Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer.

BACKGROUND: Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information. METHODS: We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years. RESULTS: Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1). CONCLUSIONS: Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).

Impact of non-adherence to endocrine therapy on recurrence risk in older women with stage I breast cancer after breast-conserving surgery.

PURPOSE: We examined the impact of non-adherence to adjuvant endocrine therapy (ET) on the risk and site of recurrence among older women with early stage, hormone receptor positive (HR+) breast cancer (EBC). METHODS: A population-based cohort of women age ≥ 65 years with T1N0 HR + EBC who were diagnosed between 2010 and 2016 and treated with breast-conserving surgery (BCS) + ET was identified. Treatment and outcomes were ascertained through linkage with administrative databases. ET non-adherence was examined as a time-dependent covariate in multivariable cause-specific Cox regression models to evaluate its effect on the risks of ipsilateral local recurrence (LR), contralateral breast cancer, and distant metastases. RESULTS: The population cohort includes 2637 women; 73% (N = 1934) received radiation (RT) + ET and 27% (N = 703) received ET alone. At a median follow-up of 8.14 years, the first event was LR in 3.6% of women treated with ET alone and 1.4% for those treated with RT + ET (p < 0.001); the risk of distant metastases was < 1% in both groups. The proportion of time adherent to ET was 69.0% among those treated with RT + ET and 62.8% for those treated with ET alone. On multivariable analysis, increasing proportion of time non-adherent to ET was associated with increased risk of LR ((HR = 1.52 per 20% increase in time; 95%CI 1.25, 1.85; p < 0.001), contralateral BC (HR = 1.55; 95%CI 1.30, 1.84; p < 0.001), and distant metastases (HR = 1.44; 95%CI 1.08, 1.94; p = 0.01) but absolute risks were low. CONCLUSION: Non-adherence to adjuvant ET was associated with an increased risk of recurrence, but absolute recurrence rates were low.

The Association Between Surgical Axillary Staging, Adjuvant Treatment Use and Survival in Older Women with Early Stage Breast Cancer: A Population-Based Study.

BACKGROUND: Choosing Wisely guidelines recommend against surgical axillary staging (AS) in women ≥70 years with ER+/HER2- early stage breast cancer (BC). This study examined the impact of AS omission on survival in older patients with BC. METHODS: This was a population-based cohort study using health administrative data in Ontario, Canada. We identified women aged 65-95 years who underwent surgery for Stage I/II BC between 2010 and 2016. Patients were weighted by propensity scores for receipt of AS that included patient and disease characteristics using overlap weights. Association with overall survival (OS) was calculated using weighted Cox models, and breast cancer-specific survival (BCSS) was calculated using weighted Fine and Gray models, adjusting for biomarkers and adjuvant treatments. Adjuvant treatment receipt was modelled with weighted log-binomial models. RESULTS: Among 17,370 older women, the 1771 (10.2%) who did not undergo AS were older, more comorbid, and less likely to undergo mastectomy. Women who did not undergo AS were less likely to receive adjuvant chemotherapy (RR 0.68, 95% CI 0.57-0.82), endocrine therapy (RR 0.85, 95% CI 0.81-0.89) or radiotherapy (RR 0.69, 95% CI 0.65-0.74). After weighting and adjustment, there was no significant difference in BCSS (sdHR 0.98, 95% CI 0.77-1.25), but women who did not undergo AS had worse OS (HR 1.14, 95% CI 1.04-1.25). The results among 6215 ER+/HER2- women ≥70 years undergoing SLNB vs no AS were similar. CONCLUSIONS: The omission of AS in older women with early stage BC was not associated with adverse BCSS, although OS was worse.

Long-term outcomes of women with large DCIS lesions treated with breast-conserving therapy.

PURPOSE: The paucity of data on women with large (≥ 40 mm) DCIS tumors lead to uncertainty on the safety of breast-conserving surgery (BCS) for these patients. We evaluated the impact of large tumor size on local recurrence (LR) among women with DCIS treated with BCS ± radiotherapy (RT). METHODS: Treatment and outcomes were ascertained through administrative databases for all women with DCIS in Ontario from 1994 to 2003 treated with BCS ± RT with negative margins; 82% had pathology review. Cox proportional hazards model was used to evaluate the impact of tumor size on LR. 10- and 15-year LR-free survival (LRFS) were calculated using Kaplan-Meier method. RESULTS: The cohort includes 2049 women treated by BCS (N = 1073 with RT). Median follow-up is 14 years (IQR 9-17 years). Referenced to tumors ≤ 10 mm, the risk of LR following BCS was significantly higher for larger tumors: HR ≥ 40 mm = 3.67 (95% CI 2.13, 6.33; p < 0.001), HR 26-39 mm = 2.27 (95% CI 1.47, 3.50, p < 0.001), and HR 11-25 mm = 1.42 (95% CI 1.06, 1.92, p = 0.02). However, for individuals with BCS + RT, large tumor size was not associated with a significantly increased risk of LR (HR ≥ 40 mm = 1.92 (95% CI 0.97, 3.79); HR 26-39 mm = 1.81 (95% CI 1.09-2.99)). For women with tumors ≥ 40 mm, 10-year LRFS risk for those treated by BCS alone, BCS + RT without boost, and BCS + RT with boost was 58.9%, 82.8%, and 83.9%. CONCLUSION: Large DCIS lesions ≥ 40 mm are associated with higher risks of LR following BCS, but high long-term LRFS rates can be achieved with the addition of breast RT.

DUCHESS: an evaluation of the ductal carcinoma in situ score for decisions on radiotherapy in patients with low/intermediate-risk DCIS.

BACKGROUND: Identification of women with DCIS who have a very low risk of local recurrence risk (LRR) after breast-conserving surgery (BCS) is needed to de-escalate therapy. We evaluated the impact of 10-year LRR estimates after BCS, calculated by the integration of a 12-gene molecular expression assay (Oncotype Breast DCIS Score®) and clinicopathological features (CPFs), on its ability to change radiation oncologists' recommendations for RT after BCS for DCIS. METHODS: Prospective cohort study of women with DCIS treated with BCS. Eligibility criteria were as follows: age > 45 years, tumor ≤ 2.5 cm, and margins ≥ 1 mm. Radiation oncologists provided 10-year LRR estimates without RT and recommendation for RT pre- and post-assay. Primary outcome was change in RT recommendation. RESULTS: 217 patients were evaluable, with mean age = 63 years, mean tumor size = 1.1 cm, and mean DCIS Score = 32; 140 (64%) were in the low-risk (<39), 32 (15%) were in the intermediate-risk (39-54), and 45 (21%) were in the high-risk groups (≥55). The assay led to a change in treatment recommendation in 76 (35.2%) (95%CI 29.1-41.8%) patients. RT recommendations decreased from 79% pre-assay to 50% post-assay (difference = 29%; 95%CI 22-35%) due to a significant increase in the proportion of patients with a predicted low LRR (< 10%) post-assay and recommendations to omit RT for those with a low predicted risk. The assay was associated with improved patient satisfaction and reduced decisional conflict. CONCLUSION: The DCIS Score assay combined with CPFs identified more women with an estimated low (<10%) 10-yr LR risk after BCS, leading to a significant decrease in recommendations for RT compared to estimates based on CPFs alone.

Computational Radiology in Breast Cancer Screening and Diagnosis Using Artificial Intelligence.

Breast cancer screening has been shown to significantly reduce mortality in women. The increased utilization of screening examinations has led to growing demands for rapid and accurate diagnostic reporting. In modern breast imaging centers, full-field digital mammography (FFDM) has replaced traditional analog mammography, and this has opened new opportunities for developing computational frameworks to automate detection and diagnosis. Artificial intelligence (AI), and its subdomain of deep learning, is showing promising results and improvements on diagnostic accuracy, compared to previous computer-based methods, known as computer-aided detection and diagnosis.In this commentary, we review the current status of computational radiology, with a focus on deep neural networks used in breast cancer screening and diagnosis. Recent studies are developing a new generation of computer-aided detection and diagnosis systems, as well as leveraging AI-driven tools to efficiently interpret digital mammograms, and breast tomosynthesis imaging. The use of AI in computational radiology necessitates transparency and rigorous testing. However, the overall impact of AI to radiology workflows will potentially yield more efficient and standardized processes as well as improve the level of care to patients with high diagnostic accuracy.

The impact of ductal carcinoma in situ on health services utilization.

PURPOSE: To determine the intermediate-term impact of diagnosis and treatment of ductal carcinoma in situ of the breast (DCIS) on health services utilization, we compared utilization by cases of DCIS to unaffected controls. METHODS: We identified a population-based cohort of Ontario females diagnosed with DCIS between 2010 and 2015. We matched 5 controls without any history of cancer to each case, on the date of diagnosis of the case (the index date), by age, annual mammography history, socioeconomic status, and comorbidity. We identified billing claims and hospital records, during the interval 13 to 60 months prior to, and subsequent to the index date, and computed rates per 100 person-years during both intervals, to conduct a difference-in-differences analysis. We used negative binomial regression to test if the change in rates in health services differed between cases and controls. RESULTS: Visits with a breast diagnosis code, and claims for breast surgery and imaging, were significantly increased among cases compared to controls (all p values < 0.0001) after DCIS;however, there was no increase in visits for anxiety or depression (RR 1.13 (95% CI 0.97, 1.32, p = 0.11), visits to psychiatrists (RR 1.07 (95% CI 0.82, 1.40) p = 0.6), or hospital procedures other than breast surgery (RR 1.10 (95% CI 0.88, 1.37) p = 0.4). CONCLUSIONS: DCIS is associated with more visits and procedures related to the breast compared to controls following diagnosis and treatment, but other health services utilization and visits related to anxiety and depression were not increased.

Molecular Evaluation of Breast Ductal Carcinoma in Situ with Oncotype DX DCIS.

A subset of patients with ductal carcinoma in situ (DCIS) of the breast develop ipsilateral invasive breast cancer after breast-conserving surgery with or without adjuvant radiotherapy. Risk assessment and prediction of adverse outcomes for individual patients based on traditional clinical and pathological parameters are limited. The Oncotype DCIS Score is a commercially available multigene assay that has been independently validated in a prospective clinical trial and a population-based cohort. The score helps to identify a subset of women >50 years old with unifocal disease that carries <10% risk of any local recurrence after breast-conserving surgery alone. In this population, individual patients and physicians may consider omitting adjuvant radiotherapy. In this article, we review the literature and summarize the evidence regarding the role of the Oncotype DCIS Score in estimating the risk of ipsilateral local recurrence and ipsilateral invasive breast cancer recurrence. The available data on clinical utility and cost-effective analysis for optimizing decisions on adjuvant treatments are discussed.

Psychological morbidity in women diagnosed with ductal carcinoma in situ compared with women with early breast cancer receiving radiotherapy.

PURPOSE: Despite having an excellent prognosis, patients with ductal carcinoma in situ (DCIS) report significant anxiety and depression following diagnosis. This study evaluated psychological morbidity using the Edmonton Symptom Assessment Scale (ESAS) in patients with DCIS compared with women with early-stage invasive breast cancer (EIBC) receiving radiotherapy (RT). METHODS: We identified patients diagnosed with DCIS or EIBC (stage I or II breast cancer) from 2011 to 2017 who had at least one ESAS completed pre- and post-RT. Data on systemic treatment, radiation, patient demographics, and disease stage were extracted from existing databases. Psychological morbidity was evaluated through measurement of depression, anxiety, and overall wellbeing within the ESAS. The Wilcoxon rank-sum test or chi-square test was performed for continuous or categorical variables. RESULTS: This study included 137 women with DCIS and 963 women with EIBC. ESAS was completed on average 28 days before RT (baseline) and 142 days after RT. Baseline ESAS scores showed significantly higher rates of depression among women with EIBC compared with those with DCIS (p = 0.006). Patients with EIBC also reported higher levels of anxiety and lower overall wellbeing than patients with DCIS, but this difference was not statistically significant. Post-RT ESAS scores showed significantly higher anxiety in patients with EIBC compared with DCIS (p = 0.049). Post-RT measures of anxiety and overall wellbeing were higher in patients with EIBC but differences were not statistically significant. CONCLUSION: Women with DCIS experience relatively less psychological morbidity than women with EIBC, pre- and post-RT.

Patterns of adjuvant care and outcomes of elderly women with stage I breast cancer after breast-conserving surgery: a population-based analysis.

PURPOSE: Randomized trials studying endocrine therapy (ET) with and without radiation therapy (RT) following breast-conserving surgery (BCS) have detected differences in local recurrence (LR) but not survival among elderly women with hormone receptor positive stage I breast cancer (BC). We assembled a population-based cohort of such women to examine the use and outcomes associated with or without the administration of adjuvant radiotherapy (RT) or ET. METHODS: Women aged ≥ 65 years with stage I BC treated with BCS in Ontario between 2010 and 2016, their treatments and outcomes were ascertained using deterministic linkages of administrative databases. Multivariable Cox regression models were used to evaluate risks of ipsilateral LR and of any first in-breast event, categorizing women by their treatment. RESULTS: 5076 women were treated with BCS followed by RT + ET (n = 1964), RT alone (n = 1325), ET alone (n = 719), or no adjuvant treatment (n = 1068). Median follow-up was 5 years. LR occurred in 0.9% after adjuvant RT + ET, 1.4% after RT alone, 3.1% after ET alone, and 9.4% after BCS alone (p < 0.001). The adjusted risk of LR was increased in those who received no adjuvant therapy (HR = 13.43, CI: 7.89, 22.85), or ET alone (HR = 4.03, CI: 2.14, 7.59). The adjusted risk of any first in-breast event was greatest among those without any adjuvant therapy (HR = 7.61, 95%CI: 5.21, 11.11, p < 0.0001). Absolute and adjusted risks of any first in-breast event were comparable between those with ET alone (HR = 2.09, 95%CI: 1.27, 3.43, p = 0.0038) and those with RT alone (HR = 1.91, 95% CI: 1.25, 2.91, p = 0.0028). CONCLUSIONS: Older women with stage I BC who receive no adjuvant therapy have a significant absolute risk of LR and any first in-breast event, whereas the absolute risk of these events among those with either RT alone or ET alone is only slightly higher than among those treated with both.

Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence in women with ductal carcinoma in situ treated with breast-conserving surgery.

PURPOSE: The impact of Ductal Carcinoma in Situ (DCIS) with multiple foci of microinvasion (MI) (≤ 1 mm) on the risks of local recurrence (LR) and invasive LR is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment. We report a population-based analysis of the impact of multiple foci of MI, confirmed by pathology review, on the 15-year risks of LR and invasive LR treated with breast-conserving surgery (BCS) ± radiotherapy (RT). METHODS: Cohort includes all women diagnosed with DCIS ± MI from 1994 to 2003 treated with BCS ± RT. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of LR and invasive LR, adjusting for covariates. The 15-year local and invasive local recurrence-free survival rates were calculated using the Kaplan-Meier method with differences compared by log-rank test. RESULTS: The cohort includes 2988 women treated by BCS; 2721 had pure DCIS (51% received RT), 267 had DCIS with one or more foci of MI (58% had RT). Median follow-up was 13 years. Median age at diagnosis was 58 years. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR = 1.59, 95% CI 1.01-2.49, p = 0.04) but not DCIS LR (HR = 0.89, 95% CI 0.46, 1.76, p = 0.7). The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% following treatment by BCS alone, 87.2%, 89.9%, and 77% for those treated with BCS + RT without boost and 89.2%, 91.3%, and 95% for women treated with BCS + RT and boost. CONCLUSIONS: The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.

The time-varying effect of radiotherapy after breast-conserving surgery for DCIS.

BACKGROUND: A better understanding underlying radiation (RT) response after breast-conserving surgery (BCS) is needed to mitigate over-treatment of DCIS. The hazard ratio (HR) measures the effect of RT but assumes the effect is constant over time. We examined the hazard function adjusted for adherence to surveillance mammography to examine variations in LR risk and the effect of RT over time. METHODS: Crude hazard estimates for the development of LR in a population cohort of DCIS treated by BCS ± RT were computed. Multivariable extended Cox models and hazard plots were used to examine the association between receipt of RT and risk of each outcome adjusted for baseline covariates and adherence to mammography. RESULTS: Population cohort includes 3262 women treated by BCS; 1635 received RT. Median follow-up was 13 years. LR developed in 364 women treated by BCS alone and 274 treated with RT. LR risk peaked at 2 years, declined until year 7, and then remained steady. The peak hazard of LR was associated with adverse features of DCIS. Early LR risk was attenuated in patients treated with RT but late annual risks of LR and invasive LR were similar among the two treatment groups. On multivariate analysis, RT was associated with a reduction in early LR risk (HR = 0.52, 95% CI 0.43-0.63, p < 0.0001) but did not reduce the risk of late LR (HR = 0.89, 95% CI: 0.67, 1.19, p = 0.44) (interaction, p = 0.002). CONCLUSIONS: The effect of RT is not uniform over time and greatest in the first 7 years after BCS for DCIS, which can guide future research to understand mechanisms underlying RT response and optimize future management of DCIS.

Ductal carcinoma in situ of the breast: an update for the pathologist in the era of individualized risk assessment and tailored therapies.

Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of mammary ductal epithelial cells confined to the ductal-lobular system, and a non-obligate precursor of invasive disease. While there has been a significant increase in the diagnosis of DCIS in recent years due to uptake of mammography screening, there has been little change in the rate of invasive recurrence, indicating that a large proportion of patients diagnosed with DCIS will never develop invasive disease. The main issue for clinicians is how to reliably predict the prognosis of DCIS in order to individualize patient treatment, especially as treatment ranges from surveillance only, breast-conserving surgery only, to breast-conserving surgery plus radiotherapy and/or hormonal therapy, and mastectomy with or without radiotherapy. We conducted a semi-structured literature review to address the above issues relating to "pure" DCIS. Here we discuss the pathology of DCIS, risk factors for recurrence, biomarkers and molecular signatures, and disease management. Potential mechanisms of progression from DCIS to invasive cancer and problems faced by clinicians and pathologists in diagnosing and treating this disease are also discussed. Despite the tremendous research efforts to identify accurate risk stratification predictors of invasive recurrence and response to radiotherapy and endocrine therapy, to date there is no simple, well-validated marker or group of variables for risk estimation, particularly in the setting of adjuvant treatment after breast-conserving surgery. Thus, the standard of care to date remains breast-conserving surgery plus radiotherapy, with or without hormonal therapy. Emerging tools, such as pathologic or biologic markers, may soon change such practice. Our review also includes recent advances towards innovative treatment strategies, including targeted therapies, immune modulators, and vaccines.

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

BACKGROUND: This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. OBJECTIVES: To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National Cancer Institute Physicians Data Query for ongoing trials. SELECTION CRITERIA: We included phase III randomised controlled trials (RCTs) comparing WBRT versus other treatments for adults with newly diagnosed multiple brain metastases. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and abstracted information in accordance with Cochrane methods. MAIN RESULTS: We added 10 RCTs to this updated review. The review now includes 54 published trials (45 fully published reports, four abstracts, and five subsets of data from previously published RCTs) involving 11,898 participants.Lower biological WBRT doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty evidence) in favour of control. The HR for neurological function improvement (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in favour of control fractionation.Higher biological WBRT doses versus controlThe HR for OS with higher biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate-certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P = 0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to 1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence) favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to 3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P < 0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials reported worse neurocognitive outcomes and one trial reported worse quality of life outcomes when WBRT was added to radiosurgery.We could not pool data from trials related to chemotherapy, optimal supportive care (OSC), molecular targeted agents, neurocognitive protective agents, and hippocampal sparing WBRT. However, one trial reported no differences in quality-adjusted life-years for selected participants with brain metastases from non-small-cell lung cancer randomised to OSC and WBRT versus OSC alone. AUTHORS' CONCLUSIONS: None of the trials with altered higher biological WBRT dose-fractionation schemes reported benefit for OS, NFI, or symptom control compared with standard care. However, OS and NFI were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules.The addition of WBRT to radiosurgery improved local and distant brain control in selected people with brain metastases, but data show worse neurocognitive outcomes and no differences in OS.Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in OS when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or molecular targeted agents in conjunction with WBRT remains experimental.Further trials are needed to evaluate the use of neurocognitive protective agents and hippocampal sparing with WBRT. As well, future trials should examine homogeneous participants with brain metastases with focus on prognostic features and molecular markers.

Breast Cancer Patients' Preferences for Adjuvant Radiotherapy Post Lumpectomy: Whole Breast Irradiation vs. Partial Breast Irradiation-Single Institutional Study.

This study was conducted to elucidate patients with early breast cancer preference for standard whole breast irradiation (WBI) or partial breast irradiation (PBI) following lumpectomy, as well as identify important factors for patients when making their treatment decisions. Based on relevant literature and ASTRO consensus statement guidelines, an educational tool and questionnaire were developed. Consenting, eligible women reviewed the educational tool and completed the trade-off questionnaire. Descriptive statistics were calculated, as well as chi-squares and a logistic regression model. Of the 90 patients who completed the study, 62 % preferred WBI, 30 % preferred PBI, 4 % required more information, and 3 % had no preferences. Of the patients who chose WBI, 58 % preferred hypofractionated RT, whereas 25 % preferred the conventional RT regimen. The majority of patients rated recurrence rate [WBI = 55/55 (100 %), PBI = 26/26 (100 %)] and survival [WBI = 54/55 (98 %), PBI = 26/26 (100 %)] as important factors contributing to their choice of treatment preference. Financial factors [WBI = 21/55 (38 %), PBI = 14/26 (53 %)] and convenience [WBI = 36/54 (67 %), PBI = 18/26 (69 %)] were rated as important less frequently. Significantly, more patients who preferred WBI also rated standard method of treatment as important when compared to patients who preferred PBI [WBI = 52/54 (96 %), PBI = 16/26 (61 %), χ 2 = 16.63, p = 0.001]. The majority of patients with early breast cancer who were surveyed for this study preferred WBI as an adjuvant treatment post lumpectomy, yet there was a sizeable minority who preferred PBI. This was associated with the importance patients place on standard treatment. These results will help medical professionals treat patients according to patient values.

Does a groin node dissection in vulvar cancer affect groin recurrence and overall survival?: Results from a population-based cohort study.

BACKGROUND: To determine, in a population-based cohort of vulvar cancer patients, if groin node dissection (GND) decreases the risk of groin recurrence and increases overall survival. METHODS: This population-based retrospective cohort study includes all cases of invasive squamous cell carcinoma identified in a provincial cancer registry from 1998 to 2007. Data collection was completed for all clinical and pathologic factors by chart abstraction. Cumulative incidence functions for recurrence were estimated, accounting for death before recurrence as a competing risk. Multivariable Cox regression models examined the associations between GND and groin recurrence, and overall survival. RESULTS: Clinical and pathologic data were collected for 1109 patients, of which 1038 patients were eligible for GND. 647 patients (62%) had a GND, while 391 patients (38%) did not. Median follow-up was 2.8years. Cumulative incidence plots demonstrate that the risk of death without recurrence was consistently higher than groin recurrence in each year after diagnosis. On multivariate analysis, GND was not significantly associated with decreased groin recurrence (HR 0.91, 95% CI 0.58-1.44, p=0.70). The hazard of death was 15% lower for women who received GND (HR 0.85, 95% CI 0.63-1.16, p=0.32), but this difference was not statistically significant. CONCLUSIONS: There was no significant difference in groin recurrence or overall survival in those with or without GND in this population-based cohort, raising questions whether a subgroup of patients may not benefit from GND. Patients had a higher probability of dying before groin recurrence could occur. Future trial design should consider death as a competing risk.

The effect of surgery type on survival and recurrence in very young women with breast cancer.

BACKGROUND: The impact of surgical treatment on outcomes in breast cacner in very young women remains unclear. We sought to determine the effect of surgery type on risk of recurrence and survival in a population-based cohort. METHODS: All women diagnosed with breast cancer aged ≤35 (1994-2003) were identified from the Ontario Cancer Registry. Patient, tumor, and treatment variables, including primary surgery, recurrences, and death were abstracted from chart review. Cox regression models were fit to determine the effect of surgery type on recurrence and overall survival. RESULTS: We identified 1,381 patients with 11-year median follow-up of which 793 (57%) had BCS. Of the remaining mastectomy patients, 52% had postmastectomy radiation. Overall, 41% of patients sustained a recurrence of any type and 31% died. Controlling for known confounders, there was no association between type of surgery and death from any cause (HR = 0.98, 95% CI = 0.78, 1.25) or first recurrence (HR = 0.93, 95% CI = 0.75, 1.14). Distant recurrence was most common (13% in BCS; 25.3% in mastectomy) with local recurrence 12.4% after BCS and 7.5% after mastectomy. CONCLUSIONS: In this cohort of very young women who were selected for treatment with BCS and mastectomy, we found similar oncologic outcomes. J. Surg. Oncol. 2017;115:122-130. © 2017 Wiley Periodicals, Inc.

The Added Value of Pathology Review in Vulvar Cancer: Results From a Population-based Cohort Study.

We conducted a population-based patterns of care study of vulvar carcinoma. This paper describes the changes in reporting based on pathology review. This is a retrospective population-based cohort study. We obtained all pathology records available from the provincial cancer registry for primary invasive squamous cell carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were conducted centrally by a group of gynecologic pathologists and were identified during abstraction. Corresponding original reports were matched to pathology review reports based on accession numbers. We compared the reported value for presence/absence of invasion, grade, depth, thickness, size, lymphovascular space invasion, peripheral margin status, and deep margin status in the original and review report. A total of 1011 vulvar resection reports were identified. From these, we identified 316 pairs of original/review reports. Missing data were common but improved in the reviews. In total, 55 (17%) reports had at least 1 change from the original to the review based on presence of invasion, depth, lymphovascular space invasion, or margin. When we included reports where a variable was missing in the original but then completed in the review, there were clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare diagnosis and pathology reviews resulted in potentially important clinical changes in a significant proportion of cases. Referral pathologists play an important role in contributing to high-quality clinical decisions.

Quality of life (QOL) and symptom burden (SB) in patients with breast cancer.

PURPOSE: The purpose of this study was to determine the quality of life (QOL) and symptom burden (SB) among breast cancer patients. METHODS: Patients with DCIS, early stage, locally advanced, or metastatic breast cancer completed the Edmonton Symptom Assessment System (ESAS) and the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B). Patients were divided into subsequent cohorts based on their last day of treatment, age at enrollment, radiation, chemotherapy, and hormone therapy. RESULTS: A total of 1513 patients were enrolled. Metastatic patients had a lower QOL and greatest SB compared to all other patient groups. Patients ≤50 years old with early stage or locally advanced breast cancer had a lower QOL and greater SB for fatigue, depression, and anxiety compared to all other age cohorts. Patients with early stage breast cancer who received chemotherapy had a lower QOL and greater SB. Patients taking selective estrogen receptor modulator (SERM) had greater SB for depression and lower QOL compared to those not on SERM. Patients 2-10 years post-treatment had a lower QOL compared to patients ≥10 years post-treatment. CONCLUSION: Patients ≤50 years old, 2-10 years post-treatment, treated with chemotherapy or SERM had increased SB and decreased QOL. Individualized interventions and programs can be developed to tailor to physical, educational, and psychosocial needs identified across the breast cancer continuum.