A prospective health economic evaluation to determine the productivity loss due to premature mortality from oral cancer in India.

INTRODUCTION: India contributes two-thirds of the global mortality due to oral cancer and has a younger population at risk. The societal costs of this premature mortality are barely discussed. METHODS: Using the human capital approach, we aimed to estimate the productivity lost due to premature mortality, valued using individual socioeconomic data, related to oral cancer in India. A bottom-up approach was used to prospectively collect data of 100 consecutive patients with oral cancer treated between 2019 and 2020, with a follow-up of 36 months. RESULTS: The disease-specific survival for early and advanced stage was 85% and 70%, with a median age of 47 years. With 671 years lost prematurely, the loss of productivity was $41 900/early and $96 044/advanced stage. Based on population level rates, the total cost of premature mortality was $5.6 billion, representing 0.18% of GDP. CONCLUSION: India needs to implement tailored strategies to reduce the economic burden from premature mortality.

Outcome of early detection approach in control of breast, cervical, and oral cancer: Experience from a rural cancer center in India.

In low- and middle-income countries most of the cancer patients attend the hospital at a late stage and treatment completion of these cases is challenging. The early detection program (EDP), in rural areas of Punjab state, India was initiated to identify breast, cervical, and oral cancer at an early stage by raising awareness and providing easy access to diagnosis and treatment. A total of 361 health education programs and 99 early detection clinics were organized. The symptomatic and self-interested (non-symptomatic individuals who opted for screening) cases visited the detection clinic. They were screened for breast, cervical, and/or oral cancer. Further diagnosis and treatment of screen-positive cases were carried out at Homi Bhabha Cancer Hospital (HBCH), Sangrur. Community leaders and healthcare workers were involved in all the activities. The EDP, Sangrur removed barriers between cancer diagnosis and treatment with the help of project staff. From 2019 to 2023, a total of 221,317 populations were covered. Symptomatic and self-interested individuals attended the breast (1627), cervical (1601), and oral (1111) examinations. 46 breast (in situ-4.3%; localized-52.2%), 9 cervical (localized-77.8%), and 12 oral (localized-66.7%) cancer cases were detected, and treatment completion was 82.6%, 77.8%, and 50.0%, respectively. We compared cancer staging and treatment completion of cases detected through EDP with the cases attended HBCH from Sangrur district in 2018; the difference between two groups is statistically significant. Due to the early detection approach, there is disease down-staging and improvement in treatment completion. This approach is feasible and can be implemented to control these cancers in low- and middle-income countries.

Assessing frailty in older Indian patients before cancer treatment: Comparative analysis of three scales and their implications for overall survival.

INTRODUCTION: Frailty, characterized by ageing-related vulnerability, influences outcomes in older adults. Our study aimed to investigate the relationship between frailty and clinical outcomes in older Indian patients with cancer. MATERIALS AND METHODS: Our observational single-centre study, conducted at Tata Memorial Hospital from February 2020 to July 2022, enrolled participants aged 60 years and above with cancer. Frailty was assessed using the Clinical Frailty Scale (CFS), G8, and Vulnerable Elders Survey (VES)-13. The primary objective was to explore the correlation between baseline frailty and overall survival. Statistical analyses include Kaplan-Meier, Cox proportional hazards, and Harrell's C test. RESULTS: A total of 1,177 patients (median age 68, 76.9% male) were evaluated in the geriatric oncology clinic. Common malignancies included lung (40.0%), gastrointestinal (35.8%), urological (11.9%), and head and neck (9.0%), with 56.5% having metastatic disease. Using CFS, G8, and VES-13 scales, 28.5%, 86.4%, and 38.0% were identified as frail, respectively. Median follow-up was 11.6 months, with 43.3% deaths. Patients fit on CFS (CFS 1-2) had a median survival of 28.02 months, pre-frail (CFS 3-4) 13.24 months, and frail (CFS ≥5) 7.79 months (p < 0.001). Abnormal G8 (≤14) and VES-13 (≥3) were associated with significantly lower median survival (p < 0.001). Multivariate analysis confirmed CFS's predictive power for mortality (p < 0.001), with hazard ratios [HRs] for pre-frail at 1.61(95% confidence interval [CI] 1.25 to 2.06) and frail at 2.31 (95%CI 1.74 to 3.05). G8 ≤ 14 had HR 2.00 (95%CI 1.42 to 2.83), and abnormal VES-13 had HR 1.36 (95%CI 1.11-1.67). In the likelihood ratio test, CFS significantly improved the model fit (p < 0.001). Harrell's C index for survival prediction was 0.62 for CFS, 0.54 for G8, and 0.58 for VES-13. DISCUSSION: In conclusion, our study highlights varying frailty prevalence and prognostic implications in older Indian patients with cancer, emphasizing the need for personalized care in oncology for this aging population. We would recommend using CFS as a tool to screen for frailty for older Indian patients with cancer.

Tata Memorial Centre Evidence Based Management of Breast cancer.

ABSTRACT: The incidence of breast cancer is increasing rapidly in urban India due to the changing lifestyle and exposure to risk factors. Diagnosis at an advanced stage and in younger women are the most concerning issues of breast cancer in India. Lack of awareness and social taboos related to cancer diagnosis make women feel hesitant to seek timely medical advice. As almost half of women develop breast cancer at an age younger than 50 years, breast cancer diagnosis poses a huge financial burden on the household and impacts the entire family. Moreover, inaccessibility, unaffordability, and high out-of-pocket expenditure make this situation grimmer. Women find it difficult to get quality cancer care closer to their homes and end up traveling long distances for seeking treatment. Significant differences in the cancer epidemiology compared to the west make the adoption of western breast cancer management guidelines challenging for Indian women. In this article, we intend to provide a comprehensive review of the management of breast cancer from diagnosis to treatment for both early and advanced stages from the perspective of low-middle-income countries. Starting with a brief introduction to epidemiology and guidelines for diagnostic modalities (imaging and pathology), treatment has been discussed for early breast cancer (EBC), locally advanced, and MBC. In-depth information on loco-regional and systemic therapy has been provided focusing on standard treatment protocols as well as scenarios where treatment can be de-escalated or escalated.

Clinical Internal Dosimetry and Biodistribution of 177 Lu-DOTA-Trastuzumab in HER2-Positive Metastatic and Locally Advanced Breast Carcinoma.

OBJECTIVE: The aim of this study was to assess the biodistribution and dosimetry of 177 Lu-DOTA-trastuzumab in patients with HER2-positive breast carcinoma using whole-body (WB) planar imaging at multiple time points. PATIENTS AND METHODS: This study was a prospective evaluation of HER2-positive metastatic/locally advanced breast carcinoma patients who underwent gamma camera imaging for dosimetry and biodistribution studies by using 177 Lu-DOTA-trastuzumab. The standard diagnostic dosimetry protocol was followed, which included cold trastuzumab injection followed by in-house produced 177 Lu-DOTA-trastuzumab. Serial WB planar images (anterior and posterior) were obtained on gamma camera after the infusion of 177 Lu-DOTA-trastuzumab at multiple time points. Whole-body and organ regions of interest were drawn, and the numbers of disintegrations were obtained. The mean absorbed doses for the liver, spleen, kidneys, heart, red marrow, and tumor were obtained from OLINDA EXM v2.1.1 and ORIGIN software. RESULTS: The study included a cohort of 21 female breast carcinoma patients. Tracer activity ( 177 Lu-DOTA-trastuzumab) was noted in the physiological organs such as the liver, spleen, kidneys, heart, as well as in the tumors. On visual analysis of 177 Lu-DOTA-trastuzumab biodistribution, the liver activity showed gradual clearance over time, and although spleen was comparatively faintly visualized than liver and similarly, kidneys were faintly visualized suggestive of the alternate route of tracer excretion. The maximum number of patients (n = 12) showed 2 components of clearance, namely, fast and slow. The average effective half-life of all the patients (including single and 2 components of clearance) was 106.25 ± 22.14 hours (84.11-128.39 hours). The mean absorbed dose for the liver, spleen, kidneys, heart, whole body, and red marrow was 1.0702 ± 0.731, 1.4114 ± 0.462, 1.4232 ± 0.364, 1.4719 ± 0.602, 0.2412 ± 0.0295, and 0.1485 ± 0.0213 mGy/MBq, respectively, by OLINDA EXM and 0.5741 ± 0.333, 0.8096 ± 0.224, 0.7943 ± 0.235, 1.8971 ± 0.713, and 0.09619 ± 0.0144 for liver, spleen, kidneys, heart and whole body respectively by ORIGIN. The absorbed radiation dose for tumor was 1.94E+2 by OLINDA EXM software and 1.78E+2 by ORIGIN software. In this study, during and after infusion of 177 Lu-DOTA-trastuzumab, no major adverse effects were noted in any patient except 1 patient who had grade 1 nausea and managed conservatively by antiemetic drug. CONCLUSIONS: The results of our study demonstrated expected and favorable biodistribution and dosimetry with 177 Lu-DOTA-trastuzumab in HER2-positive breast carcinoma patients. We noticed the mean absorbed dose to the normal organs within the limits of maximum tolerable dose, and also tumor dose was higher than the normal liver dose. Therefore, we conclude that 177 Lu-DOTA-trastuzumab radioimmunotherapy is feasible and a safe treatment option for treating HER2-positive breast carcinoma patients.

Surgical tumour resection deregulates Hallmarks of Cancer in resected tissue and the surrounding microenvironment.

Surgery exposes tumor tissue to severe hypoxia and mechanical stress leading to rapid gene expression changes in the tumor and its microenvironment, which remain poorly characterized. We biopsied tumor and adjacent normal tissue from breast (BRC) (n=81) and head/neck squamous cancer (HNSC) patients (n=10) at the beginning (A), during (B) and end of surgery (C). Tumor/normal RNA from 46/81 breast cancer patients was subjected to mRNA-Seq using Illumina short-read technology, and from nine HNSC patients to whole transcriptome microarray with Illumina BeadArray. Pathways and genes involved in 7 of 10 known cancer hallmarks, namely, tumour promoting inflammation (TNF-A, NFK-B, IL-18 pathways), activation of invasion & migration [(various Extracellular Matrix (ECM) related pathways, cell migration)], sustained proliferative signaling (K-Ras Signaling), evasion of growth suppressors (P53 signaling, regulation of cell death), deregulating cellular energetics (response to lipid, secreted factors, adipogenesis), inducing angiogenesis (hypoxia signaling, myogenesis), and avoiding immune destruction (CTLA4 and PDL1) were significantly deregulated during surgical resection (time-points A vs B vs C). These findings were validated using NanoString assays in independent pre/intra/post-operative breast cancer samples from 48 patients. In a comparison of gene expression data from biopsy (analogous to time-point A) with surgical resection samples (analogous to time-point C) from The Cancer Genome Atlas (TCGA) study, the top deregulated genes were the same as identified in our analysis, in five of the seven studied cancer types. This study suggests that surgical extirpation deregulates the hallmarks of cancer in primary tumors and adjacent normal tissue across different cancers. Implications: Surgery deregulates hallmarks of cancer in human tissue.

Low-dose versus standard-dose olanzapine with triple antiemetic therapy for prevention of highly emetogenic chemotherapy-induced nausea and vomiting in patients with solid tumours: a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. METHODS: This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13-75 years with an Eastern Cooperative Oncology Group performance status of 0-2, who were receiving doxorubicin-cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0-120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. RESULTS: Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference -1·0% [one-sided 95% CI -100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). INTERPRETATION: Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. FUNDING: Progressive Ladies Welfare Association.

Performance of potentially inappropriate medications assessment tools in older Indian patients with cancer.

BACKGROUND: Polypharmacy and potentially inappropriate medication (PIM) use are common problems in older adults. Safe prescription practices are a necessity. The tools employed for the identification of PIM sometimes do not concur with each other. METHODS: A retrospective analysis of patients ≥60 years who visited the Geriatric Oncology Clinic of the Tata Memorial Hospital, Mumbai, India from 2018 to 2021 was performed. Beer's-2015, STOPP/START criteria v2, PRISCUS-2010, Fit fOR The Aged (FORTA)-2018, and the EU(7)-PIM list-2015 were the tools used to assess PIM. Every patient was assigned a standardized PIM value (SPV) for each scale, which represented the ratio of the number of PIMs identified by a given scale to the total number of medications taken. The median SPV of all five tools was considered the reference standard for each patient. Bland-Altman plots were utilized to determine agreement between each scale and the reference. Association between baseline variables and PIM use was determined using multiple logistic regression analysis. RESULTS: Of the 467 patients included in this analysis, there were 372 (79.66%) males and 95 (20.34%) females with an average age of 70 ± 5.91 years. The EU(7)-PIM list was found to have the highest level of agreement given by a bias estimate of 0.010, the lowest compared to any other scale. The 95% CI of the bias was in the narrow range of -0.001 to 0.022, demonstrating the precision of the estimate. In comparison, the bias (95%) CI of Beer's criteria, STOPP/START criteria, PRISCUS list, and FORTA list were -0.039 (-0.053 to -0.025), 0.076 (0.060 to 0.092), 0.035 (0.021 to 0.049), and -0.148 (-0.165 to -0.130), respectively. Patients on polypharmacy had significantly higher PIM use compared to those without (OR = 1.47 (1.33-1.63), p = <0.001). CONCLUSIONS: The EU(7)-PIM list was found to have the least bias and hence can be considered the most reliable among all other tools studied.

Deciphering the Patterns of Dual Primary Cases Registered at the Hospital-Based Cancer Registry: First Experience from Rural Cancer Center in North India.

Objectives The objective is to present the patterns of dual primary malignancies diagnosed at the Pathology Laboratory of Cancer Hospital with the support from hospital-based cancer registry (HBCR), Sangrur, Punjab, India for the years 2018 and 2019. Methods HBCR abstracts data from electronic medical records. Trained cancer registry staff abstracts cases in standard pro forma. Dual primary was coded as per the International Agency for Research on Cancer rule and was rechecked by the pathologist. Statistical Analysis Data about multiple primary was entered and documented in an Excel sheet. Time interval was calculated by subtracting the date of diagnosis for second primary and first primary. Results A total of 6,933 cases were registered, 45 cases are dual primary (26 females, 19 males) of which 64.4% are synchronous and 35.6% metachronous cases. Seventy-nine percent received cancer-directed treatment for synchronous and 87% for metachronous. The most common sites of the primary tumor were breast (33%), head and neck (22.2%), gynecological sites (11%), prostate (9%), esophagus (4%), and remaining other tumors (20.8%). Most common sites for second malignancies were gastrointestinal (GI) tract (31%), gynecological sites (18%), head and neck (16%), hematological malignancies (7%), soft tissue sarcoma (4%), breast (2%), and other sites (22%). Conclusion More than 70% of cases of primary tumors were in breast, head and neck, gynecological, and prostate. Of these, more than 60% of the second malignancy was found in the GI tract, gynecological, and head and neck sites. Around two-thirds of dual tumors are synchronous. Breast cancer cases have higher incidence of second malignancy. Regular follow-up is necessary to assess the survival of the second primary.

Effectiveness of a Decision Aid Plus Standard Care in Surgical Management Among Patients With Early Breast Cancer: A Randomized Clinical Trial.

Importance: Patients with early breast cancer must choose between undergoing breast conservation surgery or mastectomy. This decision is often difficult as there are trade-offs between breast conservation and adverse effects, and women with higher decisional conflict have a harder time choosing the therapy that suits their preferences. Objective: To study the impact of a decision aid with a patient preference assessment tool for surgical decision-making on patients' decisional conflict scale (DCS) score. Design, Setting, and Participants: This 3-group randomized clinical trial was conducted between June 2017 and December 2019 at a single high-volume tertiary care cancer center in Mumbai, India. A research questionnaire comprising 16 questions answered on a Likert scale (from 1, strongly agree, to 5, strongly disagree) was used to measure DCS scores and other secondary psychological variables, with higher scores indicating more decisional conflict. The Navya Patient Preference Tool (Navya-PPT) was developed as a survey-based presentation of evidence in an adaptive, conjoint analysis-based module for and trade-offs between cosmesis, adverse effects of radiotherapy, and cost of mandatory radiation following breast-conserving surgery. Adult patients with histologically proven early breast cancer (cT1-2, N0-1) who were eligible for breast-conserving surgery as per clinicoradiological assessment were included. Those who were pregnant or unable to read the research questionnaire or who had bilateral breast cancer were excluded. Data were analyzed from January to June 2020. Interventions: Patients were randomized 1:1:1 to study groups: standard care including clinical explanation about surgery (control), standard care plus the Navya-PPT provided to the patient alone (solo group), and standard care plus the Navya-PPT provided to the patient and a caregiver (joint group). Main Outcomes and Measures: The primary end point of the study was DCS score. The study was 80% powered with 2-sided α = .01 to detect an effect size of 0.25 measured by Cohen d, F test analysis of variance, and fixed effects. Results: A total of 245 female patients (median [range] age, 48 [23-76] years) were randomized (82 to control, 83 to the solo group, and 80 to the joint group). The median (range) pathological tumor size was 2.5 (0-6) cm. A total of 153 participants (62.4%) had pN0 disease, 185 (75.5%) were hormone receptor positive, 197 (80.4%) were human epidermal growth factor receptor 2 negative, 144 (58.6%) were of middle or lower socioeconomic status, and 114 (46.5%) had an education level lower than a college degree. DCS score was significantly reduced in the solo group compared with control (1.34 vs 1.66, respectively; Cohen d, 0.50; SD, 0.31; P < .001) and the joint group compared with control (1.31 vs 1.66, respectively; Cohen d, 0.54; SD, 0.31; P < .001). Conclusions and Relevance: The results of this study demonstrated lower decisional conflict as measured by DCS score following use of the online, self-administered Navya-PPT among patients with early breast cancer choosing between breast-conserving surgery vs mastectomy. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/11/010480.

The current status of geriatric oncology in India.

Geriatric oncology in India is relatively new. The number of older persons with cancer is increasing exponentially; at our institution, 34% of patients registered are 60 years and over. Apart from the Tata Memorial Hospital in Mumbai, there are currently no other Indian centers that have a dedicated geriatric oncology unit. Geriatric assessments (GAs) are done sporadically, and older patients with cancer are usually assessed and treated based on clinical judgement. Challenges to increasing the uptake of GA include a lack of training/time/interest or knowledge of the importance of the GA. Other challenges include a lack of trained personnel with expertise in geriatric oncology, and a paucity of research studies that seek to advance the outcomes in older Indian patients with cancer. We anticipate that over the next 10 years, along with the inevitable increase in the number of older persons with cancer in India, there will be a commensurate increase in the number of skilled personnel to care for them. Key goals for the future include increased research output, increased number of dedicated geriatric oncology units across the country, India-specific geriatric oncology guidelines, geriatric oncology training programs, and a focus on collaborative work across India and with global partners. In this narrative review, we provide a broad overview of the status of geriatric oncology in India, along with a description of the work done at our center. We hope to spark interest and provide inspiration to readers to consider developing geriatric oncology services in other settings.

Risk factors for the development of triple-negative breast cancer versus non-triple-negative breast cancer: a case-control study.

The risk factors for breast cancer have been defined in several studies but there is deficient data for specific subtypes. We report here the pathological characteristics of a breast cancer cohort and risk factors for patients with triple-negative disease. In this case-control study, a prospective breast cancer cohort was evaluated for demographic, reproductive, obesity-related and other risk factors using a validated questionnaire. Tumors were characterized for routine pathological characteristics and immunohistochemical markers of basal-like breast cancer. Patients with triple-negative breast cancer (TNBC) constituted cases and those with non-TNBC were controls. Odds ratios (OR) were calculated for each risk factor and independent associations were tested in an unconditional logistic regression analysis. Between 2011 and 2014, 1146 patients were recruited, of whom 912 [TNBC 266 (29.1%), non-TNBC 646 (70.9%)] with sufficient pathology material were analysed. Reproductive factors of parity, breastfeeding, age-at-menarche, age at first full-term pregnancy and oral contraceptive use were not significantly associated with TNBC. Higher body mass index (BMI > 24.9 vs ≤ 24.9, OR 0.89, 95%CI 0.63-1.24, p = 0.49) was not significantly associated while lesser waist circumference (> 80 cm vs ≤ 80 cm, OR 0.64, 95%CI 0.45-0.9, p = 0.012) and lower waist-to-hip ratio were significantly associated (> 0.85 vs ≤ 0.85, OR 0.72, 95%CI 0.51-1.0, p = 0.056), with TNBC. History of tobacco use was not significantly associated while lower socio-economic status was borderline associated with TNBC (socio-economic category > 5 versus ≤ 5, OR 0.73, 95%CI 0.50-1.06, p = 0.106). No factor was significant after adjustment for covariates. Central obesity seems to be preferentially associated with non-TNBC, and lower socio-economic status with TNBC in India, while most other conventional risk factors of breast cancer show no significant association with TNBC versus non-TNBC.

A National Cancer Grid pooled procurement initiative, India.

In health systems with little public funding and decentralized procurement processes, the pricing and quality of anti-cancer medicines directly affects access to effective anti-cancer therapy. Factors such as differential pricing, volume-dependent negotiation and reliance on low-priced generics without any evaluation of their quality can lead to supply and demand lags, high out-of-pocket expenditures for patients and poor treatment outcomes. While pooled procurement of medicines can help address some of these challenges, monitoring of the procurement process requires considerable administrative investment. Group negotiation to fix prices, issuing of uniform contracts with standardized terms and conditions, and procurement by individual hospitals also reduce costs and improve quality without significant investment. The National Cancer Grid, a network of more than 250 cancer centres in India, piloted pooled procurement to improve negotiability of high-value oncology and supportive care medicines. A total of 40 drugs were included in this pilot. The pooled demand for the drugs from 23 centres was equivalent to 15.6 billion Indian rupees (197 million United States dollars (US$)) based on maximum retail prices. The process included technical and financial evaluation followed by contracts between individual centres and the selected vendors. Savings of 13.2 billion Indian Rupees (US$ 166.7million) were made compared to the maximum retail prices. The savings ranged from 23% to 99% (median: 82%) and were more with generics than innovator and newly patented medicines. This study reveals the advantages of group negotiation in pooled procurement for high-value medicines, an approach that can be applied to other health systems.

Lorsque les systèmes de santé reçoivent peu de fonds publics et que leurs processus d'achat sont décentralisés, le prix et la qualité des médicaments contre le cancer ont un impact direct sur l'accès aux traitements efficaces contre la maladie. Des facteurs tels que l'application de prix différenciés, les négociations en fonction des volumes ainsi que la confiance placée dans des génériques bon marché dont la qualité n'a pas été évaluée peuvent entraîner des décalages entre l'offre et la demande, d'énormes dépenses non remboursables pour les patients et de piètres résultats thérapeutiques. Bien que les acquisitions groupées de médicaments puissent contribuer à résoudre certains de ces problèmes, le suivi du processus d'achat requiert un engagement considérable au niveau administratif. Les négociations collectives en vue de fixer les tarifs, l'établissement de contrats types assortis de conditions générales standardisées, mais aussi les achats effectués par des hôpitaux en particulier peuvent également faire baisser les coûts et améliorer la qualité sans nécessiter d'importants investissements. Le National Cancer Grid, un réseau réunissant plus de 250 centres d'oncologie en Inde, a testé un dispositif d'achat groupé visant à assurer une meilleure négociabilité pour des médicaments et soins de soutien essentiels contre le cancer. Au total, 40 substances ont été prises en compte dans ce projet pilote. La demande groupée en médicaments émise par 23 centres équivalait à 15,6 milliards de roupies indiennes (197 millions de dollars américains) d'après le prix maximal de vente au détail. Ce processus prévoyait une évaluation technique et financière, puis des contrats entre chaque centre et les distributeurs sélectionnés. Des économies de 13,2 milliards de roupies indiennes (166,7 millions de dollars américains) ont pu être réalisées par rapport au prix maximal de vente au détail. Ces économies étaient comprises entre 23 et 99% (médiane: 82%) et concernaient davantage les médicaments génériques que les marques et les médicaments récemment brevetés. La présente étude révèle les avantages que représentent les négociations collectives lors des achats groupés de médicaments essentiels, une approche applicable à d'autres systèmes de santé.

En los sistemas sanitarios con escasa financiación pública y procesos de adquisición descentralizados, el sistema de fijación de precios y la calidad de los medicamentos contra el cáncer afectan directamente al acceso a una terapia eficaz contra dicha enfermedad. Factores como los diferentes sistemas de determinación de precios, la negociación en función del volumen y la dependencia de genéricos de bajo precio sin evaluación de su calidad pueden generar retrasos en la oferta y la demanda, elevados gastos para los pacientes y malos resultados en el tratamiento. Aunque la adquisición conjunta de medicamentos puede ayudar a abordar algunos de estos retos, el seguimiento del proceso de adquisición requiere una inversión administrativa considerable. La negociación colectiva a la hora de determinar los precios, la emisión de contratos unificados con términos y condiciones estandarizados y la adquisición por parte de algunos hospitales también reducen los costes y mejoran la calidad sin necesidad de realizar una gran inversión. La Red Nacional de Cáncer, una red que cuenta con más de 250 centros oncológicos en la India, puso a prueba la adquisición conjunta con el fin de mejorar la negociabilidad de medicamentos oncológicos y de tratamiento complementario que resultaban costosos. En esta prueba piloto se incluyó un total de 40 medicamentos. La demanda conjunta de medicamentos por parte de 23 centros fue equivalente a 15 600 millones de rupias indias (197 millones USD) según los precios minoristas máximos. El proceso incluyó una evaluación técnica y financiera, así como contratos entre centros independientes y proveedores seleccionados. Se logró un ahorro de 13 200 millones de rupias indias (166,7 millones USD) en comparación con los precios minoristas máximos. El ahorro osciló entre el 23 y el 99% (media: 82%) y fue más alto con los medicamentos genéricos que con los de marca y los recién patentados. Este estudio pone de manifiesto las ventajas de la negociación colectiva en lo que respecta a la adquisición conjunta de medicamentos costosos, un enfoque que se puede aplicar a otros sistemas sanitarios.

Deciphering the mechanisms of action of progesterone in breast cancer.

A practice-changing, randomized, controlled clinical study established that preoperative hydroxyprogesterone administration improves disease-free and overall survival in patients with node-positive breast cancer. This research perspective summarizes evidences from our studies that preoperative hydroxyprogesterone administration may improve disease-free and overall survival in patients with node-positive breast cancer by modulating cellular stress response and negative regulation of inflammation. Non-coding RNAs, particularly DSCAM-AS1, play a regulatory role in this process, along with the upregulation of the kinase gene SGK1 and activation of the SGK1/AP-1/NDRG1 axis. Progesterone-induced modification of the progesterone receptor and estrogen receptor genomic binding pattern is also involved in orchestrating estrogen signaling in breast cancer, preventing cell migration and invasion, and improving patient outcomes. We also highlight the role of progesterone in endocrine therapy resistance, which could lead to novel treatment options for patients with hormone receptor-positive breast cancer and for those who develop resistance to traditional endocrine therapies.

Epidemiology of rare cancers in India and South Asian countries - remembering the forgotten.

Background: Rare cancers (RCs) are challenging to manage and are "forgotten cancers" though they collectively constitute a significant proportion of all cancers (∼20%). As a first step towards streamlining care, there is an unmet need to map the epidemiology of RCs in South Asian Association for Regional Collaboration (SAARC) countries. Methods: The authors collected data from 30 Population-Based Cancer Registries (PBCR) of India and the published national registries of Nepal, Bhutan and Sri Lanka (SL) and compared them with the standard RARECAREnet RC list. Findings: With the standard definition of crude incidence rates (CR) ≤6/100,0000 per population, 67.5%, 68.3%, 62.3% and 37% of all incident cancers qualify as RCs in India, Bhutan, Nepal and SL, respectively. An arbitrary cut-off CR ≤3 appears more appropriate with 43%, 39.5%, 51.8% and 17.2% of cancers identified as RCs, respectively, due to the lower cancer incidence.There are similarities and notable differences between the RC lists of the SAARC region with that of the European RC list. Oral cavity cancers are rare in Europe, while pancreas, rectum, urinary bladder and melanomas are common. In addition, uterine, colon and prostatic cancers are rare in India, Nepal and Bhutan. In SL, thyroid cancer is common. There are gender-related and regional differences in RC trends in the SAARC countries. Interpretation: There is an unmet need in SAARC nations to capture epidemiological nuances in rare cancers. Understanding the unique issues in the developing world may guide policymakers to adopt appropriate measures to improve RC care and tailor public health interventions. Funding: None.

Overall survival of prostate cancer from Sangrur and Mansa cancer registries of Punjab state, India.

Introduction: There is a scarcity of population-based prostate cancer survival data in India. We assessed the population-based, overall survival of patients with prostate cancer from the Sangrur and Mansa cancer registries of the Punjab state, India. Methods: In the year 2013-2016, a total of 171 prostate cancer cases were registered in these two registries. Based on these registries, survival analysis was performed using the date of diagnosis as the starting date and the last follow-up date being December 31, 2021 or the date of death. Survival was calculated using STATA software. Relative survival was calculated using the Pohar Perme method. Results: Follow up was available for all the registered cases. Of the 171 cases, 41 (24%) were alive and 130 (76.0%) were dead. Of the prescribed treatments, 106 (62.7%) cases completed the treatment and 63 (37.3%) cases did not complete the treatment. Overall, 5-year age-standardized prostate cancer relative survival was 30.3%. Patients who completed the treatment had a 7.8 times higher 5-year relative survival (45.5%) compared to those who did not (5.8%). The difference between the two groups is statistically significant (hazard ratio 0.16, 95% confidence interval [0.10-0.27]). Conclusion: To improve survival, we need to raise awareness in the community and among primary physicians so that prostate cancer cases can reach the hospital early and should be treated effectively. The cancer center should develop the systems in their hospital so that there will be no hurdles to the patients in treatment completion. We found a low overall relative survival among patients of prostate cancer in these two registries. Patients who received treatment had a significantly higher survival.

Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer.

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