaginal tightness, 14% of patients in both treatment groups described intercourse as painful. Sexual activity was enjoyable for only 43% (3/7) of the IVB patients and 60% (17/28) of the surgery alone patients (p=0.549). Conclusions: Overall the quality of life of women with early stage endometrial cancer is excellent following surgery or IVB. Patients treated with IVB report more bowel toxicity and lower extremity edema. Patients in both treatment arms report similar vaginal changes that affect sexual function. It is anticipated that additional data from other institutions participating in the study will allow more definitive exploration of these issues. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3726.