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Aims and Objectives – To evaluate the safety of adjuvant chemo-radiation (CTRT) for breast cancer. We report the cardio-pulmonary safety and quality of life outcome of this regimen. Methods – Stage II-III invasive breast cancer patients planned for adjuvant taxane-based chemotherapy and adjuvant radiotherapy (RT) between April 2019 to December 2020 were eligible irrespective of prior neo-adjuvant therapy. Patients received standard 3D conformal radiotherapy (40 Gy in 15 fractions over 3 weeks ± boost for breast conservation) along with the third cycle of adjuvant taxanes in a 3- weekly schedule or the eighth cycle in a weekly schedule. Troponin T, echo cardiography and pulmonary function test were done pre-RT and repeated at 6 months from RT conclusion while quality of life was evaluated pre-RT, at RT conclusion and after 6 months using EORTC QLQ C30 and BR23. Results – Sixty patients were analysed. The median ejection fraction pre and post CTRT was 60% (p=0.177). The median value of Troponin T at baseline was 37 which decreased to 20 post CTRT (p=0.009). Of the 54 patients who underwent the PFT, the functional vital capacity (FCV) was 2.29 litres at baseline which was 2.2 litres post CTRT (p=0.375). No significant difference was seen for forced expiratory volume (FEV) at 1 second (1.86 vs. 1.82: p=0.365), FEV1/FVC (81.5 vs. 81.43; p=0.9) and diffusing capacity for carbon monoxide (DLCO) (88.3 vs. 87.6; p=0.62) at baseline and post CTRT respectively. There was a significant improvement in QOL scores for nausea, vomiting, pain, constipation, loss of appetite and hair loss post RT 6 months. Conclusion- Patients treated with taxane-based adjuvant CTRT had stable cardio-pulmonary profile at 6 months compared to pre-RT. Quality of life scores improved after treatment for most of the domains compared to the pre-RT scores. Table 1. Calculated scores of EORTC QLQ-C30 and BR23 scales for breast cancer patients at baseline, post CTRT and at first follow up of six months. Citation Format: AKANKSHA ANUP, Tabassum Wadasadawala, CARLTON JOHNNY, RAJIV SARIN, RIMA PATHAK, REVATHY KRISHNAMURTHY, Sudeep Gupta, VANI PARMAR, Jaya Ghosh, JYOTI BAJPAI, SEEMA GULIA. Impact of Adjuvant Chemoradiation on cardiopulmonary function and Quality of Life in Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-18.

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.

Ribociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor approved in combination with endocrine-based therapy for the treatment of hormone receptor-positive (HR + )/human epidermal growth factor receptor 2-negative (HER2 − ) advanced or metastatic breast cancer. It can significantly prolong the progression-free survival and improve the objective response rate compared with hormone therapy alone. However, the combined regimen results in a higher risk of adverse events, one of them being dermatological reactions. We present a case of late severe skin toxicity in a patient who had received ribociclib for 5 months. The toxicity led to severe pruritus and maculopapular and patchy rash on upper and lower extremities, which completely resolved 1 month after cessation of the drug. We conclude that ribociclib-induced skin toxicity is a noteworthy side effect that can lead to permanent cessation of this drug and is reversible. There are clinical decision dilemmas related to continuation, withholding, or switching CDK4/6 inhibitors, and benefits should be weighed against toxicities and costs.

Background-Traditionally, endocrine therapy follows chemotherapy for hormone receptor (HR) positive breast cancer (BC) in the adjuvant setting. Concurrent chemo-hormonal therapy fell into disrepute due to previous studies showing a probable, small detriment in survival. (Albain et al, Lancet, 2009; Bedognetti et al, JNCI, 2009; Pico et al, Ann Oncol, 2004) However, the early studies are fraught with biases. The biological rationale was that endocrine therapy is cytostatic, pushing cancer cells into G0 phase which was feared to reduce the efficacy of chemotherapy which is known to act best on rapidly dividing cells. Thus, the two mechanisms of actions were thought to be antagonistic. However, this fear may be irrational and evidence at molecular level is contradictory. The current sequential strategy delays the start of an equally effective treatment modality in HR+ BC patients. Recent studies have shown that concurrent chemo-endocrine therapy is safe in metastatic HR+ setting. (Sledge et al, J Clin Oncol, 2000) One also needs to rethink neoadjuvant strategies in these patients to improve the current dismal pathological complete response (pCR) rates in this subset. (Cortazar et al, Lancet, 2014) Concurrent treatment seems to have improved pCR rate. (Sagiu K et al, Acta Med Okayama, 2015) Here, we describe a phase III, randomized study aimed to evaluate the efficacy of concurrent chemo-endocrine therapy in the adjuvant and neoadjuvant setting. (CTRI/2018/09/015643) Aims and Objectives- The primary objective is to assess the improvement in disease-free survival by administering concurrent versus sequential, (neo) adjuvant chemo-endocrine therapy in HR+, HER2 negative, non-metastatic BC. The secondary objectives are to assess improvement in overall survival, pCR rates, breast conservation rates. Biomarkers of response to treatment and tumour dormancy in HR+ BC will be studied in a subset of patients.Patients and methods-This is a prospective, open label study where non-metastatic, biopsy proven, HR+, HER2- BC patients who warrant chemotherapy in the adjuvant or neoadjuvant setting are considered. The study started accrual in December 2018 and 285 patients are randomized till date. Pregnant or lactating women and those with inflammatory breast carcinoma are excluded. After obtaining informed consent, patients are randomized to receive concurrent versus sequential chemo-endocrine treatment. Patients will receive all chemo and endocrine therapy as per the institutional standard protocols otherwise. Stratification criteria are neoadjuvant vs adjuvant therapy, pre vs postmenopausal status, node positive vs node negative status, 1st gen (anthracyclines alone) versus 2nd gen (including taxanes) chemotherapy. A two-sided log-rank test with an overall sample size of 2316 (2432 with a 5% dropout rate) (1158 in control and 1158 in treatment group) achieves 80% power at a 0.05 significance level to detect a hazard ratio of 0.80 when the proportion surviving in the control group is 0.70. An interim with respect to safety is planned in the protocol. Expected results and conclusion-Ours is a large, prospective trial evaluating the efficacy of concurrent chemo-endocrine therapy in HR+ BC patients. This has the potential to improve pCR rates in the neoadjuvant setting and change the standard of care in the management of HR+ BC patients. The biomarker analysis will help us further understand the biology of HR+ BC and shed light upon tumour dormancy signatures. Citation Format: Shalaka Joshi, Sridevi Murali-Nanavati, Vaibhav Vanmali, Rohini Hawaldar, Mujahid Gafur Shaikh, Mohammad Sadique Ansari, Sushmita Rath, Jaya Ghosh, Seema Gulia, Jyoti Bajpayi, Nita Nair, Vani Parmar, Purvi Thakkar, Garvit Chitkara, Tanuja Shet, Sangeeta Desai, Ayushi Sahay, Sudeep Gupta, Rajendra Badwe. Concurrent versus sequential chemo-endocrine therapy in er positive and her2 negative non-metastatic breast cancer- an open-label, phase III, randomized controlled trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-08-01.

Introduction Patient satisfaction constitutes a vital service quality indicator. It provides a measure of the gap in health-care requirements and patients' expectations. Objective The aim of this study was to perform linguistic validation of the questionnaire assessing satisfaction with outpatient care. Materials and Methods A tool for measuring patient satisfaction was developed and validated at our institute in the English language. This tool was translated into Hindi and Marathi. Subsequently, 339 patients diagnosed with breast cancer consulting in the outpatient department from the different parts of India and having diverse linguistic and socioeconomic backgrounds were enrolled. Patients were asked to complete the satisfaction tool after consultation at a single point of time in a prospective manner. Results All patients completed the questionnaire. The questionnaire was filled by 120, 116, and 103 patients in Hindi, Marathi, and English, respectively. Both convergent validity and discriminant validity were supported as the correlation coefficient was >0.4 for all items within a scale and 0.9 for all the questions. The mean overall satisfaction score was 88.35 (standard deviation: 19.63). Patients were satisfied in all the aspects of the consultation process, including appointment scheduling, assistant medical staff and faculty, and treating physician. However, some expressed dissatisfaction toward long-waiting times. Conclusion The translated tool is reliable and valid and effectively measures the satisfaction of patients receiving ambulatory care.

Brachytherapy (BT) for cervix cancer was listed as a level I priority and reduced number of implants and multiple fractions were recommended during COVID-19 pandemic. We present early clinical outcome of this approach.Patients treated with (chemo)radiotherapy and BT with single implant and multiple fractions BT were included. Treatment protocol included 3-5 fractions of 5-8.5 Gy with an aim to achieve point A dose of 70 Gy EQD2From April 2020 to March, 2021, 64 patients with stage IB2-IV received single implant and multi-fraction BT after external radiation of 45 Gy/25 fractions/5 weeks. Only 76.7% (n = 49) received concurrent chemotherapy. Median overall treatment time (OTT) was 56 days (38-131 days). Overall, 62.5% (n = 40) patients received IC and 37.5% (n = 24) received IC+IS. The median HRCTV was 34.7 cc (IQR 25-41). Median (IQR) point A dose, HRCTV D90, B2cc, R2cc, and S2cc for those undergoing IC was 74 Gy (71-78), 80 Gy (73-84), 86 Gy (82-89), 70 Gy (65-74), 65 Gy (59-73) respectively. For the IC+IS cohort, HRCTV D90, B2cc, R2cc, and S2cc was 84 Gy (78-89 Gy), 89 Gy (86-92), 70 Gy (67-74), 68 Gy (59-76). At a median follow-up of 16 months (5-27) the 2-year local control, pelvic control, cause specific and overall survival was 88%, 85.3%, 92.2%, and 81.3% respectively. Late gastrointestinal and genitourinary grade ≥III toxicities were 14% and 1.5% each.Abbreviated BT outcomes are encouraging for oncological outcomes despite delays in overall treatment time and omission of chemotherapy. Further mature follow up is needed.

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 Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. Methods The study (2013–2020) evaluated demographics, treatment patterns and outcomes of PABC. Results There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19–35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2–100) and 56% (95% CI: 42–75.6%) and for metastatic 24% (95% CI: 10.1%–58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. Conclusion Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs., Highlights • Pregnancy associated breast cancer (PABC) is a rare and Challenging entity with lack of data from low-middle income countries. • First Indian data showed that stage matched oncologic outcomes were comparable to non-PABC. • Obstetric outcomes were similar to non-cancer associated pregnancies with normal cognitive development. • Creating awareness and early diagnosis is of utmost importance to improve prognosis in this unique entity

Purpose In 2018, the International Federation of Gynecology and Obstetrics (FIGO) proposed a new staging for cervical cancer. The present study was designed to reclassify patients with locally advanced cervix cancer and perform a comparative evaluation with FIGO 2009. Methods and Materials Patients with locally advanced cervical cancer (stage IB2-IVA) who had baseline cross-sectional imaging and received (chemo-) radiation and brachytherapy were included. Survival outcomes were analyzed according to FIGO 2009. Patients were then reclassified according to FIGO 2018, and TNM classification outcomes were analyzed. FIGO stage and known prognostic factors were included in univariate analysis, and multivariate analysis was performed to investigate the prognostic value of clinical stage. Results Six hundred thirty-two patients were included. Overall, 185 (29.3%) patients had pelvic adenopathy, and 51 (8.2%) had positive paraortic nodes. At a median follow-up of 33 months, 116 (18.3%) patients had recurrence. Three-year disease-free survival (DFS) according to FIGO 2009 for stage IB, IIA, IIB, IIIA, IIIB, and IVA was 86%, 91%, 76%, 57%, 65%, and 61%, respectively. The 3-year DFS after restaging according to FIGO 2018 for stage IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA was 100%, 93%, 84%, 53%, 77%, 74%, 61%, and 61%, respectively. Patients with clinically significant lymphadenopathy had inferior outcomes compared with node-negative patients (62.9% vs 77.8%; P = .002). Patients with ≥3 paraortic nodes had poorer DFS than patients with 30 cm3 had worse 3-year DFS than those with primary tumor volume ≤30 cm3 (67.4% vs 78.5%; P = .002). Conclusions FIGO 2018 modification is associated with heterogenous outcomes in node-positive patients that are affected by primary tumor and nodal volume. We propose a modification to the existing TNM staging system to allow more robust classification of outcomes.

PURPOSE Women with recurrent, multiply-treated epithelial ovarian cancer (EOC) have unfavorable prognosis with limited treatment options after failure of platinum-based regimens. We report here a retrospective analysis of women with recurrent, platinum-resistant EOC treated with an oral regimen of pazopanib and cyclophosphamide. PATIENTS AND METHODS Women with recurrent platinum-resistant or -refractory EOC were treated with pazopanib (600 mg orally daily in 2 divided doses, 400 and 200 mg) and cyclophosphamide (50 mg orally daily for 21 days every 28 days) until disease progression or unacceptable toxicity. RESULTS Twenty patients (17 with platinum-resistant and 3 with platinum-refractory disease) were treated between April 2014 and April 2018. Patients had a median age of 52 years (range, 40-60 years) and median of 4 previous lines of chemotherapy (range, 2-8 previous lines), including 3 patients with progressive disease on bevacizumab. Patients received a median of 6 cycles (range, 2-48 cycles) of pazopanib and cyclophosphamide, with best responses of partial response in 9 patients (45%, including 1 of 3 patients treated previously with bevacizumab), stable disease in 6 patients (30%), and disease progression in 5 patients (25%). The median progression-free survival time was 5.5 months, and median overall survival was 9.5 months. Common adverse events (grade 3 or 4) were fatigue (25%), diarrhea (15%), hand-foot syndrome (10%), mucositis (10%), transaminitis (5%), and hypertension (5%). Dose reduction as a result of toxicity was required in 14 patients (70%), and no patient stopped treatment as a result of toxicity. CONCLUSION Pazopanib plus oral cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory EOC.

Background There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID‐19) from lower middle‐income countries (LMICs). Patients and Methods This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID‐19. The objectives were to evaluate cumulative 30‐day all‐cause mortality, COVID‐19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. Results Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1‐75) years were included. COVID‐19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty‐three patients (10%) expired during follow‐up, with COVID‐19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30‐day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28‐13.78, P, COVID‐19 attributable mortality in cancer patients on systemic therapy in LMICs appears lower than published data and slightly more than an unselected patient's cohort. Delayed recovery in terms of SARS COV‐2 negativity is seen in these patients. Treating Cancer remains the priority.

IntroductionIn locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS).Methods and analysisRadiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years.Ethics and disseminationThe trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained.Trial registration numberThe trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

In patients with recurrent or metastatic cervical cancer, the median survival time is 13 to 24 months based on the choice of palliative systemic chemotherapy. Evolving evidence suggests that the addition of radiation may lead to improved survival.Consecutive patients treated with radiation with or without systemic chemotherapy for oligometastatic or oligorecurrent disease within the period from 2017 to 2020 were included. All patients received systemic chemotherapy consultation and radiation to relapsed or metastatic sites. Progression-free survival (PFS) was determined as the period between diagnosis of relapse or metastasis and the last progression of the disease. Overall survival (OS) was defined as the time between the date of diagnosis of relapse or metastasis and follow-up or death. The effect of various prognostic and predictive factors was estimated using the Kaplan-Meier method and log-rank test.Fifty-eight consecutive patients were included. The median time to relapse was 18 months (8-205 months). At the time of first relapse, 34.4% of patients (n = 20) had locoregional relapse, 32.8% (n = 19) had distant nodal metastases, and 32.8% (n = 19) had visceral metastases. The relapse was within previously irradiated portals in 34.5% (n = 20), out of field in 50% (n = 29), and both in 15.5% (n = 9) of patients. Overall, 56% of patients (n = 33) received systemic chemotherapy. The radiation therapy dose in equivalent doses of 2 Gy at the time of retreatment was 44 Gy (31-68 Gy). The median PFS and OS from the date of first relapse were 16 (12-19) and 28 months (2-108), respectively. Grade ≥3 toxicity was observed in 19% of patients. No patient- or treatment-related factor was identified as predictive of OS on univariate analysis.The use of potentially radical doses of radiation, including reirradiation at locoregional or distant oligorelapse or metastasis, is associated with encouraging PFS and OS in patients with cervical cancer.

Background: Despite several studies, the impact of adding platinum on long-term outcomes in triple-negative breast cancer (TNBC) has not been definitively established. We conducted a single-centre randomized phase III trial to evaluate the efficacy and toxicity of adding platinum to standard neoadjuvant chemotherapy in these patients. Methods: Patients with histopathological diagnosis of TNBC without evidence of distant metastases who were planned to be treated with neoadjuvant chemotherapy (NACT) were randomized to experimental or control arms after stratification by menopausal status (premenopausal or perimenopausal, and postmenopausal) and stage [operable breast cancer (OBC, clinical T1-3, N0-1, M0), and locally advanced breast cancer (LABC, cT4 or N2-3, M0)]. NACT in control arm included paclitaxel 100 mg/m2 once per week for 8 weeks followed by doxorubicin (60 mg/m2) or epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) once every 21 days for 4 cycles while in experimental arm carboplatin (area-under-curve 2) was added once per week for 8 weeks with paclitaxel. After NACT patients received standard surgery for primary tumor and axillary lymph nodes (LN) followed by radiotherapy. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS), pathological complete response (pCR, absence of invasive cancer from breast and LN), and toxicity. Results: Between April 2010 and January 2020, 720 (355 control, 365 experimental) patients with a median age of 46 (25-69) years [< 50 years, 502 (69.7%), premenopausal 418 (58.2%)], were included in the study, of whom 285 (39.6%) had OBC and 435 (60.4%) had LABC, with a median clinical tumor size of 6.0 (1.2- 20.0) cm. At a median follow-up of 67.6 (18.9-142.2) months, in the experimental and control arms, the 5-year DFS were 70.6% (95% CI 65.7-75.5%) and 64.5% (95% CI 59.4-69.6%), respectively (HR 0.79, 95% CI 0.61-1.02, p=0.073), 5-year OS were 74.0 (95% CI 69.3-78.7%) and 66.7% (95% CI 61.6-71.8%), respectively (HR 0.75, 95% CI 0.57-0.98, p=0.034), and pCR were 55.2% (95% CI 49.7-69.5%) and 41.5% (95% CI 36.2-47.0%), respectively (p=0.0004). In subgroup analyses, the benefit of carboplatin was confined to patient’s < 50 years, with significant interaction between treatment and age. In women < 50 years of age, in experimental versus control arms, 5-year DFS and OS were 74.5% vs 62.3% (p=0.003, interaction p=0.003) and 76.8% vs 65.7% (p=0.003, interaction p=0.004), respectively. Addition of carboplatin had a significant beneficial impact on OS after adjusting for baseline clinical tumor size and age in a Cox model (HR 0.75, 95% CI 0.58-0.98, p=0.038). In experimental and control arms, numbers of patients with any grade >/=3 toxicity were 140 (38.5%) and 107/355 (30.14%), respectively, (p=0.02), grade >/=3 neutropenia were 2/364 (0.55%) and 1/355 (0.28%), respectively, grade >/=3 thrombocytopenia were 1/364 (0.27%) and 0 (0%), respectively, and febrile neutropenia were 26/364 (7.14%%) and 18/355 (5.07%), respectively (p=0.25). Conclusions: This study, to our knowledge the largest reported trial of neoadjuvant platinum in TNBC thus far, suggests that addition of carboplatin to sequential taxane-anthracycline neoadjuvant chemotherapy results in substantial and clinically meaningful improvement in disease-free and overall survival in young patients with TNBC and should be the standard of care in these patients. Citation Format: Sudeep Gupta, Nita S. Nair, Rohini Hawaldar, Vaibhav Vanmali, Vani Parmar, Seema Gulia, Jaya Ghosh, Shalaka Joshi, Rajiv Sarin, Tabassum Wadasadawala, Tejal Panhale, Sangeeta Desai, Tanuja Shet, Asawari Patil, Garvit Chitkara, Sushmita Rath, Jyoti Bajpai, Meenakshi Thakkur, Rajendra Badwe. Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS5-01.

Although chemoradiation (CTRT) is the recommended treatment, in early stages surgery is preferred over CTRT due to a common perception that CTRT leads to deterioration in quality of life (QOL), especially sexual functions as compared to surgery. Our study aims to evaluate QOL in cancer survivors treated with chemoradiation versus Neo-adjuvant chemotherapy (NACT) followed by surgery in early stage disease. In a cross-sectional descriptive study design, 100 cervical cancer survivors completed EORTC questionnaires assessing QOL during routine follow-up. Overall, 100 participants were enrolled from the NACT Carcinoma Cervix randomized study from the two arms of the trial. (Chemoradiation arm-N = 55, Neoadjuvant chemotherapy followed by surgery arm-N = 45). Mean duration of follow-up was 5 years. No significant difference was noted in long-term cervical cancer survivors between the treatment subgroups in terms of physical, social, and role functioning. Survivors reported high global QOL score (Mean score of 79). 54% were sexually active at the time of the interview. As per analysis of as treated population, sexual activity scores were higher in chemoradiation as compared to NACT followed by surgery (Mean scores 45 vs. 19, p-0.039). However, overall vaginal dysfunction and sexual anxiety scores were comparable in both arms. Other symptom scales and function scales like neuropathy, lymphedema, and menopausal symptoms showed no significant difference in subgroup analysis. Body image was consistently high across the cohort (Mean score of 90). In view of the results of the randomized NACT Carcinoma Cervix trial, chemoradiation continues to be proven as the standard for stage IB2–IIB Carcinoma Cervix. It will, therefore, be helpful to know that quality of life in long-term survivors is not more compromised in those receiving chemoradiation as compared to those who have had surgery, especially sexual quality of life in long-term survivors of early cervical cancer.

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.

Large-scale molecular profiling and DNA sequencing has revolutionized cancer research. Precision medicine is a rapidly developing area in cancer care but it is not uniformly applied across different tumor types. Biomarker-based therapy is associated with improved outcomes, both in terms of progression-free survival and overall survival. Comprehensive genomic profiling (CGP) uses next-generation sequencing to analyze the complete coding sequence of hundreds of genes from a small amount of tissue. Genes included in these assays are those associated with cancer development or have diagnostic, prognostic, familial, or therapeutic implications Genomic profiling is emerging as a clinically viable tool to personalize patient’s treatment. This article discusses how the insights gained through CGP can impact treatment plan in common gynecological cancers.

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.

The coronavirus disease 2019 pandemic has evolved into a pandemic of unheard proportions. Given the havoc wreaked by this pathogen worldwide, many countries have adopted an extreme, legally enforced method of social distancing, in the form of a lockdown. Unless appropriate preventive steps are taken, the cost of the pandemic and ensuing lockdown may prove to be irreparable. The evident implications of this lockdown, such as the escalating levels of unemployment, impending economic collapse, and severe food shortage faced by the sudden unemployed migrant labor population, have been widely reported. Cancer patients are a particularly vulnerable group even during nonpandemic times, often presenting late in the course of their disease, without the resources needed to avail recommended treatment. The prevalence of psychiatric complications and emotional distress is significantly higher than in the general population, and the trauma of both the pandemic and subsequent lockdown adds significantly to their mental trauma. This review is aimed toward addressing the problems faced by cancer patients in the face of this pandemic and subsequent lockdown, with a glimpse into possible solutions that can be implemented.

A histopathology report offers important prognostic and predictive information that helps plan systemic therapy in breast cancer. However, in many cases a pathologist fails to provide relevant information chiefly due to the lack of awareness of the impact of these parameters in clinical decision-making. This review seeks to put forth common practice points in grossing and reporting of specimens harboring breast cancer with focus on latest revisions in the same. Just as it is important to document tumor size, tumor type, margins, estrogen receptor/progesterone receptor, and human epidermal growth factor (ER/PR/HER2) in breast cancer, we need to also focus on sentinel node grossing, nodal burden, size of nodal metastasis, and extranodal extension. In parallel, increasing number of patients are getting neoadjuvant chemotherapy in breast cancer and points in grossing and reporting of such specimens are also alluded to. This article will serve as reference guide to pathologists on what we do and why we do the same.

BACKGROUND: Breast cancer is the most common malignancy in Indian women. There is scant data from Indian hospital-based populations on the prevalence of risk factors of this disease. We performed this study to quantify and analyze various epidemiological risk factors in Indian breast cancer patients. METHODS: This was a multicenter collaborative study wherein breast cancer patients older than 18 years were served a structured questionnaire after informed consent. Patients or their relatives were required to fill out the questionnaire and those who were unable to read and write were excluded. Data were abstracted from case record forms and variables were descriptively analyzed. RESULTS: Between January 2015 and February 2016, 800 patients were screened, of whom 736 patients with a mean age of 50.13 years were enrolled in the study. The mean number of pregnancies was 2.75 (0–11), the number (percentage) of women who had breastfed for more than 6 months was 628 (85.3) and 406 (55.1%) patients were post-menopausal at the time of breast cancer diagnosis. Of the enrolled patients, 91 (12.8%) had history of exposure to passive smoke, 13 (1.8%) had partners who were heavy smokers, 27 (3.7%) had history of oral contraceptive use, 4 (0.5%) had history of hormone replacement therapy, and 103 (14%) had undergone hysterectomy with oophorectomy. CONCLUSION: Our study contributes to the descriptive prevalence of some known risk factors in Indian breast cancer patients.

Background One of the primary treatment strategies for advanced epithelial ovarian cancers includes neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy. Compliance to treatment is important to possibly improve outcomes. Aim To audit treatment compliance and its effect on overall survival (OS) and disease free survival (DFS) in women undergoing IDS. Methods and results Women diagnosed with advanced epithelial ovarian cancer undergoing IDS were included. Details of compliance to chemotherapy and surgery as per standard guidelines were assessed, and correlation with survival was studied. Reasons for protocol deviation at various levels were documented and analysed. A total of 182 patients were included. The total number of deviations was 134 with deviation at any level being 89 (48.9%) and at all levels 5%. Both patient- and treatment-related factors contributed towards deviation. Deviation or noncompliance towards treatment resulted in a significantly reduced 5-year OS (34.4% vs 58.2%; P = .001) compared with compliant patients, which retained its significance on multivariate analysis (P = .024) as well. Conclusion Deviation from treatment guidelines resulted in a significantly lower 5-year OS compared with those who remained treatment compliant. Both patient- and treatment-related factors contributed towards noncompliance and hence towards lower survival.

The incidence of endometrial cancer (EC) is on the rise in India. The median age at presentation is lesser than the Western population. Majority of the patients present in early stages with excellent overall survival rates after surgery. Adjuvant therapy is essential in high-risk stages I–III for improving outcomes. The quality and extent of surgery, and complete histopathological information are important factors for outcome and tailoring adjuvant therapy. Depending on patients and histopathological factors, various risk groups have been defined for prognostication and defining adjuvant therapy. Adjuvant therapy including external radiation, vaginal brachytherapy, chemotherapy and combined chemoradiotherapy has been tried depending on various risk groups. The purpose of this article is to review and interpret and update the results of existing literature on adjuvant therapy in EC with a special focus on Indian reports and standards.

e18102 Background: To evaluate the clinicopathological factors, outcome and prognostics factors of uterine carcinosarcoma. Methods: All patients of uterine carcinosarcoma treated between January 2013 and December 2018 were identified and their clinical, laboratory and imaging details were retrieved from electronic medical record. Details of the treatment received, toxicity profile and outcome were recorded and analyzed. Patients (including stage I) were considered for four cycles of chemotherapy (Paclitaxel +Carboplatin) followed by radiation (EBRT to pelvis with vaginal brachytherapy). Survival analysis was done using the Kaplan–Meier method and compared between treatment groups using the Log-rank test. Results: Of 81 cases, 48 % presented with early stage disease (FIGOI-II) and 52 % with late stage (FIGO III-IV) disease. Median age was 58 years (30-80 years). Most women (83%) were postmenopausal and 80% of them presented with postmenopausal bleeding. Six patients developed carcinosarcoma on adjuvant tamoxifen (given for breast cancer) after a median drug intake of 8 years. In early stage, 10% patients received only surgical treatment; 46% received both chemotherapy (CT) and radiation therapy (RT) while 33 % received RT alone. In advanced stage, 31% received only CT, 14 % received only RT and 33% received both CT and RT after surgery. About 8% of patients had myelosuppression(grade I/II), 10 % had peripheral neuropathy (grade I/II) and 11% had electrolyte imbalance. At a median follow up of 2 years (1- 80 months), median DFS and OS in early stage group was 28.5 months and 31.0 months while in advanced stage group it was 13.0 months and 15.0 months respectively. Distant metastasis (omentum, peritoneum and lung being the common site) were seen in 30% of patients while local relapse was seen in 5 % cases. On univariate analysis stage of disease and receipt of adjuvant therapy were the factors found to be significantly associated with improved OS (p < 0.001) and adjuvant RT alone was associated with improved DFS (p < 0.023). Conclusions: Adjuvant treatment (chemotherapy and or radiation therapy) is associated with improved overall survival in uterine carcinosarcoma, irrespective of stage at presentation.

Background: Ovarian cancer is the fourth most common cancer in Indian women. Majority of these are epithelial ovarian cancers (EOCs), most of which present in advanced stage. Women with poor performance status and/or those unlikely to achieve optimal debulking at upfront surgery, benefit from neoadjuvant chemotherapy (NACT) followed by interval cytoreduction, with lesser surgical morbidity and equal survival rates as compared to primary cytoreduction. Methodology: This was a retrospective analysis of patients with advanced ovarian cancer, treated with NACT followed by interval debulking surgery at Tata Memorial Hospital from January 2014 to December 2014. Results: Epithelial cancers constituted 84.4% (n = 406) of all cases of ovarian malignancies. Of these, overwhelming majority (84.3%, n = 342) were in the advanced stage. Sixty percent of all EOC patients received NACT. The mean baseline serum CA-125 level in women treated with NACT was 4294.7 U/ml (range, 11–151,200 U/ml). The median number of NACT cycles (paclitaxel + carboplatin) was 3. Optimal cytoreduction was achieved in 81.5% cases. The rates of Grade 3 or 4 intraoperative and postoperative complications were 4% each. The median postoperative stay was 5 days and the median time between surgery and adjuvant chemotherapy was 20 days. The median progression-free survival (PFS) was 15.15 months (95% confidence interval [CI]: 12.95–17.34), and the median overall survival (OS) was 34.73 months. Multivariate analysis revealed that optimal cytoreduction (hazard ratio [HR] = 2.04 [95% CI: 1.15–3.62]; P = 0.015) and number of NACT cycles (3 vs. >3; HR = 1.51 [95% CI: 1.06–2.16]; P = 0.022) were significantly associated with PFS, and optimal cytoreduction (HR = 3.21 [95% CI: 1.53–6.73]; P = 0.002) and ECOG status (0–1 vs. ≥2; HR = 2.64 [95% CI: 1.25–5.55]; P = 0.011) with OS. Conclusions: High rates of optimal cytoreduction were achieved at interval cytoreductive surgery after NACT, with acceptable surgical morbidity, early start of adjuvant chemotherapy, and survival outcomes comparable to international standards.

There has been recent increase in incidence of leptomeningeal carcinomatosis, possibly due to widespread use of adjuvant trastuzumab and its known poor CNS penetration. Currently there are limited therapeutic options for these patients and outcome is poor. We report two cases of women with HER2 positive breast cancer who developed leptomeningeal carcinomatosis for which they were treated with intrathecal trastuzumab in combination with systemic therapy. Both patients had rapid symptomatic benefit and radiological response and remained progression free for at least seven months. Intrathecal trastuzumab can be considered a reasonable therapeutic option for these difficult to treat patients.