Locoregional Recurrence and Survival Outcomes in Breast Cancer Treated With Modern Neoadjuvant Chemotherapy: A Contemporary Population-based Analysis.

BACKGROUND: Data guiding radiotherapy (RT) decisions after neoadjuvant chemotherapy (NAC) is largely retrospective, based on older treatment approaches without molecular subtype information. This study evaluated outcomes in breast cancer patients treated with modern NAC by molecular subtype and locoregional treatment. MATERIALS AND METHODS: There were 949 patients diagnosed between 2005 and 2016 treated with NAC followed by surgery ± locoregional radiotherapy (LRRT). Outcomes were 7-year locoregional relapse-free survival (LRRFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: Median follow-up was 6.5 years, 92% had cT2-4 and 72% cN1-3 disease. Subtypes were: 21% Luminal A, 18% Luminal B, 35% Her2+, and 21% triple-negative breast cancer (TNBC). Combined taxane and anthracycline-based NAC was used in 91.7% of cases. All patients with Her2+ disease received anti-Her2 therapy. After NAC, the majority (84.9%) underwent mastectomy, and received LRRT (86.1%). Only 11% had mastectomy without RT. Pathologic complete response (pCR) rates were 2.5% for Luminal A, 14.4% Luminal B, 27% TNBC, and 35.1% Her2+. Overall, adjuvant LRRT was associated with improved outcomes but was most significant for improved LRRFS in TNBC (92.5% vs. 68.5%, P < .001; Her2+ 95.4% vs. 93.6%, P = .81; Luminal A 97.4% vs. 100%, P = .49; Luminal B 89.7% vs. 100%, P = .17). On multivariable analysis, factors associated with reduced LRRFS were grade 3 histology (HR 4.96, P = .009) and no pCR (HR 7.0, P = .0008). Predictors of lower BCSS and OS were age >50, grade 3, cT3-4, lack of pCR, LRRT omission, and TNBC and Her2+ subtypes. CONCLUSION: In this analysis of patients treated with modern NAC, pCR rates varied by molecular subtype. Patients who did not receive LRRT, particularly those with TNBC, had lower survival compared to those treated with LRRT. These findings support the need for prospective studies to evaluate the safety of de-escalating RT after NAC.

Locoregional therapy in breast cancer patients treated with neoadjuvant chemotherapy.

Introduction: Neoadjuvant chemotherapy (NAC) is increasingly used preoperatively in breast cancer patients to achieve disease downstaging, reduce distant dissemination, and assess chemosensitivity. While NAC indications are expanding, knowledge of its impact on subsequent locoregional treatment with surgery and radiation therapy (RT) decisions is evolving. Radiation oncologists are often called upon to estimate locoregional recurrence (LRR) risks and provide recommendations for adjuvant RT to the breast/chest wall and regional lymph nodes postoperatively. In the non-NAC setting, adjuvant RT decisions are guided by the pathology findings after definitive surgery. In the NAC setting, decisions for or against adjuvant RT are complex, particularly in patients who achieve complete pathologic response (pCR).Areas covered: This review will examine contemporary data on NAC in patients with breast cancer and discuss its impact on surgical and RT decisions. We will also evaluate controversies in the role of LRRT for these patients, focussing on prognostic factors that include biological subtypes and pCR after NAC.Expert opinion: Advances in personalized medicine and diagnostic techniques have shifted paradigms and increased complexities in locoregional treatment decisions, particularly in the setting of NAC. Despite the challenges, our goals while we await prospective data remain focused on improving survival, minimizing toxicity, and optimizing function and cosmesis.

Patient Outcomes With Dose Escalation Using Modern Radiotherapy Techniques: A Retrospective Review of Anal Cancer Treated at a Large Academic Institution Between 2010 and 2016.

INTRODUCTION: The use of modern radiotherapy techniques (MRTs) has contributed to reduced treatment-related toxicities through better avoidance of normal structures and dose tapering, and has enabled the delivery of higher doses continuously. The purpose of this study was to review retrospectively (1) outcomes for anal cancer treated at BC Cancer (Canada) using MRT, and (2) the utilization and effect of dose escalation on cancer-related outcomes. METHODS: Patients between 2010 and 2016 with biopsy-proven anal cancer, aged >18 years, and treated with primary curative-intent chemoradiation using intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) were included. Primary end points included overall survival (OS), relapse-free survival (RFS), and colostomy-free survival (CFS). Kaplan-Meier curves were created for prognostic factors, as well as dose escalation (>54 Gy vs. ≤54 Gy). Univariate and multivariate analyses were performed to evaluate predictors of the outcome. RESULTS: A total of 273 patients were assessed. The median age was 61 years with 70% being female, 6% HIV positive, and 68% with locally advanced cancer (T3-4, or node positive). The median follow-up time was 41.3 months. Time from diagnosis to treatment was 60 days, and treatment duration 42 days. Dose escalation was prescribed for 22, of whom 15 were locally advanced cases. A total of 97% completed their radiation, including all who were dose-escalated; 11% required unplanned treatment breaks, with over half of breaks <5 days. More than 90% completed at least half of their chemotherapy; 41% had pre-treatment, and 34% post-treatment positron emission tomography (PET) scans. For primary tumor response, 88% were complete and 10% partial; 23% relapsed, with 15% locoregional, 5% distant, and 3% both, and 12% had salvage surgery. The colostomy rate was 15%, with 4% pre-treatment, 10% relapse related, and only 1% treatment-toxicity related. On univariate analysis, male sex was associated with a higher risk of death (p=0.02) and relapse (p=0.041). Non-squamous histology was consistently a strong predictor of all outcomes (OS, p=0.0089; RFS, p<0.0001; CFS, p<0.0001) as was advanced T stage (OS, p=0.0075; RFS, p=0.0019; CFS, p=0.0099), and node positivity (OS, p=0.0014; RFS, p=0.001; CFS, p=0.0071). Age, HIV status, grade, longer treatment times (>42-day median), and lack of a pre- or post-treatment PET scan were not associated with the outcome. Dose escalation beyond 54 Gy was not significant, even among locally advanced tumors. On multivariate analysis, non-squamous histology (OS, p=0.043; RFS, p<0.001; CFS, p=0.01), T4 (OS, p=0.049; RFS, p=0.026; CFS, p=0.042) and node positivity (OS, p=0.05; RFS, p=0.006) remained significant predictors of the outcome, although node positivity was no longer significant for CFS (p=0.10). CONCLUSION: BC Cancer outcomes for anal cancer treated with MRTs are comparable to what has been previously reported. Unplanned breaks were notably few, and short. Treatment-related colostomies were rare. Dose-escalated regimens were infrequently prescribed, appeared tolerable, but more often required a break. Prospective trials are needed to clarify efficacy of such regimens.

Breast Cancer Patients' Perceptions of Adjuvant Radiotherapy: an Assessment of Pre-Treatment Knowledge and Informational Needs.

There is little knowledge about breast cancer patients' information-seeking behaviors, needs, and perceptions of breast radiation therapy (BRT) prior to radiation oncology consultation. This study assessed these parameters to evaluate potential gaps and overlaps in the BRT educational process. Breast cancer patients > 18 years referred for adjuvant BRT at a tertiary cancer center completed an anonymous survey prior to their consultation. Response rate was 86% (118/137). The most commonly reported sources of information about BRT were healthcare providers (55%), family or friends treated with BRT (53%), and the Internet (45%). Most (79%) had little or no knowledge about BRT. Sixty-seven percent were a little or moderately concerned about BRT, while 29% were very concerned. Half were unsure about the benefit of BRT and 46% thought it would provide a moderate to significant benefit. While seeking information about BRT, a wide range of topics were encountered. The most common ones were fatigue (68%), skin care (57%), skin problems (54%), effects on healthy body tissues (43%), the immune system (37%), and pain (34%). Topics considered most important for the radiation oncologist to address were BRT effects on the heart (74%), second cancers (74%), immune system (66%), pain (64%), and lungs (62%). Although commonly encountered, fatigue (56%) and skin care (49%) were of lesser importance. In conclusion, breast cancer patients encounter a broad range of information about BRT prior to their radiation oncology consultation, which may contribute to worry and misconceptions. Potentially rare and serious side effects were considered important to address.

Secondary mucinous carcinoma of the prostate after low dose rate brachytherapy.

Radiation induced malignancy (RIM) after treatment for prostate cancer is well documented after external beam irradiation, but less so in the setting of brachytherapy. We report a case of mucinous adenocarcinoma of the prostate, consistent with a RIM, which developed 12 years after low dose rate brachytherapy for low risk prostate adenocarcinoma. Diagnostic and therapeutic considerations of RIM are discussed. As long term survivors are followed in the community by primary care physicians and urologists, awareness of RIM as a potential late effect of brachytherapy is important to ensure that cases are diagnosed and managed appropriately.

Subventricular Zone Radiation Dose and Outcome for Glioblastoma Treated Between 2006 and 2012.

Objective Stem cells residing in the subventricular zone (SVZ) may be related to recurrence, potentially affecting outcome in glioblastoma (GBM). This study investigated the relationship of SVZ radiation dose and survival in a large cohort treated with surgery and chemoradiotherapy (CRT). Methods Patients with GBM treated between 2006 and 2012 (n = 370) were identified. SVZs were contoured from planning computed tomography (CT) with magnetic resonance imaging (MRI) registration where available. Dose was extracted from dose volume histograms. Kaplan-Meier (KM) progression-free survival (PFS) and overall survival (OS) estimates were compared with log-rank tests for SVZ doses. Multivariate analysis (MVA) identified clinical and treatment-related factors significantly associated with outcome. Results Median follow-up was 16.4 months, 48.1% underwent gross total resection (GTR), 37.5% subtotal resection, and 14.4% biopsy without resection. Median PFS was 8.9 months (95% CI: 8.3-9.8 months), and OS was 16.5 months (95% CI: 15.2-17.6 months). PFS was significantly lower for older age (>50 years, P = 0.045), poor Karnofsky performance status (KPS, P = 0.049), multifocality (P < 0.001), and incomplete adjuvant chemotherapy (P < 0.001). Worse OS was associated with poor KPS (P = 0.001), biopsy only (P = 0.003), multifocality (P = 0.009), and failure to complete adjuvant chemotherapy (P < 0.001). SVZ dose was not associated with outcome for any of the dose levels assessed. On MVA, multifocality was associated with worse PFS (P < 0.01). Poor performance status and biopsy only were associated with worse OS (both P < 0.01). Conclusion In this analysis of a large cohort of GBM treated with surgery and CRT, increased SVZ dose was not associated with improved survival.

Simple gaze analysis and special design of a virtual Morris water maze provides a new method for differentiating egocentric and allocentric navigational strategy choice.

We present a novel method of combining eye tracking with specially designed virtual environments to provide objective evidence of navigational strategy selection. A simple, inexpensive video camera with an easily built infrared LED array is used to capture eye movements at 60Hz. Simple algorithms analyze gaze position at the start of each virtual maze trial to identify stimuli used for navigational orientation. To validate the methodology, human participants were tested in two virtual environments which differed with respect to features usable for navigation and which forced participants to use one or another of two well-known navigational strategies. Because the environmental features for the two kinds of navigation were clustered in different regions of the environment (and the video display), a simple analysis of gaze-position during the first (i.e., orienting) second of each trial revealed which features were being attended to, and therefore, which navigational strategy was about to be employed on the upcoming trial.