Survival analysis in association with GST gene polymorphism and Treatment outcomes of Gemcitabine and Cisplatin/Carboplatin-based chemotherapy among patients with Gallbladder Carcinoma.

PURPOSE: Majority of the gallbladder cancer (GBC) cases are diagnosed at an advanced stage where chemotherapy alone (or in combination with other treatment methods) is mainly opted as therapeutic approach. However, success or failure of this approach largely depends on the interindividual genetic differences. Careful consideration on the genetic association could assist in the evaluation of patient's treatment response and survival rate. Hence, the present study aims to investigate the survival of patients with GBC and their treatment response to gemcitabine and cisplatin/carboplatin-based chemotherapy in association with Glutathione S-transferase (GSTs) gene polymorphism. MATERIAL AND METHODS: A total of 216 histologically confirmed cases of gallbladder cancer were recruited. A total of 180 patients were treated with gemcitabine and cisplatin/carboplatin-based chemotherapy. GSTM1, GSTT1, and GSTP1 genotypes were determined by multiplex PCR and by PCR restriction fragment length polymorphism (PCR-RFLP), respectively. The influence of genetic polymorphism on overall survival was analyzed by Kaplan-Meier method, survival rate difference was analyzed by log-rank test, and hazard ratio for mortality outcomes was estimated using Cox regression method. RESULTS: GBC patients having genotype GSTP1 (AG + GG) showed poor 3-year survival rate of 0.8% compared to 10.9% of GSTP1 (AA) genotype (χ2 = 6.456, P = 0.011). The multivariate Cox regression results showed that the death risk was significantly higher in GSTP1 (AG + GG) genotype (HR = 3.858, P = 0.050). We found no association of GSTM1 and GSTT1 gene polymorphism with the survival; however, the combined genotypes of GSM1/GSTP1, GSTT1/GSTP1, and GSTM1/GSTT1/GSTP1 were associated with survival (P = 0.053, 0.006, and 0.058, respectively). Increased death hazard was noted by the genotype combinations of GSTM1+/GSTP1AG + GG (HR = 3.484, P = 0.024), GSTM1-/GSTP1AG + GG (HR = 2.721, P = 0.014), GSTT1+/GSTP1AG + GG (HR = 20.690, P = 0.001), and GSTT1-/GSTP1AA (HR = 26.111, P < 0.0001). Our findings indicate that chemotherapy treatment response of GSTP1 (AG + GG) has 1.62-fold increased risk for progression compared to GSTP1 (AA) genotype (p = 0.018); however, none of the genotypes showed association with overall survival and death risk after chemotherapeutic treatment. CONCLUSION: We found that the presence of GSTP1 (AG + GG) genotype showed survival disadvantage and poor treatment outcomes in response to gemcitabine and cisplatin/carboplatin-based chemotherapy. This could serve as biomarker, and future research in pharmacogenomics will definitely pave the way for the development of better treatment approach for GBC.

Revolutionizing cancer treatment in India: Evaluating the unmet need, economics, and a roadmap for project implementation of particle therapy.

INTRODUCTION: This study aims to quantitatively assess eligible patients and project the demand for particle therapy facilities in India from 2020 to 2040. In addition, an economic analysis evaluates the financial feasibility of implementing this technology. The study also examines the prospective benefits and challenges of adopting this technology in India. METHODOLOGY: Cancer incidence and projected trends were analyzed for pediatric patients using the Global Childhood Cancer microsimulation model and adult patients using the Globocan data. Economic cost evaluation is performed for large-scale combined particle (carbon and proton-three room fixed-beam), large-scale proton (one gantry and two fixed-beam), and small-scale proton (one gantry) facility. RESULTS: By 2040, the estimated number of eligible patients for particle therapy is projected to reach 161,000, including approximately 14,000 pediatric cases. The demand for particle therapy facilities is projected to rise from 81 to 97 in 2020 to 121 to 146 by 2040. The capital expenditure is estimated to be only 3.7 times that of a standard photon linear accelerator over a 30-year period. Notably, the treatment cost can be reduced to USD 400 to 800 per fraction, substantially lower than that in high-income countries (USD 1000 to 3000 per fraction). CONCLUSION: This study indicates that, in the Indian scenario, all particle therapy models are cost-beneficial and feasible, with large-scale proton therapy being the most suitable. Despite challenges such as limited resources, space, a skilled workforce, referral systems, and patient affordability, it offers substantial benefits. These include the potential to treat many patients and convenient construction and operational costs. An iterative phased implementation strategy can effectively overcome these challenges, paving the way for the successful adoption of particle therapy in India. PLAIN LANGUAGE SUMMARY: In India, eligible patients benefiting from high-precision particle therapy technology projected to rise till 2040. Despite high upfront costs, our study finds the long-term feasibility of all particle therapy models, potentially offering a substantial reduction in treatment cost compared to high-income countries. Despite challenges, India can succeed with an iterative phased approach.

Clinical and Radiological Outcomes of Patients With Anterior Acetabulum Fractures Treated by the Modified Stoppa Approach.

Introduction Acetabular fractures are intra-articular fractures involving the lower extremity's weight-bearing dome. These fractures require an anatomical reduction of the fracture fragments. This aim can be accomplished by the selection of an appropriate surgical approach. This study aimed to analyze the clinical and radiological outcomes of patients with fractures in the anterior part of the acetabulum who were treated by the modified Stoppa approach. Methods This prospective observational study was conducted from April 2022 to September 2023. The inclusion criteria were: (i) age between 18 and 70 years, (ii) displaced acetabular fracture (displacement > 3 mm), (iii) within three weeks of trauma (iv) acetabular fractures with involvement of anterior column. Exclusion criteria included: (i) patients with visceral injuries requiring colostomy, (ii) pathological fracture, (iii) open fractures of the acetabulum, and (iv) neglected fracture (more than three weeks). Intraoperative data regarding surgical time, amount of blood loss, and incidence of intraoperative complications were recorded. In the postoperative period, anteroposterior X-ray and Judet views of the pelvis X-ray were obtained. Matta criteria were used to judge the quality of Fracture reduction and fixation. All the patients to be included in this study had undergone a minimum follow-up duration of six months. At the last follow-up, an assessment of the functional outcome of the affected hip by Merle d'Aubigné Hip Score and Harris Hip Score was done. Results Twenty-four patients were included in the study. The mean patient age was 36.08±11.65 years. Eighteen patients were male (75%) and six patients were female in this study. All acetabular fractures were due to high-energy trauma: road traffic accidents in 22 cases (91%) and fall from height in two cases (9%). According to Judet & Letournel's classification, there were 13 T-type fractures, five transverse fractures, and six associated both column fractures. The mean duration of surgery was 152.08 ±29.19 minutes, and the mean intraoperative blood loss was 277.08±85.95 ml. Intraoperatively one unit of blood transfusion was done in most cases. There were intraoperative complications of rent in the external iliac vein in two patients. Postoperative X-rays showed anatomical reduction in 17 cases, imperfect reduction in five cases, and poor reduction in two cases. Functional outcome of the hip by Merle d'Aubigné Hip Score was very good in 15, good in four, fair in three, and poor in two patients. Similar functional outcomes were obtained with the Harris Hip Score. Conclusion The results of the current study demonstrated that the modified Stoppa approach allows good visualization of the pelvic brim, quadrilateral surface, and posterior column. Lesser experienced orthopedic surgeons should utilize this approach to get good radiological and functional outcomes.

Yield of residues produced in 6Li reaction on Ta: A comparative analysis for 183Os.

The present work reports an analysis of the production yield of residues from the 6Li ＋ 181Ta reaction in a low-energy regime. The experimental yield of 183gOs, 183mOs, 182Os, 183Re, 183Ta, 182m2Ta, and 180Ta have been measured in the 27-43 MeV energy window and compared with equilibrium and pre-equilibrium model calculations under the framework of the nuclear reaction model code, EMPIRE-3.2.2. The maximum yield measured for 183gOs is 80.5 ± 14.9 MBq/C at 40.2 MeV energy in a 2.3 mg/cm2 thick Ta target corresponding to a cross-section of 360.1 ± 34.4 mb from the 181Ta(6Li,4n)183Os reaction and that for 183Re is 1.36 ± 0.4 MBq/C at 42.75 MeV in a 2.4 mg/cm2 thick target. The model estimations agree well with the experimental yields of 183gOs and 183Re. The possible production of stable residues has been estimated using the model-predicted cross-section in the studied energy range. A comparison of production yields of 183m,gOs from 6Li- and 7Li-induced reaction on Ta demonstrates the 6Li reaction as a better candidate. Thick target yields have been evaluated for Os and Re isotopes.

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders.

Stem cells' self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells' self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.

Metabolic Pathways, Enzymes, and Metabolites: Opportunities in Cancer Therapy.

Metabolic reprogramming enables cancer cells to proliferate and produce tumor biomass under a nutrient-deficient microenvironment and the stress of metabolic waste. A cancer cell adeptly undergoes a variety of adaptations in metabolic pathways and differential expression of metabolic enzyme genes. Metabolic adaptation is mainly determined by the physiological demands of the cancer cell of origin and the host tissue. Numerous metabolic regulators that assist cancer cell proliferation include uncontrolled anabolism/catabolism of glucose metabolism, fatty acids, amino acids metabolism, nucleotide metabolism, tumor suppressor genes, microRNAs, and many regulatory enzymes and genes. Using this paradigm, we review the current understanding of metabolic reprogramming in tumors and discuss the new strategies of cancer metabolomics that can be tapped into for cancer therapeutics.

Higher order genes interaction in DNA repair and cytokine genes polymorphism and risk to lung cancer in North Indians.

Context: Lung cancer pathological process involves cumulative effects exerted by gene polymorphism(s), epigenetic modifications, and alterations in DNA repair machinery. Further, DNA damage due to oxidative stress, chronic inflammation, and the interplay between genetic and environmental factors is also an etiologic milieu of this malignant disease. Aims: The present study aims to assess the prognostic value of DNA repair, cytokines, and GST gene polymorphism in lung cancer patients who had not received any neoadjuvant therapy. Materials and Methods: In this case-control study, 127 cases and 120 controls were enrolled. DNA from the blood samples of both patients and controls was used to genotype XRCC1Arg399Gln, XPDLys751Gln, and interleukin-1 (IL-1ß) genes by polymerase chain reaction (PCR)-restriction fragment length polymorphism method, whereas multiplex PCR was performed to genotype GSTT1 and GSTM1. Results: Binary logistic regression analysis showed that XRCC1Arg399Gln-mutant genotype (Gln/Gln, odds ratio [OR] = 4.6, 95% confidence interval [CI]: 2.2-9.6) and GSTT1 null (OR = 2.7, 95% CI: 1.6-4.5) were linked to cancer susceptibility. Generalized multidimensional reduction analysis of higher order gene-gene interaction using cross-validation testing (CVT) accuracy showed that GSTT1 (CVT 0.62, P = 0.001), XPD751 and IL-1ß (CVT 0.6, P = 0.001), and XRCC1399, XPD751, and interleukin-1 receptor antagonists (IL-1RN) (CVT 0.98, P = 0.001) were single-, two-, and three-factor best model predicted, respectively, for lung cancer risk. Classification and regression tree analysis results showed that terminal nodes which contain XRCC1399-mutant genotype (AA) had increased the risk to lung cancer. Conclusion: The present study demonstrated that XRCC1399 (Gln/Gln), GSTT1, and IL-1RN allele I, I/II served as the risk genotypes. These genes could serve as the biomarkers to predict lung cancer risk.

The long-term impact of acute renal failure after aortic arch replacement for acute type A aortic dissection.

OBJECTIVE: To determine the long-term impact of developing acute renal failure (ARF) on survival after open aortic arch reconstruction for acute type A aortic dissection (ATAAD). METHODS: This was an observational study of consecutive aortic surgeries from 2007 to 2021. Patients with ATAAD were identified via a prospectively maintained institutional database and were stratified by the presence or absence of postoperative ARF (by RIFLE criteria). Kaplan-Meier survival estimation and multivariable Cox regression analysis were performed. RESULTS: A total of 601 patients undergoing open surgery for ATAAD were identified, of which 516 (85.9%) did not develop postoperative ARF, while 85 (14.1%) developed ARF, with a median follow-up time of 4.6 years (1.6, 7.9). Baseline characteristics were similar across each group, except for higher rates of branch vessel malperfusion and lower preoperative ejection fraction in the ARF group. Patients with ARF underwent more total arch replacement and elephant trunk procedures, with longer cardiopulmonary bypass and circulatory arrest times than patients without ARF. ARF was associated with worse short-term outcomes, including increased in-hospital mortality, prolonged mechanical ventilation, higher rates of sepsis, more blood transfusions, and longer length of hospital stay. Unadjusted Kaplan-Meier survival estimates were significantly lower in the ARF group, compared to the group without ARF (p < .001, log-rank test). After multivariable adjustment, the development of postoperative ARF was significantly associated with an increased hazard of death over the study's follow-up time-period (hazard ratio: 2.74, 95% confidence interval: 1.95, 3.86, p < .001). CONCLUSIONS: ARF is a highly morbid postoperative event that may adversely impact long-term survival after aortic surgery.

Is hepatocellular carcinoma complicated with portal vein tumor thrombosis potentially curable by radiotherapy in the form of stereotactic body radiation therapy?

PURPOSE: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal. Despite best treatment and care, the patients with this malignancy only showed 2.7-4 months of overall survival. It is debatable whether liver transplantation helps PVTT sufferers. The effectiveness of radiation therapy in treating HCC patients with PVTT should not be undervalued. By limiting the high dosage region to a small planning target volume, stereotactic radiation delivery has shifted toward hypofractionation, limiting the radiation exposure to healthy organs and tissues. Stereotactic body radiotherapy (SBRT) has a local control rate of 75-100%, depending on the treatment. The major limitation in SBRT for hepatocellular carcinoma with PVTT is the paucity of prospective evidence for longer periods beyond the first two years after treatment. More prospective studies/randomized clinical trials with a longer follow-up, larger sample size, and adequate statistical power are the dire need of the present situation to ascertain the curative effect of SBRT as primary therapy for advanced HCC with PVTT. CONCLUSION: SBRT can improve survival, particularly for patients receiving multidisciplinary treatment. This review sums up our most current understanding of how radiation therapy, notably SBRT, can be used to treat hepatocellular carcinoma when combined with PVTT. Recent research has led us to believe that irradiation in the form of SBRT may cure hepatocellular carcinoma complicated by PVTT.

Is Regular Probiotic Practice Safe for Management of Sepsis?

For decades, the gut has been thought to play an important role in sepsis pathogenesis. Sepsis is a serious life-threatening, chronic condition of an infection caused by dysregulated host immune response in most of the intensive care unit patients. Probiotics have dual roles in polymicrobial sepsis i.e. probiotics may induce sepsis in many cases and may prevent its prognosis in many cases. Experimental evidence from both pre-clinical and clinical studies have demonstrated that probiotic therapy ameliorates various inflammatory mediators such as tumor necrosis factor, interleukin-10 (IL-10), IL-6, etc., in septicemia. In addition, probiotic use was also found to reduce the severity of pathological conditions associated with irritable bowel disorder and prevent development of endocarditis in septicemia. On contrary, probiotic therapy in neonatal and athymic adult mice fail to provide any beneficial effects on mortality and sepsis-induced inflammation. Importantly, in few clinical trials probiotic use was found to aggravate sepsis by promoting inflammatory cascade rather than suppressing it. This review discusses various studies regarding the beneficial or harmful effects associated with probiotic therapy in sepsis.

Endogenous T1ρ cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. METHODS: HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15-20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE --); otherwise, the image was labeled equivocal (LGE + -). RESULTS: In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman's rho = 0.61, p < 1e-5) and T1ρ percent enhancement area (Spearman's rho = 0.48, p < 0.001e-3) correlated with LGE percent enhancement area. T1 and T1ρ percent enhancement areas were also correlated (Spearman's rho = 0.28, p = 0.047). For both T1 and T1ρ, HCM patients demonstrated significantly longer relaxation times compared to controls in each LGE category (p < 0.001 for all). HCM patients also showed significantly higher ECV compared to controls in each LGE category (p < 0.01 for all), and LGE -- slices had lower ECV than LGE + + (p = 0.01). CONCLUSIONS: Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients.

Efficacy and toxicity of SBRT in advanced hepatocellular carcinoma with portal vein tumor thrombosis - a retrospective study.

BACKGROUND: The purpose of this study was to evaluate the outcome of stereotactic body radiation therapy (SBRT) in patients of unresectable hepatocellular carcinoma (HCC ) complicated with portal vein tumor thrombosis (PVTT) who are also unsuitable for other locoregional therapies. MATERIALS AND METHODS: Between May 2018 and January 2020, twenty-nine patients with advanced unresectable HCC s, treated with SBRT, were enrolled in this retrospective audit. Patients of Child status A5-B7 and with healthy liver volume, ≥ 700 ccs were treated. Local control (LC), overall survival (OS), progression-free survival (PFS), PVTT opening rate, and effect of prognostic factors were analyzed. RESULTS: The median tumor diameter was 8.6 cm (5-14), and the median tumor volume was 275 cc (151-1196). The median SBRT dose prescription was 48 Gy in 6 fractions (32-50 Gy in 5-6 fractions). The median follow up was eight months (1-20), 1-year local control, progression-free survival, and overall survival were 95%, 53.4%, and 60%, respectively. Overall rate of grade III toxicity was less than 5%, and the most common toxicity was lymphocytopenia. Tumors of more than 350cc had worse OS and PFS when compared to tumors < 350 cc (median OS and PFS of tumors > 350 cc was 4 months and two months, p = .01 and .003, respectively). A total of fifteen patients progressed with the disease and the median time to progression was two months [1-4]. CONCLUSION: SBRT is safe and provides excellent local control in advanced HCC complicated with PVTT. The out of field failure pattern and time to failure in these patients highlights the need for adjuvant systemic therapy after completion of local treatment. Our data warrant the need for multimodality trials in this patient cohort.

Dosimetric impact of contrast-enhanced 4d computed tomography for stereotactic body radiation therapy of hepatocelluar carcinoma.

BACKGROUND: A purpose of the study was to investigate the dosimetric impact of contrast media on dose calculation using average 4D contrast-enhanced computed tomography (4D-CECT) and delayed 4D-CT (d4D-CT) images caused by CT simulation contrast agents for stereotactic body radiation therapy (SBRT) of liver cases. MATERIALS AND METHODS: Fifteen patients of liver SBRT treated using the volumetric modulated arc therapy (VMAT) technique were selected retrospectively. 4D-CECT, and d4D-CT were acquired with the Anzai gating system and GE CT. For all patients, gross target volume (GTV) was contoured on the ten phases after rigid registration of both the contrast and delayed scans and merged to generate internal target volume (ITV) on average CT images. Region of interest (ROI) was drawn on contrast images and then copied to the delayed images after rigid registration of two average CT datasets. The treatment plans were generated for contrast enhanced average CT, delayed average CT and contrast enhanced average CT with electron density of the heart overridden. RESULTS: No significant dosimetric difference was observed in plans parameters (mean HU value of the liver, total monitor units, total control points, degree of modulation and average segment area) except mean HU value of the aorta amongst the three arms. All the OARs were evaluated and resulted in statistically insignificant variation (p > 0.05) using one way ANOVA analysis. CONCLUSIONS: Contrast enhanced 4D-CT is advantageous in accurate delineation of tumors and assessing accurate ITV. The treatment plans generated on average 4D-CECT and average d4D-CT have a clinically insignificant effect on dosimetric parameters.

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.

Identifying Patterns of Failure and Risk Factors for Recurrence in Patients of Paratesticular Sarcomas: Protocol of a Systematic Review and Meta-Analysis.

INTRODUCTION: Para testicular sarcomas are rare mesenchymal tumors that affect patients of all ages. Unlike other sites of sarcoma, they tend to be of lower grade and have a higher propensity for lymphatic spread. Management is hampered by the small number of patients who differ in terms of tumor grade and histology. Current treatment approaches are based on case reports, small case series and literature reviews, resulting in a number of unresolved issues. The consensus on the type of surgery and adjuvant treatment is yet to be determined. The local relapse rates in the scrotum and groin after orchidectomy comes out to be 25%-37%, indicating the need for either aggressive surgery or adjuvant treatment. There is a paucity of data identifying the patterns of failure and risk factors for recurrence, which will help clinicians tailor appropriate treatment. METHODS: We aim to perform a systematic review and meta-analysis of the available data in the last 50 years in a methodologically rigorous and transparent manner to identify patterns of failure and high-risk factors for recurrence. The protocol is prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA-P) 2015 guidelines. The protocol is registered in the International Prospective Register of Systematic Reviews (CRD42021237134). HIGHLIGHTS: Para testicular sarcomas are rare mesenchymal tumors that affects patients of all ages. Current treatment approaches are based on case reports, small case series and literature reviews, resulting in a number of unresolved issues. A systemic review was performed in 2013 based on survival rates, prognostic factors, and relapse sites on paratesticular sarcomas. However, it lacks a comprehensive review that can guide radiation oncologists to select in which patient's postoperative radiotherapy is warranted and define the target volume based on histopathological type, stage, and grade of the tumor. After 2013, new case series with improved methodology and sample size are published, which adds new information to the literature. In one case series, 22 patients with spermatic cord sarcoma were discussed, while in another study, long-term outcome analysis of 51 patients was discussed, and another study discussed eight patients.

Comparison of treatment response in cervical carcinoma patients infected with human papillomavirus 16 and human papillomavirus 18 who are treated with chemoradiation.

OBJECTIVES: The primary objective of this study was to compare the treatment response of cervical carcinoma patients infected with human papillomavirus (HPV) 16 and HPV 18 who are treated with chemoradiation. MATERIALS AND METHODS: Ninety-six biopsy-proven cervical cancer patients, suitable for curative treatment with definitive radio-chemotherapy with International Federation of Gynecology and Obstetrics Stage IB2-IIIB, were included in this prospective study. HPV testing was done using TRUPCR® HPV 16 and 18 real-time polymerase chain reaction kit. All the patients received a dose of 83-90 Gy total equieffective dose to the high risk clinical target volume(HRCTV) using tele- and brachytherapy. RESULTS: Of the 96 patients, 79 (82.3%) patients were positive for HPV DNA. Seventy-three patients showed HPV genotype 16 positivity and six patients were positive for genotype 18. The response was correlated with HPV genotype. There was a statistically significant increase in complete radiological response in HPV 16 compared to HPV 18 and negative groups at 3 months, 80.8%, 50%, and 52.9%, respectively (χ2 = 36.5, P < 0.001). There was also a statistically significant increase in clinical response at 3 months in HPV 16 group compared to HPV 18 and negative groups, 87.5%, 50%, and 50%, respectively (χ2 = 29.9, P < 0.001). The age, volume of the disease, overall treatment time, average hemoglobin level, and the number of blood transfusions did not have any correlation. CONCLUSION: HPV genotype 16 positivity shows higher complete response in cervical carcinoma patients treated with definitive chemoradiation compared to HPV 18 genotype. Further HPV genotyping could potentially help stratify cervical cancer patients for more effective therapeutic regimens.

Impact of dose heterogeneity in target on TCP and NTCP for various radiobiological models in liver SBRT: different isodose prescription strategy.

INTRODUCTION: The impact of dose heterogeneity within the tumor on TCP and NTCP was studied using various radiobiological models. The effect of the degree of heterogeneity index (HI) on TCP was also analyzed. MATERIALS AND METHODS: Thirty-seven pre-treated liver SBRT cases were included in this study. Two different kinds of treatment techniques were employed. In both arms, the prescribed dose was received by 95% of the PTV. Initially, the inhomogeneous treatment plans (IHTP) were made in which the spatial change of dose within the PTV was high and the maximum dose within the PTV can go up to 160%. Subsequently, in another arm, homogeneous treatment plans (HTP) were generated in which PTV was covered with the same prescription isodose and the maximum dose can go up to 120%. As per RTOG 1112, all organs at risk (OAR's) were considered while optimization of the treatment plans. TCP was calculated using the Niemierko and Poisson model. NTCP was calculated using the Niemierko and LKB fractionated model. RESULTS: For the IHTP, TCP was decreasing as 'a' value decreased in the Niemierko model whereas, for HTP, TCP was found to be the same. NTCP of the normal liver was less in IHTP as compared to HTP, and the Niemierko model overestimates the NTCP as compared to LKB fractionated model. NTCP for all other OAR's was <1% in both kinds of treatment plans. CONCLUSION: IHTP is found to be clinically better than HTP because NTCP of the normal liver was significantly less and TCP was more for certain 'a' values of the Niemierko model and the Poisson model. There is not any effect of HI on TCP was observed. Advances in knowledge: IHTP could be used clinically because of the dose-escalation and subsequently, leads to an increase in the TCP.

Evaluation and evolution of apparent diffusion coefficient (ADC) in image-guided adaptive brachytherapy (IGABT) for cervical cancer.

PURPOSE: Image-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy. METHODS AND MATERIALS: Thirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge. RESULTS: The measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10-3 mm2/s, respectively. The TBadc (ADC at brachytherapy, center), TEBadc (tumor edge ADC at brachytherapy), and TE1cmBadc (1 cm from edge brachytherapy) were 1.2, 1.8, and 2.3 × 10-3 mm2/s, respectively, p-value <0.00001. No abnormal ADC was present outside the high-risk clinical target volume contours. CONCLUSION: MRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.

A prospective comparative dosimetric study between diffusion weighted MRI (DWI) & T2-weighted MRI (T2W) for target delineation and planning in cervical cancer brachytherapy.

AIM: To evaluate the difference between GTVBT (Gross Tumor Volume at Brachytherapy) and HR CTV (High Risk Clinical Tumor Volume) delineated with DWI and T2W MRI. To evaluate doses to organs at risk and targets from plans generated using T2W and DWI. BACKGROUND: Functional imaging with DWI can improve cervical tumor distinction as it is more sensitive than T2W MRI even in detecting parametrial invasion. This study does a dosimetric comparison between a T2W and DWI based plan. METHODS: Fifty carcinoma cervix patients were subjected to MRI based brachytherapy. T2W and a diffusion weighted sequence were acquired. Target delineation and brachytherapy planning was done on both T2W and DWI. Standard DVH parameters were recorded and the treatment was given using the plan generated from T2W images. RESULTS: GTVBT and HRCTV contours on DWI were different when compared with T2W. Mean GTVBT volume on T2W and DWI was 5.25 and 5.23, respectively (p value 0.8). Mean HRCTV on T2W and DWI was 28.3 and 27 cc, respectively (p value 0.003). Planning on the above volumes resulted in a superior coverage in terms of HRCTV D90 and D100 for DWI based plan, HRCTV D90 - 735.1 and 741 cGy for T2W and DWI, respectively (p value 0.006), HRCTV D100 - 441.05 and 444.5 for T2W and DWI plans, respectively (p value = 0.006). Doses to the OAR were not significantly increased. CONCLUSION: GEC ESTRO based contouring guidelines cover all the functionally abnormal areas on DWI. DWI should only be used as a supplement to T2W for contouring target volumes.