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Background and Aims: South Asian (SA) ethnicity is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, the implications of considering SA ethnicity as a "risk-enhancing factor" per recent American College of Cardiology/American Heart Association guidelines are not fully understood., Methods: We used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, a community-based cohort study of individuals of SA ancestry living in the US. The Pooled Cohort Equations were used to estimate 10-year ASCVD risk. Metabolic risk factors and coronary artery calcium (CAC) scores were assessed., Results: Among 1114 MASALA participants included (median age 56 years, 48% women), 28% were already using a statin at baseline, 25% had prevalent diabetes, and 59% qualified for 10-year ASCVD risk assessment for statin allocation purposes. The prevalence of low, borderline, intermediate, and high estimated ASCVD risk was 65%, 11%, 20% and 5%, respectively. Among participants at intermediate risk, 30% had CAC = 0 and 37% had CAC>100, while among participants at borderline risk, 54% had CAC = 0 and 13% had CAC>100. Systematic consideration of intermediate and, particularly, of borderline risk individuals as statin candidates would enrich the statin-consideration group with CAC = 0 participants up to 35%. Prediabetes and abdominal obesity were highly prevalent across all estimated risk strata, including among those with CAC = 0., Conclusions: Our findings suggest that systematic consideration of borderline risk SAs as statin candidates might result in considerable overtreatment, and further risk assessment with CAC may help better personalize statin allocation in these individuals. Early, aggressive lifestyle interventions aimed at reducing the risk of incident diabetes should be strongly recommended in US SAs, particularly among those considered candidates for statin therapy for primary prevention. Longitudinal studies are needed to confirm the favorable prognosis of CAC = 0 in SAs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To identify subgroups of hormone receptor-positive (HR+) breast cancer patients that might not benefit from adding endocrine therapy (ET) to their local treatment., Background: De-escalation in breast cancer treatment has included surgery, radiation, and chemotherapy and has often focused on older patient populations. Systemic ET has yet to be de-escalated, though it carries serious side-effects, decreasing quality of life over 5 to 10 years. We hypothesize the 21-gene recurrence score (RS) could identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET., Methods: The National Cancer Database was used to identify women aged ≥50, with HR+, HER2-negative tumors, ≤3 cm in size, N0 status, and a RS≤25, who underwent breast-conserving surgery in 2010 to 2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS)., Results: Of the 45,217 patients identified, 80.6% were 50 to 69 years old. 42,632 (94.3%) patients received ET and 2585 (5.7%) did not. The 5-year OS was 96.4% for patients receiving ET and 93.1% for those who did not (P < 0.001). After adjusting for all covariates, patients aged 50 to 69 with RS < 11 showed no statistically significant improvement in OS when adding ET to surgery, with or without radiation (P = 0.40). With RS 11 to 25, there was a significant improvement of OS with ET plus radiation (P < 0.001)., Conclusions: Local treatment only, with de-escalation of long-term ET, for patients aged 50 to 69 with RS < 11, seems not to impact OS and should have an anticipated quality of life improvement. Prospective studies investigating this approach are warranted., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Patients with small cell lung cancer (SCLC) who have brain metastases require whole-brain radiation therapy (WBRT). When there is no emergent indication for WBRT, patients may receive systemic therapy first and WBRT afterward. In scenarios when systemic therapy is initiated first, it has not been previously investigated whether delaying WBRT is harmful., Methods and Materials: The National Cancer Database was queried (2004-2016) for patients with SCLC with brain metastases who received 30 Gy in 10 fractions of WBRT. Patients were divided into groups based on whether they received early WBRT (3-14 days after initiation of chemotherapy) or late WBRT (15-90 days after initiation of chemotherapy). Demographic and clinicopathologic categorical variables were compared between those who had early WBRT (3-14 days) and those who had late WBRT (15-90 days). Factors predictive for late WBRT were determined. Overall survival (OS), which was defined as days from diagnosis to death, was evaluated and variables prognostic for OS were determined., Results: A total of 1082 patients met selection criteria; 587 (54%) had early WBRT and 495 (46%) received late WBRT. Groups were similarly distributed aside from days from initiating chemotherapy to initiating WBRT ( P < .001). The early WBRT group had a median of 7 days (interquartile range [IQR], 5-10 days) from initiating chemotherapy to initiating WBRT and the late WBRT group had a median of 34 days (IQR, 21-57 days). On binary logistic regression analysis, a longer time interval between diagnosis and the start of systemic therapy was predictive for later WBRT. Median OS was 8.7 months for early WBRT and 7.5 months for late WBRT (hazard ratio [HR], 1.165; P  = .008). Early WBRT ( P  = .02), female sex ( P  = .045), and private insurance ( P  = .04) were favorable prognostic factors for OS on multivariable analysis, whereas older age ( P  = .006) was an unfavorable prognostic factor., Conclusions: Patients with SCLC and brain metastases who received early WBRT were found to have a modest improvement in OS compared with patients who received late WBRT. These findings suggest that early WBRT should be offered to patients who have brain metastases, even in the absence of an indication for emergent WBRT., (© 2021 The Author(s).)

Purpose: Telehealth has been an integral response to the COVID-19 pandemic. However, no studies to date have examined the utility and safety of telehealth for oncology patients undergoing systemic treatments. Concerns of the adequacy of virtual patient assessments for oncology patients include the risk and high acuity of illness and complications while on treatment., Methods: We assessed metrics related to clinical efficiency and treatment safety after propensity matching of newly referred patients starting systemic therapy where care was in large part replaced by telehealth between March and May 2020, and 206 newly referred patients from a similar time period in 2019 where all encounters were in-person visits., Results: Patient-initiated telephone encounters that capture care or effort outside of visits, time to staging imaging, and time to therapy initiation were not significantly different between cohorts. Similarly, 3 month all-cause or cancer-specific emergency department presentations and hospitalizations, and treatment delays were not significantly different between cohorts. There were substantial savings in travel time with virtual care, with an average of 211.4 minutes saved per patient over a 3-month interval., Conclusion: Our results indicate that replacement of in-person care with virtual care in oncology does not lead to worse efficiency or outcomes. Given the increased barriers to patients seeking oncology care during the pandemic, our study indicates that telehealth efforts may be safely intensified. These findings also have implications for the continual use of virtual care in oncology beyond the pandemic., Competing Interests: Adam YoppResearch Funding: Merck Muhammad S. BegConsulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend BiotechResearch Funding: Celgene, Bristol Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Agios, Five Prime Therapeutics, MedImmune, ArQule, Genentech, Sillajen, CASI Pharmaceuticals, ImmuneSensor Therapeutics, Tolero PharmaceuticalsNo other potential conflicts of interest were reported.

Purpose: The utility of post-mastectomy radiotherapy (PMRT) in women with a nodal complete response (CRn) to neoadjuvant chemotherapy (NAC) is unknown. The NSABP B-51 trial is evaluating this question, but has not reported results thus far. Therefore, we sought to answer this question with the National Cancer Database., Methods: The National Cancer Database was queried for women with cT1-4N1-3M0 breast cancer who had undergone NAC and were ypN0 upon mastectomy. Statistics included multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis, Cox proportional hazards modeling, and construction of forest plots., Results: Of 14,690 women, 10,092 (69%) underwent adjuvant PMRT and 4598 (31%) did not. The median follow-up was 55.6 months. In all patients, the 10-year OS was 76.3% for PMRT and 78.6% without (p = 0.412). There were no notable effects of PMRT on OS based on age or the axillary management (number of nodes removed). Specifically, in the NSABP B-51 population of cT1-3 cN1 patients, the 10-year OS was 82.6% for PMRT and 80.0% without (p = 0.250). PMRT benefitted women with increasing cT stage (i.e. cT3-4), increasing ypT stages (with the exception of ypT4 potentially owing to small sample sizes), and cN3 cases (p < 0.05 for all)., Conclusions: In the absence of published results from NSABP B-51, this assessment of over 14,000 women from a contemporary US database revealed that PMRT may be most useful for a "moderately-high" risk group - women with more advanced primary and/or nodal disease at diagnosis, yet with tumor biology favorable enough that the disease does not progress or remain stable after NAC. The OS findings notwithstanding, this study cannot exclude potential differences between groups in recurrence-free survival, which is the primary endpoint of NSABP B-51, While the results of the NSABP B-51 will confirm optimal management for patients with limited nodal disease having a CRn following NAC, the present results suggest PMRT should remain the standard of care for more advanced disease than NSABP B-51 eligibility criteria., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma., Methods and Materials: Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated., Results: With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm)., Conclusion: Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma., (Copyright © 2021. Published by Elsevier Inc.)

Hepatitis E virus (HEV) infection is a significant public health issue in many developing countries, causing waterborne outbreaks as well as sporadic hepatitis. We report here an outbreak of HEV genotype 1f infection during April-May 2018 among people living at Halisohor, a low land in the southern part of Chottogram District of Bangladesh. A total of 933 patients were admitted to Combined Military Hospital (CMH), Chottogram, with symptoms of acute hepatitis. Among them, 550 patients were tested by ELISA for HEV-specific (IgM) and all were positive. Genotyping, sequencing, and phylogenetic analysis based on ORF2 region revealed that the outbreak was caused by genotype 1f and the strains were closely related to the previously reported HEV strains that caused the outbreak in Bangladesh in 2010. The current outbreak was most likely linked with water supply as fecal contamination in water was evident and could be prevented by ensuring access to safe drinking water., (© 2020 Wiley Periodicals LLC.)

Background: This study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials., Materials and Methods: The National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS ). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling., Results: Of 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER-/HER2+ and ER-/HER2- disease had worse OS than patients with ER+/HER2- disease, for both patients treated with SRS and for patients treated with WBRT., Conclusions: Molecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes., Competing Interests: Conflict of interest All authors declare that conflicts of interest do not exist., (© 2021 Greater Poland Cancer Centre.)

Purpose: Tubular carcinoma (TC) is an invasive breast cancer with favorable prognosis. While pathology-specific guidelines exist for TC regarding adjuvant chemotherapy and endocrine therapy, no recommendations exist regarding locoregional treatment based on tumor histology. Prognostic impact of radiotherapy for patients with TC remains unclear., Materials and Methods: The National Cancer Database was queried (2004-2015) for patients with pN0M0 TC who underwent lumpectomy. Chi-square testing compared categorized variables between those who did and did not receive radiotherapy. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazard analysis identified variables prognostic for OS. Patients were divided into age cohorts ≤60 years and >60 years. Propensity score matching (PSM) was utilized to create similar cohorts., Results: 9705 patients met selection criteria; 6182 (75.1%) received radiotherapy while 2045 (24.9%) did not. After PSM, radiotherapy (HR 0.582; 95% CI 0.494-0.686) and endocrine therapy (HR 0.737; 95% CI 0.623-0.872) were favorable prognostic factors on multivariate Cox regression analysis while age > 60 years (HR 5.131; 95% CI 3.753-7.016), Black race (HR 1.445; 95% CI 1.016-2.055), and Charlson-Deyo comorbidity score > 0 (HR 1.708; 95% CI 1.403-2.079) were unfavorable prognostic factors. After PSM, 5-year OS was 91.7% for those who received radiotherapy and 84.5% for those who did not; 10-year OS was 76.1% and 64.1%, respectively (p < 0.001)., Conclusion: This is the largest study to date on TC and the prognostic impact of adjuvant radiotherapy. Postoperative radiotherapy is a favorable prognostic factor for OS in patients with pN0M0 TC, suggesting adjuvant radiotherapy should remain standard of care in these patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic disorder caused by severe deficiency of ADAMTS13. Platelets are transfused prophylactically in non-TTP patients for central venous catheter (CVC) with a count <20 × 10 9 /L to prevent bleeding. However, transfusing platelets in TTP prior to CVC placement remains controversial due to concern for arterial thrombosis and mortality. At our center, platelet transfusion is contraindicated in TTP, therefore, we analyzed data for bleeding complications following CVC placement., Study Design and Methods: 95 acute episodes of TTP were identified. Twenty-six episodes were excluded for insufficient documentation or no CVC placement. The charts of 69 remaining episodes were reviewed., Results: Of 69 TTP episodes, nine (13 %) had bleeding after a CVC placement. Of these, seven bleeds were minor, and the two were major related to the technical issues during femoral venous access causing arterial bleeds. Median platelet count before the CVC placement among those experiencing bleeding complications was 12 × 10 9 /L (range 3-44) as compared to median count of 15 × 10 9 /L (range 4-257) in those who did not bleed (p = 0.258). Among 44 episodes with a platelet count <20 × 10 9 /L, seven (16 %) had bleeds., Conclusion: Major bleeding complications following CVC placement in TTP is uncommon and most likely related to technical challenges. Median platelet count was similar in patients who bled versus those who did not, suggesting that platelet transfusion is unnecessary to correct platelet count prior to a CVC placement in TTP., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Multisystem inflammatory syndrome in adults (MIS-A) is a rare but often severe complication of SARS-CoV-2 infection. While several case reports about MIS-A in the setting of COVID-19 have been published since the term was first coined in June 2020, a clear description of the underlying pathophysiology and guideline-based recommendations on the diagnostic and therapeutic approach are lacking. What has been reported is that in the absence of severe respiratory illness, MIS-A can present with hypotension or shock, high-grade fever, abdominal pain, diarrhoea and severe weakness days to weeks after SARS-CoV-2 infection. Here, we present a case of a 28-year-old man who presented with a rarely described initial symptom: unilateral neck swelling. His presentation, disease progression and treatment course provide further information about MIS-A as a complication and in formulating diagnostic guidelines., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study sought to assess the value, in terms of sample size and cost, of using the coronary artery calcium (CAC) score to enrich the study population of primary prevention randomized controlled trials (RCTs) with participants at high absolute risk of atherosclerotic cardiovascular disease (ASCVD) events., Background: The feasibility of RCTs assessing the efficacy of novel add-on therapies for primary prevention among high-risk individuals treated with statins may be limited by sample size and cost., Methods: We evaluated 3,075 statin-naive participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with estimated 10-year ASCVD risk of ≥7.5%. CAC of >100, CAC of >400, high sensitivity C-reactive protein levels of >2 and >3 mg/l, ankle-brachial index of <0.9, and triglyceride levels of >175 mg/dl were each evaluated as enrichment criteria on top of estimated ASCVD risk of ≥7.5%, ≥10%, ≥15% and ≥20%. For each criterion, using the observed 5-year incidence of CVD, we projected the incidence of CVD assuming a 28% relative risk reduction with high-intensity statin therapy and after addition of novel therapy with additive relative risk reductions of 15% and 25%. Sample size and cost of a hypothetical primary prevention 5-year RCT of a novel therapy on top of statins versus statins alone were then computed by using the projected incidences. Yearly costs per included participant of $6,000 to $9,000 and of $500/$600 per screened nonparticipant were assumed., Results: CAC of >400, present in 15% to 23% participants, consistently identified the subgroups with highest 5-year incident events and outperformed the other features yielding the smallest projected sample size, ranging 33% to 58% lower than using risk estimations alone for participant selection. CAC of >400 also yielded the lowest projected RCT costs, at least $40 million lower than using risk estimations alone. CAC of >100 showed the second-best performance in most scenarios., Conclusions: High CAC scores used as study entry criteria can improve the efficiency and feasibility of primary prevention RCTs evaluating the incremental efficacy of novel add-on therapies., Competing Interests: Funding Support and Author Disclosures This research was supported by contracts HHSN268201500003I and N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, and UL1-TR-001881 from the National Center for Advancing Translational Sciences. Dr. Ray acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre and Imperial College London is grateful for support from the NIHR Applied Research Collaboration for North West London. Dr. Bhatt has served on the Advisory Board of Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; has served on the Board of Directors for Boston Veterans Affairs Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has served as chair of the American Heart Association Quality Oversight Committee; has served on the Data Monitoring Committee for the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), and Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; vice chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor-in-chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), Medtelligence/ReachMD (continuing medical education [CME] steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, and steering committee and U.S. national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees); reports the following roles: Clinical Cardiology (deputy editor), National Cardiovascular Data Registry (NCDR)-ACTION Registry Steering Committee (chair), Veteran Affairs Clinical Assessment, Reporting and Tracking Program (VA CART) Research and Publications Committee (chair); has received research funding from Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease) has served as site coinvestigator for Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; has served as trustee for the American College of Cardiology; and has performed unfunded research for FlowCo, Merck, Novo Nordisk, and Takeda. Dr. Ray reports personal fees from Aegerion, grants and personal fees from Amgen, Sanofi/Regeneron, Pfizer, and Merck Sharp & Dohme Corp. (MSD), personal fees from AstraZeneca, Cerenis, Akcea, The Medicines Company, Kowa, Novartis, Cipla, Lilly, Algorithm, Takeda, Boehringer Ingelheim, AbbVie, and Silence Therapeutics. Dr. Reddy’s has received personal fees from Bayer, Daiichi Sankyo, Esperion, AbbVie, Zuelling Pharma, and Resverlogix, outside the submitted work. Dr. Nasir is on the Advisory Boards of Amgen, Novartis, and The Medicine Company; and his research is partly supported by the Jerold B. Katz Academy of Translational Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Teledermatology has been leveraged during the COVID-19 pandemic as a means of adopting novel ways to treat patients while reducing the risk of viral transmission. Although teledermatology offers benefits related to patient convenience and improved access to care, key challenges in the areas of reimbursement, licensure, and diagnostic accuracy remain. In this commentary, we discuss these three obstacles and potential solutions.

Background: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER 2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients., Materials and Methods: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS., Results: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy., Conclusion: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding., Competing Interests: Conflict of interest The authors declare that no conflicts of interest exist., (© 2021 Greater Poland Cancer Centre.)

Background: Pharmaceutical payments may affect the interpretation of clinical research and prescribing patterns of physicians. Additionally, they may reflect gender disparities in academic dermatology with regard to social recognition and opportunities for career advancement., Objective: We examined relationships with industry among male and female journal editors who accepted pharmaceutical payments in leading dermatology journals., Methods: We assessed the seven US journals among the leading 20 dermatology journals as determined by impact factor and gathered data via the CMS Open Payments dataset., Results: In a cross-sectional study of 329 editors eligible to appear in the Open Payments website, we found that 218 (66.3%) received industry payments totaling $21,952,402. The mean and median dollar value of payments per editor was $100,699 and $3,638 (interquartile range, $364-$57,108). Food and beverage payments accounted for 63.0% of the $28,992 total payments, and the associated dollar value was $887,617 (4.04%). Gender disparities in corporate payments were observed in other contexts, but we did not find a similar relationship among leading dermatology journals., Conclusion: Our work highlights that pharmaceutical payments exist among dermatology editors, providing a rationale for future research to address whether editor bias related to pharmaceutical payments exists and more granular studies on the role of gender with regard to navigating such payments., Competing Interests: None., (© 2021 Published by Elsevier Inc. on behalf of Women's Dermatologic Society.)

Background: Limited brain metastasis is treated definitively with stereotactic radiosurgery when surgical resection is not indicated. Although this has historically been performed in a single fraction, multi-fraction approaches such as fraction radiosurgery (FSRS) and staged radiosurgery (SSRS) have been recently examined as alternative approaches for larger lesions to permit better tumor control without increased toxicity., Case Report: We present the case of a patient who developed symptomatic radionecrosis in two brain metastasis, 2.3 cm and 2.1 cm in size, which were treated with 18 Gy in one fraction, but no radionecrosis in a 3.3 cm lesion treated in two fractions of 15 Gy nor in two punctate lesions that were treated in one fraction of 20 Gy. Although she did not respond to steroids, she responded to bevacizumab symptomatically and on neuroimaging., Conclusion: Congruent with other recent studies, our report suggests that large brain metastasis should be considered for FSRS/SSRS., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Grade 3 gliomas are aggressive primary brain tumors. Promoter methylation of methyl guanine methyl transferase (MGMT) has been associated with a favorable prognosis in patients with glioblastoma, but the impact of MGMT promoter methylation in patients with grade 3 gliomas is less clear. The purpose of the present study was to evaluate the utilization of MGMT testing in patients with Grade 3 glioma, as well its prognostic and predictive value., Methods: The National Cancer Database (NCDB) was queried (2004-2016) for patients with newly diagnosed grade 3 glioma without 1p19q codeletion. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling., Results: Of 20,488 total patients, 1,209 (5.0%) had MGMT testing. Of these patients, 561 (46.4%) were MGMT methylated (mMGMT), and 648 (53.6%) were MGMT unmethylated (uMGMT). mMGMT patients experienced greater median overall survival (OS) than both uMGMT patients as well as patients with no MGMT status reported (p < 0.05 for both). mMGMT was associated with improved OS for patients receiving adjuvant chemoradiation or adjuvant radiation, but not for patients receiving adjuvant chemotherapy or no adjuvant treatment., Conclusions: This is the largest study to date describing the utilization of and outcomes for mMGMT patients with grade 3 glioma. The present results demonstrate that mMGMT is a prognostic factor and possibly a predictive biomarker, and is currently under-utilized within the US. MGMT methylation status could be used to risk-stratify and select patients for treatment intensification., Importance of Study: The present study is the largest of its kind to examine the prognostic and predictive impact of MGMT methylation (mMGMT) amongst patients with Grade 3 Glioma. The results suggest that mMGMT is prognostic, as amongst all patients, mMGMT was associated with improved overall survival. These results also suggest that mMGMT is predictive, as patients treated with adjuvant chemoradiation or adjuvant radiation therapy did have improved overall survival with mMGMT, though there was no difference in overall survival observes amongst patients receiving adjuvant chemotherapy or those patients receiving no adjuvant treatment. The study also found that only 5% of patients nationwide with Grade 3 Glioma are tested for MGMT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The 21-gene recurrence score assay (RS) has not been prospectively validated to predict adjuvant chemotherapy benefit in hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer patients. Nevertheless, de-escalation based on RS has been demonstrated and partially advocated by retrospective data. The purpose of this study was to identify subgroups of node-positive patients with low to intermediate RS who still benefit from adjuvant chemotherapy., Methods: The National Cancer Database was used to identify 28,591 women with stage I-III, T1-T3, N1, HR+, HER2- breast cancer and a RS ≤ 25 between 2010 and 2016. Univariate and multivariate analyses were used to identify variables correlating with chemotherapy use and 5-year survival. Subgroup analysis was performed to discern patients in whom the use of adjuvant chemotherapy correlated with better survival., Results: A 35% decline in chemotherapy use was observed from 2010 to 2016. Patients with younger age, higher RS, larger tumors and more positive lymph nodes, and those treated by mastectomy, axillary lymph node dissection and radiation, were more likely to receive chemotherapy. Chemotherapy use was associated with an improved 5-year survival (HR = 1.63, 95% CI 1.28-2.07). Upon subgroup analysis, this association was lost in patients > 70 years and those with a RS ≤ 11, while patients ≤ 70 with a RS of 12-25 treated with chemotherapy had an absolute 5-year survival advantage of 3.0% (HR = 1.91, 95% CI 1.42-2.57)., Conclusion: Clinicians should be cautious when considering omission of adjuvant chemotherapy in patients ≤ 70 years, with HR+, HER2-, N1 tumors and a RS 12-25, at least until the results of the anticipated RxPONDER trial become available.

Purpose: Primary spinal cord tumors are rare, particularly in the adult population, and national guidelines remain ambiguous with regard to management approaches. To address this knowledge gap, we evaluated management, outcomes, and prognostic factors of these neoplasms., Methods: The National Cancer Database was queried (2004-2016) for newly-diagnosed, histologically-confirmed WHO grades I-III astrocytomas and glioblastoma. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling., Results: Of 1,033 subjects, 196 (19%) were pilocytic astrocytomas (PAs), 539 (52%) were grade II/III astrocytomas, and 298 (29%) were glioblastomas (GBMs). Respectively, 11%, 30%, and 27% did not undergo resection (biopsy only). RT was delivered to 27%, 54%, and 73%; chemotherapy was given to 5%, 21%, and 37%, respectively. The median OS was not reached for PAs, but was 101.2 months for grade II/III astrocytomas, and 23.9 months for GBMs (p < 0.001). Neither chemotherapy nor RT (or dose thereof) was associated with increased OS for grade II/III astrocytomas (p > 0.05 for all), though there was a trend toward improved OS with the use of chemotherapy for patients with GBM. Surgical resection was associated with improved OS for grade II/III astrocytomas and GBM (p < 0.05). Independent prognostic factors for survival in this cohort included histologic classification and resection (compared to biopsy only) (p < 0.05 for both)., Conclusions: This study sheds light onto the management of these rare tumors; surgery was associated with OS benefit for patients with GBM and Grade II/III astrocytomas. Neither RT nor chemotherapy were associated with OS benefit. Although not implying causation, these data can be used to guide patient counseling and therapeutic approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: For malignant pleural mesothelioma (MPM), the benefit of resection, as well as the optimal surgical technique, remain controversial. In efforts to better refine patient selection, this retrospective observational cohort study queried the National Cancer Database in an effort to quantify and evaluate predictors of 30- and 90-day mortality between extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D), as well as nonoperative management., Methods: After applying selection criteria, cumulative incidences of mortality by treatment paradigm were graphed for the unadjusted and propensity-matched populations, as well as for six a priori age-based intervals (≤60, 61-65, 66-70, 71-75, 76-80, and ≥81 years). The interaction between age and hazard ratio (HR) for mortality between treatment paradigms was also graphed. Cox multivariable analysis ascertained factors independently associated with 30- and 90-day mortality., Results: Of 10,723 patients, 2,125 (19.8%) received resection (n=438 EPP, n=1,687 P/D) and 8,598 (80.2%) underwent nonoperative management. The unadjusted 30/90-day mortality for EPP, P/D, and all operated cases was 3.0%/8.0%, 5.4%/14.1%, and 4.9%/12.8%, respectively. There were no short-term mortality differences between EPP and P/D following propensity-matching, within each age interval, or between age subgroups on interaction testing (P>0.05 for all). Nonoperative patients had a crude 30- and 90-day mortality of 9.9% and 24.6%, respectively. Several variables were identified as predictors of short-term mortality, notably patient age (HR 1.022, P<0.001), Charlson-Deyo comorbidity index (HR 1.882, P<0.001), receipt of treatment at high-volume centers (HR 0.834, P=0.032) and induction chemotherapy (HR 1.735, P=0.025), among others. The patient (yearly) incremental increase in age conferred 2.0% (30 day) and 2.2% (90 day) increased risk of mortality (P<0.001)., Conclusions: Quantitative estimates of age-associated 30- and 90-day mortality of EPP and P/D should be considered when potentially operable patients are counseled regarding the risks and benefits of resection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1779). CB Simone 2nd serves as an unpaid editorial board member of Journal of Thoracic Disease from Jan 2020- Dec 2021. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Currently, South Asia accounts for a quarter of the world population, yet it already claims ≈60% of the global burden of heart disease. Besides the epidemics of type 2 diabetes mellitus and coronary heart disease already faced by South Asian countries, recent studies suggest that South Asians may also be at an increased risk of heart failure (HF), and that it presents at earlier ages than in most other racial/ethnic groups. Although a frequently underrecognized threat, an eventual HF epidemic in the densely populated South Asian nations could have dramatic health, social and economic consequences, and urgent interventions are needed to flatten the curve of HF in South Asia. In this review, we discuss recent studies portraying these trends, and describe the mechanisms that may explain an increased risk of premature HF in South Asians compared with other groups, with a special focus on highly relevant features in South Asian populations including premature coronary heart disease, early type 2 diabetes mellitus, ubiquitous abdominal obesity, exposure to the world's highest levels of air pollution, highly prevalent pretransition forms of HF such as rheumatic heart disease, and underdevelopment of healthcare systems. Other rising lifestyle-related risk factors such as use of tobacco products, hypertension, and general obesity are also discussed. We evaluate the prognosis of HF in South Asian countries and the implications of an anticipated HF epidemic. Finally, we discuss proposed interventions aimed at curbing these adverse trends, management approaches that can improve the prognosis of prevalent HF in South Asian countries, and research gaps in this important field.

Purpose: There is no current randomized data comparing the efficacy of brachytherapy and enucleation for patients with larger sized tumors. The purpose of the present study was to use a large, contemporary database to determine current practice patterns and compare survival outcomes between different management options for patients with choroidal melanoma of various sizes., Material and Methods: The National Cancer Database was queried (2004-2014) for histologically-confirmed choroidal melanoma for patients treated with brachytherapy versus enucleation. Chi-square test was used to compare categorized demographic and clinical variables in both arms. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazards assessment determined variables associated with OS. Patients were divided into cohorts representing small, medium, and large tumors. Propensity scores matching (PSM) was utilized to compare more similar cohorts., Results: A total of 7,096 patients met the selection criteria; 5,501 (78%) patients received brachytherapy and 1,595 (22%) patients were treated with enucleation. After PSM, 5-yr OS for small tumors was 87% vs. 64%, for medium tumors was 77% vs. 57%, and for large tumors was 68% vs. 46% for brachytherapy and enucleation, respectively ( p < 0.001). Following PSM, multivariate Cox regression found older age (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.51-2.06), more comorbidities (HR = 1.46, 95% CI = 1.25-1.70), extraocular extension (EOE) (HR = 1.25, 95% CI = 1.06-1.48), ciliary body invasion (CBI) (HR = 1.20, 95% CI = 1.02-1.40), and larger size (HR = 1.52, 95% CI = 1.40-1.66) were negative prognosticators of survival. Brachytherapy was a positive prognosticator of survival (HR = 0.45, 95% CI = 0.40-0.51)., Conclusions: Patients selected for brachytherapy had improved survival compared to enucleation in all size cohorts. EOE and CBI are significantly higher in the enucleation cohort and are important negative prognosticators for survival selected against patients having brachytherapy. Brachytherapy is a reasonable treatment option for certain patients with large size tumors., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Termedia.)

Purpose: Adult medulloblastoma is rare, and management is extrapolated from pediatric cases. This investigation evaluated the prognostic role of chemotherapy (and sequencing thereof), the degree of resection, and craniospinal irradiation (CSI) dose., Methods: The National Cancer Database was queried for adult (age ≥18) medulloblastoma. Resection was coded as gross (GTR) or subtotal resection (STR) or biopsy only; concurrent chemoradiotherapy (CRT) was defined as receipt within 14 days of each other. Statistics included Kaplan-Meier overall survival (OS) analysis and Cox proportional hazards modeling., Results: Of 1144 patients, 613 had coded surgical information; 242 (39%) did not undergo surgery, 277 (45%) underwent STR, and 94 (15%) had GTR. A total of 428 (37.4%) did not receive chemotherapy, 348 (30.4%) received sequential CRT, and 368 (32.2%) underwent concurrent CRT. Of the 711 patients with CSI dose information, 202 (28.4%) received 23-30 Gy CSI and 509 (71.6%) patients received 30-36 Gy. Median follow-up was 56.5 months. Extent of resection did not correlate with 10-year OS (74.2% biopsy only, 72.7% STR, 82.2% GTR, p > 0.05 all comparisons) or on Cox multivariate analysis. Chemotherapy was associated with higher OS (65.6% vs. 51.2%, p = 0.035) and a trend towards significance on multivariate assessment (p = 0.082). Sequencing of chemotherapy and CSI dose were not associated with OS (p > 0.05 for both)., Conclusions: Although causation cannot be implied, neither the extent of resection nor CSI dose associated with OS in adult medulloblastoma. Chemotherapy could have utility in higher-risk patients; concurrent administration may not be beneficial, especially given therapy-induced neuro-cognitive sequelae., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Journal editors are gatekeepers of knowledge, and pharmaceutical industry payments to oncology editors have not been previously characterized. We performed a cross-sectional study of nonresearch industry payments to editors of 26 oncology research journals. A total of 433 editors were eligible for inclusion in the CMS Open Payments database from 2013 to 2018. A total of 80% of eligible editors had nonresearch payments, and the mean value of payments per editor was $106,778, which has increased over time. Only 5 out of 26 journals disclosed editor conflicts of interest and 3 of these journals reported at least one editor with no nonresearch industry payments but were found to have nonresearch payments. There was a positive correlation between journal impact factor and the average payment per editor for each journal. Our study shows the high prevalence and lack of transparency of nonresearch industry payments to oncology editors. Higher impact journals appear to be associated with greater nonresearch industry payments., (© AlphaMed Press 2020.)

Objective: To assess outcomes of thyroid nodules analyzed with the AFIRMA gene expression classifier (GEC) and to perform a comprehensive literature review., Study Design: Retrospective analysis of patients with thyroid nodules who underwent AFIRMA GEC testing at our institution., Settings: A tertiary care academic institution., Subjects and Methods: We collected clinical outcomes for 416 thyroid nodules that were analyzed with AFIRMA GEC between 2011 and 2015, including long-term follow-up through 2019. We performed a comprehensive literature review., Results: The resection rate for nodules with "suspicious" GEC results was 85% with a positive predictive value of 37%. The resection rate for nodules with "benign" GEC results was 24% with a negative predictive value of 90%. The prevalence of thyroid malignancy in patients with thyroid nodules with indeterminate cytology at our institution during this timeframe was 41%, thus lowering our negative predictive value. Mean follow-up duration for unresected nodules was 27.8 months. Our resection rates for nodules with "benign" GEC were among the highest reported in the literature., Conclusions: Molecular marker testing of thyroid nodules with indeterminate cytology can aid in the surgical decision making by obviating the need for diagnostic surgery and/or guiding extent of resection. Patients with other indications for surgery may not benefit from such costly testing.

Background: Glioblastoma (GBM) presents as a solitary lesion (unifocal), or as multiple discrete lesions (multifocal). Multifocal GBM may have a worse prognosis as compared to unifocal GBM, but existing data are limited to small institutional series. The purpose of the present study was to evaluate demographic and clinical characteristics of patients with unifocal versus multifocal GBM to highlight demographic differences and clinical outcomes for two groups of patients., Methods: The National Cancer Database (NCDB) was queried (2004-2016) for patients newly diagnosed with either unifocal or multifocal GBM. Statistics included Kaplan-Meier overall survival (OS) analysis, along with Cox proportional hazards modeling., Results: Of 45,268 total patients, 37,483 (82.8%) had unifocal GBM and 7,785 (17.2%) had multifocal GBM. Patients with unifocal GBM more frequently received gross total resection (GTR) (41.2% versus 25.8%, p < 0.001) and conventionally fractionated radiation therapy (RT) (48.2% versus 42.7%, p < 0.001). Patients with multifocal GBM had a higher rate of surgery with biopsy only (34.0% compared to 24.1%, p < 0.001). Median OS was 12.8 months versus 8.3 months (p < 0.001) for patients with unifocal GBM or multifocal GBM, respectively. On multivariate analysis, factors associated with improved OS included unifocal disease, MGMT methylation, RT use, and chemotherapy use., Conclusions: This is the largest study to date describing outcomes for patients with multifocal GBM, and it shows that multifocal GBM is associated with a decreased use both of GTR and conventionally fractionated RT, as well as worse median OS. Further research is needed to improve clinical outcomes for patients with multifocal GBM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Breast adenomyoepithelioma (AME) is a rare tumor with the published literature mainly in the form of case reports. Thus, there is currently only limited published data to guide evidence-based management. We sought to use a large, contemporary US database to evaluate how these patients are managed and describe expected outcomes. The National Cancer Database was queried (2004-2013) for women with AME. Statistics included multivariable logistic regression, Kaplan-Meier analysis to evaluate overall survival (OS) and Cox proportional hazards modeling. Overall, 110 patients were analyzed. At diagnosis, the median age was 67 years and the median tumor size was 2.0 cm. All but four patients had node-negative disease. A majority (55%) of tumors were estrogen receptor negative, and only one was positive for HER2/neu. The most common surgical procedure was lumpectomy (60%); a minority (10.9%) of subjects underwent complete axillary nodal dissection, with one-quarter not undergoing pathologic nodal sampling. Chemotherapy, hormonal therapy, and radiotherapy were utilized in a minority of patients (26%, 8%, and 36%, respectively), and none were associated with OS. At median follow-up of 52 months, the 5-year OS for the entire population was 74.4%. Disease-related characteristics and practice patterns are described for AME, the largest study of this rare tumor to date. Resection is the most important aspect of management, and based on this dataset the low rate of nodal involvement suggests that in some cases nodal sampling could be safely omitted. Adjuvant therapy may be considered on a case-by-case basis. Taken together, these data provide valuable insight into a rare neoplasm that may better inform management of these patients., (© 2019 Wiley Periodicals, Inc.)

Objectives : To assess the safety and reactogenicity of single oral dose of heat-stable rotavirus vaccine (HSRV) in healthy adults aged 18-45 years followed by assessment of safety, reactogenicity, and immunogenicity of three doses of HSRV in healthy infants aged 6-8 weeks at enrollment. Trial Design : Single-center randomized controlled, sequential, blinded (adults) and open-label (infants). Setting : Single site at International Center for Diarrheal Disease Research, Bangladesh (icddr,b). Participants : Fifty eligible adults randomized in 1:1 ratio (HSRV: Placebo) followed by 50 eligible infants randomized in 1:1 ratio (HSRV: Comparator (RotaTeq®, pentavalent human-bovine (WC3) reassortant live-attenuated, rotavirus vaccine)). Intervention : Adults received either a single dose of HSRV or placebo and followed for 14 days. Infants received three doses of either HSRV or comparator with a follow-up for 28 days after each dose. Main Outcome Measures : Solicited and unsolicited adverse events (AEs) along with any serious adverse events (SAEs) were part of the safety and reactogenicity assessment in adults and infants whereas serum anti-rotavirus IgA response rates were part of immunogenicity assessment in infants only. Post-vaccination fecal shedding of vaccine-virus rotavirus strains was also determined in adults and infants. Results : In this study, HSRV, when compared with placebo, did not result in increase in solicited adverse events (solicited AEs) in adults. In infants, HSRV had a safety profile similar to comparator vis-à-vis solicited AEs. In infants, fecal shedding of vaccine-virus strains was not detected in HSRV recipients but was observed in two comparator recipients. Percentage of infants exhibiting threefold rise in serum anti-rotavirus IgA titers from baseline to 1-month post-dose 3 in HSRV group was 88% (22/25) and 84% (21/25) in comparator group. Conclusion : HSRV was found to be generally well-tolerated in both adults and infants and immunogenic in infants.

Purpose: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC., Methods: The National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS., Results: Altogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS., Conclusions: MBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein., Competing Interests: Declaration of competing interest The authors have no conflicts of interest. There was no funding for this study. Ethical approval was not required for the present manuscript., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis in the developing world and is a public health problem, in particular among pregnant women, where it may lead to severe or fatal complications. A recombinant HEV vaccine, 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China), is licensed in China, but WHO calls for further studies to evaluate the safety and immunogenicity of this vaccine in vulnerable populations, and to evaluate protection in pregnancy. We are therefore conducting a phase IV trial to assess the effectiveness, safety and immunogenicity of the HEV 239 vaccine when given in women of childbearing age in rural Bangladesh, where HEV infection is endemic., Methods and Analysis: Enrolment of a target of approximately 20 000 non-pregnant women, aged 16-39 years, started on 2 October 2017 in Matlab, Bangladesh. Sixty-seven villages were randomised by village at a 1:1 ratio to receive either the HEV vaccine or the control vaccine (hepatitis B vaccine). A 3-dose vaccination series at 0, 1 and 6 months is ongoing, and women are followed up for 24 months. The primary outcome is confirmed HEV disease among pregnant women. After vaccination, participants are requested to report information about clinical hepatitis symptoms. Participants who become pregnant are visited at their homes every 2 weeks to collect information about pregnancy outcome and to screen for clinical hepatitis. All suspected hepatitis cases undergo laboratory testing for diagnostic evaluation. The incidence of confirmed HEV disease among pregnant and non-pregnant women will be compared between the HEV vaccinated and control groups, safety and immunogenicity of the vaccine will also be evaluated., Ethics and Dissemination: The protocol was reviewed and approved by the International Centre for Diarrhoeal Disease Research, Bangladesh Research Review Committee and Ethical Review Committee, and the Directorate General of Drug Administration in Bangladesh, and by the Regional Ethics Committee in Norway. This article is based on the protocol version 2.2 dated 29 June 2017. We will present the results through peer-reviewed publications and at international conferences., Trial Registration Number: The trial is registered at clinicaltrials.gov with the registry name "Effectiveness Trial to Evaluate Protection of Pregnant Women by Hepatitis E Vaccine in Bangladesh" and the identifier NCT02759991., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Group A rotavirus (RVA) associated diarrhoea in piglets represents one of the major causes of morbidity and mortality in pig farms worldwide. A diarrhoea outbreak occurred among nomadic piglets in north-western district of Bangladesh in February 2014. Outbreak investigation was performed to identify the cause, epidemiologic and clinical features of the outbreak. Rectal swabs and clinical information were collected from diarrhoeic piglets (n = 36). Rectal swabs were tested for RVA RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR) using NSP3-specific primers. The G (VP7) and P (VP4) genes were typed by conventional RT-PCR and sanger sequencing and full genome sequences were determined using next-generation sequencing. We found the attack rate was 61% (50/82) among piglets in the nomadic pig herd, and the case fatality rate was 20% (10/50) among piglets with diarrhoea. All study piglets cases had watery diarrhoea, lack of appetite or reluctance to move. A novel RVA strain with a new P[49] genotype combined with G4 was identified among all piglets with diarrhoea. The genome constellation of the novel RVA strains was determined to be G4-P[49]-I1-R1-C1-M1-A8-N1-T7-E1-H1. Genetic analysis shows that the novel G4P[49] strain is similar to Indian and Chinese porcine or porcine-like G4 human strains and is genetically distant from Bangladeshi human G4 strains. Identification of this novel RVA strain warrants further exploration for disease severity and zoonotic potential., (© 2019 Blackwell Verlag GmbH.)

Background: Although randomized data support omitting adjuvant radiotherapy (RT) following breast conservation for T1-2N0 estrogen receptor positive breast cancer in ≥70-year-old women, there remains a knowledge gap regarding its omission for triple-negative BC (TNBC)., Methods and Materials: The National Cancer Database (NCDB) was queried for ≥70-year-old females with newly diagnosed T1-2N0M0 TNBC treated with breast conservation. Multivariable logistic regression ascertained factors associated with adjuvant RT administration. Overall survival (OS) between patients treated with or without adjuvant RT was estimated using the Kaplan-Meier method. Cox proportional hazards modeling determined variables associated with OS., Results: Of 8526 patients, 6283 (74%) patients received adjuvant RT, and 2243 (26%) did not. RT was more frequently withheld in older patients, those with higher comorbidities, lower income, pT2 disease, following margin-positive resection, receipt of chemotherapy, and at academic centers (P < 0.05 for all). Median follow-up was 38.0 months. Five-year OS was greater in the adjuvant RT group (77.2% vs 55.3%, P < 0.001); these differences persisted when stratifying for age, T stage, and chemotherapy utilization (P < 0.001 for all). Omission of RT was also independently associated with poorer OS on multivariate analysis (P < 0.001)., Conclusions: This investigation, the largest known such study to date, observed that omission of adjuvant RT for elderly women with T1-2N0 TNBC was associated with poorer OS; this was observed across a range of age groups, as well as following stratification by T stage and chemotherapy usage. Although these results do not imply causation, caution must be exercised when considering omission of adjuvant RT in node-negative TNBC patients., (© 2019 Wiley Periodicals, Inc.)

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)-positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow-up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2- disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR-HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African-American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes., (© 2019 Wiley Periodicals, Inc.)

Background: Invasive micropapillary carcinoma (IMPC) is an uncommon subtype of breast cancer. Previous studies of this subtype demonstrated a higher propensity for lymph node metastases as compared with invasive ductal carcinoma (IDC). The purpose of the present study was to determine the clinical characteristics, outcomes, and propensity for lymph node metastasis of patients with IMPC of the breast recorded in the National Cancer Database (NCDB)., Methods: Records of patients with IMPC diagnosed between 2004 and 2014 were retrieved from the NCDB. Log-rank test was performed to evaluate associations of clinical characteristics with overall survival (OS). Cox proportional hazards model was used to determine variables associated with OS., Results: Overall, 2660 patients with IMPC met the selection criteria; the 5-year OS rate was 87.5% and 24.9% of patients had nodal involvement at presentation. Patients with ≥ 4 positive lymph nodes had shorter OS than node-negative patients, whereas patients with 1-3 positive nodes had similar OS to node-negative patients. Age < 65 years, receipt of radiotherapy, and estrogen receptor positivity were also associated with prolonged OS. The benefit of radiotherapy was limited to IMPC patients undergoing lumpectomy; there was no benefit for the patients undergoing mastectomy (regardless of nodal positivity/negativity)., Conclusions: Favorable prognostic factors of IMPC patients included age < 65 years, < 4 positive lymph nodes, receipt of radiotherapy, and estrogen receptor positivity. The results presented herein suggest a survival benefit associated with radiotherapy in IMPC treatment, though this may be limited to the patients treated with lumpectomy.

Background: Muscle-invasive bladder cancer (MIBC) may be managed with radical cystectomy (RC) or chemoradiotherapy (CRT). Because patient selection for RC is important to avoid treatment-related mortality, this study addressed a knowledge gap by quantifying short-term mortality with both approaches, as well as predictors thereof., Materials and Methods: The National Cancer Database was queried (2004-2014) for clinically staged T2-4aN0M0 MIBC that received either CRT or RC. Statistics included cumulative incidence comparisons of 30- and 90-day mortality between patients treated with either CRT or RC and Cox regression to evaluate predictors thereof., Results: Of 16,658 patients, 15,208 (91.3%) underwent RC and 1450 (8.7%) CRT. Crude rates of post-treatment mortality at 30 days were 2.7% versus 0.6% (P < .001) and at 90 days were 7.5% versus 4.5% (P = .017) for patients treated with RC and CRT, respectively. When stratifying by age, worse 30- and 90-day mortality with RC was observed for patients aged ≥ 76 years., Conclusions: This study describes 30- and 90-day mortality following RC versus CRT. Both approaches yield statistically similar treatment-related mortality rates in patients ≤ 75 years of age; however, worse post-treatment mortality was observed with use of RC in patients ≥ 76 years of age. These results may be utilized to better inform shared decision-making between patients and providers when weighing both RC and CRT for MIBC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Neoadjuvant therapy is a strategy for resectable and borderline resectable pancreatic cancer, but a consensus approach regarding optimal management is undetermined. Neoadjuvant options include chemotherapy with/without radiotherapy. Stereotactic body radiation therapy (SBRT) is a novel radiation technique that may provide benefit over conventionally fractionated radiation therapy (CFRT) in the neoadjuvant setting. The purpose of the present study is to determine neoadjuvant treatment with SBRT to other neoadjuvant treatment options for patients with resectable pancreatic cancer. Material and methods: The National Cancer Database was queried (2004-2015) for patients with nonmetastatic pancreatic adenocarcinoma receiving neoadjuvant therapy followed by pancreatectomy. Patients were categorized based on the type of neoadjuvant treatment administered. Statistics included temporal trend assessment by annual percent change (APC), predictors for SBRT by multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling for univariable OS analysis. Results: Of 5828 patients, 332 (5.7%), 3234 (55.5%) and 2262 (38.8%) received neoadjuvant chemo-SBRT, chemotherapy, and chemo-CFRT, respectively. SBRT utilization increased from 0% in 2004 to 9.5% in 2015, with a greater APC after 2010 ( p  < .001). SBRT was more likely to be utilized in patients with T3-4 and node-positive disease ( p  < .05 for all). The chemo-SBRT cohort was associated with a higher OS rate before and after propensity matching ( p  < .05 for both). The rate of R0 resection was higher in radiotherapy groups than the chemotherapy cohort ( p  < .001). Conclusions: Utilization of neoadjuvant SBRT for pancreatic cancer is increasing. In the neoadjuvant setting, chemo-SBRT may improve R0 resection and OS over chemotherapy and chemo-CFRT, although confirmatory prospective studies are needed for confirmation.

Immunotherapy for metastatic melanoma has rapidly expanded, but racial and/or socioeconomic factors often impact the type of therapies delivered for cancer care. This study addressed a crucial public health priority by evaluating disparities in administration of immunotherapy for metastatic melanoma. The National Cancer Database was queried for newly diagnosed metastatic melanoma. Patients were dichotomized based on receipt of immunotherapy based on National Cancer Database coding. Multivariable logistic regression ascertained factors associated with immunotherapy delivery. Subgroup analysis evaluated the interaction between race, insurance status, and income. Secondarily, Cox multivariate and propensity-matched Kaplan-Meier analyses assessed overall survival based on immunotherapy receipt. Of 15,941 patients meeting the selection criteria, 2448 (15.4%) received immunotherapy, and 13,493 (84.6%) did not. Temporal trends showed that utilization of immunotherapy was 8%-12% of patients between 2004 and 2010, with utilization increasing to 29.7% of patients in 2014. Immunotherapy was more likely administered to younger and healthier patients, at academic centers, and in the absence of chemotherapy and brain metastases (P<0.05 for all). African Americans, along with patients with Medicaid and lower incomes were less likely to receive immunotherapy (P<0.05 for all). As expected, immunotherapy was associated with improved overall survival (median 16.3 vs. 8.3 mo, P<0.001). Although immunotherapy for metastatic melanoma is markedly escalating, not all populations experience this rise equally. Because immunotherapy utilization is expected to amplify even further in the future, these public health and economic issues are essential to identify and address appropriately, and have implications on public health policy, pharmaceutical and insurance companies, and value-based oncology. Methods to address these inequalities are also discussed.

Background/aim: Because aggressive oncological management just prior to death constitutes a substantial proportion of end-of-life (EOL) costs, we investigated patterns of EOL oncologic care for stage IV non-small cell lung cancer (NSCLC) in USA to better determine at which point in the patient's management new treatments were being initiated., Materials and Methods: The National Cancer Database was queried for stage IV NSCLC patients who received any cancer-directed therapy with known timing thereof., Results: A total of 281,990 stage IV NSCLC patients were analyzed. Of all patients, 10.8% commenced any first-course cancer therapy within four weeks of death, and 24.5% within eight weeks of death., Conclusion: 10-15% of stage IV NSCLC patients start cancer therapy within four weeks of death, and 25-30% within eight weeks. This represents a population for whom cancer therapy may not be required, which has implications on reducing EOL healthcare costs., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The purpose of this study was to discover the elements required for a successful learning community (LC) faculty member educator of medical students., Method: The authors in this qualitative study evaluated six 90-min focus groups of faculty members. The groups included 31 experienced and 19 inexperienced LC faculty members at the University of Texas Southwestern Medical School. After achieving excellent interrater reliability, transcriptions of the discussions were subjected to thematic analysis using ATLAS.ti software., Results: Five major themes emerged: (1) LC faculty characteristics/competency, (2) suggested faculty development methods, (3) factors outside the LC environment influencing student relationships, (4) student attributes influencing teaching techniques, and (5) measuring and improving history and physical skills. Faculty characteristics/competency subthemes included role-modeling, mentoring, and teaching competence. Suggested faculty development methods subthemes included assessing and giving feedback to faculty, peer development, and learning from experts. Experienced LC faculty focused more attention on teaching competence and mentoring competence than inexperienced LC faculty., Discussion: The themes with the most extensive discussion among the experienced LC faculty groups may represent qualities to be sought in future mentor recruitment and faculty development. Future studies could build on this study by similarly investigating student perceptions., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2019.)

Background: Anal adenocarcinoma (AA) is a rare histologic subtype of anal cancer believed to have worse outcomes than anal squamous cell carcinoma (AS). This study aimed to examine practice patterns and treatment outcomes for this rare subtype using the National Cancer Data Base (NCDB)., Methods: Patients who had new diagnoses of anal cancer treated with chemoradiation were selected from the NCDB from 2004 to 2015. The patients were divided into two histologic groups (AA or AS). Statistics included the Chi square test to analyze categorical proportions in demographic information, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS., Results: The study analyzed 24,461 patients. Compared with AS patients, AA patients were more likely to be male, to present with a higher cancer stage, to be older (> 65 years), and to undergo surgery with an abdominoperineal resection (APR). The median OS was 72.5 months for the AA patients and 143.8 months for the AS patients (P < 0.001). Survival was longer for the AA patients undergoing APR within 6 months after chemoradiation (CRT) than for the AA patients who had an APR 6 months after CRT (88.3 vs. 58.1 months; P < 0.001). In the multivariable analysis, the factors associated with worse survival included adenocarcinoma subtype, age of 55 years or older, male gender, T stage of 3 or higher, comorbidity score of 1 or higher, lower income, and treatment at a nonacademic institution., Conclusions: In this largest study of anal adenocarcinoma to date, trimodality therapy was associated with better survival than chemoradiation alone.

Background: Up-front stereotactic radiosurgery (SRS) has been historically thought of as inadequate for brain metastases (BM) from newly diagnosed small cell lung cancer (SCLC). This study evaluates national practice patterns and clinical outcomes for BM from SCLC., Material and Methods: The National Cancer Database was queried (2004-2013) for patients with newly diagnosed metastatic SCLC receiving intracranial radiotherapy. Patients were grouped into three categories: upfront SRS, whole-brain radiotherapy (WBRT) alone, or WBRT with boost (SRS or fractionated radiotherapy). Statistics included temporal trend assessment by annual percent change (APC), logistic regression, exploratory Kaplan-Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling., Results: A total of 14,722 patients met selection criteria, of whom 487 (3.3%), 13,657 (92.8%), and 578 (3.9%) received upfront SRS, WBRT and WBRT with boost, respectively. Utilization of SRS showed a slight increasing trend from 2004 to 2013 (2.7-4.3%). In addition to socioeconomic factors, other variables associated with SRS use included diagnosis after 2010, treatment at academic centers, and residing in higher-educated regions. SRS was less often delivered to patients with node-positive disease (p < .05). On exploratory analysis, SRS cohort was observed to have a higher overall survival (OS) than WBRT-based groups (p < .001), namely in patients without extracranial metastases., Conclusions: Utilization of up-front SRS for SCLC BM has been increasing over time but is driven by socioeconomic disparities. Although there are likely numerous biases associated with the OS findings herein, further research is needed to validate this finding as well as the role of SRS on patients with brain metastases due to SCLC.

Purpose: From prospective studies, pathologic nodal clearance (PNC, ypN0) and pathologic complete response (pCR, ypT0N0) correlate with overall survival (OS) following neoadjuvant chemoradiation for cN2 non-small cell lung cancer (NSCLC). Contemporary cooperative group trials attempt to increase radiation doses to achieve nodal clearance and/or pCR. However, long-term comparative outcomes of dose-escalated neoadjuvant chemoradiation are lacking. The goal of this study was to evaluate rates of PNC and pCR in a large population of cN2 NSCLC, predictors thereof, and long-term outcomes thereafter., Methods: The National Cancer Database was queried (2004-2015) for histologically-confirmed cT1-4N2M0 NSCLC undergoing neoadjuvant chemoradiation followed by lobectomy. Statistics included multivariable logistic regression, Kaplan-Meier OS analysis before and following propensity matching, Cox proportional hazards modeling, and sensitivity analysis when varying neoadjuvant radiation dose., Results: Of 1750 patients, the pCR and PNC rates were 17% and 37%, respectively. Radiation dose >54 Gy independently predicted for pCR. Patients achieving pCR experienced significantly higher OS than non-pCR cases (p < 0.001) and ypT + ypN0 cases (p < 0.001). In the subset of non-PNC patients, there was a trend towards higher OS in patients in whom ypT0 was achieved (p = 0.059). On sensitivity analysis, when separating the cohort into doses of 45.0-50.4 Gy, 50.5-54.0 Gy, 54.1-59.4 Gy, and >59.4 Gy, 30-day mortality rates in the respective groups were 2.9%, 1.8%, 1.2%, and 3.4%., Conclusions: Although neoadjuvant dose-escalation increases pCR rates, there is no OS benefit with dose-escalation, and high dose-escalation (i.e., >59.4 Gy) was associated with numerically higher mortality rates, indicating the importance of careful multidisciplinary discussion., (Copyright © 2019 Elsevier B.V. All rights reserved.)