Breast conserving surgery combined with radiation therapy offers improved survival over mastectomy in early-stage breast cancer.

INTRODUCTION: Landmark trials established equivalent survival regardless of extent of breast surgery in early-stage breast cancer. However, recent studies suggest a survival advantage for breast conserving surgery (BCS) with radiotherapy (BCT). This study assesses the impact of type of surgery on overall survival (OS), breast cancer specific survival (BCSS) and local recurrence (LR) in a modern population-based cohort. METHODS: Female patients aged ≥18, pT1-2pN0, who had surgery between 2006 and 2016 were identified from Breast Cancer Outcome Unit prospective database. Neoadjuvant chemotherapy patients were excluded. Multivariable Cox regression was used to assess the effect of surgical procedure on OS, BCSS, and LR on cohort with complete data. RESULTS: BCT was performed in 8422 patients and TM in 4034 patients. The baseline characteristics differed between the groups. Mean follow up was 8.3 years. BCT was associated with increased OS HR 1.37, p < 0.001, BCSS survival HR 1.49, p < 0.001, and similar LR HR 1.00, p > 0.90. CONCLUSION: This study supports that in early-stage breast cancer, BCT has improved BCSS compared to TM without an increased risk of LR.

Impact of the COVID-19 Pandemic on Access to Cancer Surgery: Analysis of Surgical Wait Times in British Columbia, Canada.

OBJECTIVE: As coronavirus disease 2019 (COVID-19) spread, efforts were made to preserve resources for the anticipated surge of COVID-19 patients in British Columbia, Canada. However, the relationship between COVID-19 hospitalizations and access to cancer surgery is unclear. In this project, we analyze the impact of COVID-19 patient volumes on wait time for cancer surgery. METHODS: We conducted a retrospective study using population-based datasets of regional surgical wait times and COVID-19 patient volumes. Weekly median wait times for urgent, nonurgent, cancer, and noncancer surgeries, and maximum volumes of hospitalized patients with COVID-19 were studied. The results were qualitatively analyzed. RESULTS: A sustained association between weekly median wait time for priority and other cancer surgeries and increase hospital COVID-19 patient volumes was not qualitatively discernable. In response to the first phase of COVID-19 patient volumes, relative to pre-COVID-19 pandemic levels, wait time were shortened for urgent cancer surgery but increased for nonurgent surgeries. During the second phase, for all diagnostic groups, wait times returned to pre-COVID-19 pandemic levels. During the third phase, wait times for all surgeries increased. CONCLUSION: Cancer surgery access may have been influenced by other factors, such as policy directives and local resource issues, independent of hospitalized COVID-19 patient volumes. The initial access limitations gradually improved with provincial and institutional resilience, and vaccine rollout.

Factors influencing suboptimal pathologic margins and re-excision following breast conserving surgery for ductal carcinoma in-situ.

INTRODUCTION: Re-excisions following breast conserving surgery (BCS) are common, occurring more frequently in ductal carcinoma in-situ (DCIS) than its' malignant counterpart. Although one quarter of patients with breast cancer will have DCIS, there is limited information available regarding factors predisposing to inadequate pathologic margins, and the need for re-excision. METHODS: Retrospective review of patients treated for DCIS between the years 2010-2016 was conducted. Patients with DCIS undergoing BCS were identified and evaluated for demographic and pathologic factors associated with suboptimal pathologic margins and re-excision. Multivariate analysis with Wald Chi-Square testing was performed. RESULTS: 241 patients underwent BCS with suboptimal margins (SOM) in 51.7% (123/238), with 27.8% undergoing re-excision (67/241). Tumor size was the most influential variable, positively associated with SOM (OR = 10.25, CI: 5.50-19.13) and re-excision (OR = 6.36, CI: 3.92-10.31). Patient age was inversely associated with SOM (OR = 0.58, CI: 0.39-0.85) and subsequent re-excisions (OR = 0.56, CI: 0.36-0.86). Low tumour grade was associated with re-excision (OR = 1.31, CI: 0.63-2.71), while ER negative disease was associated with SOM (OR = 2.24, CI: 1.21-4.14). DISCUSSION: Inadequate pathologic margins following BCS, and subsequent re-excision rates are common in patients with DCIS, and consistent with the literature. Tumour size is the dominant factor driving this occurrence, with patient age and tumour grade also impacting outcomes.

Patient reported outcomes following breast conserving surgery are improved by minimizing re-excisions and excessive breast tissue removal.

BACKGROUND: Patient reported outcomes (PRO's) are a valuable tool in obtaining the patients' perspective on the effectiveness of breast conservation surgery. Investigation has primarily been focused on patient and disease related factors impacting PRO's, with a limited focus on surgically modifiable factors. We investigate the impact that the volume of breast tissue removed, and performance of re-excisions have on PRO's. METHODS: Retrospective evaluation of the BREAST-Q (breast conservation module) in patients undergoing breast conserving surgery over a 3 year period. Multivariate analysis of patient, disease, and treatment related factors impacting PRO's. RESULTS: 163 patients completed the BREAST-Q. The median satisfaction with breast score was 67 (IQR, 48-88). Increasing volume of resected breast tissue was negatively associated with appearance of the breast (-0.05/cm3 (CI; -0.08 to -0.01)), as was the performance of re-excisions (-6.59 (CI; -14.73 - 0)). Physical well-being of chest was negatively associated with the volume of breast tissue removed (-0.05/cm3 (CI; -0.08 - 0)), but not re-excisions. Psychosocial well-being was negatively affected by the volume of tissue removed ((-0.04/cm3(CI; -0.07 - 0)), and re-excisions (-2.88 (CI; -10.96 - 0)). Patient body mass index, disease stage, receipt of Tamoxifen, as well as axillary lymph node dissection also impacted BREAST-Q domain scores. CONCLUSION: The removal of larger volumes of breast tissue and performance of re-excisions negatively impact patient quality of life and breast satisfaction following breast conserving surgery. Optimal patient reported outcomes are associated with accurate tumour removal, which minimizes re-excisions and the removal of normal breast tissue.

Lowering Re-excision Rates After Breast-Conserving Surgery: Unraveling the Intersection Between Surgeon Case Volumes and Techniques.

BACKGROUND: The re-excision rates after breast-conserving surgery (BCS) are significantly varied, with surgeon case volume as one influential factor. Surgeons with higher case volumes have been shown to have lower reoperation rates. This study attempted to determine whether this may be attributable to excessive breast tissue removal during initial BCS. METHODS: A retrospective study analyzed referrals to the authors' cancer center during 3 years. Patients undergoing initial BCS for ductal carcinoma in situ or T1-T3 breast cancers were included. Patient age, tumor factors, surgeon case volume, and the calculated resection ratio (CRR) were analyzed. The total resection volume was divided by the optimal resection volume to produce the CRR, which reflected the magnitude of excess tissue resected during initial BCS. Comparison of the mean CRR between surgeon case-volume categories was performed with a repeated measures analysis of variance. A multivariate regression model assessed the effects of the CRR and surgeon case volume on re-excision rates. RESULTS: Larger tumor size, lobular histology, and lower CRR were associated with increased re-excision rates. The CRR was similar for each surgeon case-volume group. Surgeon case volume was not independently associated with re-excision rates, but surgeons with very high case volumes had lower odds of re-excision than surgeons with intermediate case volumes (odds ratio 0.44; 95% confidence interval 0.21-0.91). CONCLUSIONS: When control was used for the CRR, apparent differences in re-excision rates between surgeon case-volume groups were observed, suggesting that surgeons with higher case volumes may be more accurate when performing BCS.

Premature Fecal Immunochemical Testing in British Columbia Canada: a Retrospective Review of Physician and Screening Participant Characteristics.

BACKGROUND: Colorectal cancer (CRC) screening is an evidence-based strategy to reduce CRC-related mortality. OBJECTIVE: This study identifies physician and participant characteristics, as well as previous FIT values associated with premature FIT usage. DESIGN: This is a retrospective review of all FITs ordered from January 1, 2016, until June 30, 2017. For each ordered FIT, the participant's chart was reviewed to identify if a previous FIT had occurred in the prior 21 months. A premature FIT was defined as an ordered test with a negative FIT in the preceding 21 months. PARTICIPANTS: Screening participants were average risk for CRC, aged 50-74, and had a FIT ordered by their primary care provider in British Columbia, Canada. MAIN MEASURES: The BC College of Physicians and Surgeons' database was used to identify the location of referring physician, date of graduation from medical school, and gender. The participant's age, gender, and value of previous FIT were recorded. Physician and participant variables and previous FIT value were examined with logistic regression to identify associations with premature FIT ordering. KEY RESULTS: In total, 385,375 FITs were ordered during this period with 116,727 representing participants returning following a previous negative FIT. In total, 35,148 (30.1%) returned early for screening. Men were more likely to return early than women (OR 1.14; 95% CI 1.11-1.17; p < 0.0001). Male physicians were more likely to order premature FITs (OR 1.15; 95% CI 1.06-1.24; p < 0.0001). A higher quantitative FIT value (ng/mL) of the previous FIT was also associated with early screening (OR 1.11; 95% CI 1.09-1.14; < 0.0001). CONCLUSIONS: This study found that approximately 30% of FIT tests, ordered for CRC screening, were ordered before they were due. This may lead to wasted resources, unnecessary participant stress, and unwarranted patient risk.

Primary organ preservation vs total laryngectomy for T4a larynx cancer.

BACKGROUND: There is a lack of consensus regarding the management of T4a larynx cancer. We evaluated the outcomes of organ preservation and laryngectomy for T4a laryngeal cancer. METHODS: Retrospective analysis of patients with T4a larynx cancer at BC Cancer from 1984 to 2014 was performed. Outcomes in patients treated with surgery alone (Sx) (n = 47), surgery with adjuvant radiotherapy (Sx/RT) (n = 94), radiation alone (RT) (n = 152), and radiation with concurrent chemoradiotherapy (chemoRT) (n = 36) were compared. RESULTS: The 5-year overall survival (OS) was 40% for chemoRT, 34% for RT, 23% for Sx, and 45% for Sx/RT. On multivariate analysis (MVA), Sx/RT (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.48-0.91) and chemoRT (HR, 0.44; 95% CI, 0.26-0.72) were associated with better OS than RT alone (P = .001). Sx had similar OS compared to RT (HR, 1.17; 95% CI, 0.82-1.68). CONCLUSIONS: ChemoRT and Sx/RT were associated with better OS compared to single modality treatment. ChemoRT may be considered as an option for T4a larynx cancer.

The TEACHH model to predict life expectancy in patients presenting for palliative spine radiotherapy: external validation and comparison with alternate models.

INTRODUCTION: The TEACHH score was developed to identify patients with predicted short (< 3 months) and long (> 1 year) life expectancy. We aimed to validate this model in an independent group of patients presenting for palliative spine radiotherapy and to compare it to alternate prognostic models. METHODS: We retrospectively reviewed charts of 195 consecutive patients referred for palliative spine radiotherapy. Patients were grouped according to the number of risk factors from the TEACHH model, Chow model, and Oswestry Risk Index. RESULTS: One hundred and eighty patients with a median age of 65 years were included. Follow-up was 5.8 months in all patients and 31.8 months in living patients. For the TEACHH model, patients in groups 1, 2, and 3 had a median (95% CI) overall survival (OS) of 22.3 (15.7-36.1), 4.9 (3.8-6.6), and 1.5 (0.8-5.4) months, respectively. Wilcoxon pairwise comparisons showed statistically different survival between groups 1 and 2, and 1 and 3. In the Chow model, patients in groups 1, 2, and 3 had a median (95% CI) OS of 16.1 (10.0-22.3), 5.9 (3.8-9.2), and 1.9 (1.2-2.5) months, respectively. There was a significant difference between all groups. The Oswestry Risk Index identified five prognostic groups with median OS (95% CI) ranging from 22.2 (12.9-30.2) to 2.1 (0.8-4.0) months. Only group 1 was statistically different from the others. Although the effect of age was small, the TEACHH model performed best with the inclusion of all parameters. CONCLUSIONS: The TEACHH model is useful to identify patients with spinal metastases with predicted short, intermediate, and long LE. Its prognostic ability is similar to the Chow model.

Proteasome regulation of the chromodomain protein MRG-1 controls the balance between proliferative fate and differentiation in the C. elegans germ line.

The level of stem cell proliferation must be tightly controlled for proper development and tissue homeostasis. Multiple levels of gene regulation are often employed to regulate stem cell proliferation to ensure that the amount of proliferation is aligned with the needs of the tissue. Here we focus on proteasome-mediated protein degradation as a means of regulating the activities of proteins involved in controlling the stem cell proliferative fate in the C. elegans germ line. We identify five potential E3 ubiquitin ligases, including the RFP-1 RING finger protein, as being involved in regulating proliferative fate. RFP-1 binds to MRG-1, a homologue of the mammalian chromodomain-containing protein MRG15 (MORF4L1), which has been implicated in promoting the proliferation of neural precursor cells. We find that C. elegans with reduced proteasome activity, or that lack RFP-1 expression, have increased levels of MRG-1 and a shift towards increased proliferation in sensitized genetic backgrounds. Likewise, reduction of MRG-1 partially suppresses stem cell overproliferation. MRG-1 levels are controlled independently of the spatially regulated GLP-1/Notch signalling pathway, which is the primary signal controlling the extent of stem cell proliferation in the C. elegans germ line. We propose a model in which MRG-1 levels are controlled, at least in part, by the proteasome, and that the levels of MRG-1 set a threshold upon which other spatially regulated factors act in order to control the balance between the proliferative fate and differentiation in the C. elegans germ line.