Consensus guidelines for the management of HR-positive HER2/neu negative early breast cancer in India, SAARC region and other LMIC by DELPHI survey method.

BACKGROUND: Precise prognostication is the key to optimum and effective treatment planning for early-stage hormone receptor (HR) positive, HER2/neu negative breast cancer patients. Differences in the breast cancer incidence and tumor anatomical features at diagnosis, pharmacogenomics data between Western and Indian women along with the vast diversity in the economic status and differences in insurance policies of these regions; suggest recommendations put forward for Western women might not be applicable to Indian/Asian women. Opinions from oncologists through a voting survey on various prognostic factors/tools to be considered for planning adjuvant therapy are consolidated in this report for the benefit of oncologists of the sub-continent, SAARC and Asia's LMIC (low and middle-income countries). METHODS: A three-phase DELPHI survey was conducted to collect opinions on prognostic factors considered for planning adjuvant therapy in early-stage HR+/HER2/neu negative breast cancer patients. A panel of 25 oncologists with expertise in breast cancer participated in the survey conducted in 2021. The experts provided opinions as 'agree' or disagree' or 'not sure' in phases-1 and 2 which were conducted virtually; in the final phase-3, all the panel experts met in person and concluded the survey. RESULTS: Opinions on 41 statements related to prognostic factors/tools and their implications in planning adjuvant endocrine/chemotherapy were collected. All the statements were supported by the latest data from the clinical trials (prospective/retrospective). The statements with opinions of consensus less than 66% were disseminated in phase-2, and later in phase-3 with supporting literature. In phase-3, all the opinions from panelists were consolidated and guidelines were framed. CONCLUSIONS: This consensus guideline will assist oncologists of India, SAARC and LMIC countries in informed clinical decision-making on adjuvant treatment in early HR+/HER2/neu negative breast cancer patients.

Hypo-fractionated accelerated radiotherapy with concurrent and maintenance temozolomide in newly diagnosed glioblastoma: updated results from phase II HART-GBM trial.

BACKGROUND: Glioblastoma (GBM) patients have poor survival outcomes despite treatment advances and most recurrences occur within the radiation field. Survival outcomes after dose escalation through hypofractionated accelerated RT(HART) were evaluated in this study. We previously reported the study's initial results showing similar survival outcomes with acceptable toxicities. Updated results after 5 years are being analysed to determine long-term survival trends. PATIENTS AND METHODS: 89 patients of newly diagnosed GBM after surgery were randomized to conventional radiotherapy (CRT) or HART. CRT arm received adjuvant RT 60 Gy in 30 fractions over 6 weeks and the HART arm received 60 Gy in 20 fractions over 4 weeks, both with concurrent and adjuvant temozolomide. RESULTS: 83 patients were eligible for analysis. After a median follow-up of 18.9 months, the median OS was 26.5 months and 22.4 months in the HART and CRT arms respectively. 5 year OS was 18.4% in the HART arm versus 3.8% in the CRT arm. This numerical difference in overall survival between the two arms was not statistically significant. The median PFS was not significantly different. CONCLUSION: The long-term results of the trial support HART as a promising treatment option with comparable survival outcomes to the current standard of care. Phase III trials are required for further validation of this regimen which has the potential to become the new standard of care in GBM.

Indian Council of Medical Research consensus document on hepatocellular carcinoma.

This document aims to assist oncologists in making clinical decisions encountered while managing their patients with hepatocellular carcinoma (HCC), specific to Indian practice, based on consensus among experts. Most patients are staged by Barcelona Clinic Liver Cancer (BCLC) staging system which comprises patient performance status, Child-Pugh status, number and size of nodules, portal vein invasion and metastasis. Patients should receive multidisciplinary care. Surgical resection and transplant forms the mainstay of curative treatment. Ablative techniques are used for small tumours (<3 cm) in patients who are not candidates for surgical resection (Child B and C). Patients with advanced (HCC should be assessed on an individual basis to determine whether targeted therapy, interventional radiology procedures or best supportive care should be provided. In advanced HCC, immunotherapy, newer targeted therapies and modern radiation therapy have shown promising results. Patients should be offered regular surveillance after completion of curative resection or treatment of advanced disease.

Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

Hypofractionated accelerated radiotherapy (HART) with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: a phase II randomized trial (HART-GBM trial).

INTRODUCTION: Maximal safe surgical resection followed by adjuvant chemoradiation has been standard for newly diagnosed glioblastoma multiforme (GBM). Hypofractionated accelerated radiotherapy (HART) has the potential to improve outcome as it reduces the overall treatment time and increases the biological effective dose. METHODS: Between October 2011 and July 2017, a total of 89 newly diagnosed GBM patients were randomized to conventional fractionated radiotherapy (CRT) or HART. Radiotherapy was delivered in all patients with a three-dimensional conformal radiotherapy technique in CRT arm (60 Gy in 30 fractions over 6 weeks @ 2 Gy/per fraction) or simultaneous integrated boost intensity modulated radiotherapy in HART arm (60 Gy in 20 fractions over 4 weeks @ 3 Gy/per fraction to high-risk planning target volume (PTV) and 50 Gy in 20 fractions over 4 weeks @ 2.5 Gy/per fraction to low-risk PTV). The primary endpoint of the trial was overall survival (OS). RESULTS: After a median follow-up of 11.4 months (Range: 2.9-42.5 months), 26 patients died and 39 patients had progression of the disease. Median OS for the entire cohort was 23.4 months. Median OS in the CRT and HART arms were 18.07 months (95% CI 14.52-NR) and 25.18 months (95% CI 12.89-NR) respectively, p = 0.3. Median progression free survival (PFS) for the entire cohort was 13.5 months (Range: 11.7-15.7 months). In multivariate analysis patients younger than 40 years of age, patients with a gross total resection of tumor and a mutated IDH-1 had significantly better OS. PFS was significantly better for patients with a gross total resection of tumor and a mutated IDH-1. All patients included in the trial completed the planned course of radiation. Only two patients required hospital admission for features of raised intracranial tension. One patient in the HART arm required treatment interruption. CONCLUSION: HART is comparable to CRT in terms of survival outcome. HART arm had no excess treatment interruption and minimal toxicity. Dose escalation, reduction in overall treatment time, is the advantages with use of HART.

Patterns of care and impact of prognostic factors in the outcome of NUT midline carcinoma: a systematic review and individual patient data analysis of 119 cases.

INTRODUCTION: NUT midline carcinoma is a rare tumour occurring in young adults which is frequently misdiagnosed as poorly differentiated squamous cell carcinoma or germ cell tumour. Though considered highly aggressive, there is limited information about the clinical behaviour of such patients. We intended to perform this review of published literature to assess the demographic profile, pattern of care and assess survival outcomes. METHODS: Two authors independently searched PubMed and Google search for eligible studies from 1950 till July 1 2017 published in English language using MESH terms NUT midline carcinoma; NUT midline carcinoma and radiotherapy and translocation 15:19 tumour. RESULTS: Data of 119 patients were retrieved from 64 publications for statistical analysis. Median age of the entire cohort was 23 years (range 0-68 years). The analysis revealed equal incidence in males and females (60:58). The present analysis revealed that the most common location is the lung (n = 42) followed by head and neck (n = 40). Median OS for the entire cohort was only 5 months with 1 and 5 year OS for the entire cohort was 24.99 and 7.09% respectively. Radiotherapy and chemotherapy inclusion in primary treatment had a significant impact on overall survival on univariate analysis while surgery did not affect survival significantly. No impact on overall survival was found based on type of molecular translocation, i.e., NUT-BRD4, NUT-BRD3 or other variants. Inadequate data were available for identify impact of BET inhibitors and HiDAc on PFS and OS. CONCLUSION: NUT midline carcinoma has dismal prognosis. Radiotherapy and chemotherapy improves survival, but do not provide long term control except in anecdotal cases. Further research is needed to improve outcomes in future.

Surviving Triple Trouble: Synchronous Breast and Cervical Cancer, HIV Infection and Myocardial Infarction.

Breast and cervical cancer are the two most common cancers in female. However, owing to the contrasting risk factors, synchronous breast and cervical cancer has very rarely been reported. However, noncommunicable disease like cardiovascular disease and different infections has tended to make situations complicated because of complex interaction. In recent years, such cases are being seen frequently and their management is challenging. We report such a case of synchronous breast and cervical cancer complicated by HIV infection and myocardial infarction. This highlights the importance of a wide spectrum of clinical knowledge and skill and interdisciplinary coordination.

Extent of surgical resection and adjuvant temozolomide improves survival in pediatric GBM: a single center experience.

BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance of concurrent and adjuvant temozolomide is not known in this subset of patients. METHODS: We retrospectively analyzed our database between 2000 and 2015. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation with concurrent daily temozolomide at 75 mg/m2. Radiation dose was 60 Gy in 30 fractions planned by 3-dimensional conformal radiotherapy. Concurrent and adjuvant temozolomide was used in all patients treated after 2007. Four weeks later, adjuvant temozolomide was started at 150 mg/m2, day 1 to 5 every 28 days and escalated to 200 mg/m2 from the second cycle onwards if well tolerated. Log-rank test was used to compare survival distribution. The data was analyzed using SPSS (version 16). RESULTS: Fifty-one patients were analyzed. Median age was 14 years (range: 5 to 21 years). Thirty-five males and 16 females were noted. Median symptom duration was 4 months. Twenty-eight patients underwent a gross total resection (GTR) while 17 underwent a subtotal resection; six patients underwent decompression. Thirty-three patients received concurrent chemotherapy while 27 received adjuvant chemotherapy. Median progression-free survival (PFS) was 15.1 months. One- and 3-year PFS was 54.4% and 3-year PFS was 24.6.7%. The median overall survival was 17.4 months. In univariate analysis survival was better for gross total resection (17.4 months vs. 11.5 months; p = 0.037), and significance maintained after multivariate analysis p = 0.026, HR 3.069, 95% CI 1.14-8.23. In univariate analysis, survival was better for patients receiving temozolomide but did not achieve significance. However, in multivariate analysis, use of temozolomide was associated with significantly improved survival p = 0.036, HR 3.315, 95% CI 1.07-10.19. CONCLUSIONS: GTR improves survival significantly in pGBM. Adjuvant temozolomide may improve survival in pGBM.

Treatment Outcome in Patients with Primary Central Nervous System Germ Cell Tumour: Clinical Experience from a Regional Cancer Centre in North India.

BACKGROUND: Primary intracranial germ cell tumour is a rare entity and constitutes 2-3% of all paediatric brain tumours in Western countries. We herein intend to report the clinical features and treatment outcome of patients with primary central nervous system germ cell tumour treated at our institute. METHODS: Clinical data were collected by retrospective chart review from 2006 to 2012. Histopathology slides were reviewed and relevant immunohistochemistry stains were done. Overall survival (OS) and progression-free survival (PFS) were analysed by the Kaplan-Meier product-limit method. RESULTS: Twenty patients met the study criterion (male:female = 7:3). Median age at presentation was 13 years. Tumour location was pineal in 10 patients, suprasellar in 6, thalamic in 2, basal ganglion in 1, and spinal in 1. Leptomeningeal spread was noted in 1 patient at presentation. Surgical resection was gross-total in 7 patients (35%), near-total in 2 (10%), subtotal in 4 (20%), and limited to biopsy in 6 (30%). The tumours were germinomatous, non-germinomatous, and of mixed germ cell subtype in 17 patients (85%), 2 patients (10%), and 1 patient (5%), respectively. Systemic chemotherapy (median of 4 cycles) was given to 19 patients (95%). The common regimens used were a combination of bleomycin, etoposide and cisplatin (BEP) in 14 patients (70%) and etoposide and cisplatin (EP) in 5 patients (25%). Radiation therapy (40-50 Gy in conventional fractionation; median of 42 Gy) was delivered to 17 patients (85%): local radiation in 6 and whole ventricular, whole brain, and craniospinal irradiation followed by a boost in 5, 3, and 3 patients, respectively. After a median follow-up of 44.52 months, 17 patients (85%) were in complete response and 3 (15%) had progressive disease. Death and disease recurrence were noted in 6 patients (30%) and 1 patient, respectively. Median OS and PFS were not reached. The actuarial rates of OS at 3 and 5 years were 75.8 and 68.9%, respectively. The actuarial rates of PFS at both 3 and 5 years were 81.6%. CONCLUSION: Multimodality treatment consisting of limited resection followed by platinum-based systemic chemotherapy and radiotherapy (40-50 Gy) is a reasonable treatment strategy in patients of primary central nervous system germ cell tumour in a developing nation.

Orbital medulloepithelioma in an adult patient: Radiation-induced second neoplasia?

Second cancers in survivors of hereditary retinoblastoma occur much more commonly than in the general population. This can be attributed both to the germline mutation of the RB gene and chemoradiation used for treatment of this paediatric cancer. Medulloepithelioma is an uncommon tumor of neuroectodermal origin, seen largely in the paediatric population and rarely reported in adults. Though the incidence of second malignancies is common in retinoblastoma, medulloepithelioma as a second malignancy in retinoblastoma survivors is rare, with only one case reported so far. Herein, we present a case of a 29-year-old patient presenting with medulloepithelioma of the right orbit, arising in the radiation field of previously treated retinoblastoma. This case was also peculiar in that though the origin of tumor was in the eyeball it had a very aggressive clinical course.

Treatment outcome and patterns of failure in patients of pinealoblastoma: review of literature and clinical experience from a regional cancer centre in north India.

PURPOSE: Pinealoblastoma is a highly malignant embryonal tumour of the pineal region affecting children and young adults. We herein intend to report the clinical features and treatment outcome of patients of pinealoblastoma treated at our institute. METHODS: Clinical data was collected by retrospective chart review from 2003-2012. Histopathology slides were reviewed, and relevant immunohistochemistry stains were done. Overall survival (OS) and recurrence-free survival (RFS) were analysed by Kaplan-Meier product-limit method. Univariate and multivariate analyses of prognostic factors were done by log rank test and Cox proportional hazard regression model, respectively. RESULTS: Seventeen patients met the study criterion (male:female = 11:6). Median age at presentation was 14 years (range 4-47 years). Surgical resection was gross total in 6 (35.29%), near-total in 2 (11.76%), sub-total in 2 (11.76%), and limited to biopsy in 7 (41.18 %) patients. At presentation, 4 patients had leptomeningeal dissemination. Radiation therapy was delivered in all patients-craniospinal irradiation in 15 (88.24%), whole brain irradiation in 1 (5.88%), and whole ventricular irradiation followed by boost in 1 (5.88%) patient. Systemic chemotherapy (median 6 cycles) was given in 14 (82.35%) patients. The most common regimen was a combination of carboplatin and etoposide, used in 10 (58.82%) patients. After a median follow-up of 30.3 months (mean 32.01 months), death and disease recurrences were noted in 3 (17.65%) and 7 (41.18%) patients. Amongst the patients with recurrent disease, 4 had spinal drop metastases and 3 had local recurrence along with spinal drop metastases. Median OS was not reached, and estimated median RFS was noted to be 5.49 years. The actuarial rates of OS and RFS at 2 years were 85.6 and 73.1%, respectively. On univariate analysis, age more than 8 years (P = 0.0071) and M0 stage (P = 0.0483) were significant predictors of improved RFS. Age retained significance on multivariate analysis of RFS (P = 0.02932). CONCLUSION: Maximal safe resection followed by craniospinal irradiation and systemic chemotherapy with 6 cycles of carboplatin-etoposide regimen is a reasonable treatment strategy in patients of pinealoblastoma more than 8 years of age in a developing nation. However, the same strategy is less effective in younger children and innovative study designs of intensification of post-operative treatment must be explored in this age group.

Pediatric gliosarcoma treated with adjuvant radiotherapy and temozolomide.

PURPOSE: Primary pediatric gliosarcoma (pPGS) is an extremely rare entity with only 25 cases reported in the English literature. The value of concurrent and adjuvant temozolomide is not known in this group of patient. METHODS: Five patients of pPGS treated from 2006 to 2011 were included in this retrospective analysis. All patients underwent maximal safe surgical resection. Adjuvant therapy included conformal radiation 60 Gy in 30 fractions (2 Gy daily for 5 days in a week) with concurrent temozolomide 75 mg/m(2) daily followed by six cycles of maintenance temozolomide 150-200 mg/m(2) (day 1 to day 5) every 4 weeks. We combined the survival data of 25 patients (already published) and five of our patients and analyzed them in terms of progression free survival (PFS) and overall survival (OS) using Kaplan-Meier method. RESULTS: Male to female ratio was 1:4 and median age was 12 years (range, 7-19 years). All but one patient underwent gross total resection and four patients completed adjuvant radiotherapy as well as concurrent and adjuvant temozolomide. At a median follow up of 22.6 months (range, 0 to 45.3 months), two patients were dead and two were alive without disease while one was lost to follow up. For the pooled data, estimated median PFS and OS of all 30 patients reported in literature were 12 and 43 months, respectively. Two years PFS and OS rate for all patients was 44.2 and 62.9%, respectively. CONCLUSION: Adjuvant radiotherapy and temozolomide is well tolerated and show an encouraging survival in pPGS.

Intracranial atypical teratoid rhabdoid tumor: current management and a single institute experience of 15 patients from north India.

OBJECTIVE: We intended to assess the clinicopathological features and treatment outcome in patients of intracranial atypical teratoid rhabdoid tumor (AT/RT), a rare malignant tumor of the brain. METHODS: Medical records were reviewed and clinical data collected on AT/RT in a 6-year period (2006-2012). Overall survival was analyzed by Kaplan-Meier method. Univariate analysis of factors predictive of overall survival was done by log-rank test. RESULTS: Fifteen patients met the study criterion (male:female = 4:1). Median age at presentation was 5 years (range, 0.8-8 years). Presenting complaints included vomiting (73.33 %), headache (46.67 %), orbital symptoms (33.33 %), motor impairment (26.67 %), gait abnormality (20 %), and seizure (20 %). Median duration of symptoms was noted to be 2 months (range, 0.5-6 months). On contrast-enhanced MRI of brain, tumor location was supratentorial in 60 % patients and infratentorial in 40 % of patients. Cystic component and hydrocephalus were noted in 73.33 % patients each, whereas contrast enhancement and calcification were discerned in 53.33 and 40 % of the patients, respectively. All patients underwent tumor resection-gross total (26.67 %), near-total (13.33 %) and subtotal (60 %). Histopathology was confirmative of AT/RT with MIB-1 labeling index varying from 11 to 85 % (median 45 %). There was a lack of immunostaining for INI-1 protein, suggesting INI-1gene mutation or deletion. Adjuvant radiation (36 Gray/20 fractions/4 weeks to entire neuraxis followed by local boost 20 Gray/10 fractions/2 weeks) was started in six patients (40 %) and completed in five patients. Young age at presentation and poor performance status precluded the use of radiation in the remainder. Systemic chemotherapy was administered in ten (66.67 %) patients. Median number of cycles given was three (range, 1-12) with ICE (ifosfamide, carboplatin, etoposide) and VAC (vincristine, dactinomycin, cyclophosphamide) being the common regimens (26.67 and 20 %, respectively). After a median follow-up of 8.33 months (mean, 12.27 months), median overall survival was noted to be 10 months. At last follow-up, two patients are in complete response, one patient is on treatment, three patients are alive with evidence of disease, and nine patients expired due to disease progression. The 1- and 2-year actuarial rate of overall survival was noted to be 48.1 and 24.1 %, respectively. On univariate analysis, extent of surgery (p = 0.0149), use of craniospinal radiation (p = 0.0087), and MIB1 labeling index (p = 0.0034) were significant predictors of overall survival while age (≥5 years versus <5 years) was of borderline significance (p = 0.08). CONCLUSIONS: Median survival of 10 months reflects the aggressive biology of this rare neoplasm. Maximal safe resection followed by craniospinal irradiation and systemic chemotherapy with ICE or VAC regimen is a reasonable treatment strategy in this uncommon malignancy.

Treatment outcome and patterns of failure in patients of non-pineal supratentorial primitive neuroectodermal tumor: review of literature and clinical experience form a regional cancer center in north India.

BACKGROUND: Supra-tentorial primitive neuroectodermal tumors (SPNET) are high-grade, hemispheric tumors, which account for around 2-3 % of pediatric brain tumors. We herein intend to report the clinical features and treatment outcome of patients with nonpineal SPNET treated at our institute. METHODS: Clinical data were collected by retrospective chart review from 2006 to 2012. Histopathology slides were reviewed, and relevant immunohistochemistry stains were done. Overall survival (OS), recurrence-free survival (RFS) and event-free survival (EFS) were analyzed by the Kaplan-Meier product-limit method. RESULTS: Fifteen patients met the study criterion (male: female = 2:1). Median age at presentation was 11 years (range 3-49 years). Surgical resection was gross total in 6 (40%) and subtotal in 8 (53.33%) patients. At presentation, two patients had leptomeningeal dissemination. Radiation therapy was delivered in 11 (73.33%) patients: craniospinal irradiation in 8 (36 Gy/20 fractions/4 weeks to the craniospinal axis followed by a local boost of 20 Gy/10 fractions/2 weeks) and focal RT in 3 patients. Systemic chemotherapy (median 6 cycles; range 1-16 cycles), given in 13 (86.67%) patients, included the VAC regimen (vincristine, adriamycin, cyclophosphamide) alternating with IE (ifosfamide,etoposide). After a median follow-up of 22.6 months (mean, 24.47 months), complete response and progressive disease were noted in 8 (53.33%) and 7 (46.67%) patients, respectively. Median OS was not reached, and estimated median EFS was noted to be 4.12 years (actuarial rate of EFS at 2 years, 55.2%). CONCLUSION: Maximal safe resection followed by craniospinal irradiation and systemic chemotherapy with 6-12 cycles of an alternating regimen of VAC and IE is a reasonable treatment strategy in patients with nonpineal SPNET.

The issues and challenges with cancer biomarkers.

A biomarker is a measurable indicator used to distinguish precisely/objectively either normal biological state/pathological condition/response to a specific therapeutic intervention. The use of novel molecular biomarkers within evidence-based medicine may improve the diagnosis/treatment of disease, improve health outcomes, and reduce the disease's socio-economic impact. Presently cancer biomarkers are the backbone of therapy, with greater efficacy and better survival rates. Cancer biomarkers are extensively used to treat cancer and monitor the disease's progress, drug response, relapses, and drug resistance. The highest percent of all biomarkers explored are in the domain of cancer. Extensive research using various methods/tissues is carried out for identifying biomarkers for early detection, which has been mostly unsuccessful. The quantitative/qualitative detection of various biomarkers in different tissues should ideally be done in accordance with qualification rules laid down by the Early Detection Research Network (EDRN), Program for the Assessment of Clinical Cancer Tests (PACCT), and National Academy of Clinical Biochemistry. Many biomarkers are presently under investigation, but lacunae lie in the biomarker's sensitivity and specificity. An ideal biomarker should be quantifiable, reliable, of considerable high/low expression, correlate with the outcome progression, cost-effective, and consistent across gender and ethnic groups. Further, we also highlight that these biomarkers' application remains questionable in childhood malignancies due to the lack of reference values in the pediatric population. The development of a cancer biomarker stands very challenging due to its complexity and sensitivity/resistance to the therapy. In past decades, the cross-talks between molecular pathways have been targeted to study the nature of cancer. To generate sensitive and specific biomarkers representing the pathogenesis of specific cancer, predicting the treatment responses and outcomes would necessitate inclusion of multiple biomarkers.

MAGAT gel and EBT2 film-based dosimetry for evaluating source plugging-based treatment plan in Gamma Knife stereotactic radiosurgery.

This work illustrates a procedure to assess the overall accuracy associated with Gamma Knife treatment planning using plugging. The main role of source plugging or blocking is to create dose falloff in the junction between a target and a critical structure. We report the use of MAGAT gel dosimeter for verification of an experimental treatment plan based on plugging. The polymer gel contained in a head-sized glass container simulated all major aspects of the treatment process of Gamma Knife radiosurgery. The 3D dose distribution recorded in the gel dosimeter was read using a 1.5T MRI scanner. Scanning protocol was: CPMG pulse sequence with 8 equidistant echoes, TR = 7 s, echo step = 14 ms, pixel size = 0.5mm × 0.5mm, and slice thickness of 2 mm. Using a calibration relationship between absorbed dose and spin-spin relaxation rate (R2), we converted R2 images to dose images. Volumetric dose comparison between treatment planning system (TPS) and gel measurement was accomplished using an in-house MATLAB-based program. The isodose overlay of the measured and computed dose distribution on axial planes was in close agreement. Gamma index analysis of 3D data showed more than 94% voxel pass rate for different tolerance criteria of 3%/2 mm, 3%/1 mm and 2%/2 mm. Film dosimetry with GAFCHROMIC EBT 2 film was also performed to compare the results with the calculated TPS dose. Gamma index analysis of film measurement for the same tolerance criteria used for gel measurement evaluation showed more than 95% voxel pass rate. Verification of gamma plan calculated dose on account of shield is not part of acceptance testing of Leksell Gamma Knife (LGK). Through this study we accomplished a volumetric comparison of dose distributions measured with a polymer gel dosimeter and Leksell GammaPlan (LGP) calculations for plans using plugging. We propose gel dosimeter as a quality assurance (QA) tool for verification of plug-based planning.

Advances in Radiation Oncology: Current Status and Future Directions in India.

Radiation therapy is one of the core components of the comprehensive cancer care. Several new advancements in the radiation physics, radiation biology, and technical upgradation have led us in to a new era of radiation oncology. The access to quality radiation therapy treatment however remains a concern, and this mini-review emphasizes on these issues and also focuses on the future directions for radiation oncology in India.

Cancer immunotherapy: Recent advances and challenges.

Immunotherapy is a treatment that uses specific components of a person's immune system to fight diseases. This is usually done by stimulating or assisting one's immune system is attacking the offending agent - for instance, in the case of cancer - the target of immunotherapy will be cancer cells. Some types of immunotherapy are also called biologic therapy or biotherapy. One of the fundamental challenges that a living cell encounters are to accurately copy its genetic material to daughter cells during every single cell cycle. When this process goes haywire, genomic instability ensues, and genetic alterations ranging from nucleotide changes to chromosomal translocations and aneuploidy occur. Genomic instability arising out of DNA structural changes (indels, rearrangements, etc.,) can give rise to mutations predisposing to cancer. Cancer prevention refers to actions taken to mitigate the risk of getting cancer. The past decade has encountered an explosive rate of development of anticancer therapy ranging from standard chemotherapy to novel targeted small molecules that are nearly cancer specific, thereby reducing collateral damage. However, a new class of emerging therapy aims to train the body's defense system to fight against cancer. Termed as "cancer immunotherapy" is the new approach that has gained worldwide acceptance. It includes using antibodies that bind to and inhibit the function of proteins expressed by cancer cells or engineering and boosting the person's own T lymphocytes to target cancer. In this review, we summarized the recent advances and developments in cancer immunotherapy along with their shortcoming and challenges.

A systematic review of clinical and laboratory parameters of 3,000 COVID-19 cases.

The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical characteristics and laboratory parameters of COVID-19 patients were compiled systematically, with special reference to pregnant women in order to understand the disease course. An extensive literature search on various scientific databases for relevant manuscripts was conducted, which yielded 7 manuscripts for final analysis. The most common symptoms were fever (85%), cough (70.63%), chest tightness (37.36%), expectoration (33.27%), fatigue (32%), dyspnea (31.95%), and shortness of breath (31.19%), while hemoptysis (1.0%) was the least common. The associated comorbidities were hypertension (21.6%) and diabetes (10.0%). In terms of hematological parameters, lower total leukocyte counts were observed in 65% of cases and biochemical parameters, patients demonstrated elevated levels of albumin (53.72%), lactate dehydrogenase (45.71%), and natriuretic peptide (34.84%); however, total bilirubin was elevated in only 8% of cases. In the acute inflammatory cytokine profile, C-reactive protein (59.0%), tumor necrosis factor (58.0%), erythrocyte sedimentation rate (57.0%), interleukin-2 (IL- 2, 54.0%), and IL-6 (52.0%) levels were increased, while prolactin levels (6.5%) were minimally elevated. The recovery rate was approximately 41%, and mortality was about 6.5%. The study also concluded that the clinical symptoms of COVID-19 were similar among pregnant and non-pregnant women. There was no evidence of vertical transmission of COVID-19 infection. This review critically analyzed COVID-19 as a public health hazard in order to help policy makers, health care givers, and primary physicians to promote early diagnosis and prevention.

Low-dose radiotherapy for COVID 19: A radioimmunological perspective.

The world is fighting the onslaught of COVID 19 for the last 10 months, ever since the first case was reported in December 2019 in Wuhan, China. Now, it has spread to over 200 countries. COVID 19-associated respiratory syndrome is causing a lot of mortality and morbidity. There are reports suggesting that the complications and ARDS associated with COVID 19 is an immune response reaction. The cytokine storm associated with severe cases of COVID 19 acts as a cause of death in many sick patients. It has been shown that COVID 19 is associated with a peculiar immune profile: Decrease in CD3, CD4, CD8, natural killer cell and B-cells; Rise in interleukin (IL)-4, IL-6 and tumor necrosis factor (TNF) alpha; Decrease in IL-10; Decrease in interferon-gamma. Low-dose radiotherapy (LDRT) immunosuppressive features resulting from M2 macrophage phenotype activation, increase in IL-10, transforming growth factor beta, a decrease in IL-6, TNF alpha and an increase in CD3, CD4, and CD8 T cell counts may negate the harmful effects of cytokine release syndrome. Literature review shows that radiation was previously used to treat viral pneumonia with a good success rate. This practice was discontinued in view of the availability of effective antibiotics and antivirals. As there are no scientifically proven treatment for severe COVID 19-associated respiratory distress today, it is prudent that we understand the benefits of LDRT at this critical juncture and take rational decisions to treat the same. This article provides an radioimmunological rationale for the treatment of immune crisis mediated complications in severe cases of COVID 19.