Advanced cutaneous squamous cell carcinoma: Impact of age on the safety and efficacy of cemiplimab and the prognostic significance of blood biomarkers.

INTRODUCTION: Age-related differences in the safety profile of cemiplimab for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) have not been well described. We investigated the association of increasing age with immune related adverse events (irAE) from cemiplimab, efficacy outcomes, and the prognostic significance of pre-treatment blood biomarkers in contemporary practice. MATERIALS AND METHODS: Patients starting first-line cemiplimab for locally advanced or metastatic cSCC at British Columbia Cancer between April 2019 and January 2023 were identified. Landmark four-month logistic regression analysis compared the odds of developing irAE or sequelae amongst patients aged <75 years to those aged 75-84 or ≥ 85. Objective responses were determined using Response Evaluation Criteria in Solid Tumors version 1.1. Univariable Cox proportional hazard (PH) regression modelling of factors associated with overall survival (OS) was performed. RESULTS: Of 106 patients, the proportions aged <75, 75-84, and ≥ 85 years were 34%, 45%, and 21%, respectively. Overall, the proportion of patients with irAE ≥ grade 3, cemiplimab discontinuation, and hospitalization for immune toxicity was 27.4%, 31.1%, and 11.3%, respectively. There was no clear association between age and the odds of high grade irAE. However, increased odds of cemiplimab discontinuation was observed in patients aged 75-84 years (p = 0.05). Patients ≥85 years had increased hospitalizations due to irAE (OR = 5.00, 95% CI = 0.97-37.52) with two treatment-related deaths. Objective responses were similar across age cohorts (50.0%, 60.4%, and 54.5%) but progressive disease was higher in the age ≥ 85 group (22.2%, 18.8%, and 31.8%). On Cox PH regression analysis, age ≥ 85 years (vs. <75), Eastern Cooperative Oncology Group performance status 2-3 (vs. 0-1), and neutrophil to lymphocyte ratio (NLR) ≥7.80 (vs. <7.80) were associated with shorter survival. DISCUSSION: While the odds of high grade irAE were similar across age groups, significant age-related differences in treatment discontinuation and hospitalization due to immune toxicity were observed. Despite a higher incidence of primary progression and shorter OS in the oldest cohort, cemiplimab yielded robust objective responses regardless of age. Higher pre-treatment NLR was associated with shorter survival and the cut-point identified requires further study.

First-line osimertinib for patients with EGFR-mutated advanced non-small cell lung cancer: efficacy and safety during the COVID-19 pandemic.

Background: The FLAURA trial demonstrated improved overall survival (OS) with first-line osimertinib for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). We studied the efficacy and safety of osimertinib in a cohort treated during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Patients diagnosed with EGFR-mutated advanced NSCLC between 11 March 2020 to 31 December 2021 who received first-line osimertinib in British Columbia, Canada were identified retrospectively. Kaplan-Meier curves of OS and progression-free survival (PFS) from the start of osimertinib were plotted. The associations of baseline characteristics with PFS, and development of pneumonitis or dose reductions due to toxicity with OS were evaluated with hazard ratios estimated using univariable and multivariable Cox models. Results: The cohort comprised 231 individuals. 58.7% of patients with de novo advanced NSCLC were initially diagnosed after presentation to the Emergency Room. At osimertinib initiation, 31.6% were aged ≥75 years and 45.5% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Median PFS and OS were 18.0 months [95% confidence interval (CI): 16.1-26.2] and 25.4 months (95% CI: 20.3-not reached), respectively. On multivariable analysis, age ≥75 years (vs. <75), ECOG PS 2/3 (vs. 0/1), ECOG PS 4 (vs. 0/1), current smokers (vs. never smokers), programmed death ligand 1 (PD-L1) expression ≥50% (vs. <1%), and L858R mutation (vs. exon 19 deletion) were associated with shorter PFS. Among 110 patients who progressed, 33.6% received subsequent therapy. A proportion of 16.5% of the cohort developed grade ≥3 adverse events. Pneumonitis from osimertinib (3.9% incidence) was weakly associated with shorter OS (hazard ratio: 2.59, 95% CI: 0.94-7.12, P=0.066); dose reductions were not associated with worse OS. 10.8% of patients developed COVID-19. Conclusions: In a cohort receiving first-line osimertinib during the COVID-19 pandemic, ECOG PS ≥2 was observed in nearly half of patients at treatment initiation contributing to a median OS shorter than in FLAURA. The incidence of severe adverse events was low and dose reduction for drug toxicity did not impact OS. Identifying and reducing barriers to the diagnosis of NSCLC during the COVID-19 pandemic are required.

Safety and efficacy of pembrolizumab for advanced nonsmall cell lung cancer: before and during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic changed diagnostic and treatment pathways in oncology. We compared the safety and efficacy of pembrolizumab amongst advanced nonsmall cell lung cancer (NSCLC) patients with a PD-L1 tumor proportion score (TPS) ≥ 50% before and during the pandemic. METHODS: Advanced NSCLC patients initiating pembrolizumab between June 2015 and December 2019 ("pre-pandemic cohort") and between March 2020 and March 2021 ("pandemic cohort") at BC Cancer were identified retrospectively. Multivariable logistic regression evaluated risk factors for immune-related adverse events (irAE) ≥ grade 3 at the 6 week, 3 month, and 6 month landmarks. Cox regression models of overall survival (OS) were constructed. RESULTS: The study population comprised 417 patients in the pre-pandemic cohort and 111 patients in the pandemic cohort. Between March and May 2020, 48% fewer advanced NSCLC cases with PD-L1 TPS ≥ 50% were diagnosed compared to similar intervals in 2018-2019. Telemedicine assessment [new patient consultations (p < 0.001) and follow-up (p < 0.001)] and extended interval pembrolizumab dosing (p < 0.001) were more common in the pandemic cohort. Patients initiating pembrolizumab after February 2020 (vs. before January 2020) experienced similar odds of developing severe irAE. 2/111 (1.8%) patients receiving pembrolizumab during the pandemic tested positive for COVID-19. On multivariable analysis, no association between pembrolizumab treatment period (before vs. during the COVID-19 pandemic) and OS was observed (p = 0.18). CONCLUSION: Significant changes in healthcare delivery in response to the pandemic did not result in increased high grade toxicity or lower survival outcomes in patients with advanced NSCLC treated with pembrolizumab.

Survival Outcomes in Metastatic Ewing Sarcoma Treated With Whole-Lung Radiation.

Background and objective There is a scarcity of research on outcomes in patients with metastatic Ewing sarcoma limited to pulmonary metastases who receive whole-lung radiotherapy (WLRT). In light of this, this study aimed to evaluate the use of WLRT and compare the survival outcomes between patients with metastatic Ewing sarcoma who received treatment with WLRT and those who did not. Materials and methods Patients of all ages with metastatic Ewing sarcoma restricted to the lung who were referred to the British Columbia (BC) Cancer from 1995 to 2017 were identified from the Sarcoma Outcomes Unit (SARCOU). Patient demographics and tumor and treatment characteristics were compared between cohorts treated with WLRT versus those who did not undergo WLRT. Five-year progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier (KM) estimates and compared between treatment groups with log-rank tests. Results The study cohort comprised 30 patients (median follow-up time: 6.8 years). Overall, the median age of the patients was 16 years (range: 4-86 years) and 60% were female; the primary disease sites were as follows: 27% axial skeleton, 53% appendicular skeleton, 20% visceral, 86% had ≥2 lung metastases, and 60% had bilateral disease. Fifteen (50%) patients received WLRT (median of 1500 cGy in 10 fractions). Chemotherapy was used in 97% of patients. The rate of surgery for lung metastases was 40%, which was similar between the WLRT and non-WLRT groups. The median size of the largest lung metastasis in the WLRT cohort was 1 cm (range: 0.3-1.8 cm), compared to 2 cm (range 0.5-6.7 cm) in the non-WLRT cohort (p=0.05). Demographics and tumor characteristics were otherwise not significantly different between the two treatment groups (all p>0.05). Among patients who received WLRT, 53% had complete response (CR), 7% partial response (PR), and 40% had disease progression. The five-year PFS was 86% vs. 59% (p=0.33) and OS was 78% vs. 54% (p=0.24) respectively for patients in the WLRT group vs. those in the non-WLRT group. The five-year PFS outcomes were higher on univariate analysis in patients with appendicular skeletal compared to axial skeletal and visceral primary sites (87.5% vs. 58% vs. 50%, respectively, p=0.02) and in patients with the size of the largest lung metastasis <2 cm vs. those with a size ≥2 cm (80% vs. 25%, p=0.04). Conclusions Patients treated with WLRT had a smaller-volume lung disease and over half of the patients who received WLRT had either complete or partial response. Trends of improved PFS and OS at five years were observed among patients who received WLRT compared to the non-WLRT group, but these were not statistically significant.

A multi-institutional prediction model to estimate the risk of recurrence and mortality after mastectomy for T1-2N1 breast cancer.

BACKGROUND: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial. METHODS: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM). RESULTS: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more adverse risk factors than those patients not receiving PMRT: younger age, larger tumors, more positive lymph nodes, lymphovascular invasion, extracapsular extension, and positive margins (p < .05 for all). On competing risk regression analysis, receipt of PMRT was significantly associated with a decreased risk of LRR (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.14-0.31; p < .001) and OR (HR, 0.76; 95% CI, 0.62-0.94; p = .011). Model performance metrics for each end point showed good discrimination and calibration. An online prediction model to estimate predicted risks for each outcome based on individual patient and tumor characteristics was created from the model. CONCLUSIONS: In a large multi-institutional cohort of patients, PMRT for T1-2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision-making regarding PMRT in this population.

Locoregional Treatments for Metastatic Gastrointestinal Stromal Tumor in British Columbia: A Retrospective Cohort Study from January 2008 to December 2017.

INTRODUCTION: The role of surgery and non-surgical locoregional treatments (LRT) such as radiation therapy (RT) and local ablation techniques in patients with metastatic gastrointestinal stromal tumor (GIST) is unclear. This study examines LRT practice patterns in metastatic GIST and their clinical outcomes in British Columbia (BC). METHODS: Patients diagnosed with either recurrent or de novo metastatic GIST from January 2008 to December 2017 were identified. Clinical characteristics and outcomes were analyzed in patients who underwent LRT, including surgical resection of the primary tumor or metastectomy, RT, or other local ablative procedures. RESULTS: 127 patients were identified: 52 (41%) had de novo metastasis and 75 (59%) had recurrent metastasis. Median age was 67 (23-90 years), 58.2% were male, primary site was 33.1% stomach, 40.2% small intestine, 11% rectum/pelvis, and 15.7% others. 37 (29.1%) of patients received palliative surgery, the majority of which had either primary tumor removal only (43.3%) or both primary tumor removal and metastectomy (35.1%). A minority of patients underwent metastectomy only (21.6%). A total of 12 (9.5%) patients received palliative RT to metastatic sites only (58.3%) or primary tumors only (41.7%), mostly for symptomatic control (n = 9). A few patients (n = 3) received local ablation for liver metastatic deposits with 1 patient receiving microwave ablation (MWA) and 2 receiving radiofrequency ablation (RFA). Most patients (n = 120, 94.5%) received some type of systemic treatment. It is notable that prolonged progression free survival (PFS) was observed for the majority of patients who underwent surgery in the metastatic setting with a median PFS of 20.5 (95% confidence interval (CI): 14.29-40.74) months. In addition, significantly higher median overall survival (mOS) was observed in patients who underwent surgery (97.15 months; 95% CI: 77.7-not reached) and LRT (78.98 months; 95% CI: 65.58-not reached) versus no surgery (45.37 months; 95% CI: 38.7-64.69) and no LRT (45.27 months; 95% CI: 33.25-58.66). Almost all patients (8 out of 9) achieved symptomatic improvement after palliative RT. All 3 patients achieved partial response and 2 out of 3 patients had relatively durable responses of 1 year or more after local ablation. DISCUSSION: This study is among the first to systematically examine the use of various LRT in metastatic GIST management. Integration of LRT with systemic treatments may potentially provide promising durable response and prolonged survival for highly selected metastatic GIST patients with low volume disease, limited progression and otherwise well controlled on systemic treatments. These observations, consistent with others, add to the growing evidence that supports the judicious use of LRT in combination with systemic treatments to further optimize the care of metastatic GIST patients.

Immune related adverse events and treatment discontinuation in patients older and younger than 75 years with advanced melanoma receiving nivolumab or pembrolizumab.

BACKGROUND: Programmed cell-death 1 antibodies (PD-1 Ab) improve overall survival (OS) for patients with advanced melanoma in trials; however, safety data in patients ≥75 years are lacking. The prognostic significance of and risk factors for PD-1 Ab discontinuation due immune related adverse events (irAE) are also uncertain. METHODS: Patients with advanced melanoma receiving frontline PD-1 Ab at British Columbia Cancer outside of clinical trials between 10/2015-10/2019 were retrospectively analyzed. The incidence and subtypes of irAE were compared between age subgroups <75 and ≥ 75 years. Univariable logistic regression identified variables associated with treatment discontinuation within four months of PD-1 Ab initiation. Cox proportional hazard regression models were used to determine factors significantly associated with OS. RESULTS: 302 patients were identified, of whom 126 (41.7%) were ≥ 75 years. During all follow-up, 15.9% of patients experienced irAE grade 3/4 and 27.2% of the cohort stopped PD-1 Ab due to immune toxicity. irAE incidence, hospitalization, and need for steroids by the four-month landmark were similar amongst age groups. Advanced age was not associated with risk of PD-1 Ab discontinuation from irAE on logistic regression. For the entire cohort, pre-treatment factors associated with shorter OS on multivariable analysis were ECOG performance status ≥1, M1d stage, lactate dehydrogenase >224, and neutrophil/ lymphocyte ratio ≥ 5. On four-month landmark multivariable analysis, treatment discontinuation due to irAE was significantly associated with worse OS. CONCLUSION: Patients aged ≥75 years experienced similar irAE rates and treatment discontinuation for immune toxicity compared to younger patients. As PD-1 Ab discontinuation due to irAE was associated with shorter OS, efforts to treat irAE early are warranted to potentially avoid therapy cessation.

Time to Treatment With Nivolumab or Pembrolizumab for Patients With Advanced Melanoma in Everyday Practice.

Background The anti-programmed cell death one antibodies (Anti-PD-1 Ab) pembrolizumab or nivolumab are commonly prescribed to patients with advanced melanoma. The purpose of the current study is to identify baseline clinical characteristics associated with time to treatment initiation (TTI) of pembrolizumab or nivolumab for advanced melanoma and whether treatment delays are associated with differences in survival outcomes. Methods All patients receiving Anti-PD-1 Ab as a first-line treatment for advanced melanoma outside of clinical trials at British Columbia Cancer Agency between 10/2015 and 10/2019 were identified retrospectively. TTI was defined as the interval from pathologic diagnosis of advanced melanoma to first Anti-PD-1 Ab treatment. To determine the association between TTI and baseline characteristics, multivariable Cox proportional hazard regression analyses provided an estimate of the instantaneous relative risk of starting treatment at any time point (hazard ratio [HR] >1 indicates shorter TTI). To describe changes in overall survival (OS) observed for each four-week delay in treatment initiation, multivariable cox proportional hazard regression modelling was also performed. Results In a cohort of 302 patients, the median TTI was 52 days (interquartile range 30.2-99.0). Pulmonary metastases (M1b)/non-central nervous system visceral metastases (M1c) vs. metastases to skin or non-regional lymph nodes (M1a)(HR=1.50, 95% CI=1.12-2.02; p=0.007) and pre-treatment Eastern Cooperative Oncology Group Performance Status (ECOG PS) >1 (vs 0/1, HR=1.50, 95% CI= 1.11-2.01; p=0.008) were associated with earlier TTI. An association between treatment delay and improved OS was observed. Conclusion Patients having visceral metastases and poor baseline ECOG PS were more likely to initiate Anti-PD-1 Ab sooner. The association of shorter TTI with worse OS likely represents confounding by indication (urgent treatment offered to patients with aggressive disease).

Hypofractionated Adjuvant Radiation Therapy Is Effective for Patients With Lymph Node-Positive Breast Cancer: A Population-Based Analysis.

PURPOSE: This study evaluated long-term, population-based, breast cancer-specific outcomes in patients treated with radiation therapy (RT) to the breast/chest wall plus regional nodes using hypofractionated (HF) (40-42.5 Gy/16 fractions) versus conventionally fractionated (CF) regimens (50-50.4 Gy/25-28 fractions). METHODS AND MATERIALS: A prospective provincial database was used to identify patients with lymph node-positive breast cancer treated with curative-intent breast/chest wall + regional nodal RT from 1998 to 2010. The effect of RT fractionation on locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) was assessed for the entire cohort and for high-risk subgroups: grade 3, ER-/HER2-, HER2+, and ≥4 positive nodes. Multivariable analysis and 2:1 case-match comparison of HF versus CF were also performed. RESULTS: A total of 5487 patients met the inclusion criteria (4006 HF and 1481 CF). Median age was 55 years, and median follow-up was 12.7 years. On multivariable analysis, no statistically significant differences were identified in 10-year LRRFS (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.59-1.27; P = .46), DRFS (HR 0.90; 95% CI, 0.76-1.06; P = .19), or BCSS (HR 0.92; 95% CI, 0.76-1.10; P = .36) between the HF and CF cohorts. There was no statistical difference in breast cancer-specific outcomes in the high-risk subgroups. On analysis of 2962 HF cases matched to 1481 CF controls, no statistical difference was observed in LRRFS (HR 0.98; 95% CI, 0.71-1.33; P = .87), DRFS (HR 0.97; 95% CI, 0.85-1.11; P = .68), or BCSS (HR 1.00; 95% CI, 0.87-1.16; P = .92). CONCLUSIONS: This large, population-based analysis with long-term follow-up after locoregional RT demonstrated that modest HF provides similar breast cancer-specific outcomes compared with CF. HF is an effective option for patients with stage I to III breast cancer receiving nodal RT.

Comparison of Nodal Target Volume Definition in Breast Cancer Radiation Therapy According to RTOG Versus ESTRO Atlases: A Practical Review From the TransAtlantic Radiation Oncology Network (TRONE).

Regional nodal irradiation has gained interest in recent years with the publication of several important randomized trials and the availability of more conformal techniques. Target volume delineation represents a critical step in the radiation planning process. Adequate coverage of the microscopic tumor spread to regional lymph nodes must be weighed against exposure of critical structures such as the heart and lungs. Among available guidelines for delineating the clinical target volume for the breast/chest wall and regional nodes, the Radiation Therapy Oncology Group and European Society for Radiotherapy and Oncology guidelines are the most widely used internationally. These guidelines have been formulated based on anatomic boundaries of areas historically covered in 2-dimensional field-based radiation therapy but have not been validated by patterns-of-failure studies. In recent years, an important body of data has emerged from mapping studies documenting patterns of local and regional recurrence. We aim to review, discuss, and compare contouring guidelines for breast cancer radiation therapy in the context of contemporary data on locoregional relapse to improve their implementation in modern practice.

Hypofractionated radiation treatment for breast cancer: The time is now.

While there is now Level I data with long-term follow-up supporting the routine use of hypofractionated (HF) whole-breast radiation therapy (WBRT) after breast-conserving surgery, its adoption has been slow and variable. This article will review the literature supporting the efficacy and safety of hypofractionated radiation for breast cancer, discuss the radiobiological rationale specific to breast tumors, and make an argument for justifying the routine adoption of shorter, HF-WBRT courses when delivering breast radiation. Data using HF with regional nodal irradiation and in the post-mastectomy setting will also be reviewed. The aim is to provide an in-depth understanding of the use of hypofractionated radiation therapy for breast cancer, its applicability, and topics warranting future research.

Local Relapse and Survival Outcomes in Patients with Scalp Sarcoma: A Retrospective Study of 95 Patients Treated in a Provincial Cancer Care Institution Over 25 Years.

Objectives There is limited literature on the optimal treatment of sarcoma arising in the scalp. This study evaluates local relapse (LR) and survival outcomes of patients with scalp sarcoma treated at a provincial cancer care institution. Methods A retrospective review of 95 patients with a primary diagnosis of scalp sarcoma referred from 1990-2015 was completed. Kaplan-Meier statistics were used to estimate LR-free survival (LRFS) and overall survival (OS). Survival curves were compared using log-rank tests. Regression analyses were performed using Cox proportional hazards model. Results The median age at diagnosis was 77 years. The most common histologies were angiosarcoma (27%), undifferentiated pleomorphic sarcoma (24%), and pleomorphic dermal sarcoma (21%). Final margins were 36% positive, 28% close, 31% negative, and 5% unknown. Of 73 patients treated with curative-intent, 32 (44%) experienced LR. Five-year LRFS was 56.0% and overall survival was 48.3%. Patients with close or positive margins who received pre- or post-operative radiotherapy (n=19) had similar LR risk compared to patients who did not (n=34) (five-year LRFS 41.8% vs 69.1%; p=0.145). On multivariate analysis, angiosarcoma was associated with a higher LR risk (Hazard ratio (HR) 12.06, p<0.001). The use of radiotherapy showed a trend towards reduced LR risk but did not reach statistical significance (HR 0.37, p=0.066). Conclusions Patients with scalp sarcoma have high risk of LR, particularly in cases with positive margins. Adjuvant radiation was not associated with improved local control for close or positive margins. Complete surgical excision to establish negative margins remains the primary standard treatment for patients with this rare disease.

Controversies in locoregional management of breast cancer with low volume pN0(i+) and pN1mi nodal disease.

Introduction: The pathologic status of the axillary lymph nodes is an important prognostic factor in patients with breast cancer. With the transition from axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB) for patients with clinically node negative breast cancer, there has been an increase in detection of pN0(i+) breast cancer with isolated tumor cells and pN1mi disease with micrometastatic nodal involvement. The prognostic impact of small volume nodal involvement and the role of locoregional radiotherapy, especially in the era of modern systemic therapy, are unclear. Areas covered: This review examines contemporary data evaluating the prognostic impact of pN0(i+) and pN1mi breast cancer on locoregional recurrence and survival outcomes, then discusses controversies related to the use of adjuvant locoregional radiation therapy in the presence of low volume nodal disease. Relevant papers were identified by searching multiple engines for articles published since 2000. Expert opinion: Sentinel lymph node biopsy without completion ALND is a standard surgical option for patients with pN0(i+) and pN1mi disease. The available evidence does not support routine use of adjuvant locoregional radiation therapy in patients with pN0i+ or pN1mi disease, but locoregional radiotherapy should be considered in the presence of concomitant high-risk features and patient factors.

Abscopal Effect after Palliative Radiation Therapy for Metastatic Adenocarcinoma of the Esophagus.

The abscopal effect is a rare phenomenon in the treatment of metastatic cancer where tumor regression occurs distant from the irradiated volume. It is thought that local radiation induces immunogenic cell death by systemically enhancing the host's antitumor immune system. We present a rare case of the abscopal effect in esophageal adenocarcinoma. After palliative radiation therapy to the primary tumor and adjacent lymph nodes, a complete response was observed not only in the irradiated tissues, but also in non-irradiated metastatic lymph nodes. The patient remains cancer-free one year later. A better understanding of the abscopal effect may lead to novel research to improve patient outcome in the often dismal case of esophageal adenocarcinoma.

Close Margins Less Than 2 mm Are Not Associated With Higher Risks of 10-Year Local Recurrence and Breast Cancer Mortality Compared With Negative Margins in Women Treated With Breast-Conserving Therapy.

PURPOSE: The 2014 Society of Surgical Oncology-American Society for Radiation Oncology consensus suggested "no ink on tumor" is a sufficient surgical margin for invasive breast cancer treated with breast-conserving surgery (BCS). Whether close margins <2 mm are associated with inferior outcomes remains controversial. This study evaluated 10-year outcomes by margin status in a population-based cohort treated with BCS and adjuvant radiation therapy (RT). METHODS AND MATERIALS: The subjects were 10,863 women with invasive cancer categorized as pT1 to T3, any N, and M0 referred from 2001 to 2011, an era in which the institutional policy was to re-excise close or positive margins, except in select cases. All women underwent BCS and whole-breast RT with or without boost RT. Local recurrence (LR) and breast cancer-specific survival (BCSS) were examined using competing-risk analysis in cohorts with negative (≥2 mm; n = 9241, 85%), close (<2 mm; n = 1310, 12%), or positive (tumor touching ink; n = 312, 3%) margins. Multivariable analysis and matched-pair analysis were performed. RESULTS: The median follow-up period was 8 years. Systemic therapy was used in 87% of patients. Boost RT was used in 34.1%, 76.9%, and 79.5% of patients with negative, close, and positive margins, respectively. In the negative, close, and positive margin cohorts, the 10-year cumulative incidence of LR was 1.8%, 2.0%, and 1.1%, respectively (P = .759). Corresponding BCSS estimates were 93.9%, 91.8%, and 87.9%, respectively (P < .001). On multivariable analysis, close margins were not associated with increased LR (hazard ratio, 1.25; 95% confidence interval 0.79-1.97; P = .350) or reduced BCSS (hazard ratio, 1.25; 95% confidence interval 0.98-1.58, P = .071) relative to negative margins. On matched-pair analysis, close margin cases had similar LR (P = .114) and BCSS (P = .100) to negative margin controls. CONCLUSIONS: Select cases with close or positive margins in this population-based analysis had similar LR and BCSS to cases with negative margins. While these findings do not endorse omitting re-excision for all cases, the data support a policy of accepting carefully selected cases with close margins for adjuvant RT without re-excision.

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.

Hypofractionated Nodal Radiation Therapy for Breast Cancer Was Not Associated With Increased Patient-Reported Arm or Brachial Plexopathy Symptoms.

PURPOSE: To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx. METHODS AND MATERIALS: Two cancer registries were used to identify subjects who received computed tomography-planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions. After ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale, a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living. Clinicopathologic characteristics and Self-reported Arm Symptom Scale scores were compared between HF/CF cohorts using nonparametric analysis, χ2 analysis, and multivariate ordinal regression. RESULTS: Of 1759 patients, 800 (45.5%) returned a completed survey. A total of 708 eligible cases formed the study cohort. Of these, 406 (57%) received HFRT (40 Gy/16 fx, 45 Gy/20 fx), and 302 (43%) received CFRT (45-50 Gy/25 fx, 50.4 Gy/28 fx). Median time interval after RT was 5.7 years. Forty-three percent and 75% of patients received breast-conserving surgery and chemotherapy, respectively. Twenty-two percent received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (P<.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (P=.44), as were the mean sums of responses in arm symptoms (P=.17) and activities of daily living (P=.85). Patients receiving HF reported lower rates of shoulder stiffness (P=.04), trouble moving the arm (P=.02), and difficulty reaching overhead (P<.01) compared with the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy. CONCLUSIONS: Nodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared with CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.