Citations

88 Background: There is not yet a consensus on the efficacy and safety of IMRT for the treatment of patients with esophageal carcinomas. We report on our experience with outcomes and toxicity with IMRT for these patients. Methods: Fifty-five patients with esophageal carcinoma were treated with IMRT at our institution from 12/2008 and 12/2014. Medical records were retrospectively reviewed. All patients received concurrent chemotherapy (majority 5-FU with oxaliplatin). Thirty-one (56%) patients underwent surgery. Fifty (91%) received 50.4 Gy in 28 fractions. Seventy-three percent of cases were adenocarcinoma. Regions include mid-thoracic (15%), lower thoracic (64%), and GE junction (22%). Clinical uT-stages were as follows: T1 (2%), T2 (20%), T3 (69%), and T4a (5%). Clinical N-stages were as follows: N0 (33%), N1 (53%), N2 (13%), and N3 (2%). Results: Median follow-up for all patients was 15 months (1.5 - 64.5) and 25.5 months (1.5 - 64.5) for patients who were alive at follow-up (n = 31). Fifty-one (93%) patients completed RT. Of the 31 patients who underwent surgery, 9 (29%) were found to have a complete pathologic response. Site of first recurrence was local (n = 2, 4%), regional (n = 3, 6%), and distant (n = 14, 26%). At 12 and 24 months, overall survival was 72% and 58%, freedom from recurrence was 78% and 65%, and freedom from distant recurrence was 78% and 68%. On univariate analysis, improved OS was noted with patients who underwent surgery (RR 0.29) or were cN0 (RR 0.27). Twenty eight patients (51%) experienced > / = CTCAE v.4grade 3 acute toxicity; notable were hematologic (n = 14, 25%), esophagitis (n = 6, 11%), acute coronary event (n = 1, 2%), and post-chemoRT pneumonia (n = 1, 2%). Fifteen patients (31%) experienced > grade 3 late toxicity; notable were esophageal stricture (n = 7, 14%), post-op pneumonia (n = 3, 6%), post-CRT pneumonia (n = 2, 4%), and COPD exacerbation (n = 1, 2%). Conclusions: Patient receiving IMRT with concurrent chemotherapy for esophageal carcinomas have good LC rates, with or without surgery. Majority of patients are able to finish treatment with acceptable rates of late toxicity. Patient who underwent surgery or were cN0 had better OS.

75 Background: The focus of palliative radiotherapy (RT) is on improving quality of life (QOL) for patients with serious illnesses by eliminating or decreasing physical symptoms. The importance of assessing distress levels in palliative care patients is recognized due to the relevance of QOL, as treatment is given to provide symptom-relief rather than curative results. We sought to identify the most common causes of patient reported distress during palliative RT. Methods: Retrospective review was performed for patients who received palliative RT from 11/1/2012 to 6/4/2015 for various types of metastatic cancer at our institution. All patients completed a Patient Reported Distress (PRD) questionnaire with 30 specific questions and an overall distress thermometer prior to beginning treatment. The PRD survey quantified 30 areas of current concern ranging in patient-reported values from 1 to 5 in addition to a linear analog measure from 0 to 10 of overall reported distress in the last month. Results: Completed PRD surveys were available for a total of 297 patients, 149 (50.2%) female and 148 (49.8%) male. All patients were undergoing external beam radiation therapy for treatment of metastatic disease. 49 (16%) received chemotherapy and 46 (9%) underwent surgery. Overall distress ranged from 0 to 10, with a median of 5.0. The mean distress scores for the top five concerns ranged from 1.4 to 2.7. Top distresses were “Fatigue” (2.7), “Pain that affects daily functioning” (2.6), “How will I feel during treatment” (2.5), “Sleep difficulties” (2.4), and “Out of pocket medical costs” (2.3). Least troubling symptoms were “Transportation” (1.4), “A loved one relying on me for their physical care” (1.5), “My job” (1.5), “Housing during treatment” (1.5), “Spirituality” (1.5), and “Anger” (1.5). Conclusions: Patients demonstrated concern for distress related to interruption of activities of normal life, such as tiredness and insomnia, pain, and overall burdens from treatment. Medical costs were also a major concern. Importantly, housing and transportation were not issues in the current study but could be of concern in other regions. Providers should be aware that patients’ primary concerns may not be directly related to the symptom being palliated.

211 Background: Distress is known to be elevated in patients receiving cancer therapy, such as palliative radiotherapy (PRT). Many patients will experience distress during treatment and it is not always addressed in part due to a lack of guidance regarding the significance of distress. Methods: All RT patients in our clinic are asked to complete a patient reported distress (PRD) survey during treatment course. PRD forms consist of 30 categorical questions that assess distress subscales. Patients have the option to rate each question from 1 (low distress) to 5 (high distress). The survey also includes the National Comprehensive Cancer Network distress thermometer, which allows patients to rate overall distress level from 0 (no distress) to 10 (extreme distress). Patients’ records were retrospectively reviewed to abstract the needed information to assess survivorship. Results: 270 patients were included from 01/18/2012-08/07/2015. Overall PRD was analyzed as a continuous and a categorical variable (low: 0-3, moderate: 4-6, high: 7-10). Continuous and categorical variable PRD did not show a correlation of distress to survival (P = 0.26) and (P = 0.10) respectively. A correlation was noted in moderate distress category (RR: 1.51, P = 0.034), however, this was not noted in high distress category (RR: 1.25, P = 0.33). There was no statistical significant correlation with the adjusted variables. Patients with primary site of gastrointestinal cancer had worst prognosis (RR: 1.34, P: 0.14), while hematological origin had best prognosis (RR: 0.35, P: 0.038).Age had the strongest correlation with survival, as older patients receiving RT had poorer survival (RR: 1.13, P: 0.079). Conclusions: This study suggests that PRD is not predictive of survival in PRT. The primary goal of PRT is to improve quality of life (QoL) by assessing, anticipating and alleviating suffering; not necessarily improve survival. It also demonstrated that the most common stressors were related to reversible short-term side effects of RT such as fatigue and pain rather than long-term stressors related to daily activities and social measures which might affect QoL. It is imperative to explore assessment tools to mitigate suffering and improve strategies to enhance QoL in all medical disciplines.

79 Background: A significant percentage of cancer patients experience psychosocial distress with the highest prevalence observed in breast cancer patients. The importance of psychosocial distress screening and assessment in women with breast cancer has clearly been established. Patients in our clinic are screened for distress. The results were reviewed in an attempt to better understand the psychosocial distress of breast cancer patients undergoing radiotherapy. Methods: Patients treated curatively for breast cancer prospectively completed the 30 question patient reported distress (PRD) survey that also included a linear analog measure of overall distress. The recorded clinical results of the PRD survey were retrospectively assessed in patients receiving breast radiotherapy from June 1, 2013 to February 2, 2015. Results: Completed PRD questionnaires were available on 179 female patients. 21 (12%) were treated for ductal carcinoma in situ and 91 (51%), 35 (20%), and 32 (18%) were treated for invasive carcinoma Stages I, II, and III. 85 (47%) received chemotherapy. Overall distress ranged from 0 to 10, with a median value of 5. Mean distress scores per category ranged from a low of 1.25 to a high of 2.52. Top concerns in descending order of importance were: “How will I feel during treatment” (2.52), “Fatigue” (2.46), “Sleep difficulties” (2.32), “How will I feel about appearance related to treatment” (2.23), & “Pain that affects daily functioning” (2.19). Least distressing symptoms “Spirituality” (1.25), “Housing during treatment” (1.26), “Control of anger” (1.28), “End of life concerns” (1.32), & “Transportation” (1.34). Conclusions: Distress over tumor related issues ranked low among women’s concerns in comparison to distress related to the side effects of therapy concerning treatment related discomfort, fatigue, and changes in appearance, and anxiety. Pain was a significant concern, although in this group of patients receiving definitive, adjuvant or neoadjuvant therapy, this was likely related to treatment associated discomfort rather than from disease progression. These findings highlight the importance of careful patient education and communication of the expected symptoms and effects of therapy.

LBA500 Background: The primary endpoint of NSABP B-35, a phase III trial comparing 1 mg/day anastrozole to 20 mg/day tamoxifen, each given for 5 years, was breast cancer-free interval (BCFI), defined as the time from randomization to any breast cancer (BC) event including local, regional, or distant recurrence or contralateral disease, invasive or DCIS. Methods: Postmenopausal women with ER-receptor or PgR-receptor positive (by IHC analysis) DCIS and no invasive BC who had undergone a lumpectomy with clear resection margins were randomly assigned to receive either 20 mg/day tam or 1 mg/day A (blinded) for 5 years. Stratification was by age (<60 v ≥60). Results: From 1/6/2003 to 6/15/2006, 3,104 pts were entered and randomized (1552 in groups tam and A each). As of 2/28/15, follow-up information was available on 3,083 pts for OS and on 3,077 pts for all other disease-free endpoints, with mean time of follow-up of 8.6 years. There were 198 BCFI events, 114 in the tam group and 84 in the A group (HR, 0.73; p=0.03). 10-year point estimates for BCFI were 89.2% for tam and 93.5% for A. A significant time-by-treatment interaction (p=0.02) indicated that the effect was not evident until later in the study. There was a significant interaction between treatment and age group (p=0.04); benefit of A is only in women <60 years old. As to secondary endpoints, there were 495 DFS events, 260 in the tam group and 235 in the A group (HR, 0.89; p=0.21). 10-year point estimates for DFS were 77.9% for tam and 82.7% for A. There were 186 deaths, 88 in the tam group and 98 in the A group (HR, 1.11; p=0.48). 10-year point estimates for OS were 92.1% for tam, 92.5% for A. There were 8 deaths due to breast cancer in the tam group and 5 in the A group. There were 63 cases of invasive breast cancer in the tam group and 39 in the A group (HR, 0.61; p=0.02). There was a non-significant trend for a reduction in breast second primary cancers with A (HR, 0.68; p=0.07). Conclusions: Anastrozole provided a significant improvement compared to tamoxifen for BCFI, which was seen later in the study, primarily in women <60 years. Support: CA12027, 37377, 69651, 69974; 180868, 180822, 189867 196067, 114732; AstraZeneca Pharmaceuticals LP. Clinical trial information: NCT00053898.

Abstract Background The clinical results of NSABP B-35, phase III trial comparing 1 mg/day A to 20 mg/day tam, each given for 5 years, were reported at ASCO 2015. B-35 demonstrated a statistically significant benefit in breast cancer free interval for women assigned to A, primarily in women &lt;60 years. A secondary endpoint of B-35 was quality of life (QOL) and symptom (SX) outcomes in the two treatment groups. The primary hypotheses of the PRO study were that there would be no differences in QOL between the two treatments, and that patients receiving A would report higher rates of hot flashes compared to patients receiving tam. Other SX comparisons were secondary endpoints. Methods QOL and SX were assessed at baseline (prior to randomization), and every 6 months thereafter for 5 years of treatment and in the following 12 months. QOL was measured with the SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS). SX were measured with selected scales from the BCPT symptom-checklist, and other standardized instruments. Stratification was by age (&lt;60 v ≥60) as in the main trial. Study hypotheses and endpoints were examined by comparing PROs in the two treatment arms using a mixed model for repeated measures analysis with adjustment for the baseline scores, time point and age category, using an intention-to-treat principle and including only patients who completed the baseline and at least one follow-up questionnaire. Patients with protocol events were censored. Only data through 60 months are reported here. The accrual goal for the sub-study was 1,150 consecutive patients. Results Between January 6, 2003 and June 15, 2006, a total of 3,104 patients were entered and randomly assigned to NSABP Protocol B-35. Accrual to the PRO study of B-35 closed on December 28, 2004, at which time 1,275 patients were entered, with 1,193 patients included in this analysis. There were no medical or demographic differences between patients assigned to A or tam in the PRO sub-study, and they reflected the characteristics of the parent trial. Adherence to data collection across the 60 months was 87%. There were no significant differences in QOL outcomes by treatment for the PCS (p=0.16) or the MCS (p=0.38). SX subscales: hot flash scale was greater in tam group and this difference varied over time (p=0.001); musculoskeletal pain was significantly greater in A group for time points 6-24 months (all p&lt;.001); vaginal problems were greater in A group (p=0.03). Hot flash and vaginal problems were significantly worse in women &lt;60 years. Additional SX outcomes (depression, fatigue, sexual function) will be reported at presentation. Conclusion In this large, double-blind, placebo-controlled trial comparing A to tam in patients with DCIS, there was no significant difference in QOL between the two treatments. However, there were important treatment differences in SX outcomes, which should be considered as part of treatment decision-making discussions, along with the clinical breast cancer outcome results. Support: CA-180868, 180822, 189867, 196067, 114732; AstraZeneca Pharmaceuticals LP. Citation Format: Ganz PA, Cecchini RS, Julian TB, Margolese RG, Costantino JP, Vallow LA, Albain KS, Whitworth PW, Cianfrocca ME, Brufsky A, Gross HM, Soori GS, Hopkins JO, Fehrenbacher L, Sturtz K, Wozniak TF, Seay TE, Mamounas EP, Wolmark N. Patient-reported outcome (PRO) results, NRG Oncology/NSABP B-35: A clinical trial of anastrozole (A) vs tamoxifen (tam) in postmenopausal patients with DCIS undergoing lumpectomy plus radiotherapy. [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 S6-04.

Abstract Background: Targeting immune checkpoint programmed death receptor 1 (PD-1)/PD-L1 pathway has shown promising clinical activity with some preliminary association of clinical benefit with PD-L1 expression on tumors. Recent preclinical and clinical studies highlight the beneficial immunomodulatory potential of epigenetic therapy. Entinostat is a class I specific histone deacetylase inhibitor (HDACi). A promising preclinical study showed that entinostat in combination with immune checkpoint blockade agent can eradicate modestly immunogenic breast tumors in mice via reduction in immunosuppressive myeloid-derived suppressor cells. In this study, we investigated the effects of entinostat on expression of immune-related genes in breast cancer cells to further explore the potential mechanism of its combined activity. Method: Gene expression was assessed on Nanostring platform using the nCounter GX Human ImmunologyV2 panel comprised of 594 immune-related and 15 reference genes. Gene expression was normalized to the internal positive controls and reference genes using nSolver2.0 software. Hormone receptor-positive (HR+) breast cancer (MCF-7 and T47D) and triple negative breast cancer (TNBC) cell lines (MDA-MB-231 and Hs578T) were used for the analysis. Gene expression analysis was performed on control and after 24-hour treatment of entinostat at clinically relevant 125 and 500 nM concentrations. Results: Overall, a greater number of immune-related genes were induced &gt; 2 fold with entinostat at 125 and 500 nM in TNBC compared to HR+: 77 and 118 genes in MDA-MB-231, 80 and 147 genes in Hs578T, 20 and 64 genes in MCF-7, and 73 and 72 genes in T47D, respectively. In particular, MHC class I (HLA-A, HLA-B, HLA-C) and II (HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, and HLA-DRB1) genes were induced by entinostat in a dose dependent manner (range 1.5-22.44 fold). These inductions were observed in both HR+ and TNBC cell lines. Interestingly, we found higher baseline expression and a several fold increase in PD-L1 expression in TNBC. PD-L1 mRNA expression increased by 1.74 and 2.14 fold in MDA-MB-231 and 3 and 9.6 fold in Hs578T with 125 and 500 nM treatment, respectively. Corresponding increase in PD-L1 protein expression after entinostat treatment was also observed. In contrast, there appeared to be no significant changes in PD-L1 expression after entinostat treatment in MCF-7 and T47D. Furthermore, we also identified 21 genes that were differentially induced by entinostat in TNBC but not in HR+. These genes include PTPN22, ARG2, CISH, IL17A, ICAM2, KIR3DL1, CXCR3, TLR2, CFD, CCR5, IL13, LILRA3, IL8, TNFRSF9, DPP4, MR1, SELPLG, PTGS2, IL1B, CD3D, and MBL2. No significant change in PDL2 expression was observed in any of the cell lines. Conclusion: Our data suggest that entinostat induces immune-related genes involved in antigen presentation in both ER+ and TNBC cells, potentially increasing the immunogenicity of these tumors. Given the significant induction of PD-L1 expression with entinostat in TNBC, our preclinical data provides support for further investigation of entinostat in combination with anti-PD1 or anti-PD-L1 in this subtype of breast cancer. Citation Format: Chumsri S, Necela BM, Ordentlich P, Advani P, Moreno-Aspitia A, McLaughlin SA, Geiger X, McDonough M, Vallow LA, Perez EA, Thompson EA. Immunomodulatory effects of entinostat on PD-L1 and MHC class I and II in different subtypes of breast cancer. [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 P2-04-02.

Hidradenocarcinoma is a rare aggressive form of cutaneous adnexal skin carcinoma originating from the sweat gland. Due to its low incidence, prognostic and treatment strategies are still being explored both for primary and advanced disease. This tumor most often presents as either solid or cystic appearing subcutaneous nodules, which may be associated with pruritus or ulceration. To date the mainstay of treatment for local disease has been surgical excision; however, the paucity of historical data available has shown that these tumors often behave aggressively with high rates of local recurrence, metastasis, and poor overall outcomes. There are few case reports describing the utility of radiation therapy in the treatment of hidradenocarcinoma. Herein, we present a case of metastatic apocrine hidradenocarcinoma in a 32-year-old Caucasian male. The patient initially underwent excisional biopsy which confirmed the diagnosis of poorly differentiated, highly infiltrative, apocrine hidradenocarcinoma. He received systemic chemotherapy for metastatic disease, followed by radiation therapy to areas of grossly palpable adenopathy. Prior to radiation therapy the patient had an enlarged hypermetabolic conglomerate of lymph nodes in the right axilla, and borderline enlarged low activity nodes within the left axilla. He received 3 cycles of chemotherapy followed by tamoxifen and radiation therapy (50.4 Gy in 28 fractions) to areas of progressive disease in the bilateral axilla, lower neck, and axillary skin. Following treatment, the patient had complete resolution of skin nodules and improvement of his pruritus. While the role of radiation therapy in the treatment of hidradenocarcinoma has not been well established, this case report demonstrated the potential benefit of external beam radiotherapy in the management of this rare disease.

Objective To update a previously proposed prognostic scoring system that predicts risk of biochemical recurrence ( BCR ) after salvage radiation therapy ( SRT ) for recurrent prostate cancer when using additional patients and a PSA value of 0.2 ng/ mL and rising as the definition of BCR . Patients and Methods We included 577 patients who received SRT for a rising PSA after radical prostatectomy in this retrospective cohort study. Clinical, pathological, and SRT characteristics were evaluated for association with BCR using relative risks ( RR s) from multivariable Cox regression models. Results With a median follow‐up of 5.5 years after SRT , 354 patients (61%) experienced BCR . At 5 years after SRT , 40% of patients were free of BCR . Independent associations with BCR were identified for the PSA level before SRT ( RR [doubling]: 1.25, P < 0.001), pathological tumour stage ( RR [T3a vs T2] 1.21, P = 0.19; RR [T3b/T4 vs T2] 2.09, P < 0.001; overall P < 0.001), Gleason score ( RR [7 vs <7] 1.63, P < 0.001; RR [8–10 vs <7] 2.28, P < 0.001; overall P < 0.001), and surgical margin status ( RR [positive vs negative] 0.71, P = 0.003). We combined these four variables to create a prognostic scoring system that predicted BCR risk with a c ‐index of 0.66. Scores ranged from 0 to 7, and 5‐year freedom from BCR for different levels of the score was as follows: Score = 0–1: 66%, Score = 2: 46%, Score = 3: 28%, Score = 4: 19%, and Score = 5–7: 15%. Conclusion We developed a scoring system that provides an estimation of the risk of BCR after SRT . These findings will be useful for patients and physicians in decision making for radiation therapy in the salvage setting.