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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.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.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.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.

PURPOSE A COVID-19 lockdown in India posed significant challenges to the continuation of radiotherapy (RT) and systemic therapy services. Although several COVID-19 service guidelines have been promulgated, implementation data are yet unavailable. We performed a comprehensive audit of the implementation of services in a clinical oncology department. METHODS A departmental protocol of priority-based treatment guidance was developed, and a departmental staff rotation policy was implemented. Data were collected for the period of lockdown on outpatient visits, starting, and delivery of RT and systemic therapy. Adherence to protocol was audited, and factors affecting change from pre-COVID standards analyzed by multivariate logistic regression. RESULTS Outpatient consults dropped by 58%. Planned RT starts were implemented in 90%, 100%, 92%, 90%, and 75% of priority level 1-5 patients. Although 17% had a deferred start, the median time to start of adjuvant RT and overall treatment times were maintained. Concurrent chemotherapy was administered in 89% of those eligible. Systemic therapy was administered to 84.5% of planned patients. However, 33% and 57% of curative and palliative patients had modifications in cycle duration or deferrals. The patient’s inability to come was the most common reason for RT or ST deviation. Factors independently associated with a change from pre-COVID practice was priority-level allocation for RT and age and palliative intent for systemic therapy. CONCLUSION Despite significant access limitations, a planned priority-based system of delivery of treatment could be implemented.

Low-cost sensors (LCS) provide opportunities for neighborhood-level air pollution data collection, yet significant knowledge gaps remain regarding the accurate application and interpretation of LCS. In this study, we present an in-field calibration of a network of 20 low-cost ambient particulate matter sensors (LCS) in greater Kolkata, India, operating between October 2018-April 2019. In order to understand LCS performance in relation to local reference-grade PM2.5 monitors (RGMs), three of these LCS were co-located with RGMs operated by the West Bengal Pollution Control Board at Rabindra Bharati University (RBU), Victoria Memorial (VICTORIA), and Padmapukur (Howrah, PDM). Data from the co-locations were used to calibrate the LCS network using random forest regression and multiple linear regression approaches. Measured relative humidity and temperature were significant model features. Agreement between the LCS and RGM for 24-h averaged PM2.5 measurements was strongest at RBU, with an uncalibrated root mean squared error (RMSE) of 27.1 μg m-3, followed by PDM (32.6 μg m-3) and VICTORIA (50.7 μg m-3). Multiple linear regression was used to derive calibration models. Cross-calibration between co-located LCS-RGM pairs was tested. The LCS data after cross-calibration correctly identified days as being in or out of attainment with the 24h National Ambient Air Quality Standard of 60 μg m-3 91% of the time. The corrected data accurately identifies days with an India scale Air Quality Index of “poor” or worse 94% of the time. This suggests that LCS can be a useful supplement to RGM networks for air quality management.

IntroductionPeer review of target volume is recommended as an important step for ensuring high quality radiotherapy. The Royal College of Radiologists considers gynecological cancers as one of the sites where peer review of individual target volumes is required. We report results of an on-demand peer review system for gynecological cancers in our institute. MethodsPeer review was planned for gynecological cancer cases planned for curative intent radiotherapy. On demand peer review was conducted by two senior clinical oncologists specializing in gynecological cancers after segmentation was completed by junior clinical oncologists. Peer review discussions were recorded prospectively in an electronic database. In the present study, data of patients planned from radiotherapy between 15th September 2021 - September 2022 is audited. The compliance to the audit process, proportion of patients requiring major and minor modifications in target volumes, direction of changes noted as well as factors influencing the changes have been reported.ResultsIn the study period, 230 patients underwent planning for curative intent radiotherapy and 204 (88.3%) patients had at least one peer review. Major target volume changes were required in 108 patients, with the majority of changes reported in the nodal CTV. Analysis of P-charts showed a rapid change in proportion of patients requiring major modifications with stabilization at the end of 3 months to 38.2% and 28% for nodal and primary CTV respectively. Modifications were primarily required in the para-aortic and common iliac region for nodal CTV. Multivariable analysis showed that major modifications were associated with the use of extended field radiotherapy and use of radical radiation in non-cervical primaries. ConclusionAn on-demand peer review system was feasible and resulted in clinically meaningful changes in 53% of patients.

IntroductionThe COVID-19 pandemic has affected cancer care worldwide. We audited adherence to 19 predefined quality indicators (QI) of treatment in patients with carcinoma cervix in our institute. MethodsPatients with carcinoma cervix treated with curative intent radical radiotherapy were eligible for this study. Patients who started treatment between 24 March 2019 and 24 March 2021 were evaluated. We divided participants into two groups, the pre pandemic period between 24 March 2019 and 23 March 2020, and the period of pandemic from 24 March 2020 - 24 March 2021. Adherence to 19 predefined QI was evaluated for each patient’s treatment course. Multivariable analysis of adherence to QI was performed using proportional odds regression. Results154 patients underwent treatment, of whom 83 (53.9%) received treatment during the pandemic. 17 patients had COVID-19 infection before or during treatment. Adherence to QI decreased during the pandemic, primarily driven by delays in the start and delivery of treatment. The median number of QI adhered to in the pre pandemic period was 17 (IQR: 16 - 17.5) versus 17 during the pandemic (IQR: 16 - 17). Multivariable analysis showed that treatment during the pandemic period was associated with a lower adherence to QI (Odds ratio 3.30, 95% confidence intervals 1.70 - 6.50). ConclusionsThe COVID-19 pandemic was associated with reduced adherence to QI. Treatment delivery was affected not only by COVID-19 infection, but also logistic challenges due to restrictions related to the pandemic.

Human epidermal growth factor receptor 2 (HER2) is one of the widely used Immunohistochemical (IHC) markers for prognostic evaluation amongst the patient of breast cancer. Accurate quantification of cell membrane is essential for HER2 scoring in therapeutic decision making. In modern laboratory practice, expert pathologist visually assesses the HER2-stained tissue sample under the bright field microscope for cell membrane assessment. This manual assessment is time consuming, tedious and quite often results in interobserver variability. Further, the burden of increasing number of patients is a challenge for the pathologists. To address these challenges, there is an urgent need with a rapid HER2 cell membrane extraction method. The proposed study aims at developing an automated IHC scoring system, termed as AutoIHC-Analyzer, for automated cell membrane extraction followed by HER2 molecular expression assessment from stained tissue images. A series of image processing approaches have been used to automatically extract the stained cells and membrane region, followed by automatic assessment of complete and broken membrane. Finally, a set of features are used to automatically classify the tissue under observation for the quantitative scoring as 0/1+, 2+ and 3+. In a set of surgically extracted cases of HER2-stained tissues, obtained from collaborative hospital for the testing and validation of the proposed approach AutoIHC-Analyzer and publicly available open source ImmunoMembrane software are compared for 90 set of randomly acquired images with the scores by expert pathologist where significant correlation is observed [(r = 0.9448; p < 0.001) and (r = 0.8521; p < 0.001)] respectively. The output shows promising quantification in automated scoring. LAY DESCRIPTION: In cancer prognosis amongst the patient of breast cancer, human epidermal growth factor receptor 2 (HER2) is used as Immunohistochemical (IHC) biomarker. The correct assessment of HER2 leads to the therapeutic decision making. In regular practice, the stained tissue sample is observed under a bright microscope and the expert pathologists score the sample as negative (0/1+), equivocal (2+) and positive (3+) case. The scoring is based on the standard guidelines relating the complete and broken cell membrane as well as intensity of staining in the membrane boundary. Such evaluation is time consuming, tedious and quite often results in interobserver variability. To assist in rapid HER2 cell membrane assessment, the proposed study aims at developing an automated IHC scoring system, termed as AutoIHC-Analyzer, for automated cell membrane extraction followed by HER2 molecular expression assessment from stained tissue images. The input image is preprocessed using modified white patch and CMYK and RGB colour space were used in extracting the haematoxylin (negatively stained cells) and diaminobenzidine (DAB) stain observed in the tumour cell membrane. Segmentation and postprocessing are applied to create the masks for each of the stain channels. The membrane mask is then quantified as complete or broken using skeletonisation and morphological operations. Six set of features were assessed for the classification from a set of 180 training images. These features are: complete to broken membrane ratio, amount of stain using area of Blue and Saturation channels to the image size, DAB to haematoxylin ratio from segmented masks and average R, G and B from five largest blobs in segmented DAB-masked image. These features are then used in training the SVM classifier with Gaussian kernel using 5-fold cross-validation. The accuracy in the training sample is found to be 88.3%. The model is then used for 90 set of unknown test sample images and the final labelling of stained cells and HER2 scores (as 0/1+, 2+ and 3+) are compared with the ground truth, that is expert pathologists' score from the collaborative hospital. The test sample images were also fed to ImmunoMembrane software for a comparative assessment. The results from the proposed AutoIHC-Analyzer and ImmunoMembrane software were compared with the expert pathologists' score where significant agreement using Pearson's correlation coefficient [(r = 0.9448; p < 0.001) and (r = 0.8521; p < 0.001) respectively] is observed. The results from AutoIHC-Analyzer show promising quantitative assessment of HER2 scoring.

Pathogenesis of different diseases showed that some of them, especially thalassemia (T) and rheumatoid arthritis (RA) have an implicit association with oxidative stress and altered levels of reactive oxygen species (ROS). Introducing ROS level and the balance between ROS and antioxidants as essential metrics, an attempt was made to classify T and RA from normal individuals (treated as controls)(C) using synchronous fluorescence spectroscopy (SFS) and Raman line intensity of water. This non-invasive and label-free approach was backed up by a categorization algorithm that helped in the prediction of disease types from serum samples. The predictive system constituted principal component analysis (PCA) with four parameters, namely spectral intensity ratios of reduced nicotinamide adenine dinucleotide (NADH) to tryptophan (Trp) (NADH/Trp), kynurenine (Kyn) to tryptophan (Kyn/Trp), kynurenine to NADH (Kyn/NADH), and logarithmic changes in Raman line intensity of water (Rline), with the index headers containing the disease types. Rline has a positive correlation with both Kyn/Trp and Kyn/NADH and a negative correlation with NADH/Trp ratio, implying its direct or indirect association with oxidative stress. In addition to the classification of T, RA, and C a sub-classification of T into beta major and E-beta in their post and pre-splenectomized surgical stages could also be realized. Furthermore, receiver operating characteristic (ROC) analysis was deployed to ascertain that the misclassification error (ME) was negligible for the disease types. Graphical Abstract A schematic representation of the workflow converging into the categorical classification of disease classes.

Breast cancer is the most common cancer among women in India, and adjuvant radiotherapy is an integral part of curative treatment in most patients. The recent decades have witnessed several advances in radiation therapy delivery. Several advances in radiation oncology have been identified which include technological advances, change in fractionation used, use of cardiac-sparing radiotherapy as well as efforts to personalize radiotherapy using accelerated partial breast irradiation or avoidance of radiotherapy in certain subpopulations. Indian data are available in most areas which have been summarized. However, increasing emphasis on research in these areas is needed so that effectiveness and safety in our setting can be established. Advances in breast cancer radiotherapy have resulted in improved outcomes. Data published from India suggest that these improved outcomes can be replicated in patients when appropriate treatment protocols are followed.

Management of breast cancer is multidisciplinary requiring critical analysis of emerging evidence especially with its appropriateness to local practice. A high level expert committee meeting was held to arrive at a consensus on controversial practical breast cancer management policies for Indian patients. Indian experts (n=39) from government and private centres who were part of the breast cancer multidisciplinary group, participated in the consensus meeting. A set of controversial yet practical questions were circulated among the experts at least two weeks in advance of the consensus meeting. International experts from the UK (n=6) also participated in the scientific discussions to add further light on the topics. The experts voted on the practical acceptable management policy for India. Consensus was defined as overwhelming (90-100% concurrence in voting), moderate (70-89% concurrence), low (50-70% concurrence) and non-consensus (50% concurrence). Fifty eight questions based on pragmatic management strategies were framed and circulated to 39 participants. An overwhelming consensus was received in 51 of the 58 questions. The group considered the available evidence with a view for its practical applicability in Indian patients. This consensus document may aid in shaping breast cancer care for the breast oncology practitioners as well as the policymakers in the country.

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.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.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.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.

Randomised controlled trials (RCT) are important for generating high-quality evidence about efficacy and adverse effects associated with various types of interventions. RCTs are expensive and time consuming to conduct. Therefore, a significant portion of the research funding available for clinical research would be utilised for funding randomised clinical trials. The objective of the current study is to report the extent of funding received by investigators of academic RCT in India and the areas where the funding is allocated to in the clinical trials.

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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.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.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.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.NCT02941926 (Registered 2016).

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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.

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.

Background The Z0011 trial results have shown that axillary lymph node dissection (ALND) can be avoided in cT1-2 patients undergoing breast conservation surgery with 1–2 metastatic sentinel lymph nodes (SLNs). We compared the clinicopathological characteristics of the Z0011 eligible non-screen detected breast cancer patients’ cohort with the Z0011 trial study population. Additionally, we have explored the effect of non-sentinel metastasis on adjuvant treatment decisions and survival. Methods The details of early breast cancer (EBC) patients fulfilling Z0011 eligibility criteria were retrieved from a prospectively maintained database (2013–2017) and electronic medical records. We used Statistical Package for the Social Sciences 25 and Stata V15 for the data analysis. Results 128/194 (66%) sentinel lymph node biopsy positive patients had fulfilled the Z0011 inclusion criteria. Compared to the Z0011 study, our cohort patients were younger, with more aggressive disease (higher T2, Grade 3), had a higher rate of macrometastasis (82.8% versus 58.8%) and non-SLN metastasis (48% versus 27%). The information gained by ALND had changed decisions for chemotherapy in 3% and no change of radiotherapy in Z0011 eligible patients. Further nodal positivity in completion ALND was not significantly associated with overall survival (p = 0.86) and disease-free survival (p = 0.5). Conclusion Z0011 eligible Indian EBC patients are significantly different from the Z0011 study population, with younger age of presentation, higher grade, a higher rate of both SLN macro metastasis and non-SLN positivity. The impact of non-sentinel metastasis on adjuvant treatment decisions and survival is minimal.