Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project.

INTRODUCTION: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved. METHODS AND ANALYSIS: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance. ETHICS AND DISSEMINATION: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely. REGISTRATION: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).

Are oral cancers effectively palliated with radiotherapy? Outcomes of treatment with a modified QUAD SHOT regimen.

BACKGROUND: This study assessed a palliative radiotherapy regimen using daily radiation over 4 days for three courses in inoperable head and neck cancers, emphasizing oral primary cancers. METHODS: Retrospective data of 116 patients treated with a daily dose of 3.6-3.7 Gy in four fractions over 4 days to a total of three courses, with a 2-week gap after every course, were analyzed for survival outcomes. A subgroup analysis was done for oral cancer. RESULTS: Ninety-nine (85%) completed three courses. Overall subjective response rate was 77%. Median overall survival and progression-free survival were 12 months (95% confidence interval [CI]: 8-20) and 8 months (95% CI: 6-10), with numerically higher overall survival in oral cancer. The treatment was well tolerated, with no on-treatment hospitalization or grade 3-4 toxicities. CONCLUSION: The modified QUAD SHOT regimen is practical for palliation in head and neck cancers.

Enhancing quality assurance in radiotherapy for gynaecological cancers: implementation of an on-demand peer review process.

OBJECTIVES: Ensuring high-quality radiotherapy requires peer-reviewing target volumes. The Royal College of Radiologists recommends peer review specifically for individual target volumes in cases of gynaecological cancers. This study presents the outcomes of implementing an on-demand peer review system for gynaecological cancers within our institute. METHODS: The peer review process was planned for gynaecological cancer cases intended for curative radiotherapy. After junior clinical oncologists (COs) completed the segmentation, two senior COs specializing in gynaecological cancers conducted the peer review. All peer review outcomes were recorded prospectively. The audit process compliance, the proportion of patients requiring major and minor modifications in target volumes, the direction of changes, and the factors influencing these changes were reported. RESULTS: A total of 230 patients were eligible, and out of these, 204 (88.3%) patients underwent at least one peer review. Among the patients, 108 required major modifications in their target volumes. P-charts revealed a stabilization in the need for major modifications at the end of three months, indicating that 38.2% and 28% of patients still required major modifications for the nodal and primary CTV, respectively. Multivariable analysis demonstrated that major modifications were associated with the use of extended field radiotherapy and radical radiation in non-cervical primary cases. CONCLUSIONS: An on-demand peer review system was feasible and resulted in clinically meaningful, major modifications in the target volumes for 53% of patients. ADVANCES IN KNOWLEDGE: Gynaecological cancers require ongoing peer review to ensure quality of care in radiotherapy. A flexible on-demand system not only ensures that patient treatment start is not delayed but also has an important educational role for junior trainees.

Oncologic safety of breast conservation following NACT in women with locally advanced breast cancer.

Introduction: Breast conservation surgery (BCS) is the accepted standard of treatment for early breast cancer, with evidence from randomized controlled and population-based studies. The oncological outcome of BCS in locally advanced breast cancer (LABC) is mainly available from retrospective series with a small sample size and a shorter follow-up duration. Methods: A retrospective observational study of 411 non-metastatic LABC patients who received neoadjuvant chemotherapy (NACT) followed by surgery from 2011 to 2016. We retrieved the data from a prospectively maintained database and electronic medical records. Survival data were analyzed by Kaplan-Meier curves and Cox regression using Statistical Package for the Social Sciences 25 and STATA 14. Results: 146/411 (35.5%) women had BCS with a margin positivity rate of 3.42%. With a median follow-up of 64 months (IQR 61, 66), the local relapse rate was 8.9% in BCS and 8.3% after mastectomy. The estimated 5-year locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS) rates of BCS were 86.9%, 63.9%, 71% and 79.3%, and 90.1%, 57.9%, 58.3% and 71.5% in the mastectomy group. On univariate analysis, BCS showed superior survival outcomes compared to mastectomy (unadjusted HR (95% CI) for RFS: 0.70 (0.50-1), DDFS: 0.57 (0.39-0.84), OS: 0.58 (0.36-0.93)). After adjusting for age, cT stage, cN stage, poorer chemotherapy response (ypT0/is, N0) and radiotherapy, BCS and mastectomy groups were found comparable in terms of LRFS (HR: 1.1, 0.53-2.3), DDFS (HR: 0.67, 0.45-1.01), RFS (HR: 0.80, 0.55-1.17) and OS (HR: 0.69, 0.41-1.14). Conclusion: BCS is technically feasible in LABC patients. LABC patients who respond well to NACT can be offered BCS without compromising survival outcomes.

Definitive chemoradiation for oropharyngeal squamous carcinomas: Outcomes with intensity-modulated radiation therapy using simultaneous integrated boost, in a majorly p16 negative cohort.

BACKGROUND: The literature on modern-era outcomes of oropharyngeal squamous carcinoma (OPSCC) in India is limited. MATERIALS AND METHODS: We analyzed records of consecutive patients with OPSCC treated using a curative SIB IMRT regimen of 66 Gy/30#/6 weeks. RESULTS: One hundred fifteen patients from July 2011 to December 2018 were analyzed. Twenty of 69 patients tested positive for p16. In p16 positive patients, the K-M probability of being disease free and alive at 2 years, with at least one follow-up 3 months after treatment, was 83% (median not reached) compared with 48% if p16 was unknown/negative. Patients staged as IVB p16 negative had a 2-year DFS of 25%. Patients unfit for cisplatin and consequently received other agents had 2-year DFS estimated at 20%. CONCLUSIONS: Intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) and concurrent chemotherapy was feasible, with toxicity and disease control comparable to available literature. AJCC Stage IVB p16 negative disease had notably poor outcome.

Alleviating Morbidity From Locally Advanced Breast Cancer Using a Practical and Short Radiation Therapy Regimen: Results of the HYPORT Palliative Studies.

PURPOSE: Locally advanced breast cancers lead to debilitating local symptoms. Treatment of these women encountered commonly in less resourced countries is not backed by strong evidence. We formulated the  HYPORT and HYPORT B phase 1/2 studies to evaluate the safety and efficacy of hypofractionated palliative breast radiation therapy. METHODS AND MATERIALS: Two studies (35 Gy/10 fractions; HYPORT ) and (26 Gy to breast/32 Gy tumor boost in 5 fractions; HYPORT B) were designed with increasing hypofractionation to save overall treatment time from 10 to 5 days. We report the acute toxicity, symptomatic, metabolic response, and quality of life (QOL) changes after radiation therapy. RESULTS: Fifty-eight patients, the majority of whom were pretreated with systemic therapy, completed the treatment. No grade 3 toxicity was reported. Response assessment at 3 months showed improvement in ulceration (58% vs 22%, P = .013) and bleeding (22% vs 0%, P = .074) within the HYPORT study. Similarly, in the HYPORT B study, ulceration (64% and 39%, P = .2), fungating (26% and 0%, P = .041), bleeding (26% and 4.3%, P = .074), and discharge (57% and 8.7%, P = .003) was reduced. Metabolic response was noted in 90% and 83% of patients, respectively, in the 2 studies. Improvement in the QOL scores were evident in both studies. Only 10% of the patients relapsed locally within 1 year. CONCLUSIONS: Palliative ultrahypofractionated radiation therapy to the breast is well tolerated, is effective, and results in a durable response with improved QOL. This could be considered a standard for locoregional symptom control.

HYPORT adjuvant acute toxicity and patient dosimetry quality assurance results - Interim analysis.

BACKGROUND: HYPORT adjuvant trial is a randomised phase III open-label noninferiority trial comparing standard moderately hypofractionated 3 week adjuvant radiation therapy in breast cancer with a novel 1-week schedule. The trial was initiated in March 2019 and is open to recruitment with a total sample size of 2100. We report the results of dosimetric quality assurance, acute toxicity and pre planned first interim safety analysis in the first 271 patients. METHODS: Stage I-III breast cancer planned for adjuvant radiation therapy to the breast/chest-wall (along with regional nodes as indicated) were randomised to receive 40 Gy/15 fractions/3 weeks or 26 Gy/5 fractions/1 week. For simultaneous integrated boost, the patients in the control arm received 8 Gy/15 fractions/3 weeks, while those in the experimental arm received 6 Gy/5 fractions/1 week (to the tumour bed). For sequential boost, the prescribed dose was 12 Gy/4 fractions/4 days in both arms. Compliance to pre specified dosimetric parameters and acute toxicities were evaluated. RESULT: Data of the first 271 patients was analysed of whom 104 patients received tumour bed boost using SIB. All mandatory dosimetric criteria were met apart from one patient with a higher contralateral breast dose due to optimal internal mammary nodal coverage. Overall three patients (1.1%) experienced grade 3 radiation dermatitis (none received SIB), no other Grade 3 or higher toxicities reported. CONCLUSION: This acute toxicity interim analysis demonstrates that hypofractionated adjuvant radiotherapy with SIB for patients with breast cancer is feasible, and associated with minimal severe acute toxicities.

Evaluating Quality Indicators of Glioblastoma Care: Audit Results From an Indian Tertiary Care Cancer Center.

PURPOSE: There are limited reports of quality metrics in glioblastoma. We audited our adherence to quality indicators as proposed in the PRIME Quality Improvement study. METHODS: This is a retrospective audit of patients treated between 2017 and 2020. After postsurgical integrated diagnosis, patients received radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Multiparametric magnetic resonance imaging at predefined times guided management. Numbers with proportions for indices were calculated. Survival was estimated using the Kaplan-Meier method. RESULTS: One hundred six patients were consecutively treated. The median age was 55 years (interquartile range of 47-61 years) with a male preponderance (68%). Ninety-six (90.6%) patients underwent subtotal resection, and 10 (9.4%) biopsy alone. Isocitrate dehydrogenase was wild-type in 96 (91%), and O6-methylguanine-DNA methyltransferase was unmethylated in 70 (66.0%) patients. Telomerase reverse transcriptase promoter was mutated in 64 (60.4%), and TP53 was mutated in 22 (20.8%). Concurrent radiation and TMZ were planned for 104 (98.1%), and radiation alone for 2 (1.9%). The median time to concurrent RT-TMZ was 36 days (interquartile range 30-44 days). All patients planned for RT-TMZ completed treatment, but only 81 (76%) completed adjuvant TMZ. Sixty-three (59%) completed six cycles, 18 (17%) received less than six cycles, and 25 (24%) did not receive adjuvant TMZ. At a median follow-up of 24 months (range 21-31 months), the median (95% CI) progression-free survival and overall survival were 11 (95% CI, 9.4 to 13.0) and 20.0 (95% CI, 15 to 26) months, respectively. CONCLUSION: Our patients met quality indices in most domains; outcomes are comparable with global results. Metrics will be periodically evaluated to include new standards and assess continuous service appropriateness.

Design and Development of a Medical Image Databank for Assisting Studies in Radiomics.

CompreHensive Digital ArchiVe of Cancer Imaging - Radiation Oncology (CHAVI-RO) is a multi-tier WEB-based medical image databank. It supports archiving de-identified radiological and clinical datasets in a relational database. A semantic relational database model is designed to accommodate imaging and treatment data of cancer patients. It aims to provide key datasets to investigate and model the use of radiological imaging data in response to radiation. This domain of research area addresses the modeling and analysis of complete treatment data of oncology patient. A DICOM viewer is integrated for reviewing the uploaded de-identified DICOM dataset. In a prototype system we carried out a pilot study with cancer data of four diseased sites, namely breast, head and neck, brain, and lung cancers. The representative dataset is used to estimate the data size of the patient. A role-based access control module is integrated with the image databank to restrict the user access limit. We also perform different types of load tests to analyze and quantify the performance of the CHAVI databank.

Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial.

PURPOSE: CompLEEment-1 (NCT02941926) is a single-arm, open-label, multicentre phase IIIb study investigating the safety and efficacy of ribociclib plus letrozole (RIB + LET) in a large, diverse cohort who have not received prior endocrine therapy (ET) for advanced disease. We present an exploratory analysis of male patients. METHODS: Eligible patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), who had no prior ET and ≤ 1 line of prior chemotherapy for advanced disease, received RIB + LET. Male patients also received goserelin or leuprolide. Primary endpoint was safety and tolerability; efficacy was a secondary endpoint. RESULTS: In total, 39/3246 patients were male. Baseline characteristics were similar to the overall population. Male patients experienced fewer treatment-related adverse events (AEs) and treatment-related serious AEs compared with the overall population; fewer male patients had treatment-related AEs leading to discontinuation, adjustment/interruption, or additional therapy. One male patient died as a result of a serious AE that was not considered to be treatment-related. The most common AE was neutropenia; the incidence of grade ≥ 3 neutropenia in males (41.0%) was lower than in the overall population (57.2%). Median follow-up was 25.4 months; median time to progression was not reached in males versus 27.1 months for the overall population. CONCLUSION: The clinical benefit and overall response rates in males were consistent with the overall population. This analysis demonstrates the safety and efficacy of ribociclib in a close-to-real-world setting, supporting the use of RIB + LET in male patients with HR+, HER2- ABC. TRIAL REGISTRATION NUMBER: NCT02941926 (Registered 2016).

Xerostomia quality of life and resource requirements following parotid sparing adaptive radiotherapy in head and neck cancers: Results of a prospective cohort study (Study ID CTRI/2017/11/010683).

BACKGROUND AND PURPOSE: Parotid sparing adaptive radiotherapy (PSART) is resource intensive to implement. Selection criteria for using ART and its impact on quality of life (QoL) is poorly reported. This has been addressed in our study. MATERIALS AND METHODS: Patients planned for curative radiotherapy for Head Neck Cancers were recruited following informed consent in a prospective cohort study. PSART was planned if the mean dose to index parotid(s) increased by 2% from the baseline approved plan. To assess the resource requirements of PSART manpower and time required for treatment planning both for initial as well as PSART was documented. Patient reported QoL using QualiXeQLS and EORTC QLQ C30 and HN35 were obtained pre radiotherapy, and at 3 and 9 months post radiotherapy. RESULTS: Of the ninety patients accrued, 87 were evaluable. 45 (51%) received PSART based on the prespecified criteria. The average time spent in contouring (276 min versus 133 min) and treatment planning (293 min versus 108 min) were almost doubled when PSART was implemented. XeQoL scores at 3 months were significantly worse in those receiving PSART (mean 2.3 vs 1.2, p 0.002). Despite this, xerostomia related QoL recovered to near baseline scores by 9 months after receiving PSART. CONCLUSION: Implementation of PSART is resource intensive. The proposed cutoff for implementing PSART identifies a higher risk population that have worse xerostomia related quality of life. This study lays the foundation for a randomized trial to determine the efficacy of PSART on xerostomia related QoL.

Radiation-induced hypothyroidism in patients of oral squamous cell carcinoma: A retrospective analysis of 195 patients.

Background: Radiation-induced hypothyroidism (RIH) is common after neck irradiation, and biochemical evaluation of thyroid function is recommended periodically for early diagnosis and treatment. This study aimed to evaluate the predictors of RIH after completion of adjuvant radiotherapy (RT) for primary oral squamous cell carcinoma (OSCC). Methods: This is a retrospective study involving 195 patients who received RT after surgery for OSCC between August 2011 and December 2016. Thyroid function tests were obtained every 6 months and patients were considered to be hypothyroid if thyroid-stimulating hormone level was >5 mIU/mL. Results: The study cohort comprised 130 men with a median age of 52 years (range 21-77 years). About 107 (54.87%) patients developed hypothyroidism, with a median of 21 months (range 2-67 months) for the development of RIH. Women [41 (63.1%) versus 66 (50.8%), p=0.035], addition of chemotherapy [36 (63.2%) versus 71 (51.4%), p= 0.019], and higher cumulative dose to the thyroid gland (median dose 4690 cGy versus 2981 cGy, P < 0.001) resulted in higher incidence of RIH on univariate analysis. On multivariate Cox regression analysis, female sex (P = 0.042), bilateral irradiation (P = 0.046), and cumulative dose to the thyroid (P = 0.001) were factors associated with increased risk of developing RIH. Conclusion: The addition of chemotherapy, high dose of radiation to the thyroid gland, bilateral irradiation, and female sex were at higher risk of developing RIH. However, more studies are required to identify the dose-volume constraints of the thyroid gland.

Imaging Features of Postradiotherapy Changes in Head and Neck Cancers.

Radiation therapy is the mainstay in the treatment of head and neck cancers, in addition to surgery and chemotherapy. Expected radiotherapy changes evolving over time may be confused with recurrent tumor. Conversely, even residual or recurrent tumor in the setting of postradiotherapy changes may be difficult to identify clinically or even by radiological imaging. Therefore, it is important to be familiar with the temporal evolution of these changes. The purpose of this pictorial essay is thus to illustrate distinctly the expected radiotherapy changes and radiotherapy-related complications in the head and neck region and to differentiate them from tumor recurrence on routine cross-sectional imaging techniques (computed tomography and magnetic resonance imaging).

Real-world results of definitive chemoradiation in carcinoma oesophagus: can SCOPE1 results be replicated outside trial setting?

BACKGROUND: Definite concurrent chemoradiation is the standard of care for locally advanced unresectable oesophageal cancers. However, heterogeneity exists in the practice of concurrent chemoradiation approaches. Here we describe the efficacy and toxicities of the standard arm of SCOPE1 protocol implemented at our institute. METHODS: Treatment records of 36 patients with unresectable oesophageal cancers treated with concurrent chemoradiation between January 2015 and June 2019 were audited. Treatment was based on the standard arm of SCOPE1 protocol (neoadjuvant and concurrent platinum and capecitabine with external beam radiation to a dose of 50 Gy/25 fractions/5 weeks). The electronic hospital information system and oncology information system were queried to obtain information on patient characteristics and treatment delivery patterns. RESULTS: Out of 36 patients, 35 had squamous cell carcinomas. 25% of the patients (9/36) were 70 years or older. 66.7% of patients (24/36) had T4 disease, and 16 (44.4%) had N2-N3 nodal disease at presentation. A total of 30 patients (83.3%) could not undergo surgery because of the location and locoregional extent of the disease. The median follow-up of the entire cohort and the surviving patients was 10 months (range 3-51 months) and 13 months (range 4-51 months), respectively. The median overall survival (OS) of the entire cohort was 28 months. The 2-year local progression-free survival and OS were 71.2% (95% CI: 48.5%-85.3%) and 57.4% (95%CI: 29.6%-77.6%), respectively. Commonly observed acute Grade 3 toxicities were dysphagia (22.2%) and thrombocytopenia (19.4%). CONCLUSION: The outcomes of the SCOPE1 protocol have been validated for the first time in a different geographical, racial and ethnic population. Implementation of the standard arm of SCOPE1 protocol is feasible in our setting with acceptable adverse effects and good treatment compliance. Results are comparable to the results of the published trial.

Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population.

PURPOSE: CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. METHODS: Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL). RESULTS: Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment. CONCLUSION: Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2- ABC. TRIAL REGISTRATION: linicalTrials.gov NCT02941926.

Research Goal-Driven Data Model and Harmonization for De-Identifying Patient Data in Radiomics.

There are various efforts in de-identifying patient's radiation oncology data for their uses in the advancement of research in medicine. Though the task of de-identification needs to be defined in the context of research goals and objectives, existing systems lack the flexibility of modeling data and normalization of names of attributes for accomplishing them. In this work, we describe a de-identification process of radiation and clinical oncology data, which is guided by a data model and a schema of dynamically capturing domain ontology and normalization of terminologies, defined in tune with the research goals in this area. The radiological images are obtained in DICOM format. It consists of diagnostic, radiation therapy (RT) treatment planning, RT verification, and RT response images. During the DICOM de-identification, a few crucial pieces of information are taken about the dataset. The proposed model is generic in organizing information modeling in sync with the de-identification of a patient's clinical information. The treatment and clinical data are provided in the comma-separated values (CSV) format, which follows a predefined data structure. The de-identified data is harmonized throughout the entire process. We have presented four specific case studies on four different types of cancers, namely glioblastoma multiforme, head-neck, breast, and lung. We also present experimental validation on a few patients' data in these four areas. A few aspects are taken care of during de-identification, such as preservation of longitudinal date changes (LDC), incremental de-identification, referential data integrity between the clinical and image data, de-identified data harmonization, and transformation of the data to an underlined database schema.

PDL1 expression and its correlation with outcomes in non-metastatic triple-negative breast cancer (TNBC).

PURPOSE: Triple-negative breast cancer (TNBC) has a poor outcome compared to other subtypes, even in those with early disease. Immune checkpoint inhibitors (ICIs) have been approved in metastatic diseases and are being tested as a neoadjuvant strategy also. The response to ICIs is largely determined by the programmed death ligand 1 (PDL1) score, which also acts as a prognostic marker for outcomes. Here, we report the proportion of PDL1 expression in non-metastatic TNBC and its correlation with response to chemotherapy and outcomes. METHODS: We included all patients who had non-metastatic TNBC treated with neoadjuvant chemotherapy, followed by surgery with/without adjuvant radiotherapy between September 2011 and November 2017. PDL1 testing was carried out on pre-treatment tumour cells with immunohistochemistry (Ventana SP142) and was correlated with pathological response, relapse-free survival (RFS) and overall survival (OS). PDL1 staining was interpreted as negative or positive (more than 1% staining). RESULTS: A total of 107 patients were included for analysis with a median age of 47 years (28-65 yrs). The PDL1 expression of more than 1% was seen in 31 (28.97%) patients. After a median follow-up of 55 months (range: 4-93 months), median RFS and OS were not reached. PDL1 expression did not affect the achievement of pathological complete response (pCR). However, PDL1 expression improved OS (p = 0.016) and trend towards RFS (p = 0.05). Patients who achieved pCR had better RFS and OC compared to those who did not. CONCLUSION: Our study shows PDL1 expression in 29% of the cases. PDL1 expression leads to better RFS and OS. Also, pCR improves survival.

Geographic disparities in access to cancer clinical trials in India.

INTRODUCTION: The current study was aimed at quantifying the disparity in geographic access to cancer clinical trials in India. METHODS: We collated data of cancer clinical trials from the Clinical Trial Registry of India and data on state-wise cancer incidence from the Global Burden of Disease Study. The total sample size for each clinical trial was divided by the trial duration to get the sample size per year. This was then divided by the number of states in which accrual was planned to get the sample size per year per state (SSY).For interventional trials investigating a therapy, the SSY was divided by the number of incident cancers in the state to get the SSY per 1,000 incident cancer cases. The SSY data was then mapped to visualise the geographical disparity. RESULTS: We identified 181 ongoing studies, of which 132 were interventional studies. There was a substantial inter-state disparity-with a median SSY of 1.55 per 1,000 incident cancer cases (range 0.00-296.81 per 1,000 incident cases) for therapeutic interventional studies. Disparities were starker when cancer site-wise SSY was considered. Even in the state with the highest SSY, only 29.7% of the newly diagnosed cancer cases have an available slot in a therapeutic cancer clinical trial. Disparities in access were also apparent between academic (range: 0.21-226.60) and industry-sponsored trials (range: 0.17-70.21). CONCLUSION: There are significant geographic disparities in access to cancer clinical trials in India. Future investigations should evaluate the reasons and mitigation approaches for such disparities.