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Background The Covid-19 pandemic and subsequent lockdown in India caused disruptions in cancer treatment due to the restriction on movement of patients. We aimed to maintain continuity in cancer treatment during the lockdown through teleconsultations. We tried to reach out to our patients using telephonic consultations by establishing a Teleconsult Centre facility run by a team of doctors and patient navigators. Methods We telephonically contacted all patients who had outpatient appointments from 23 March to 30 April 2020 at our centre through the Teleconsult Centre to understand their current circumstances, feasibility of follow-up, local resources and offered best possible alternatives to continue cancer treatment, if required. Results Of the 2686 patients scheduled for follow-up during this period, we could contact 1783 patients in 9 working days. Through teleconsultations, we could defer follow-ups of 1034 patients (57.99%, 95% confidence interval [CI] 55.6%–60.3%), thus reducing the need for patients to travel to the hospital. Change in systemic therapy was made in 75 patients (4.2%, 95% CI 3.3%–5.2%) as per the requirements and available resources. Symptoms suggestive of disease progression were picked up in 12 patients (0.67%, 95% CI 0.35%–1.17%), who were advised to meet local physicians. Conclusion Our study suggests that the majority of patients on follow-up can be managed with teleconsultation in times of crisis. Teleconsultation has the potential of being one of the standard methods of patient follow-up even during periods of normalcy.

PURPOSE Preventing metastases by using perioperative interventions has not been adequately explored. Local anesthesia blocks voltage-gated sodium channels and thereby prevents activation of prometastatic pathways. We conducted an open-label, multicenter randomized trial to test the impact of presurgical, peritumoral infiltration of local anesthesia on disease-free survival (DFS). METHODS Women with early breast cancer planned for upfront surgery without prior neoadjuvant treatment were randomly assigned to receive peritumoral injection of 0.5% lidocaine, 7-10 minutes before surgery (local anesthetics [LA] arm) or surgery without lidocaine (no LA arm). Random assignment was stratified by menopausal status, tumor size, and center. Participants received standard postoperative adjuvant treatment. Primary and secondary end points were DFS and overall survival (OS), respectively. RESULTS Excluding eligibility violations, 1,583 of 1,600 randomly assigned patients were included in this analysis (LA, 796; no LA, 804). At a median follow-up of 68 months, there were 255 DFS events (LA, 109; no LA, 146) and 189 deaths (LA, 79; no LA, 110). In LA and no LA arms, 5-year DFS rates were 86.6% and 82.6% (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95; P = .017) and 5-year OS rates were 90.1% and 86.4%, respectively (HR, 0.71; 95% CI, 0.53 to 0.94; P = .019). The impact of LA was similar in subgroups defined by menopausal status, tumor size, nodal metastases, and hormone receptor and human epidermal growth factor receptor 2 status. Using competing risk analyses, in LA and no LA arms, 5-year cumulative incidence rates of locoregional recurrence were 3.4% and 4.5% (HR, 0.68; 95% CI, 0.41 to 1.11), and distant recurrence rates were 8.5% and 11.6%, respectively (HR, 0.73; 95% CI, 0.53 to 0.99). There were no adverse events because of lidocaine injection. CONCLUSION Peritumoral injection of lidocaine before breast cancer surgery significantly increases DFS and OS. Altering events at the time of surgery can prevent metastases in early breast cancer (CTRI/2014/11/005228). [Media: see text]

Triple-negative breast cancer (TNBC) is characterized by the lack of expression of estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). However, pathways responsible for downregulation of therapeutic receptors, as well as subsequent aggressiveness, remain unknown. In this study, we discovered that lactoferrin (Lf) efficiently downregulates levels of ER-α, PR, and HER-2 in a proteasome-dependent manner in breast cancer cells, and it accounts for the loss of responsiveness to ER- or HER-2–targeted therapies. Furthermore, we found that lactoferrin increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that lactoferrin directly stimulates the transcription of endothelin-1 (ET-1), a secreted proinvasive polypeptide that acts through a specific receptor, ET(A)R, leading to secretion of the bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor-antagonist blocked lactoferrin-dependent motility and invasiveness of breast cancer cells. The physiologic significance of this newly discovered Lf–ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue lactoferrin and ET-1 levels in patients with TNBC compared with those in ER+ cases. These findings describe the first physiologically relevant polypeptide as a functional determinant in downregulating all three therapeutic receptors in breast cancer, which uses another secreted ET-1 system to confer invasiveness. Results presented in this article provide proof-of-principle evidence in support of the therapeutic effectiveness of ET-1 receptor antagonist to completely block the lactoferrin-induced motility and invasiveness of the TNBC as well as non-TNBC cells, and thus, open a remarkable opportunity to treat TNBC by targeting the Lf–ET-1 axis using an approved developmental drug. Cancer Res; 71(23); 7259–69. ©2011 AACR.

Introduction Paclitaxel can cause peripheral neuropathy in up to 60% of patients. Chemotherapy-induced peripheral neuropathy (CIPN) compromises quality of life and often leads to dose reduction or discontinuation of lifesaving chemotherapy. Preclinical models have suggested the possible neuroprotective effect of progesterone through remyelination and other mechanisms. Objectives The aim of this study was to evaluate the incidence of CIPN for different menopausal status. Materials and Methods We evaluated the effect of menopausal status, as a surrogate for circulating progesterone levels, on the risk of developing paclitaxel-induced peripheral neuropathy, in an audit of breast cancer patients. Data on CIPN (by clinical history and examination) and other variables were collected from the case charts of patients who had received paclitaxel-based chemotherapy for breast cancer at our institution. Results Five hundred and fifty women were treated with either neoadjuvant or adjuvant paclitaxel in this period. Of these, 262 (47.6%) women were premenopausal, 49 (8.9%) were perimenopausal, and 239 (43.5%) were postmenopausal at the time of diagnosis. Forty-five (8.1%) women had pre-existing diabetes mellitus. Two hundred and fifty-six (82.31%) developed chemotherapy-induced amenorrhea (CIA).CIPN was seen in 32.7% of women who continued to be premenopausal after receiving chemotherapy and 62.3% of postmenopausal women. Thirty-five (77.8%) out of forty-five diabetic women developed CIPN. On a multivariate logistic regression model, pre-existing diabetes mellitus (risk ratio [RR] = 2.64, 95% confidence interval [CI]: 1.26–5.52, p = 0.009), postmenopausal (RR = 2.84, 95% CI = 1.48–5.45, p = 0.002), and CIA status (RR = 2.17, 95% CI = 1.14–4.12, p = 0.018) were significantly associated with the development of CIPN. Number of cycles did not appear to have an impact (p= 0.819). Conclusions Postmenopausal status was independently associated with higher incidence of CIPN. One of the possible mechanisms could be lower circulating progesterone levels in these patients. A randomized controlled trial (CTRI/2015/11/006381) is ongoing to test this hypothesis.

Objectives: Although commonly practiced, the accuracy, effectiveness, and safety of screening patients for COVID-19 at hospital entrances is not well documented. Material and Methods: We performed a retrospective analysis of single institution data involving screening patients for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at hospital entrances by trained health personnel, with thermal scanning and administration of a standard questionnaire eliciting risk factors and symptoms of COVID-19. SARS-CoV-2 positivity among patients screened positive and negative and among personnel involved in screening were estimated. Results: Between May 22, 2020, and July 4, 2020, a total of 20152 patients involving 54955 hospital visits were screened at hospital entrances of whom 668 (3.31%, 95% CI 3.07–3.57) were screened positive for suspected COVID-19 and 19484 (96.69%, 95% CI 96.44–96.93) were screened negative. Among patients screened positive, of the 638 patients with available records, 109 (17.08%, 95% CI 14.24–20.23) were confirmed to be SARS-CoV-2 positive by polymerase chain reaction test, 288 (45.14%, 95% CI 41.23–49.10) were negative, 71 (11.13%, 95% CI 8.79–13.83) were not tested after secondary assessment, and 170 (26.65%, 95% CI 23.25–30.26) patients declined the test. Among screen negative patients, 162 (0.83%, 95% CI 0.71–0.97) were SARS-CoV-2 positive. Of the 104 personnel involved in screening, 03 (2.88%, 95% CI 0.60–8.20) were confirmed to be SARS-CoV-2 positive during study period. Conclusion: Screening patients with a combination of thermal scanning and a standard questionnaire for COVID-19 has a high positive predictive value for detecting this infection with low risk of SARS-COV-2 transmission to the involved health personnel.

Objectives: Continuation of health-care facilities for non-COVID illness during the SARS-CoV-2 pandemic is mired with apprehension of infection to health care workers (HCWs). The lack of facilities can result in dire outcomes for patients of NCDs such as cancer. The Objective of this paper is to assess the risk of running a healthcare facility during the pandemic. Material and Methods: A retrospective analysis was carried out at a tertiary cancer hospital to understand the quantum of risk to HCWs while providing care to patients of cancer and to SARS-CoV-2 patients, within the same set-up with optimal segregation. Data were collected for 6 weeks during which attendance, exposure, and infection status of doctors and nurses were recorded along with comorbidities. Results: Of 1041 doctors and nurses who attended duties during the study period, 299 worked in dedicated COVID care areas while 742 worked in routine cancer care areas. The proportion of HCWs that developed symptoms or were tested positive for COVID-19 was 3.7% and 3.9%, respectively, with no statistically significant difference between the two. The proportion for the same was found to be 1.2% among the 645 staffs who were on leave. No correlation could be established between pre-existing comorbidities and risk of acquiring infection. Conclusion: Providing COVID care and routine specialty care within the same hospital premises do not put the HCWs at a drastically increased risk of acquiring infection subject to clear demarcation of work areas, screening at gates by trained personnel, regulation of number of hospital visitors, and optimal use of PPEs.

Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research.

Surgery is the primary treatment of phyllodes tumor of the breast, and margins are the most important risk factor associated with local recurrence. We conducted a retrospective audit of 433 patients treated at our center.Women who presented with phyllodes tumors between 1999 and 2017 were included in the analysis. Data was collected from the hospital medical records, telephonic interviews, and electronic mail.Of the 433 women included in this study, 177 (40.9%) had benign phyllodes tumors, 84 (19.4%) were borderline, 131 (30.3%) were malignant, and 41 (9.5%) had sarcoma. A history of previous excision was noted in 154 (35.6%) patients, of which 104 presented with local recurrence. Of the total patients, 209 (48.3%) underwent breast conservation surgery; the median pT was 6 cm. At a median follow-up of 37.9 months, the 5-year disease-free survival (DFS) was 82.9%. On multivariate analysis, the factors that impacted DFS were histology (hazard ratio, 4.1; 95% confidence interval [CI], 1.5-10.9; P = .005) and history of previous excision biopsy (hazard ratio, 3.39; 95% CI, 1.76-6.52; P .001). We analyzed 231 women who presented without any prior excision separately, wherein at a median follow-up of 44.1 months, the DFS was 92.1% (95% CI, 92.05%-92.15%). In addition, less recurrences were noted in this cohort (5.6% [13/231] in no-excision biopsy vs. 12.5% with surgery done prior to presentation to our institute).A previous history of excision and the histologic subtype of phyllodes tumor are factors that have an impact on DFS, thus emphasizing the need for appropriate surgical planning and en bloc excision of the phyllodes at presentation.

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

Background: Ductal carcinoma in situ (DCIS) identified by screening mammography accounts for 20% of breast cancer diagnoses, and microinvasion (DCIS-M) is found in 5%-10%. There are no defined treatment guidelines for palpable DCIS or DCIS-M. The role of screening mammography is now being questioned across the world and in the developing world with no national screening programs, women with DCIS present with a palpable lump in the breast. We conducted a retrospective audit of women with DCIS treated at our institution to classify palpable DCIS and DCIS-M as distinct clinical stages and emphasize the need for a change in management of ‘palpable DCIS’ Methods: Annually we register approximately 1700 new cases of early breast cancer of which DCIS and DCIS-M constitutes less than 1%. Between 2005-2016 we registered 784 cases of with DCIS, DCIS-M and early invasive cancer with extensive intraductal component (EIC) at our centre. A retrospective analysis of these cases was performed. Results: Of the 784 patients case records reviewed, 113 (14.4%) had Tis, 87 (11.1% of all early cases and 43.5% of DCIS) had T1mic, the rest had invasive cancer with EIC, of which 46 (5.9%) wereT1a, 28(3.6%) were T1b, 146 (18.6%) were T1c and 364 (46.4%) wereT2. The median age at presentation was 48 years, median clinical tumour size was 3cm; 740 (94.4%) presented with palpable breast lumps.At a median follow up of 86 months , the disease free survival was 95.6% for Tis, 96.6% T1mic, 90.5% T1 and 82.7% T2 (p=0.00). On follow up distant recurrences were noted in 5(4.4%) patients with Tis, 3(3.4%) with T1mic, 21(9.5%) with T1 and 63(17.3%) with T2, (p=0.00). Limited use of adjuvant chemotherapy in Tis and T1mic may have contributed to the high distant recurrences in that group. Also palpable Tis,T1mic and T1a had higher percentage of HR negative compared to those with larger invasive tumours. Conclusions: DCIS presenting in palpable lesions poses a clinical dilemma for the use of adjuvant therapy. In our cohort 43.5% of the palpable DCIS showed evidence of microinvasion with high risk of distant recurrence compared to screen detected DCIS. We thus need to reconsider grossing techniques to accurately identify foci of invasion, redefine DCIS-M based on number and size of foci of invasion and explore the possible role of adjuvant chemotherapy in treating large palpable DCIS. ResultsTis (N%)T1mic (N%)T1a (N%)T1b (N%)T1c (N%)T2 (N%)cT >2 cm63 (55.8)68 (78.2)28 (60.9)6 (21.4)1 (0.7)363 (99.7)Palpable lump85 (75.2)81 (93.1)39 (83)28 (100)144 (98.6)363 (99.7)Nipple discharge26 (23)6 (6.8)7 (14.9)0 (0)2 (1.3)1 (0.3)Hormone receptor positive (HR+ve)60 (53.1)18 (20.7)18 (38.3)15 (53.6)92 (63)218 (60.6)HER2neu +ve31 (27.4)41 (47.1)13 (27.7)8 (28.6)27 (18.5)93 (25)Axilla +ve6 (5.3)9 (10.3)9 (19.1)9 (32.1)50 (34.2)184 (50.7) Citation Format: Karishma Kirti, Nita Nair, Tanuja Shet, Rohini Hawaldar, Vani Parmar, Seema Gulia, Shalaka Joshi, Sridevi Murali, Vaibhav Vanmali, Bipin Bandre, Sudeep Gupta, Rajendra Badwe. Reconsidering the management of palpable DCIS - A single institution audit [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-23.

Background: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots. Methods: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020. Findings: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV – VI). Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in

Cancer research currently is heavily skewed toward high-income countries (HICs), with little research conducted in, and relevant to, the problems of low- and middle-income countries (LMICs). This regional discordance in cancer knowledge generation and application needs to be rebalanced. Several gaps in the research enterprise of LMICs need to be addressed to promote regionally relevant research, and radical rethinking is needed to address the burning issues in cancer care in these regions. We identified five top priorities in cancer research in LMICs based on current and projected needs: reducing the burden of patients with advanced disease; improving access and affordability, and outcomes of cancer treatment; value-based care and health economics; quality improvement and implementation research; and leveraging technology to improve cancer control. LMICs have an excellent opportunity to address important questions in cancer research that could impact cancer control globally. Success will require collaboration and commitment from governments, policy makers, funding agencies, health care organizations and leaders, researchers and the public.

Low- and middle-income countries (LMICs) have limited financial resources and proportionately smaller portions allocated for health budget. With competing health priorities, treatment of the diagnosed cases and establishment of treatment facilities are the main concerns in LMICs. Infectious diseases, reducing infant, child and maternal mortality may seem crucial as compared to early cancer detection. LMICs that are committed to providing comprehensive cancer care, will need to judiciously choose the screening tool depending on specifics of how the tool is expected to perform in the population and the cost-effectiveness with respect to the number of lives expected to be saved. Increasing awareness about breast health in general and common cancers and non communicable diseases (NCDs), in particular, may lead to symptomatic women approaching the healthcare facilities at an earlier stage. When the limited available resources are mobilized towards cancer screening, increasing awareness would lead to greater acceptability of the programme. The reach of the programme to achieve good population coverage, the establishment of the diagnostic referral linkages and the availability and accessibility of treatment facilities, will all decide the outcome of the screening programme.

Background Patients with cancer who develop COVID-19 are at higher risk for severe disease and death. We aimed to study the outcomes of patients with cancer who were infected with SARS CoV2, and identify risk factors for adverse outcomes after COVID-19. Methods We included patients with cancer, who were diagnosed with SARS CoV2 between 11th April 2020 and February 2021 at a tertiary referral cancer centre in India. We collected data on age, sex, coexisting medical conditions, type of cancer, intent of cancer management, cancer treatment details, and severity and outcome of COVID-19. The primary outcome was a composite of severe COVID (defined as grade 6 or more on the WHO ordinal scale) or death within 30 days. We performed multivariable logistic regression analysis to identify risk factors for severe COVID or death. Results We obtained data on 1253 patients with cancer and SARS CoV2 infection, of whom 293 (23.6%) had hematological malignancies. The severity of COVID was mild (grade 1 to 3 on WHO ordinal scale) in 1014 (81%) patients, moderate (WHO grade 4 or 5) in 167 (13%) patients and severe (WHO grade 6 or 7) in 72 (6%) patients. The primary outcome was seen in 160 patients (12.8%) and the all-cause 30-day mortality was 10.9% (138 deaths). Advanced age [adjusted OR 1.84 (0.86; 3.94)], history of smoking [aOR 1.78 (1.10; 2.91)], palliative intent of treatment [aOR 3.57 (2.48 to 5.12)] and presence of more than 2 comorbidities [aOR 1.66 (1.03 to 2.67)] were significant risk factors for severe COVID or death. Advanced age and palliative intent of treatment remained significant risk factors for 30-day mortality. Recent systemic anti-cancer therapy, sex or cancer type did not influence outcomes. Conclusion Most patients with cancer who developed COVID-19 in our setting had mild disease; the elderly and those treated with palliative intent were at higher risk of severe COVID-19 or death. Recent cancer therapy did not impact COVID-19 severity or outcomes suggesting that in most patients with cancer, the management of cancer should continue uninterrupted during the pandemic.

Background and Objectives There are reports of outcomes of elective major cancer surgery during the COVID‐19 pandemic. We evaluated if reinforcement of hand hygiene, universal masking, and distancing as a part of pandemic precautions led to a decrease in the incidence of surgical site infections (SSIs) in major oncologic resections. Methods Propensity score matching using the nearest neighbor algorithm was performed on 3123 patients over seven covariates (age, comorbidities, surgery duration, prior treatment, disease stage, reconstruction, and surgical wound type) yielding 2614 matched (pre‐COVID 1612 and COVID 1002) patients. Conditional logistic regression was used to identify if SSI incidence was lower amongst patients operated during the pandemic. Results There was a 4.2% (p = 0.006) decrease in SSI in patients operated during the pandemic. On multivariate regression, surgery during the COVID‐19 period (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.61–0.98; p = 0.03), prior chemoradiation (OR = 2.46; CI = 1.45–4.17; p 4 h (OR = 2.17; 95%CI = 1.55–3.05; p

Most of the long-term care for older adults with chronic or debilitating illnesses is provided by unpaid family members or informal caregivers. There is limited information on caregiver burden among caregivers of older patients with cancer in India. Hence, we assessed the prevalence and severity of caregiver burden among caregivers of older Indian patients with cancer.This was an observational study conducted at the geriatric oncology clinic at Tata Memorial Centre, Mumbai, India. Caregivers of patients aged 60 years and over with a diagnosis of cancer were assessed for caregiver burden using the Zarit Burden Interview. Descriptive statistics were used for demographic and clinical variables. Factors impacting caregiver burden were analyzed using multiple linear regression analysis.Caregiver burden was assessed among 127 caregivers of older Indian patients with cancer. The median patient age was 69 years (range 60-90). Most patients were men (75.6%). There were 33 female caregivers (26%), and 94 male caregivers (74%). The median caregiver burden score was 12 (IQR 6-20). Caregiver burden was "little/none" in 97 (76.4%), "mild-moderate" in 25 (19.7%), "moderate-severe" in four (3.1%) and "severe" in one (0.8%) of the caregivers assessed. On multivariate analysis, factors that significantly impacted caregiver burden scores were the presence of psychological issues in the patient and the caregiver's educational level.Caregiver burden was low among caregivers of older Indian patients with cancer seen at a single center. Caregivers of patients with psychological disorders, and those who had less schooling reported higher caregiver burden.

Background: Navya is a validated online cancer informatics solution that combines artificial intelligence (AI) based analysis of the guidelines and evidence, and rapid review (2 mins/case) by organ specific tumor board experts at Academic Medical Centers to deliver multidisciplinary expert treatment plan to patients within 24 hours. Initially developed for bresat cancer patients in India without ready access to expertise, over 28,000 patients across 68 countries with all cancers have since reached out to Navya. Prior research (SABCS 2014-2018 and ASCO 2017) showed, 1) 97% concordance of Navya predictions with an academic medical center in India and in the US 2) 97% of patients experienced significant anxiety relief due to the rapid, 24 hours turnaround time at the time of making a critical decision. 3) 79% of patients received treatment concordant with Navya recommendations on the ground. Unlike synchronized 1 patient: 1 doctor virtual consults in telemedicine where multidisciplinary collaborations are difficult, Navya uses AI to summarize medical cases and predict treatment plans that can be rapidly modified/vetted by multidisciplinary experts in 1-2 minutes asynchronously and collaboratively on a mobile app. This scales access to expertise for patients around the world beyond the limited availability of experts' time for telemedicine and in-person consults. Methods: Three patient centered outcomes (travel distance, cost and time to receive expert treatment plan) were studied. All consecutive breast cancer patients who reached out to Navya between 1/1/17-1/31/19 but ultimately opted for in-person visit to an academic medical center were contacted by prospective phone follow up. This was compared to a balanced random sample of patients who only used Navya to obtain treatment plans. Results: 195 in-person patients were reached for a prospective phone follow-ups and 132 of them had completed their visit at the academic medical center. 335 Navya patients were analyzed in the control group. The groups did not differ significantly in demographics or disease characteristics. In-person patients and Navya patients differed significantly with respect to 1) median travel distance (838 miles, IQR (237 -1105 miles) vs. 0 miles (p < 0.05)) 2) travel related costs of $1597 [95% CI +/- $240] vs $105 online processing fee 3) total time to receipt of treatment plan (7.23 days, IQR (0.45 - 22.35 days) vs. 0.51 days IQR (0.19-1.057) (p < 0.05)). Conclusions: Cancer informatics solutions like Navya leverage AI to summarize the case, and predict guidelines and evidence based options. Combined by design with expert vetting from academic medical centers, such solutions can generate multidisciplinary treatment plans tailored to an individual patient. This scales ready access to expertise around the world. For patients with limited access to academic medical centers, such solutions eliminate travel burden, and significantly reduce cost and wait time to obtain a treatment plan. For experts who have no time to engage in telephone, video or written remote consults, vetting recommendations from the AI system with concise case summaries only takes 1-2 minutes per case. This model has shown significant ability to create access to specialty expertise, reduce the movement of patients to obtain treatment opinions, save costs and tremendously reduce waiting time for expertise in breast cancer, globally. Citation Format: Rajendra Badwe, Benjamin Anderson, Nancy Feldman, Sudeep Gupta, Shona Nag, CS Pramesh. Prospective comparison of cost, travel burden, and time to obtain multidisciplinary tumor board treatment plan through in-person visits vs. an AI enabled health technology [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-13-04.

Introduction: As a tertiary referral cancer centre, 20-30 % of patients seen in our breast clinic present after excision of the primary breast tumour without oncological principles maintained and no details on the excision margins. We evaluated the safety of excision biopsy (ExBx) as a diagnostic procedure by comparing the outcomes against patients who underwent definitive surgery after a core biopsy/FNAC (CxBx) for diagnosis. Methods: We performed a retrospective audit of the case charts of women with breast cancer treated at our institution. We included women with operable breast cancer (OBC) who presented post ExBx of the primary tumour and those who were treatment naïve and operated after only a CxBx for diagnosis. Results: Of the 1022 women included in the analysis, 551 underwent ExBx for primary diagnosis and 471 had CxBx prior to definitive breast surgery. The excision biopsy group were younger women (median age 44 years) with smaller tumours (median T size 2.5cm), lower HR ( hormone receptor) positive (58.3%) and less number were Her2+ve (16.7 %). In this group 17% received NACT, with 66.4% undergoing breast conservation surgery (BCS), and 37.6% node positive. While in the core biopsy group, the women were older women (median age 50 years) had larger tumours, median 3 cm, with 71.3% HR positive, 18.3% Her2 +ve, 72.8% underwent breast conservation surgery with 44.6 % node positive At a median follow up of 46 months, there was no difference in four year disease free survival (DFS) between ExBx group (83.8% versus 86.8%) and non-ExBx (HR=1.29,95%CI=0.93-1.79, p=0.13). When matched for T size, 699/1022 (69%) had T2 tumours and DFS in ExBx group was 80.7% in compared to 85.7% in non ExBx group. (HR=1.46, 95%CI=1.0-2.11, p=0.04). On multivariate cox regression, T size (HR=1.45,95%CI=1.02-2.07, p=0.03), HR negative (HR=1.61,95%CI=1.15-2.26,p=0.006), node positivity (HR=1.82,95%CI=1.31-2.53,p Conclusion: ExBx of the primary tumour as a diagnostic procedure not performed with oncological principles prior to definitive surgery has a detrimental impact on survival in women with operable breast cancer. Citation Format: Nita Sukumar Nair, Rohini W Hawaldar, Quarratulain Chougle, Vani Parmar, Vaibhav Vanmali, Shabina Siddique, Ashwini Devade, Aarti Pandey, Shalaka Joshi, Sudeep Gupta, Rajendra A Badwe. Impact of lumpectomy for diagnosis of primary tumor on disease free survival in women with operable breast cancer: An institutional audit [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-25.

PURPOSE To understand the preferences and attitudes of patients and family caregivers on disclosure of cancer diagnosis and prognosis in an Indian setting. METHODS Overall, 250 adult patients with cancer and 250 family caregivers attending the outpatients of a tertiary cancer hospital for the first time were recruited purposively. The mean ages of patients and caregivers were 49.9 years (range, 23-80 years) and 37.9 years (range, 19-67 years), respectively. Separately, they completed prevalidated, close-ended preference questions and were interviewed for open-ended attitude questions. RESULTS A total of 250 adult patients (response rate, 47.17% overall, 73.2% in men, and 26.8% in women) and 250 family caregivers (response rate, 40.65% overall, 84.0% in men, and 16.0% in women) participated. Significant differences were observed in the preference to full disclosure of the name of illness between patients (81.2%) and caregivers (34.0%) and with the expected length of survival between patients (72.8%) and caregivers (8.8%; P < .001). The patients felt that knowing a diagnosis and prognosis may help them be prepared, plan additional treatment, anticipate complications, and plan for future and family. The caregivers felt that patients knowing a diagnosis and prognosis may negatively affect the future course of illness and cause patients to experience stress, depression, loss of hope, and confidence. CONCLUSION Patients with cancer preferred full disclosure of their diagnoses and prognoses, whereas the family caregivers preferred nondisclosure of the same to their patients. This novel information obtained through a large study with varied participants from different parts of the country will help formulate communication strategies for cancer care.

India accounts for almost a third of the global burden of oral cancer, a situation worsened by the inability to afford care. When available, aid is often insufficient, and costing is based on informal estimations. This study objectively determines direct healthcare costs of oral cancer in India. The study was performed from a healthcare provider’s perspective using a validated bottom-up method. Care pathways were determined by prospectively observing the natural management of 100 oral cancer patients treated between October 2019 and March 2020. Specific costing categories were built across services, and apportioned values for each interaction was averaged. Costs of treatment and service utilisation were obtained using probabilistic sensitivity analyses. The unit cost of treating advanced stages (United States Dollar (USD) 2,717) was found to be 42% greater than early stages (USD1,568). There was an 11% reduction in unit costs with increases in socioeconomic status. Medical equipment accounted for 97.8% of capital costs, with the highest contributor being imaging services. Variable costs for surgery in advanced stages were 1.4 times higher than early stages. Compared to surgery alone, the average cost of treatment increased by 44.6% with adjuvant therapy. These results show that over the next decade, India will incur an economic burden of USD 3 billion towards the direct healthcare of oral cancer. Early detection and prevention strategies leading to 20% reduction in advanced stage disease could save USD 30 million annually. These results are critical to deliver a disease-driven and objective reform for oral cancer care.

ObjectiveTo understand the outcome of hospitalised patients from Mumbai City, which had the highest number of COVID-19 cases in India.DesignObservational study with follow-up.SettingData extraction from medical records of patients with COVID-19 admitted to Nair Hospital & TN Medical College, Mumbai, India.Participants689 patients with COVID-19 were admitted in the hospital from 26 March 2020 to 11 May 2020.Primary and secondary outcome measuresIn-hospital mortality; joint effect of comorbidity and age on the risk of dying.ResultsA total of 689 patients (median age 44 years) admitted with RT-PCR-confirmed COVID-19 were included in the study. Of these, 77.36% of patients were discharged alive while 22.64% died. 11.61% required some kind of oxygen support while 2.8% of patients required intensive care unit admissions. Older age (HR 2.88, 95% CI 2.09 to 3.98), presence of comorbidities (HR 2.56, 95% CI 1.84 to 3.55), history of hypertension (HR 3.19, 95% CI 1.67 to 6.08), and presence of symptoms at the time of admission (HR 3.21, 95% CI 1.41 to 7.26) were associated with increased risk of in-hospital mortality. Treatment with a combination of azithromycin with hydroxychloroquine, antiviral or steroid compared with no treatment did not alter the disease course and in-hospital mortality. The combined effect of old age and presence of comorbid conditions was more pronounced in women than men.ConclusionsIn-hospital patients were younger, less symptomatic with lesser need of ventilators and oxygen support as compared with many western countries.Trial registrationNot applicable (observational study, not a clinical trial).

In low and middle-income countries, access to cancer diagnosis and treatment is suboptimal. Further, compliance to cancer treatment is a major issue due to various reasons including financial barriers, lack of family support and fear of treatment. This article discusses the determinants of treatment completion in cancer patients of a government-run hospital, in a rural part of Punjab in India. The Sangrur hospital-based cancer registry data for the year 2018 have been used. We have registered 2,969 cancer cases, out of which 2,528 (85%) cases were eligible for the analysis. Of the total 2,528 cases, 1,362 (54%) cases completed the cancer directed treatment and 1,166 (46%) did not. The data have been collected from the electronic medical record (EMR) department and entered into CanReg5 software. The bivariate and multivariate binary logistic regression analysis was performed to see the effect of variables on the treatment completion. The results indicate that the elderly age group (>60 years) (odds ratio (OR): 0.52, (95% confidence interval (CI): 0.31–0.86)), distance from hospital (OR: 0.67, (95% CI: 0.50–0.89)) and access to government health schemes (OR: 0.13, (95% CI: 0.10–0.19)] have direct correlation with the treatment completion. The educated patients (OR: 1.49, (95% CI: 1.13–1.96)) and patients who received curative treatment (OR: 2.7, (95% CI: 1.88–3.88)) have shown 58% and 84% compliance to treatment completion, respectively. The other variables like the clinical extent of disease, religion, gender and income do not have any significant effect on the treatment completion. Determinants like age (young), education, distance from the hospital, curative treatment and availability of government health schemes for financial support have shown positive effects on treatment completion. These factors have to be considered by the cancer hospitals, health departments and policymakers while planning for cancer care or control in India.

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment.This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity.A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients.The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

In a previous retrospective audit from our institution we reported that patients had limited access to HER2-targeted therapy due to financial constraints. Subsequently, the advent of biosimilar versions of trastuzumab and philanthropic support has potentially changed this situation. Herein, we reanalyzed and reported access to HER2-targeted therapy in a more recent cohort of patients.Medical records of new breast cancer patients registered in one calendar year were retrospectively reviewed, supplemented by online pharmacy data to extract information on receptor status, use of HER2-targeted therapy, and other relevant variables. Since not all HER2 immunohistochemistry (IHC) 2+ tumors underwent fluorescent in-situ hybridization (FISH) testing, we estimated the probable HER2 amplified from this group based on a FISH amplified fraction in those HER2 2+ tumors who did undergo FISH.Between January 2016 and December 2016, 4717 new BC patients were registered at our institution, of whom 729 (20.04%) had HER2 IHC 3+ tumors while 641 (17.62%) had HER2 IHC 2+ tumors. The final number of HER2 overexpressing/amplified tumors was estimated to be 928 (729 HER2 IHC 3+, 105 known FISH amplified, and 94 estimated FISH amplified), of whom 831 received treatment at our institution. Overall 474 (57.03%, 95% confidence interval [CI] 53.6-60.4) of these 831 patients received trastuzumab for durations ranging from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in metastatic setting compared to 8.61% (95% CI 6.2-11.6) usage of HER2-targeted therapy in the 2008 cohort.Access to HER2-targeted therapy has substantially increased among patients treated at a public hospital in the past decade, likely due to the advent of biosimilars, the use of shorter duration adjuvant regimens, and philanthropic support. However, further efforts are required to achieve universal access to this potentially life-saving treatment.

Clinical research is an essential part of evidence-based medicine. The conduct of high-quality clinical research requires the backing of strong infrastructure, especially well-trained clinical research professionals. Tata Memorial Centre is the largest public cancer center in India and has been offering a Masters degree in Clinical Research since 2014. In this article, we look at the need for clinical research training, the evolution of this course and the impact it has had on clinical research capacity in India.

Objective To test the efficacy of screening by clinical breast examination in downstaging breast cancer at diagnosis and in reducing mortality from the disease, when compared with no screening. Design Prospective, cluster randomised controlled trial. Setting 20 geographically distinct clusters located in Mumbai, India, randomly allocated to 10 screening and 10 control clusters; total trial duration was 20 years (recruitment began in May 1998; database locked in March 2019 for analysis). Participants 151 538 women aged 35-64 with no history of breast cancer. Interventions Women in the screening arm (n=75 360) received four screening rounds of clinical breast examination (conducted by trained female primary health workers) and cancer awareness every two years, followed by five rounds of active surveillance every two years. Women in the control arm (n=76 178) received one round of cancer awareness followed by eight rounds of active surveillance every two years. Main outcome measures Downstaging of breast cancer at diagnosis and reduction in mortality from breast cancer. Results Breast cancer was detected at an earlier age in the screening group than in the control group (age 55.18 (standard deviation 9.10) v 56.50 (9.10); P=0.01), with a significant reduction in the proportion of women with stage III or IV disease (37% (n=220) v 47% (n=271), P=0.001). A non-significant 15% reduction in breast cancer mortality was observed in the screening arm versus control arm in the overall study population (age 35-64; 20.82 deaths per 100 000 person years (95% confidence interval 18.25 to 23.97) v 24.62 (21.71 to 28.04); rate ratio 0.85 (95% confidence interval 0.71 to 1.01); P=0.07). However, a post hoc subset analysis showed nearly 30% relative reduction in breast cancer mortality in women aged 50 and older (24.62 (20.62 to 29.76) v 34.68 (27.54 to 44.37); 0.71 (0.54 to 0.94); P=0.02), but no significant reduction in women younger than 50 (19.53 (17.24 to 22.29) v 21.03 (18.97 to 23.44); 0.93 (0.79 to 1.09); P=0.37). A 5% reduction in all cause mortality was seen in the screening arm versus the control arm, but it was not statistically significant (rate ratio 0.95 (95% confidence interval 0.81 to 1.10); P=0.49). Conclusions These results indicate that clinical breast examination conducted every two years by primary health workers significantly downstaged breast cancer at diagnosis and led to a non-significant 15% reduction in breast cancer mortality overall (but a significant reduction of nearly 30% in mortality in women aged ≥50). No significant reduction in mortality was seen in women younger than 50 years. Clinical breast examination should be considered for breast cancer screening in low and middle income countries. Trial registration Clinical Trials Registry of India CTRI/2010/091/001205; ClinicalTrials.gov NCT00632047 .

Background In India, as elsewhere, the incidence of gall-bladder cancer (GBC) is substantially higher in women than in men. Yet, the relevance of reproductive factors to GBC remains poorly understood. Methods We used logistic regression adjusted for age, education and area to examine associations between reproductive factors and GBC risk, using 790 cases of histologically confirmed GBC and group-matched 1726 visitor controls. We tested the interaction of these associations by genetic variants known to increase the risk of GBC. Results Parity was strongly positively associated with GBC risk: each additional pregnancy was associated with an ∼25% higher risk {odds ratio [OR] 1.26 [95% confidence interval (95% CI) 1.17–1.37]}. After controlling for parity, GBC risk was weakly positively associated with later age of menarche [postmenopausal women, OR 1.11 (95% CI 1.00–1.22) per year], earlier menopause [OR 1.03 (95% CI 1.00–1.06) per year] and shorter reproductive lifespan [OR 1.04 (95% CI 1.01–1.07) per year], but there was little evidence of an association with breastfeeding duration or years since last pregnancy. Risk alleles of single-nucleotide polymorphisms in the ABCB4 and ABCB1 genetic regions had a multiplicative effect on the association with parity, but did not interact with other reproductive factors. Conclusions We observed higher GBC risk with higher parity and shorter reproductive lifespan, suggesting an important role for reproductive and hormonal factors.

Background: The very few research studies done on risk of cancer among population living vicinity of Nuclear Power Plants (NPPs) locations in India. This is first study to examine cancer incidence, Mortality and Tobacco related cancers in population living near to nuclear power plants (NPPs). Methods: All sites of cancer data collected during 2011-15 period from six population-based cancer registries established near to nuclear power plant locations in India. The statistical tools such as age-standardized rate (ASRs), age-standardized mortality rate (ASMRs), Cumulative risk, mortality to incidence ratio, and probability of developing cancer is used to examine cancer burden among population near nuclear facilities. Results: The cancer incidence in population near NPPs are lower than the other non-NPP registries in India, and even national average. In males, mouth, tongue, oesophagus, larynx and lung are most common cancers; and breast, cervix and ovary are more predominate among females in all six NPP registries. Nearly, 50% of cancer are related to tobacco consummation in all registries. This study does not found any excess risk of cancer incidence in population living near to the nuclear facilities. Conclusion: Overall, our study findings are consistent with other well document studies on the risk of cancer among population near nuclear facilities. The main strength of this study is that this is first large study on cancer risk in population living near to NPPs areas. Also, this highlighted the need for the ecological study of multiple cancer types in the population living near nuclear facilities; and record linkage-based case-control study of cancer in children and adults near nuclear facilities.

Background India accounts for a quarter of the world cervical cancer burden. Cervical cancer is highly preventable. However, low level of participating women in screening is one of the major issues. The aim of this work was to study the factors that influence women to participate in cervical cancer screening by providing menstrual pads for human papillomavirus (HPV) testing. Methods Menstrual clothes were collected from two different populations from the rural areas of Maharashtra state for HPV testing to screen for cervical cancer. For this study, out of 945 participated women, 557 (58.9%) provided their menstrual pads. Multivariate logistic regression was applied to calculate the odds ratio (OR) and 95% confidence interval (95% CI). Results The probability of providing the menstrual pads was high among the women who were highly educated compared to those with less education (OR: 1.4; 95% CI: 1.0-1.9), having mobile phone facilities as compared to those with no mobile phones (OR: 1.4; 95% CI: 1.0-2.0), who were using new cloths as menstrual pads compared to those who did not use the same (OR: 8.5; 95% CI: 5.0-14.3), who did not have tobacco habit as compared to those who had tobacco habit (OR: 1.4; 95% CI: 1.1-1.9) and in the village where health worker was stationed as compared to the village where health worker was not stationed (OR: 1.8; 95% CI: 1.4-2.5). Conclusion Factors including health worker availability, using mobile phones for communication and high education level facilitate women's participation. To improve the participation, there is need to apply special strategies for older age group, less educated women and women having tobacco habit.

Background: Past history of gallstones is associated with increased risk of gallbladder cancer in observational studies. We conducted complementary observational and Mendelian randomization (MR) analyses to determine whether history of gallstones is causally related to development of gallbladder cancer in an Indian population. Methods: To investigate associations between history of gallstones and gallbladder cancer, we used questionnaire and imaging data from a gallbladder cancer case–control study conducted at Tata Memorial Hospital, Mumbai, Maharashtra, India (cases = 1,170; controls = 2,525). We then used 26 genetic variants identified in a genome-wide association study of 27,174 gallstone cases and 736,838 controls of European ancestry in an MR approach to assess causality. The association of these genetic variants with both gallstones and gallbladder cancer was examined in the gallbladder cancer case–control study. Various complementary MR approaches were used to evaluate the robustness of our results in the presence of pleiotropy and heterogeneity, and to consider the suitability of the selected SNPs as genetic instruments for gallstones in an Indian population. Results: We found a strong observational association between gallstones and gallbladder cancer using self-reported history of gallstones [OR = 4.5; 95% confidence interval (CI) = 3.5–5.8] and with objective measures of gallstone presence using imaging techniques (OR = 2.0; 95% CI = 1.5–2.7). We found consistent causal estimates across all MR techniques, with ORs for gallbladder cancer in the range of 1.3–1.6. Conclusions: Our findings indicate a causal relationship between history of gallstones and increased risk of gallbladder cancer, albeit of a smaller magnitude than those found in observational analysis. Impact: Our findings emphasize the importance of gallstone treatment for preventing gallbladder cancer in high-risk individuals.

PURPOSE We tested low axillary sampling (LAS) and sentinel node biopsy (SNB) performed in the same patient to predict axillary nodal status post–neoadjuvant chemotherapy (NACT) in women undergoing elective breast surgery, clinically N0 after NACT. PATIENTS AND METHODS A total of 751 women clinically node negative post-NACT underwent LAS (excision of lymph node [LN] and fat below first intercostobrachial nerve). Of these women, 730 also underwent SNB by dual technique (methylene blue plus radioisotope). SNB (defined as targeted plus palpable LNs) and LAS specimens were distinctly examined for metastasis. All patients underwent completion axillary lymph node dissection. Post-NACT, 290 (38.6%) of 751 women had residual positive lymph nodes on pathology. RESULTS The median clinical tumor size was 5 cm (range, 1-15 cm), and 533 (71%) of patients were N1 or N2 at presentation. Targeted sentinel node (SN) identification was 85.7% (626 of 730; median, two LNs); SN with palpable nodes was found in 95.2% (695 of 730; median, five LNs); LAS node was identified in 98.5% (740 of 751; median, seven LNs). In all but one case, the SN was found within the LAS specimen. The false negative rate (FNR) of SNB (blue, hot, and adjacent palpable nodes) was 19.7% (47 of 238; one-sided 95% CI upper limit, 24.0), compared with an FNR of 9.9% for LAS (29 of 292; one-sided 95% CI upper limit, 12.8; P < .001). If SNB was confined to blue/hot node, excluding adjacent palpable nodes, the FNR was 31.6% (74 of 234; one-sided 95% CI upper limit, 36.6). The FNR could be brought down to < 8.8% if three or more LNs were identified by LAS. CONCLUSION LAS is superior to SNB in identification rate, FNR, and negative predictive value in predicting node-negative axilla post-NACT. LAS can be safely used to predict negative axilla with < 10% chance of leaving residual disease.

Importance The optimum duration of adjuvant trastuzumab among patients with early breast cancer is uncertain but of great therapeutic relevance. Objective To compare shorter durations with 1 year of adjuvant trastuzumab for patients with early breast cancer. Data Sources PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings were searched from January 1, 2005, to June 30, 2019, for relevant randomized clinical trials (RCTs). Study Selection To be eligible, the trial had to be randomized, compare a shorter duration with 1 year of trastuzumab as adjuvant treatment, and include patients with early breast cancer. Data Extraction and Synthesis Individual patient data for disease-free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed. The DFS and OS hazard ratios (HRs) were estimated from the reconstructed survival curves as well as published estimates. The HR for DFS was used to test noninferiority using the median noninferiority margin of eligible RCTs. This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Main Outcomes and Measures The primary outcome was DFS; OS and cardiac toxic effects were secondary outcomes. Results There were 6 eligible RCTs with a median DFS noninferiority margin of 1.3 (range, 1.15-1.53), 5 of which had extractable individual patient data for 11 376 patients, 1659 DFS events, and 871 deaths. For shorter duration vs 1 year of trastuzumab, the 5-year DFS was 85.42% (95% CI, 84.41%-86.38%) vs 87.12% (95% CI, 86.15%-88.02%) (HR, 1.14; 95% CI, 1.03-1.25, 1-sidedPfor noninferiority = .004), and OS was 92.39% (95% CI, 91.61%-93.10%) vs 93.46% (95% CI, 92.73%-94.13%) (HR, 1.17; 95% CI, 1.02-1.33). Using trial-level published estimates from 6 RCTs, including 11 603 patients, 1760 DFS events, and 930 deaths, the HR for DFS was 1.15 (95% CI, 1.04-1.26; 1-sidedPfor noninferiority = .002) and, for OS, 1.17 (95% CI, 1.03-1.33). There was significantly less risk of congestive heart failure with shorter-duration trastuzumab (relative risk, 0.53; 95% CI, 0.38-0.74). Conclusions and Relevance In this study, a shorter duration of adjuvant trastuzumab was noninferior to its 1-year administration and resulted in lower rates of cardiac toxic effects. These results suggest that a shorter duration may be the preferred option for patients with low-risk disease or a predisposition to cardiac toxic effects.

Triple negative breast carcinoma is a problematic subtype with poor outcomes. Many clinical trials are underway to find possible target to increase treatment options. Epidermal growth factor receptor (EGFR) has emerged as one such molecule which is over expressed in some of these patients and can be targeted by tyrosine kinase inhibitors. We describe a diagnostically challenging case of metastatic breast carcinoma, with extensive lung disease and poor Eastern Cooperative Oncology Group (ECOG) performance status, which expressed an uncommon EGFR mutation (Exon 21L861Q) and which benefitted from erlotinib following failure of all primary treatment modalities. The case uncovers the presence of these unusual mutations in breast carcinoma and highlights the importance of performing molecular analysis and the appropriate targeted therapy. This approach can be an important problem-solving tool, especially in cases where the patient is not fit for the other standard treatment options.

BackgroundTo be universally applicable in treatment of severe COVID-19, novel therapies, especially those with little toxicity and low cost, are urgently needed. We report here the use of one such therapeutic combination involving two commonly used nutraceuticals, namely resveratrol and copper in patients with this disease. This study was prompted by pre-clinical reports that sepsis-related cytokine storm and fatality in mice can be prevented by oral administration of small quantities of resveratrol and copper. Since cytokine storm and sepsis are major causes of death in severe COVID-19, we retrospectively analyzed outcomes of patients with this condition who had received resveratrol and copper.Methods & FindingsOur analysis comprised of 230 patients with severe COVID-19 requiring inhaled oxygen who were admitted in a single tertiary care hospital in Mumbai between April 1 and May 13 2020. Thirty of these patients received, in addition to standard care, resveratrol and copper at doses of 5.6 mg and 560 ng, respectively, orally, once every 6 hours, until discharge or death. These doses were based on our pre-clinical studies, and were nearly 50 times and 2000 times less, respectively, than those recommended as health supplements. A multivariable-adjusted analysis was used to model the outcome of death in these patients and evaluate factors associated with this event. A binary logistic regression analysis was used, with age, sex, presence of comorbidities and receipt of resveratrol-copper as covariates. Data were updated as of May 30 2020. The number of deaths in resveratrol-copper and standard care only groups were 7/30 (23.3%, 95% CI 8.1%-38.4%) and 89/200 (44.5%, 95% CI 37.6%-51.3%), respectively. In multivariable analysis, age >50 years [odds ratio (OR) 2.558, 95% CI 1.454-4.302, P=0.0011] and female sex (OR 1.939, 95% CI 1.079-3.482, P=0.0267) were significantly associated, while presence of co-morbidities was not significantly associated (OR 0.713, 95% CI 0.405-1.256, P=0.2421) with death. There was a trend towards reduction in death in patients receiving resveratrol-copper (OR 0.413, 95% CI 0.164-1.039, P= 0.0604).ConclusionsWe provide preliminary results of a novel approach to the treatment of severe COVID-19 using a combination of small amounts of commonly used nutraceuticals, which is non-toxic and inexpensive, and therefore could be widely accessible globally. The nearly two-fold reduction in mortality with resveratrol-copper observed in our study needs to be confirmed in a randomized controlled trial.

PURPOSE The role of axillary conservation after neoadjuvant chemotherapy (NACT) is debatable. We routinely carry out complete axillary lymph node dissection (ALND). This study was conducted to understand the pathologic axillary complete response (pAxCR) after NACT. MATERIALS AND METHODS We evaluated a prospective database of patients with breast cancer who underwent surgery after NACT in the year 2017 at our institution. NACT was administered to downstage locally advanced breast cancer or facilitate breast-conservation surgery. RESULTS Of 793 patients who underwent surgery after NACT, 97(12.2%) had cN0 disease, 407 (51.3%) had cN1, 262 (32%) had cN2, and 27 (3.4%) had cN3 at presentation. Eighty-eight patients (11.1%) had cT1-2 primary tumor stage, and 623 patients (78.6%) had cT3-4 primary tumor stage; primary tumor stage details were unavailable for 82 patients (10.3%). The median age was 46 years (range, 21-74 years). On histopathology, the overall pAxCR rate was 52.8%. In the cN1 and cN2 settings, 58.7% and 36.6% of patients achieved ypN0 status, respectively. The overall pathologic complete response rate was 22.64% (161 of 711 patients). On univariable analysis, cN stage, histologic grade, hormone receptor status, NACT duration, and lymphovascular invasion were significantly associated with pAxCR ( P CONCLUSION At least half of patients with cN1 and a third of patients with cN2 breast cancer who develop pAxCR may be suitable candidates for axillary conservation. A careful postchemotherapy assessment followed by a conservative axillary procedure may be an alternative to ALND, but this needs to be studied prospectively.

COVID-19 pandemic has spawned the need for mass production of N-95 respirators. We used Sterilization Wraps to produce face masks which maintained 93% particle capture efficacy post sterilization. This ubiquitously available material could be explored for production of high quality face masks at a cost less than 30 US cents.