Application of deep learning on mammographies to discriminate between low and high-risk DCIS for patient participation in active surveillance trials.

BACKGROUND: Ductal Carcinoma In Situ (DCIS) can progress to invasive breast cancer, but most DCIS lesions never will. Therefore, four clinical trials (COMET, LORIS, LORETTA, AND LORD) test whether active surveillance for women with low-risk Ductal carcinoma In Situ is safe (E. S. Hwang et al., BMJ Open, 9: e026797, 2019, A. Francis et al., Eur J Cancer. 51: 2296-2303, 2015, Chizuko Kanbayashi et al. The international collaboration of active surveillance trials for low-risk DCIS (LORIS, LORD, COMET, LORETTA),  L. E. Elshof et al., Eur J Cancer, 51, 1497-510, 2015). Low-risk is defined as grade I or II DCIS. Because DCIS grade is a major eligibility criteria in these trials, it would be very helpful to assess DCIS grade on mammography, informed by grade assessed on DCIS histopathology in pre-surgery biopsies, since surgery will not be performed on a significant number of patients participating in these trials. OBJECTIVE: To assess the performance and clinical utility of a convolutional neural network (CNN) in discriminating high-risk (grade III) DCIS and/or Invasive Breast Cancer (IBC) from low-risk (grade I/II) DCIS based on mammographic features. We explored whether the CNN could be used as a decision support tool, from excluding high-risk patients for active surveillance. METHODS: In this single centre retrospective study, 464 patients diagnosed with DCIS based on pre-surgery biopsy between 2000 and 2014 were included. The collection of mammography images was partitioned on a patient-level into two subsets, one for training containing 80% of cases (371 cases, 681 images) and 20% (93 cases, 173 images) for testing. A deep learning model based on the U-Net CNN was trained and validated on 681 two-dimensional mammograms. Classification performance was assessed with the Area Under the Curve (AUC) receiver operating characteristic and predictive values on the test set for predicting high risk DCIS-and high-risk DCIS and/ or IBC from low-risk DCIS. RESULTS: When classifying DCIS as high-risk, the deep learning network achieved a Positive Predictive Value (PPV) of 0.40, Negative Predictive Value (NPV) of 0.91 and an AUC of 0.72 on the test dataset. For distinguishing high-risk and/or upstaged DCIS (occult invasive breast cancer) from low-risk DCIS a PPV of 0.80, a NPV of 0.84 and an AUC of 0.76 were achieved. CONCLUSION: For both scenarios (DCIS grade I/II vs. III, DCIS grade I/II vs. III and/or IBC) AUCs were high, 0.72 and 0.76, respectively, concluding that our convolutional neural network can discriminate low-grade from high-grade DCIS.

Multianalyte liquid biopsy to aid the diagnostic workup of breast cancer.

Breast cancer (BC) affects 1 in every 8 women in the United States and is currently the most prevalent cancer worldwide. Precise staging at diagnosis and prognosis are essential components for the clinical management of BC patients. In this study, we set out to evaluate the feasibility of the high-definition single cell (HDSCA) liquid biopsy (LBx) platform to stratify late-stage BC, early-stage BC, and normal donors using peripheral blood samples. Utilizing 5 biomarkers, we identified rare circulating events with epithelial, mesenchymal, endothelial and hematological origin. We detected a higher level of CTCs in late-stage patients, compared to the early-stage and normal donors. Additionally, we observed more tumor-associated large extracellular vesicles (LEVs) in the early-stage, compared to late-stage and the normal donor groups. Overall, we were able to detect reproducible patterns in the enumeration of rare cells and LEVs of cancer vs. normal donors and early-stage vs. late-stage BC with high accuracy, allowing for robust stratification. Our findings illustrate the feasibility of the LBx assay to provide robust detection of rare circulating events in peripheral blood draws and to stratify late-stage BC, early-stage BC, and normal donor samples.

Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk.

Forkhead box class O (FOXO) transcription factors play a pivotal role in regulating a variety of biological processes, including organismal development, cell signaling, cell metabolism, and tumorigenesis. Therefore, we hypothesize that genetic variants in FOXO pathway genes are associated with breast cancer (BC) risk. To test this hypothesis, we conducted a large meta-analysis using 14 published genome-wide association study (GWAS) data sets in the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study. We assessed associations between 5214 (365 genotyped in DRIVE and 4849 imputed) common single-nucleotide polymorphisms (SNPs) in 55 FOXO pathway genes and BC risk. After multiple comparison corrections by the Bayesian false-discovery probability method, we found five SNPs to be significantly associated with BC risk. In stepwise multivariate logistic regression analysis with adjustment for age, principal components, and previously published SNPs in the same data set, three independent SNPs (i.e., FBXO32 rs10093411 A>G, FOXO6 rs61229336 C>T, and FBXO32 rs62521280 C>T) remained to be significantly associated with BC risk (p = 0.0008, 0.0011, and 0.0017, respectively). Additional expression quantitative trait loci analysis revealed that the FBXO32 rs62521280 T allele was associated with decreased messenger RNA (mRNA) expression levels in breast tissue, while the FOXO6 rs61229336 T allele was found to be associated with decreased mRNA expression levels in the whole blood cells. Once replicated by other investigators, these genetic variants may serve as new biomarkers for BC risk.

Clinician Burnout Associated With Sex, Clinician Type, Work Culture, and Use of Electronic Health Records.

Importance: Electronic health records (EHRs) are considered a potentially significant contributor to clinician burnout. Objective: To describe the association of EHR usage, sex, and work culture with burnout for 3 types of clinicians at an academic medical institution. Design, Setting, and Participants: This cross-sectional study of 1310 clinicians at a large tertiary care academic medical center analyzed EHR usage metrics for the month of April 2019 with results from a well-being survey from May 2019. Participants included attending physicians, advanced practice providers (APPs), and house staff from various specialties. Data were analyzed between March 2020 and February 2021. Exposures: Clinician demographic characteristics, EHR metadata, and an institution-wide survey. Main Outcomes and Measures: Study metrics included clinician demographic data, burnout score, well-being measures, and EHR usage metadata. Results: Of the 1310 clinicians analyzed, 542 (41.4%) were men (mean [SD] age, 47.3 [11.6] years; 448 [82.7%] White clinicians, 52 [9.6%] Asian clinicians, and 21 [3.9%] Black clinicians) and 768 (58.6%) were women (mean [SD] age, 42.6 [10.3] years; 573 [74.6%] White clinicians, 105 [13.7%] Asian clinicians, and 50 [6.5%] Black clinicians). Women reported more burnout (survey score ≥50: women, 423 [52.0%] vs men, 258 [47.6%]; P = .008) overall. No significant differences in EHR usage were found by sex for multiple metrics of time in the EHR, metrics of volume of clinical encounters, or differences in products of clinical care. Multivariate analysis of burnout revealed that work culture domains were significantly associated with self-reported results for commitment (odds ratio [OR], 0.542; 95% CI, 0.427-0.688; P < .001) and work-life balance (OR, 0.643; 95% CI, 0.559-0.739; P < .001). Clinician sex significantly contributed to burnout, with women having a greater likelihood of burnout compared with men (OR, 1.33; 95% CI, 1.01-1.75; P = .04). An increased number of days spent using the EHR system was associated with less likelihood of burnout (OR, 0.966; 95% CI, 0.937-0.996; P = .03). Overall, EHR metrics accounted for 1.3% of model variance (P = .001) compared with work culture accounting for 17.6% of variance (P < .001). Conclusions and Relevance: In this cross-sectional study, sex-based differences in EHR usage and burnout were found in clinicians. These results also suggest that local work culture factors may contribute more to burnout than metrics of EHR usage.

Hymenolepis diminuta-based helminth therapy in C3(1)-TAg mice does not alter breast tumor onset or progression.

BACKGROUND AND OBJECTIVES: An individual's risk of breast cancer is profoundly affected by evolutionary mismatch. Mismatches in Western society known to increase the risk of breast cancer include a sedentary lifestyle and reproductive factors. Biota alteration, characterized by a loss of biodiversity from the ecosystem of the human body as a result of Western society, is a mismatch known to increase the risk of a variety of inflammation-related diseases, including colitis-associated colon cancer. However, the effect of biota alteration on breast cancer has not been evaluated. METHODOLOGY: In this study, we utilized the C3(1)-TAg mouse model of breast cancer to evaluate the role of biota alteration in the development of breast cancer. This model has been used to recapitulate the role of exercise and pregnancy in reducing the risk of breast cancer. C3(1)-TAg mice were treated with Hymenolepis diminuta, a benign helminth that has been shown to reverse the effects of biota alteration in animal models. RESULTS: No effect of the helminth H. diminuta was observed. Neither the latency nor tumor growth was affected by the therapy, and no significant effects on tumor transcriptome were observed based on RNAseq analysis. CONCLUSIONS AND IMPLICATIONS: These findings suggest that biota alteration, although known to affect a variety of Western-associated diseases, might not be a significant factor in the high rate of breast cancer observed in Western societies. LAY SUMMARY: An almost complete loss of intestinal worms in high-income countries has led to increases in allergic disorders, autoimmune conditions, and perhaps colon cancer. However, in this study, results using laboratory mice suggest that loss of intestinal worms might not be associated with breast cancer.

Variants in SNAI1, AMDHD1 and CUBN in vitamin D pathway genes are associated with breast cancer risk: a large-scale analysis of 14 GWASs in the DRIVE study.

Vitamin D has a potential anticarcinogenic role, possibly through regulation of cell proliferation and differentiation, stimulation of apoptosis, immune modulation and regulation of estrogen receptor levels. Because breast cancer (BC) risk varies among individuals exposed to similar risk factors, we hypothesize that genetic variants in the vitamin D pathway genes are associated with BC risk. To test this hypothesis, we performed a larger meta-analysis using 14 published GWAS datasets in the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Study. We assessed associations between 2,994 (237 genotyped in the DRIVE study and 2,757 imputed from the 1000 Genomes Project) single nucleotide polymorphisms (SNPs) in 33 vitamin D pathway genes and BC risk. In unconditional logistic regression analysis, we found 11 noteworthy SNPs to be associated with BC risk after multiple comparison correction by the Bayesian false-discovery probability method (<0.80). In stepwise logistic regression analysis, with adjustment for age, principal components and previously published SNPs in the same study populations, we identified three independent SNPs (SNAI1 rs1047920 C>T, AMDHD1 rs11826 C>T and CUBN rs3914238 C>T) to be associated with BC risk (P = 0.0014, 0.0020 and 0.0022, respectively). Additional expression quantitative trait loci analysis revealed that the rs73276407 A allele, in a high LD with the rs1047920 T allele, was associated with decreased SNAI1 mRNA expression levels, while the rs11826 T allele was significantly associated with elevated AMDHD1 mRNA expression levels. Once replicated by other investigators and additional mechanistic studies, these genetic variants may serve as new biomarkers for susceptibility to BC.

Cutaneous Adverse Events of Anti-PD-1 Therapy and BRAF Inhibitors.

OPINION STATEMENT: The treatment of advanced melanoma has undergone a dramatic transformation over the last decade with the advent of targeted and immunomodulatory therapies. This transition from cytotoxic chemotherapy has yielded improvements in both survival and quality of life; yet despite their therapeutic advantages, these treatments have been associated with a diverse range of cutaneous adverse events (AEs). These range from relatively benign eczematous conditions to more severe inflammatory and bullous disorders, and can include induction of second malignancies. AEs can result in serious morbidity and risk of mortality if not recognised and managed early. As a consequence of their novelty, and rapid uptake, these agents have been subject to intense scrutiny and there is a general understanding that cutaneous AEs should be anticipated in treatment plans. Dermatologists should be integrated into management teams to assist in the development of treatment protocols for anticipated common AEs and to provide expert management of more severe, rare or unusual AEs. Our experience has shown a reduction in treatment interruptions, more rapid recognition of unusual AEs and improved management pathways for patients suffering cutaneous AEs.

Acquired lipodystrophy associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors have become the mainstay of treatment for metastatic melanoma. This article presents a new case of acquired generalised lipodystrophy (AGL) during anti-programmed cell death-1 (anti-PD-1) therapy and a systematic review of the literature with an aim to further understand the pathogenesis. A comprehensive search was conducted using PubMed, Embase, MEDLINE and Cochrane Central databases. We identified four cases of lipodystrophy associated with anti-PD-1 immunotherapy, including our own. Of these, three were associated with nivolumab, and one with pembrolizumab. Body composition changes occurred at a median of 7 months after anti-PD-1 initiation. All cases reported AGL, with subcutaneous fat loss affecting majority of the body. There were three reported cases of insulin resistance associated with AGL. AGL should be a recognised adverse event associated with anti-PD-1 therapy.

The impact of patient characteristics and lifestyle factors on the risk of an ipsilateral event after a primary DCIS: A systematic review.

OBJECTIVE: The majority of 'low-risk' (grade I/II) Ductal Carcinoma In Situ (DCIS) may not progress to invasive breast cancer during a women's lifetime. Therefore, the safety of active surveillance versus standard surgical treatment for DCIS is prospectively being evaluated in clinical trials. If proven safe and selectively implemented in clinical practice, a significant group of women with low-risk DCIS may forego surgery and radiotherapy in the future. Identification of modifiable and non-modifiable risk factors associated with prognosis after a primary DCIS would also enhance our care of women with low-risk DCIS. METHODS: To identify modifiable and non-modifiable risk factors for subsequent breast events after DCIS, we performed a systematic literature search in PUBMED, EMBASE and Scopus. RESULTS: Six out of the 3870 articles retrieved were included for final data extraction. These six studies included a total of 4950 patients with primary DCIS and 640 recorded subsequent breast events. There was moderate evidence for an association of a family history of breast cancer, premenopausal status, high BMI, and high breast density with a subsequent breast cancer or further DCIS. CONCLUSION: There is a limited number of recent studies published on the impact of modifiable and non-modifiable risk factors on subsequent events after DCIS. The available evidence is insufficient to identify potential targets for risk reduction strategies, reflecting the relatively small numbers and the lack of long-term follow-up in DCIS, a low-event condition.

Survival and prognosis of individuals receiving programmed cell death 1 inhibitor with and without immunologic cutaneous adverse events.

BACKGROUND: The treatment response to new immunotherapy in advanced melanoma patients remains varied between individuals. Immune-related cutaneous side effects might have prognostic value. OBJECTIVE: To determine whether development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival. METHODS: A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1. RESULTS: In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months; 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of individuals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for individuals who had ≥1 cutaneous adverse event (CAE) develop. Compared with individuals with no CAE, the hazard ratio for disease progression and death for individuals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91; P = .025) by the time-dependent Cox proportional hazards model. LIMITATIONS: Single-center study. CONCLUSION: This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.

Genetic variants of genes in the NER pathway associated with risk of breast cancer: A large-scale analysis of 14 published GWAS datasets in the DRIVE study.

A recent hypothesis-free pathway-level analysis of genome-wide association study (GWAS) datasets suggested that the overall genetic variation measured by single nucleotide polymorphisms (SNPs) in the nucleotide excision repair (NER) pathway genes was associated with breast cancer (BC) risk, but no detailed SNP information was provided. To substantiate this finding, we performed a larger meta-analysis of 14 previously published GWAS datasets in the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) study with 53,107 subjects of European descent. Using a hypothesis-driven approach, we selected 138 candidate genes from the NER pathway using the "Molecular Signatures Database (MsigDB)" and "PathCards". All SNPs were imputed using IMPUTE2 with the 1000 Genomes Project Phase 3. Logistic regression was used to estimate BC risk, and pooled ORs for each SNP were obtained from the meta-analysis using the false discovery rate for multiple test correction. RegulomeDB, HaploReg, SNPinfo and expression quantitative trait loci (eQTL) analysis were used to assess the SNP functionality. We identified four independent SNPs associated with BC risk, BIVM-ERCC5 rs1323697_C (OR = 1.06, 95% CI = 1.03-1.10), GTF2H4 rs1264308_T (OR = 0.93, 95% CI = 0.89-0.97), COPS2 rs141308737_C deletion (OR = 1.06, 95% CI = 1.03-1.09) and ELL rs1469412_C (OR = 0.93, 95% CI = 0.90-0.96). Their combined genetic score was also associated with BC risk (OR = 1.12, 95% CI = 1.08-1.16, ptrend < 0.0001). The eQTL analysis revealed that BIVM-ERCC5 rs1323697 C and ELL rs1469412 C alleles were correlated with increased mRNA expression levels of their genes in 373 lymphoblastoid cell lines (p = 0.022 and 2.67 × 10-22 , respectively). These SNPs might have roles in the BC etiology, likely through modulating their corresponding gene expression.

Risk factors for severe acute pain and persistent pain after surgery for breast cancer: a prospective observational study.

BACKGROUND AND OBJECTIVES: There are few prospective studies providing comprehensive assessment of risk factors for acute and persistent pain after breast surgery. This prospective observational study assessed patient-related, perioperative, and genetic risk factors for severe acute pain and persistent pain following breast cancer surgery. METHODS: Women presenting for elective breast cancer surgery completed State Trait Anxiety Inventory, Beck Depression Inventory, and Pain Catastrophizing Scale questionnaires preoperatively. Diffuse noxious inhibitory control and mechanical temporal summation were assessed. A blood sample was obtained for genetic analysis. Analgesic consumption and pain scores were collected in the post-anesthesia care unit, and at 24 and 72 hours. Patients were contacted at 1, 3, 6, and 12 months to assess persistent pain. Primary outcome was maximum acute pain score in first 72 hours and secondary outcome was persistent pain. RESULTS: One hundred twenty-four patients were included in analysis. Increased duration of surgery, surgeon, and higher pain catastrophizing scores were associated with increased severity of acute pain, while preoperative radiotherapy was associated with reduced severity. Persistent pain was reported by 57.3% of patients. Postdischarge chemotherapy (OR 2.52, 95% CI 1.13 to 5.82), postdischarge radiation (OR 3.39, 95% CI 1.24 to 10.41), severe acute pain (OR 5.39, 95% CI 2.03 to 15.54), and moderate acute pain (OR 5.31, 95% CI 1.99 to 15.30) were associated with increased likelihood of persistent pain. CONCLUSIONS: Increased duration of surgery, higher pain catastrophizing score, and surgeon were associated with increased severity of acute pain. Preoperative radiation was associated with lower acute pain scores. Postsurgery radiation, chemotherapy, and severity of acute pain were associated with increased likelihood of persistent pain. TRIAL REGISTRATION: NCT03307525.

Cutaneous adverse events of anti-programmed death 1 antibodies combined with anti-cytotoxic T-lymphocyte-associated protein 4 therapy use in patients with metastatic melanoma.

To date, cutaneous toxicities of combination therapies of anti-programmed death-1 (anti-PD1) and ipilimumab are poorly described. Understanding cutaneous presentations will aid clinicians with early diagnoses and treatments. We aim to describe and compare the cutaneous toxicities between the combination therapies and anti-PD1 monotherapy. This is a cohort study comparing previously published data on 82 patients with metastatic melanoma on anti-PD1 monotherapy, with a new group of 25 patients with metastatic melanoma receiving combined ipilimumab and pembrolizumab between January 2015 to February 2016. A single institution, internal referrals were received from medical oncology teams from May 2012 to February 2015 for the anti-PD1 monotherapy group and from January 2015 to February 2016 for combination group. All patients who were treated with either anti-PD1 therapy or combination therapies during the timeframe within the institution were included in the study. Kaplan-Meier curves were used to illustrate the time taken to develop cutaneous toxicities in the monotherapy and combination groups. Of the 25 patients, 88% developed new cutaneous lesions since the treatment. Immune-related lesions; lichenoid reaction (64%) and vitiligo (28%) were the most frequent. The incidence of lichenoid reaction increased rapidly in the early phase of treatment. Approximately one-third developed their first lichenoid reaction within 12 days of commencing treatment in combination group compared to 14 months in the anti-PD1 monotherapy. The rate of incidence of vitiligo was comparable in both groups. There was no statistical significance in the development of cutaneous toxicities and the treatment response between the two groups. The time taken to develop immune-related cutaneous toxicities was shorter for those on combination therapy versus anti-PD1 monotherapy.

A National Snapshot of Patient-Reported Outcomes Comparing Types of Abdominal Flaps for Breast Reconstruction.

BACKGROUND: This study aimed to identify differences in patient-reported abdominal well-being, satisfaction, and quality of life in women with muscle-preserving free abdominal versus pedicle transverse rectus abdominis musculocutaneous (TRAM) flap for breast reconstruction. METHODS: Women with a history of breast cancer surgery were recruited from the Army of Women foundation to take the BREAST-Q and a background questionnaire. Descriptive statistics and regression analyses were used to compare abdominal physical well-being, breast satisfaction, chest physical, psychosocial well-being, and sexual well-being in women undergoing free versus pedicle TRAM flaps. RESULTS: Of 657 women, 273 (41 percent) underwent free flap surgery and 384 (58 percent) underwent pedicle TRAM flap surgery. Compared with unilateral pedicle TRAM flaps, those with unilateral free flaps scored an average of 9.5 points higher (95 percent CI, 5.4 to 13.6; p < 0.0001) and those with bilateral free flaps reported no difference in physical well-being of the abdomen. Compared with bilateral pedicle TRAM flaps, the following groups scored higher in physical well-being of the abdomen: unilateral free flaps, an average of 17.4 (95 percent CI, 11.5 to 23.3; p < 0.0001); bilateral free flaps, an average of 6.8 (95 percent CI, 0.3 to 13.3; p = 0.04); and unilateral pedicle TRAM flaps, an average of 7.9 (95 percent CI, 2.4 to 13.4; p = 0.005) higher. Women with bilateral pedicle flaps reported sexual well-being scores 7.4 (95 percent CI, 0.6 to 14.3; p = 0.03) and 6.8 (95 percent CI, 0.3 to 13.2; p = 0.04) points lower than those with unilateral free and unilateral pedicle flaps. CONCLUSIONS: Muscle-preserving techniques result in improved abdominal wall function and decreased morbidity compared with pedicle TRAM flap reconstruction. These data highlight the importance of offering patients the option of microsurgical techniques.

Anti-programmed cell death-1 therapy-associated bullous disorders: a systematic review of the literature.

Bullous disorders are rare adverse events associated with anti-programmed cell death-1 (anti-PD1) therapy. This paper presents two new cases of bullous disorders under anti-PD1 therapy and systematically reviewed the literature to foster a better understanding of the presentation and pathogenesis of bullous disorders under anti-PD1. A systematic review of the literature was completed using MEDLINE, Embase, PubMed and LILACS databases. We identified 29 cases of bullous disorders under anti-PD1 therapy, including our two new cases. This includes 18 cases of bullous pemphigoid (BP), five cases of toxic epidermal necrolysis (TEN)/Stevens-Johnson syndrome (SJS) spectrum, one case of erythema multiforme (EM), four cases of bullous lichenoid reactions and one case of vesiculobullous eczema. In BP, blistering occurred by a median of 23 weeks after anti-PD1 therapy initiation and is often preceded by a prodrome, which lasts for a median of 9.5 weeks. Limbs and trunk were the most frequently involved body sites. Most cases (76%) achieved remission. In TEN/SJS/EM, blistering was usually preceded by a prodrome of interface dermatitis that lasted for a median of 1.5 weeks. Most cases (80%) died from either TEN/SJS or disease progression. Bullous disorders under anti-PD1 may be classified clinically as BP, SJS/TEN/EM, bullous lichenoid reactions and vesiculobullous eczema and histologically by intraepidermal splitting and subepidermal splitting. BP is usually preceded by a pruritic eruption and has a relatively good prognosis. SJS/TEN is usually preceded by a maculopapular eruption and has a very poor prognosis.

Ensuring Equity, Diversity, and Inclusion in Academic Surgery: An American Surgical Association White Paper.

OBJECTIVE: The leadership of the American Surgical Association (ASA) appointed a Task Force to objectively address issues related to equity, diversity, and inclusion with the discipline of academic surgery. SUMMARY OF BACKGROUND DATA: Surgeons and the discipline of surgery, particularly academic surgery, have a tradition of leadership both in medicine and society. Currently, we are being challenged to harness our innate curiosity, hard work, and perseverance to address the historically significant deficiencies within our field in the areas of diversity, equity, and inclusion. METHODS: The ASA leadership requested members to volunteer to serve on a Task Force to comprehensively address equity, diversity, and inclusion in academic surgery. Nine work groups reviewed the current literature, performed primary qualitative interviews, and distilled available guidelines and published primary source materials. A work product was created and published on the ASA Website and made available to the public. The full work product was summarized into this White Paper. RESULTS: The ASA has produced a handbook entitled: Ensuring Equity, Diversity, and Inclusion in Academic Surgery, which identifies issues and challenges, and develops a set of solutions and benchmarks to aid the academic surgical community in achieving these goals. CONCLUSION: Surgery must identify areas for improvement and work iteratively to address and correct past deficiencies. This requires honest and ongoing identification and correction of implicit and explicit biases. Increasing diversity in our departments, residencies, and universities will improve patient care, enhance productivity, augment community connections, and achieve our most fundamental ambition-doing good for our patients.

Incidence of Basal Cell Carcinoma and Squamous Cell Carcinoma in Patients on Antiprogrammed Cell Death-1 Therapy for Metastatic Melanoma.

Systemic melanoma therapies have the potential to affect basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cuSCC) development. In this study, we aim to compare the incidence of BCC and cuSCC in patients with metastatic melanoma treated with antiprogrammed cell death-1 (anti-PD1), BRAF inhibitor (BRAFi) monotherapy or dabrafenib and trametinib combination therapy (CombiDT) with a group of control patients having similar risk factors. We reviewed the records of melanoma patients on anti-PD1, BRAFi, or CombiDT, and patients from the High-Risk Melanoma Clinic, Westmead Hospital. We also performed an immunohistochemical analysis of BCCs under anti-PD1 compared with controls using PD1, PD-L1, CD3, CD8, and CD20 stains. For the results, in all, 340 patients were included; 82 on anti-PD1, 134 on BRAFi, 69 on CombiDT, and 55 controls. BRAFi had the highest incidence of BCC (12.7%), followed by CombiDT (10.1%) and anti-PD1 (2.4%). The incidence of BCC was significantly lower in patients on anti-PD1 (2.4% vs. 19.4%; P<0.001) compared with controls. Patients on anti-PD1 were 8.54 times less likely to develop BCC than the controls [hazard ratio, 0.117 (95% confidence interval, 0.026-0.526), P=0.005]. BRAFi and CombiDT showed no significant differences in BCC incidence compared with controls. BRAFi had the highest cuSCC incidence (23.9%), followed by anti-PD1 (7.3%) and CombiDT (2.9%). The incidence of cuSCC was significantly higher in patients on BRAFi (23.9% vs. 3.5%; P<0.001) compared with controls, but anti-PD1 and CombiDT showed no differences in cuSCC incidence compared with controls. Immunohistochemistry analysis of 10 BCC from under anti-PD1 and 8 BCC from controls patients showed that while all BCC had negative PD-L1 staining, the percentage of PD1 staining in anti-PD1 group is significantly lower than that of the control group (independent t test, 8% vs. 26%; P<0.001). In conclusion, our study suggests that anti-PD1 therapy decreases the incidence of BCC, as a result of the PD1/PD-L1 blockade. Future studies investigating the role of anti-PD1 in suppressing or treating BCC may be warranted.

Epidemiology, Biology, Treatment, and Prevention of Ductal Carcinoma In Situ (DCIS).

Ductal carcinoma in situ (DCIS) is a highly heterogeneous disease. It presents in a variety of ways and may or may not progress to invasive cancer, which poses challenges for both diagnosis and treatment. On May 15, 2017, the Dana-Farber/Harvard Cancer Center hosted a retreat for over 80 breast specialists including medical oncologists, surgical oncologists, radiation oncologists, radiologists, pathologists, physician assistants, nurses, nurse practitioners, researchers, and patient advocates to discuss the state of the science, treatment challenges, and key questions relating to DCIS. Speakers and attendees were encouraged to explore opportunities for future collaboration and research to improve our understanding and clinical management of this disease. Participants were from Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Duke University Medical Center, and MD Anderson Cancer Center. The discussion focused on three main themes: epidemiology, detection, and pathology; state of the science including the biology of DCIS and potential novel treatment approaches; and risk perceptions, communication, and decision-making. Here we summarize the proceedings from this event.