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Purpose Higher energy (>6 MV) photons reduce dose inhomogeneity with breast tangent beams, thereby reducing late breast toxicity, but skin and superficial tissue sparing by higher energy beams raises concerns about local recurrence (LR) risk. This study aimed to determine whether beam energy and surgical bed-to-skin distance affect LR. Methods and Materials This population-based study included newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with breast-conserving surgery and adjuvant whole breast radiotherapy without bolus or beam spoilers. The primary endpoint was the cumulative incidence of LR (CILR). A multivariable analysis (MVA) included mean beam energy, age, T-stage, nodal status, overall stage, lymphovascular invasion (LVI), grade, margin status, extensive intraductal component (EIC), breast cancer subtype, hormone therapy and chemotherapy. In a subgroup with contoured surgical beds, another MVA included surgical bed-to-skin distance. Results The cohort consisted of 10,083 women treated from 2002 to 2011, 327 with 4MV, 6,006 with 6 MV, 2,083 with >6-10 MV and 1,667 with >10 MV tangents. The median follow-up time was 11.1 years. The 10-year CILR was 3.1% [95% confidence interval 1.6,5.4] with 4 MV, 2.8% [2.4,3.3] with 6 MV, 4.2% [3.4,5.3] with >6-10 MV and 2.6% [1.9,3.5] with >10 MV. On MVA of the entire cohort, LR risk was increased with positive margins, LVI, EIC, and lack of hormone therapy, but was not associated with beam energy (HR = 1.01 [0.96,1.05], p = 0.8). On MVA of 3,359 patients with contoured surgical beds, LR risk was not associated with surgical bed-to-skin distance (HR = 1.00 [0.99,1.02], p = 0.8). Conclusions Use of higher breast tangent beam energies is not associated with increased risk of local recurrence, including in cases with surgical beds that are close to the skin.

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.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 subgroups75 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.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 dehydrogenase224, and neutrophil/ lymphocyte ratio ≥ 5. On four-month landmark multivariable analysis, treatment discontinuation due to irAE was significantly associated with worse OS.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.

Aims Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear. Materials and methods Patients with unresectable stage III–IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively. Landmark 12-week Kaplan–Meier analyses and log-rank tests were used to evaluate associations between discontinuation of induction therapy on overall survival and time to treatment failure (TTF). Multivariable analysis of factors influencing overall survival and TTF was undertaken. Results Among 95 patients, the median age was 62 years, 38.9% had Eastern Cooperative Oncology Group performance status ≥1 and 22.1% had brain metastases. The median follow-up for the whole cohort was 19.8 months by the reverse Kaplan–Meier method. Any grade and grade 3–4 irAE were noted in 78.9% and 44.2% of the cohort, respectively. 44.2% of patients completed induction immunotherapy, whereas 41.1% did not due to irAE. Twelve-week landmark overall survival and TTF were similar in patients who completed induction versus those who did not due to irAE. On multivariable analysis, any grade irAE (versus none) was associated with longer overall survival (hazard ratio = 0.35, 95% confidence interval 0.15–0.82, P = 0.02) and TTF (hazard ratio = 0.38, 95% confidence interval = 0.17–0.81, P = 0.01). Grade 3–4 irAE correlated with longer TTF (hazard ratio = 0.45, 95% confidence interval = 0.20–1.01, P = 0.05). Conclusion In this population-based cohort, discontinuation of induction immunotherapy as a result of irAE did not adversely affect overall survival or TTF. irAE observed during ipilimumab and nivolumab induction were associated with improved survival outcomes.

Purpose Bolus use during postmastectomy radiation therapy doubles the risk of grade 2 and 3 skin toxicity. Despite its unknown benefit, bolus is often prescribed during postmastectomy radiation therapy for patients without skin involvement. Methods and Materials For women with breast cancer receiving photon 3-dimensional conformal radiation therapy, bolus was used routinely for chest walls but was omitted for breast reconstructions by about half of radiation oncologists from 2007 to 2011. Eligible patients had newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with adjuvant or neoadjuvant radiation therapy. For the bolus and no-bolus groups, we compared the cumulative incidence of local recurrence (LR) and locoregional recurrence (LRR) with distant recurrence and death as competing risks and breast cancer mortality (BCM). Multivariable analysis of LR and BCM included stage, subtype, lymphovascular invasion, grade, margin status, beam energy, bolus use, hormone therapy, chemotherapy, and reconstruction. Results Systemic therapy was used for 98% of the 1887 patients. The bolus group had 1569 patients and the no-bolus group had 318 patients. Bolus was used in 51% (281/550) of patients treated with reconstruction and 96% (1288/1337) of patients treated without reconstruction. The 10-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: LR 1.9% (1.3-2.7) versus 0.9% (0.3-2.6), LRR 3.1% (2.3-4.0) versus 3.2% (1.6-5.5), and BCM 19.4% (17.3-21.6) versus 18.3% (13.9-23.2). On multivariable analysis, bolus use was not associated with better LR (hazard ratio = 1.4 [0.3-6.4]) or BCM (hazard ratio = 0.8 [0.5-1.2]). Conclusions For patients treated with mastectomy, radiation therapy, and modern systemic therapy, the cumulative incidence of LR was low, with or without bolus. Because bolus use increases toxicity and does not reduce LR or BCM, it should no longer be used routinely for patients without skin involvement who receive systemic therapy.

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.

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.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.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).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.

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 p0.05). 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 metastasis2 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.

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.

Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial.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).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.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.

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.

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).

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

The optimal treatment for patients with extensive pure ductal carcinoma in situ (DCIS) ≥4 cm is controversial. This study evaluates local relapse according to type of local therapy: mastectomy, breast-conserving surgery (BCS) alone, and BCS + radiation therapy (RT).Subjects were female patients who received diagnoses of pure DCIS ≥4 cm between 1989 and 2010 and were referred to British Columbia Cancer. Clinicopathologic and treatment characteristics were compared between treatment cohorts. Local relapse (LR) was estimated using competing risk analysis. Multivariable analysis was performed using Cox regression analysis.Patients had the following treatments: 490 mastectomy, 38 BCS alone, and 192 BCS + RT. The 10-year cumulative incidence of LR was 16% after BCS (95% confidence interval [CI], 6-29%), 8% after BCS + RT (95% CI, 4-12%), and 2% after mastectomy (95% CI, 1-4%). On multivariable analysis, estrogen receptor-negative disease (hazard ratio [HR], 3.32; 95% CI, 1.08-10.18; P = .04) and positive margins (HR, 3.55; 95% CI, 1.56-8.05; P = .002) were associated with increased LR. BCS alone (HR, 7.87; 95% CI, 2.82-21.92; P .0001), BCS + RT + no boost (HR, 3.80; 95% CI, 1.56-9.28; P = .003), and BCS + RT + boost (HR, 5.76; 95% CI, 2.59-12.83; P .0001) were all associated with a higher risk of relapse relative to mastectomy.Mastectomy remains a standard local treatment option for extensive DCIS, but BCS + RT may also be reasonably considered in selected patients with a careful discussion of the benefits, side effects, and patient preferences.

To examine oncologists’ practice pattern of ordering MA in localized and metastatic GISTs in British Columbia (BC). Patients diagnosed with GIST from January 2008 to December 2017 in BC were identified. Chart review was performed to determine clinical characteristics and the use of MA as part of their oncologic care. The cohort included 411 patients: median age 64 (18–94 years), 49.1% male, primary site included stomach (53%), small intestine (32%), and others (15%). Sixty-nine percent had localized disease, while 13% presented with de novo metastatic disease and 18% had recurrent metastatic disease. MA was ordered in 41% of the patients overall, 28% in localized, and 70% in metastatic settings (63% in de novo metastasis and 78% in recurrent metastasis). Among patients with localized disease, higher MA use rates were observed among those undergoing neoadjuvant/adjuvant treatment (45%) compared to those not receiving systemic therapy (18%). While MA use rates in localized GIST did not change over time (28.5% before 2015 and 28% after 2015), MA use in metastatic disease increased from 54% before 2015 to 79% after 2015. Among all MA ordered for metastatic disease, 82.4% were ordered at the time of de novo metastatic diagnosis, and 77.4% were ordered either at the time of recurrent metastatic diagnosis or earlier when the disease was localized. MA use has remained stable for localized disease but has increased after 2015 in the metastatic setting which may be due to evolving sequencing technology, expansion of metastatic treatment options, and enhanced awareness of MA.

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.

PURPOSE To review the outcomes of patients with optic nerve sheath meningiomas (ONSM) treated with fractionated stereotactic radiotherapy. METHODS Patient characteristics, treatment, and outcomes were analyzed for all patients with primary and secondary ONSM treated from 2001 to 2012. Clinically significant visual acuity change was defined as a 2-line change on the Snellen eye chart from pre-fractionated stereotactic radiotherapy. RESULTS Forty-one patients were treated: 23 patients with primary ONSM and 18 patients with secondary ONSM. The median age at diagnosis was 56 years. The median visual follow up was 3.8 years and the median radiologic follow up was 4.4 years. At diagnosis, 36% had normal vision (20/20-20/40), 10% had mild impairment (

The abscopal effect is a rare phenomenon in the setting of radiation therapy (RT) for metastatic cancer where tumor regression occurs distant from the site of treatment. A proposed mechanism of the abscopal effect is the activation of a systemic antitumor immune response by localized RT. We report the first case, to our knowledge, of the abscopal effect in squamous carcinoma of the anal canal with metastases to pelvic lymph nodes, liver and bone. After palliative RT to the pelvis with sensitizing chemotherapy, complete response was observed not only in the primary tumor but also in bone and multiple liver metastases at 4 months after treatment, an effect that remained durable at 4-year follow-up. Understanding of the abscopal effect and the immune mechanisms associated with anal cancer may lead to new avenues of research to improve outcome for patients with this rare disease.

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.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, χOf 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.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.

This abstract was withdrawn by the authors.

Background Phyllodes tumours (PT) of the breast are uncommon fibroepithelial lesions for which optimal management remains unclear. This population-based study reports treatment and outcomes for patients with PT and evaluates characteristics that influence outcome. Methods Data were analysed on 183 patients with newly diagnosed PT referred to the BC Cancer Agency from 1999-2014. Follow-up was obtained from chart and death records and letters to general practitioners. Five-year Kaplan-Meier (KM) local recurrence (LR) and survival were compared between cohorts with benign (n=83), borderline (n=50) and malignant PT (n=49) histology. Subtype was unknown in 1 patient who did not receive surgery due to severe comorbidity. Univariate analysis was performed using Cox regression modeling. Results Median follow-up was 65 (range 0.5-197) months. Median age was 48 (range 14–87) years. Median tumour size was 4 (range 1-23) cm. Heterologous sarcomatous differentiation was seen in 15 and malignant epithelial transformation in 11 patients. Local excision was performed in 163 (89%) and mastectomy in 19 (10%) patients. Margin status after local excision were: negative (>1mm, n=121, 74%), close (≤1mm, n=21, 13%), positive (tumour touching ink, n=20, 12%), or unknown (n=1, 1%). Margin status after mastectomy were negative (n=14, 74%) or close (n=5, 26%). Tumour borders were pushing (n=62, 34%), intermediate (n=22, 12%), infiltrative (n=38, 21%) or unknown (n=60, 33%). Eleven patients with malignant PT received radiation therapy as part of initial treatment. In these cases median tumour size was 8 cm and heterologous sarcomatous differentiation was present in 46% compared to 4 cm and 16% in malignant cases who did not receive RT. LR occurred in 16 cases (5 benign, 4 borderline and 7 malignant). Distant metastases (DM) occurred in 7 patients with malignant PT leading to 6 cause specific deaths. Five-year KM outcomes among women with benign, borderline, and malignant PT were: LR 6% vs 9% vs 21%, P=0.131; overall survival 96% vs 100% vs 82%, P=0.002; and disease free survival 94% vs 91% vs 67%, P Five-year KM LR among women with negative vs close vs positive margins were 8% vs 6% vs 37%, P On univariate analyses, large tumour size, postmenopausal status, malignant classification, necrosis, positive margins, and infiltrative borders were factors associated with increased risk of any type of relapse (all P≤0.014). Positive margins and infiltrative tumour border were associated with increased LR (all P≤0.006), and the latter remained significant in exploratory analyses after adjusting for margin status and PT classification. Advanced age at diagnosis and large tumour size were predictors of DM (all P≤0.001). Conclusion In this population-based series, 5-year outcomes among women with PT are comparable to those reported in the literature. Exploratory analysis suggests that infiltrative tumour borders may be used in conjunction with margin status to assess LR risk. While close margin was not associated with increased LR, re-excision is warranted for cases with positive margins. Citation Format: Rodrigues MF, Truong PT, Weir LM, Knowling MA, Wai ES. Phyllodes tumours of the breast: The British Columbia cancer agency experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-13.

Purpose: Regional nodal radiation therapy (RT) can cause adverse arm symptoms and lymphedema. Hypofractionation (HF), defined as >2 Gy/fraction, improves convenience but whether it increases arm morbidity is unclear. This study evaluates patient-reported arm symptoms in women treated with HF compared to conventional fractionation (CF) RT (defined as ≤2Gy/fraction). Materials / Methods: Provincial cancer registries were used to identify subjects who received 3D, CT-planned nodal RT for pT1-3 pN0-2 M0 breast cancer from 2007-2009 in British Columbia and 2008 – 2010 in Alberta, Canada. Treatment eras were selected to enable sufficient follow-up time to develop late arm symptoms. Following research ethics approval, eligible patients were mailed an explanation letter and an externally validated, Self-reported Arm Symptom Scale (SASS) survey. The SASS included 8 questions about arm symptoms, with responses on a 5-point Likert scale regarding arm/hand problems (numbness, pain, stiffness, immobility and swelling), and 5 questions related to activities of daily living (ADL). Clinicopathologic characteristics and SASS scores were compared between HF vs. CF nodal RT cohorts using non-parametric analysis (on ordinal and scale responses) and binned chi-squared analysis (comparison for responses of 1 vs. > 1). Results: 800/1759 eligible patients returned a completed survey (45.5%). Upon detailed chart review of responders, 92 cases with recurrence or metastasis were excluded. The remaining 708 cases formed the study cohort. Of these, 406 (57%) patients received HF RT (modal dose/fractionation 40 Gy/15 fractions (fx) and 45 Gy/20 fx), and 302 (43%) received CF RT (45 Gy/25 fx, 48-50 Gy/25 fx, and 50.4 Gy/28 fx). A boost was delivered to the breast in 22% of subjects, equally by fractionation group (p=0.31). Median time interval since RT completion was 5.67 years. The mean age at diagnosis was 59.0 in HF vs 53.8 years in CF-treated cohorts (p The mean sums of responses for the arm symptoms / ADL components of the SASS were 12.5 / 7.6 vs. 13.3 / 7.9 for the HF and CF groups respectively (p=0.17 / 0.85). On analysis of individual questions, the CF group had a higher prevalence of self-reported symptoms, including shoulder stiffness (p=0.04), trouble moving the arm (p=0.02), and ability to reach overhead (p Conclusion: Hypofractionated nodal RT was not associated with an increase in patient-reported arm symptoms or disability compared to conventional fractionated nodal RT. Subjects treated with CF RT reported more disability in certain aspects of arm and shoulder function. These data support the use of shorter fractionation when the regional lymph nodes are part of the therapeutic target. Citation Format: Leong N, Truong P, Tankel K, Kwan W, Weir L, Olivotto I. Hypofractionated nodal radiotherapy (RT) did not increase arm morbidity compared to conventional fractionated nodal RT [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-06.

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.

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.

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

Background and purpose: We report the long-term outcomes in patients enrolled in a multicenter randomized controlled trial comparing Intensity Modulated Radiation Therapy (IMRT) with standard wedge radiotherapy. Materials and methods: Trial participants were assessed to compare long-term side effects between treatment arms. The primary endpoint was chronic breast pain assessed by trained observers blinded to treatment allocation. Secondary endpoints included cosmesis and quality of life measures. Results: Median follow-up time was 9.8 years and 241 patients were available for assessment. There was no significant difference in chronic pain between treatment arms (OR = 0.74, range 0.432-1.271). There were also no differences for the secondary endpoints. Univariate and multivariate analyses identified young age (p = 0.013) and pain during RT (p < 0.001) to be associated with chronic pain. Acute moist desquamation was associated with late subcutaneous fibrosis (p = 0.003) and telangiectasia (p = 0.039). Pain during RT was associated with a long-term poorer self-assessed cosmetic outcome (p < 0.001) and quality of life (p < 0.001). Conclusions: Breast IMRT cannot be recommended for all patients to reduce long-term side effects. However, late toxicities were significantly correlated with acute side effects, which are increased in patients having poor dose distribution. Breast IMRT may hence be useful for selected patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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.

In 1999, the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B24 trial demonstrated that tamoxifen reduced relapse risk in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and radiotherapy (RT). In 2002, Allred's subgroup analysis showed that tamoxifen mainly benefitted estrogen receptor (ER)-positive disease. This study evaluates the impact and generalizability of these trial findings at the population level.From 1989 to 2009, 2061 women with DCIS underwent BCS + RT in British Columbia. The following cohorts were analyzed: (1) pre-NSABP-B24 era (1989-1998, N = 417); (2) post-NSABP-B24 era (2000-2009, N = 1548). Cohort 2 was further divided into pre- and post-Allred eras.Endocrine therapy (ET) was used in 404/2061 (20%) patients. Median age of patients treated with compared with without ET, was 53 versus 57 years, (P0.0005). One of 417 (0.2%) versus 399/1548 (26%) patients took ET before versus after NSABP-B24. Among the post-Allred era cohort treated with ET (N = 227), tumors were ER-positive in 65%, ER-negative in 1%, and ER-unknown in 33%; whereas of those treated without ET (N = 801), ER was positive in 43%, negative in 15%, and unknown in 42% (P0.0005). On multivariable analysis of the post-NSABP-B24 era, ET was associated with improved event-free survival (EFS) (hazard ratio 0.6; P = 0.02); 5-year EFS were 96.9% with ET versus 94.5% without ET.ET use in DCIS patients treated with BCS + RT increased significantly after the NSABP-B24 study. ER+ disease and younger age were associated with increased ET use. ET was associated with improved EFS, confirming the generalizability of trial data at a population level.

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 margins2 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).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.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.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.

Phyllodes tumors of the breast are uncommon fibroepithelial lesions for which optimal management remains unclear. This retrospective population-based study reports treatment and outcomes for patients with phyllodes tumors and evaluates characteristics that influence outcome.Data were analysed on 183 patients with newly diagnosed phyllodes tumors from 1999 to 2014. Five-year Kaplan-Meier local recurrence and survival were compared between cohorts with benign (n=83), borderline (n=50) and malignant phyllodes tumor (n=49) histology.Median (range) follow-up was 65 (0.5-197) months. Local excision was performed in 163 and mastectomy in 19 patients. Eleven patients with malignant phyllodes tumors received radiation therapy. Overall, local recurrence occurred in 8.7%, distant metastases in 4.4%, and cause specific deaths in 3.8%. Five-year Kaplan-Meier outcomes among women with benign, borderline, and malignant phyllodes tumors were: local recurrence 6% vs 9% vs 21%, P=0.131; overall survival 96% vs 100% vs 82%, P=0.002; and disease-free survival 94% vs 91% vs 67%, P0.001. Five-year Kaplan-Meier local recurrence among women with negative vs close vs positive margins were 8% vs 6% vs 37%, P0.001. Corresponding rates for intermediate vs pushing vs infiltrative borders were 6% vs 6% vs 33%, P=0.006. Positive margins and infiltrative tumor borders were associated with increased local recurrence (all P≤0.006), and the latter remained significant in exploratory analyses after adjusting for margin status and phyllodes tumor classification.Five-year outcomes among women with phyllodes tumors were comparable to those reported in the literature. Exploratory analysis has suggested that infiltrative tumor borders may be used in conjunction with margin status to assess local recurrence risk.

To prospectively capture acute toxicities and pain associated with postmastectomy radiation therapy (PMRT), to analyze patient and treatment risk factors for severe side effects.Women referred for PMRT were prospectively enrolled and assessed weekly during and after radiation therapy. The endpoint included severe National Cancer Institute Common Terminology Criteria for Adverse Effects grade 3 moist desquamation, other skin symptoms, and pain.Of 257 patients, 73 (28.4%) experienced extensive moist desquamation, 84 (32.7%) Common Terminology Criteria for Adverse Effects skin toxicity grade 3, and 57 (22.2%) a pain impacting on daily life activities. Among symptoms only grade 3 moist desquamation was significantly associated with severe pain (P.001). On multivariate analysis, smoking, high-energy photons, and skin bolus were significantly associated with severe moist desquamation. Skin toxicity doubled for smokers, with 40% severe pain, 48% grade 3 moist desquamation, and 64% grade 3 skin toxicity. Without skin bolus 4.2% had severe pain, none moist desquamation, and 2.1% grade 3 skin toxicity. When skin bolus was used on alternate days, the frequency increased to 15% for pain, 22% for moist desquamation, and 26% for grade 3 skin toxicity. When bolus was used daily, 32% had pain, 41% moist desquamation, and 47% grade 3 skin toxicity. Symptoms peaked 1 to 2 weeks after the end of PMRT.The present cohort study suggests excessive radiation toxicity after PMRT. Among factors associated with an increase of toxicity are smoking habits and the use of skin bolus.

Background Phyllodes tumor (PT) of the breast is an uncommon fibroepithelial neoplasm. Malignant epithelial transformation in PT is rare. This study reports clinicopathologic characteristics and outcomes of patients with malignant epithelial transformation in PT. Methods From an institutional database of 183 patients with newly diagnosed PT referred to a Canadian provincial cancer institution between 1999 and 2014, 11 cases of PT with concomitant in situ or invasive carcinoma were identified. Descriptive analysis was performed to document the characteristics, treatment and outcomes of this cohort. Results Prevalence of malignant epithelial transformation in PT was 6.0%. Median (range) age was 54 (35-75) years. Types of carcinoma were ductal carcinoma in situ (DCIS) (n = 6), lobular carcinoma in situ (n = 4), and invasive ductal carcinoma (IDC) (n = 1). Median PT size was 5 (1-15) cm. Three PTs were classified as benign (27%), five as borderline (45%), and three as malignant (27%). Mastectomy was performed in six (55%) and breast conserving surgery in five (45%) patients. Hormonal therapy was used in two cases: one with a 1 cm, grade 2 DCIS, and one with an 11 cm, grade 1 IDC, the latter also receiving radiotherapy. Mean follow-up duration was 54 (6-175) months. None of the cases showed any evidence of disease after treatment at the time of their last follow-up. Conclusion This case series showed a higher prevalence of malignant epithelial transformation in PT than reported in previous literature. Outcomes were favourable despite the presence of either in situ or invasive carcinoma within PT.

We report on a 56-year-old Caucasian female, diagnosed with locally advanced, hormone-receptor-positive, and human epidermal growth factor receptor 2 (HER2)-positive cancer of the left breast. The patient received neoadjuvant chemotherapy with adriamycin/cyclophosphamide (AC) followed by docetaxel/trastuzumab. A partial clinical and radiographical response was documented after four cycles of AC. Approximately one week after the first cycle of docetaxel and trastuzumab, the patient presented with diffuse edema, erythema, and induration involving the entire left breast. The differential diagnoses included infection, inflammatory response/reaction to docetaxel, or cancer progression. After a multidisciplinary review, the decision was made to stop the docetaxel and deliver neoadjuvant radiation treatment concurrent with trastuzumab. Approximately four weeks after radiation therapy completion, the patient underwent a left total mastectomy and axillary dissection, with pathologic complete response (pCR) in the breast and axillary nodal disease. After surgery, systemic therapy was resumed with paclitaxel and trastuzumab, with a plan to start adjuvant endocrine therapy after completion of chemotherapy. We will discuss clinical considerations in the management of the unexpected findings of acute inflammatory response in the breast and nodal regions during neoadjuvant chemotherapy. Associations between intrinsic breast cancer subtype and pCR in locally advanced breast cancer will also be reviewed.

Objective Management of ductal carcinoma in situ (DCIS) remains controversial. This study examined long-term outcomes in a population-based cohort of patients with pure DCIS treated with breast-conserving surgery (BCS) alone, BCS + radiotherapy (RT), and mastectomy. Outcomes were compared between patients referred versus not referred for oncologic assessment after definitive surgery. Materials and methods Subjects were 2575 women diagnosed between 1985 and 1999. Data from several electronic databases were linked and analyzed. Outcomes were invasive local recurrence-free survival (ILRFS), mastectomy-free survival (MFS), breast cancer-specific survival (BCSS), and overall survival (OS). Results Median follow-up time was 9.8 years. Overall, 56% (n = 1448) of subjects were referred to a cancer centre. Factors associated with non-referral were older age, comorbidities, and travel distance. Ten-year MFS, BCSS, and OS were higher among referred patients (all p ≤ 0.001). In cohorts treated with BCS alone (n = 1314) vs. BCS + RT (n = 510) vs. mastectomy (n = 751), 10-year ILRFS were 93.7% vs. 96.6% vs. 97.7%, (p < 0.001) and BCSS were 97.6% vs. 99.8% vs. 98.6%, (p = 0.01). Corresponding rates of ipsilateral invasive breast relapse at 10 years were 6.3% after BCS alone, 3.4% after BCS + RT, and 2.3% after mastectomy (p < 0.001). On multivariable analysis, factors associated with improved ILRFS were older age at diagnosis, low comorbidity score, absence of comedo histology, mastectomy, and post-BCS RT. Conclusion Patients with DCIS referred for oncologic assessment were more likely to undergo post-BCS RT, resulting in lower mastectomy and higher survival rates compared to non-referred patients. Patients with significant comorbidities were less likely to be referred and experienced lower ILRFS and BCSS. Referral for multidisciplinary oncologic assessment after surgery is warranted to individualize management and optimize outcomes for patients with DCIS.

Importance The use of a radiotherapy (RT) boost to the tumor bed after whole-breast RT (WBRT) for ductal carcinoma in situ (DCIS) is largely extrapolated from invasive cancer data, but robust evidence specific to DCIS is lacking. Objective To compare ipsilateral breast tumor recurrence (IBTR) in women with DCIS treated with vs without the RT boost after breast-conserving surgery and WBRT. Design, Setting, and Participants This retrospective analysis pooled deidentified patient-level data from 10 academic institutions in the United States, Canada, and France from January 1, 1980, through December 31, 2010. All patients had newly diagnosed pure DCIS (no microinvasion), underwent breast-conserving surgery, and received WBRT with or without the boost with a minimum of 5 years of follow-up required for inclusion in the analysis. Given the limited events after WBRT, an a priori power analysis was conducted to estimate the DCIS sample size needed to detect the anticipated benefit of the boost. Data were uniformly recoded at the host institution and underwent primary and secondary reviews before analysis. Sample size calculations (ratio of patients who received the boost dose to those who did not, 2:1; α = .05; power = 80%) estimated that 2982 cases were needed to detect a difference of at least 3%. The final analysis included 4131 patients (2661 in the boost group and 1470 in the no-boost group) with a median follow-up of 9 years and media boost dose of 14 Gy. Data were collected from July 2011 through February 2014 and analyzed from March 2014 through August 2015. Interventions Radiotherapy boost vs no boost. Main Outcomes and Measures Ipsilateral breast tumor recurrence. Results The analysis included 4131 patients (median [SD] age, 56.1 [10.9] years; range, 24-88 years). Patients with positive margins, unknown estrogen receptor status, and comedo necrosis were more likely to have received an RT boost. For the entire cohort, the boost was significantly associated with lower IBTR (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94; P = .01) and with IBTR-free survival (boost vs no-boost groups) of 97.1% (95% CI, 0.96-0.98) vs 96.3% (95% CI, 0.95-0.97) at 5 years, 94.1% (95% CI, 0.93-0.95) vs 92.5% (95% CI, 0.91-0.94) at 10 years, and 91.6% (95% CI, 0.90-0.93) vs 88.0% (95% CI, 0.85-0.91) at 15 years. On multivariable analysis accounting for confounding factors, the boost remained significantly associated with reduced IBTR (HR compared with no boost, 0.68; 95% CI, 0.50-0.91; P = .01) independent of age and tamoxifen citrate use. Conclusions and Relevance This patient-level analysis suggests that the RT boost confers a statistically significant benefit in decreasing IBTR across all DCIS age groups, similar to that seen in patients with invasive breast cancer. These findings suggest that a DCIS RT boost to the tumor bed could be considered to provide an added incremental benefit in decreasing IBTR after a shared discussion between the patient and her radiation oncologist.

Purpose Optimal local management for young women with early-stage breast cancer remains controversial. This study examined 15-year outcomes among women younger than 40 years treated with breast-conserving surgery plus whole-breast radiation therapy (BCT) compared with those treated with modified radical mastectomy (MRM). Methods and Materials Women aged 20 to 39 years with early-stage breast cancer diagnosed between 1989 and 2003 were identified in a population-based database. Primary outcomes of breast cancer–specific survival (BCSS), overall survival (OS) and secondary outcomes of local relapse–free survival (LRFS), locoregional relapse–free survival (LRRFS), and distant relapse–free survival (DRFS) were calculated using Kaplan-Meier methods and compared between BCT and MRM cohorts using log-rank tests. A planned subgroup analysis was performed on patients considered "ideal" for BCT (ie, T1N0, negative margins and no extensive ductal carcinoma in situ) and in whom local therapy may have the largest impact on survival because of low systemic risk. Results 965 patients were identified; 616 had BCT and 349 had MRM. The median follow-up time was 14.4 years (range, 8.4-23.3 years). Overall, 15-year rates of BCSS (76.0% vs 74.1%, P =.62), OS (74.2% vs 73.0%, P =.75), LRFS (85.4% vs 86.5%, P =.95), LRRFS (82.2% vs 81.6%, P =.61), and DRFS (74.4% vs 71.6%, P =.40) were similar between the BCT and MRM cohorts. In the "ideal" for BCT subgroup, there were 219 BCT and 67 MRM patients with a median follow-up time of 15.5 years. The 15-year BCSS (86.1% vs 82.9%, P =.57), OS (82.6% vs 82.9%, P =.89), LRFS (86.2% vs 84.2%, P =.50), LRRFS (83.1% vs 78.3%, P =.24), and DRFS (84.8% vs 79.1%, P =.17) were similar in the BCT and MRM cohorts. Conclusions This population-based analysis with long-term follow-up confirmed that women younger than 40 years treated with BCT had similar 15-year outcomes compared with MRM. Young age alone is not a contraindication to BCT.

Purpose To identify clinical and pathological factors that identify groups of women with stage I breast cancer with a 5-year risk of local recurrence (LR) ≤1.5% after breast-conserving therapy (BCS) plus whole-breast radiation therapy (RT). Methods and Materials Study subjects were 5974 patients ≥50 years of age whose cancer was diagnosed between 1989 and 2006, and were referred with pT1 pN0 invasive breast cancer treated with BCS and RT. Cases of 5- and 10-year LR were examined using Kaplan-Meier methods. Recursive partitioning analysis was performed in patients treated with and without endocrine therapy to identify combinations of factors associated with a 5-year LR risk ≤1.5%. Results The median follow-up was 8.61 years. Median age was 63 years of age (range, 50 to 91). Overall 5-year LR was 1.5% (95% confidence interval [CI], 1.2%-1.9%) and 10-year LR was 3.4% (95% CI, 2.8%-4.0%). Of 2830 patients treated with endocrine therapy, patient subsets identified with 5-year LR ≤1.5% included patients with grade 1 histology (n=1038; LR, 0.2%; 95% CI, 0%-0.5%) or grade 2 histology plus ≥60 years of age (n=843; LR, 0.5%; 95% CI, 0%-1.0%). Ten-year LR for these groups were 0.8% (95% CI, 0.1%-1.6%) and 0.9% (95% CI, 0.2%-1.6%), respectively. Of 3144 patients treated without endocrine therapy, patients with grade 1 histology plus clear margins had 5-year LR ≤1.5% (n=821; LR, 0.6%; 95% CI, 0.1%-1.2%). Ten-year LR for this group was 2.2% (95% CI, 1.0%-3.4%). Conclusions Histologic grade, age, margin status, and use of endocrine therapy identified 45% of a population-based cohort of female patients over age 50 with stage I breast cancer with a 5-year LR risk ≤1.5% after BCS plus RT. Prospective study is needed to evaluate the safety of omitting RT in patients with such a low risk of LR.

While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy. Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group. Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p

Introduction:Although the value of peer review is increasingly recognized, there is little research documenting its impact in the setting of stereotactic body radiation therapy (SBRT) for lung cancer. This study determines the dosimetric effect of peer review of tumor and normal tissue contouring in lung SBRT planning.Methods:Forty anonymized lung SBRT plans were retrospectively evaluated post treatment. Each plan was independently reviewed by two to three radiation oncologists using established institutional guidelines. For each structure, reviewers recorded recommendations for “no change,” “minor change,” “major change,” or “missing contour” and provided a modified or new contour as needed. Dose–volume histograms were analyzed for dosimetric violations.Results:Among 472 contoured structures evaluated, recommendations from peer review were 107 major change (23%), 176 minor change (37%), 157 no change (33%), and 32 missing (7%). Common major changes involved the skin (n = 20), heart (n = 18), and proximal bronchial tree (n = 15). Dose constraints were not achieved for 25 new or recontoured structures (5%), of which 17 involved the planning target volume (PTV). Among cases with PTV violations, the mean prescription dose coverage to the modified PTVs was 90%, compared with the protocol standard of greater than or equal to 95% coverage. The remaining violations involved the ribs (n = 5), spinal canal (n = 2), and heart (n = 1).Conclusions:Peer review of structure contouring resulted in significant changes in lung SBRT plans. Recontouring of several plans revealed violations of dose limits, most often involving inadequate PTV coverage. Peer review, especially of target volume delineation, is warranted to improve consistency and quality in lung SBRT planning.