Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Accelerated hypofractionated chemoradiation for locally advanced head and neck cancer during COVID 19 pandemic: A tertiary care experience.

PURPOSE: To assess the role of Accelerated Hypofractionated Chemoradiation for Locally Advanced Head & Neck squamous cell cancer (HNSCC) during COVID 19 pandemic. MATERIALS AND METHODS: Previously untreated 20 patients with locally advanced HNSCC (Oral cavity/oropharynx/larynx/hypopharynx) were treated with definitive hypofractionated radiotherapy of 60Gy in 25 fractions with concurrent cisplatin @35 mg/m2 once weekly for 5 weeks from March 2020 to November 2021. The patients were treated on 6MV LINAC with Volumetric modulated arc therapy (VMAT) by the Sequential boost technique and concurrent chemotherapy @35 mg/m2. All the patients received 48Gy in 20 fractions to low-risk volume (CTV LR) in Phase I followed by 12Gy in 5 fractions boost to High-risk volume (CTV HR) in Phase II. The organs at risk (OARs) were contoured and appropriate constraints were given considering the hypofractionated regimen. RESULTS: Out of 20 patients, most of the patients were Stage IV (15;75%) & stage III 20%, out of which (55%) 11 were of the oral cavity, (40%) 8 were of the oropharynx, and (5%) 1 of larynx. All patients were treated with 60Gy/25#/5 weeks with the majority of the patients (17;85%) completing their treatment in less than 45 days. The Median follow-up was of 214 days. The locoregional control at 6 Months was 55%. Maximum acute toxicity was grade 3 mucositis which was observed in 18 (90%) patients. Ryle's tube feeding was needed in 11 (55%) patient. Out of 20 patients, 5 patients did not receive concurrent chemotherapy, and 8 (40%) patients received all 5 cycles of chemotherapy. 7, 35% of the patients could not complete all 5 cycles of concurrent chemotherapy due to grade 3 mucositis. CONCLUSION: During a pandemic crisis with limited manpower & technical resources accelerated hypofractionated radiotherapy with concurrent chemotherapy can be considered a feasible therapeutic option for HNSCC which can significantly reduce the overall Treatment Time (OTT) with comparable local control and manageable toxicities.

Assessment of toxicity, genotoxicity and oxidative stress in Fejervarya limnocharis exposed to tributyltin.

Tributyltin (TBT) is widely used in various commercial applications due to its biocidal properties. Toxicological and genotoxicological data on TBT exposure to amphibians is insufficient. Our study aimed to determine the acute toxicity and genotoxic potential of TBT in Fejervarya limnocharis tadpoles. Furthermore, oxidative stress was also investigated in TBT-treated tadpoles. Tadpoles of Gosner stage (26-30) were screened and subjected to increasing concentrations of TBT (0, 3, 7, 11, 15, 19, 23 µg/L) for determining the LC50 values for 24 h, 48 h, 72 h, and 96 h. LC50 values of TBT for 24 h, 48 h, 72 h, and 96 h were found to be 19.45, 15.07, 13.12, and 11.84 µg/L respectively. Based on the 96 h LC50 value (11.84 µg/L), tadpoles were exposed to different sub-lethal concentrations of TBT for the evaluation of its genotoxic potential and effects on oxidative balance. The role of TBT on survivability, growth, and time to metamorphosis was also assessed. TBT exposure significantly altered the life history traits measured, increased mortality, and delayed the time taken to metamorphosis. Results indicated significant induction of micronucleus (MN, p < 0.001) and other erythrocytic nuclear aberrations (ENA, p < 0.01) in the TBT-treated groups. Significant alterations in comet parameters and oxidative balance were also observed in the treated groups. The present study findings might add to the cause of the gradual population decline seen in the amphibians. This study also demonstrates the alteration of the life-history traits, oxidative balance, and DNA damage upon TBT exposure which can have long-term consequences for the anuran amphibian F. limnocharis.

A Computational Exploration of Exohedrally Transition Metal Doped Si94- Superatom Based Magnetic MSi9M' Clusters (M, M' = Sc(II) to Cu(II)).

Nanosized clusters are drawing immense attention of the scientific community due to their size and composition dependent tunability of physical and chemical properties. Silicon nanoclusters are especially important because of their abundance and ample utility in the domains of electronics and semiconductor industry. Zintl phases of Si offer an excellent opportunity in the domain of nanocluster research owing to their superior stability and multifarious possibilities of tunability of electronic properties through doping with other elements. Doping silicon clusters with transition elements is a prevalent strategy to induce magnetic properties in such clusters. Although doping silicon clusters with single transition metal atoms can induce significant magnetism in nanoclusters, the dominant covalent interaction between silicon and the transition metal causes the magnetic moment to quench. The rational strategy of inducing a sustainable magnetic moment can be to introduce ferromagnetic interaction between two sites carrying nonvanishing magnetic moments. In the present work, such a possibility is explored in terms of the stability of the clusters and corresponding magnetic exchange coupling in them. The Si94-superatomic cluster is doped with two transition metal atoms exohedrally and the neutral clusters designed thereby are investigated computationally if they reduce or reinforce the high stability of the superatom and substantiate the possibility of obtaining nanosized magnetic units as building blocks of tunable materials for various applications.

Mitigating the Public Health Issues Caused by the Filarial Vector, Culex quinquefasciatus (Diptera: Culicidae) Through Phytocontrol and Larval Source Marker Management.

Failure of conventional mosquito control strategies to curb the population of vectors have made the humans vulnerable to serious medical problems transmitted by them. This effect has been compounded by global climate change enabling the mosquitoes to cross geographical boundaries and cause trouble in regions where they were initially not found. As such, the scientific community has been compelled to devise alternative and innovative strategies of mosquito control that can be integrated with the conventional practices to implement multi-phasic approach of vector management. Culex quinquefasciatus is one such mosquito species that is reported to be one of the primary vectors of lymphatic filariasis and many other diseases of global health concern. However, not much is known about its breeding habitat ecology and microbial properties that have enabled the species to achieve reproductive success in urbanized habitats. The current investigation was carried out at Digha, West Bengal, India. The region, despite being endemic for lymphatic filariasis, has rarely been explored for its mosquito diversity and/or their breeding habitat characteristics. Therefore, these were attempted. For survey and sampling, seven villages were chosen, namely, Duttapur, Jatimati, Champabani, Padima, Gobindabasan, Bhagibaharampur and Palsandapur. The study showed that Cx. quinquefasciatus is the dominant mosquito species at the sampling sites with the highest density of their larvae being recorded from man-made structures like drains and pools close to human habitations and livestock. The study was, therefore, restricted to Cx. quinquefasciatus. Seasonal abundance showed that they were most prevalent in the monsoon followed by summer. The physicochemical characterization showed their larvae to prefer almost neutral pH (6.9 to 7.3), low chloride concentration (98 to 258 ppm) and turbidity. As far as other parameters are concerned, they were tolerant towards a wide range allowing them to adapt varied habitats in the study areas. The bacterial profiling of their natural habitat waters revealed the presence of Paenibacillus nanensis DGX1(OQ690670), Bacillus cereus DGX2(OQ690675), Bacillus sp. DGX3(OQ690700) and Escherichia coli DGX4(OQ690701). Bacillus cereus was found to have high oviposition attractant properties in oviposition assays. Bacillus cereus was also obtained from the midgut of third instar larvae indicating that they had entered from the surrounding medium and colonized the larval gut. Subsequent tests exhibited the roles of B. cereus in larval development. Numerous plant products have been reported either as insecticides for killing larvae or adult mosquitoes or as repellents for mosquito biting and the best alternatives for mosquito control. Larvicidal potential of emulsified neem oil formulation against the field collected 3rd instar larvae of Culex quinquefasciatus mosquito under laboratory conditions was also evaluated. The information thus obtained can be pooled to generate larval source markers and larval source management practices by altering their habitats that cannot be removed. Furthermore, the time of implementation of these strategies can also be planned.

Adoption in England: past and present challenges.

Over the last century, changes in legislation, social constructs and the perceptions of what family life 'should' look like have significantly transformed the process of adoption in England. The role of adoption has shifted from providing orphaned children a stable new home to today's regulated process mainly supporting children who have suffered early physical or social adversity. This provides significant challenges to adopters, paediatricians, child psychiatrists and teachers who can only support adopted children by understanding their needs.

Evaluation of survival outcome and prognostic factors for oral cavity cancer treated with volumetric arc therapy.

PURPOSE: This study aimed to evaluate the survival outcomes and identify prognostic factors for patients with oral cavity cancer (OCC) who underwent adjuvant treatment with volumetric arc therapy (VMAT) using simultaneous integrated boost (SIB). METHODS: Data was collected for post-operated patients of carcinoma of oral cavity who received adjuvant VMAT with SIB between June 2018 and December 2022. The data was entered and analyzed using SPSS software version 20.0. Survival rates were estimated using Kaplan Meier method. To determine survival difference between the groups, log rank test was used. Multivariate analyses were performed with Cox proportional hazard model and p value < 0.05 was considered as significant. RESULTS: A total of 178 patients were included in the study. The median follow-up period was 26 months (range 3-56 months). The 3-year OS, DFS, and LRC rates were 78% (95% CI 77-79%), 76% (95% CI 74-77%), and 81% (95% CI 80-82%), respectively. Univariate analysis identified age ≥ 50 years, lymph node involvement, extracapsular extension (ECE), and N2-N3 disease as significant adverse prognostic factors for OS, DFS, and LRC. Multivariate analysis confirmed age ≥ 50 years and nodal involvement as independent predictors of worse OS, DFS, and LRC. Additionally, ECE independently affected OS and DFS. CONCLUSION: Adjuvant treatment with VMAT using SIBin patients with OCC is effective. Age and nodal involvement had significant impact on LRC, DFSand OS while ECE on DFSand OS.

Cytotoxicity and genotoxicity of tributyltin in the early embryonic chick, Gallus gallus domesticus.

Tributyltin (TBT) is used in many commercial applications, including pesticides and antifouling paints, due to its biocidal properties. We examined the cytotoxicity and genotoxicity of TBT in the early chick embryo (Gallus gallus domesticus). Chick embryos (11 days) were treated with various doses of TBT to measure LD50 values for 24, 48, and 72 h exposures, which were determined to be 110, 54, and 18 µg/egg, respectively. The embryos were exposed to sub-lethal doses of TBT for evaluation of cytotoxicity and genotoxicity. An increase in the incidence of micronuclei (MN) was observed but it was not statistically significant. Induction of other nuclear abnormalities (ONA) after 72 h TBT exposure was significant. A significant increase in comet assay tail DNA content was also detected in TBT-exposed embryos. Cytotoxicity was also evidenced by alteration in the polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) ratio and by an increase in the erythroblast population in treated organisms. The cytotoxicity and genotoxicity of TBT may have long-term complications in later stages of the life cycle.

Chitosan-g-estrone Nanoparticles of Palbociclib Vanished Hypoxic Breast Tumor after Targeted Delivery: Development and Ultrasound/Photoacoustic Imaging.

Breast cancer is the leading cause of death among women globally. Approximately 80% of all breast cancers diagnosed are overexpressed with estrogen receptors (ERs). In this study, we have developed an estrone (Egen)-grafted chitosan-based polymeric nanocarrier for the targeted delivery of palbociclib (PLB) to breast cancer. The nanoparticles (NPs) were prepared by solvent evaporation using the ionic gelation method and characterized for particle size, zeta potential, polydispersity, surface morphology, surface chemistry, drug entrapment efficiency, cytotoxicity assay, cellular uptake, and apoptosis study. The developed PLB-CS NPs and PLB-CS-g-Egen NPs had a particle size of 116.3 ± 1.53 nm and 141.6 ± 1.97 nm, respectively. The zeta potential of PLB-CS NPs and PLB-CS-g-Egen NPs was found to be 18.70 ± 0.416 mV and 12.45 ± 0.574 mV, respectively. The morphological analysis demonstrated that all NPs were spherical in shape and had a smooth surface. An in vitro cytotoxicity assay was performed in estrogen receptor (ER)-expressing MCF7 cells and T47D cells, which suggested that targeted NPs were 57.34- and 30.32-fold more cytotoxic compared to the pure PLB, respectively. Additionally, cell cycle analysis confirmed that cell cycle progression from the G1 into S phase was blocked more efficiently by targeted NPs compared to nontargeted NPs and PLB in MCF7 cells. In vivo pharmacokinetic studies demonstrated that entrapment of the PLB in the NPs improved the half-life and bioavailability by ∼2-3-fold. Further, ultrasound and photoacoustic imaging of DMBA induced breast cancer in the Sprague-Dawley (SD) rat showed that targeted NPs completely vanished breast tumor, reduced hypoxic tumor volume, and suppressed tumor angiogenesis more efficiently compared to the nontargeted NPs and free PLB. Further, in vitro hemocompatibility and histopathology studies suggested that NPs were biocompatible and safe for clinical use.

Survival outcome and prognostic factors post inadvertent hysterectomy in carcinoma cervix treated with salvage chemo-radiation.

INTRODUCTION: The standard of care for treating early invasive cervical cancer is radical hysterectomy or radiation alone while chemo-radiation is a definitive treatment for advanced disease. Occasionally, a simple hysterectomy is performed in the cancer cervix and these patients merit adjuvant treatment in view of the high chances of loco-regional recurrences. The aim of the study was to analyze the survival outcome of these patients treated with salvage chemo-radiotherapy and also to determine the prognostic factors affecting survival. MATERIALS AND METHODS: The medical records of all patients with cervical cancer post simple hysterectomy outside and who received salvage treatment in our department between 2014 and 2020 were retrieved. The data regarding clinical, treatment details and survival were analyzed. RESULTS: A total of 198 patients were included. Median follow-up duration was 45.5 months. Gross disease and lymphadenopathy were seen in 60% and 28% patients, respectively. The 5-year progression-free survival(PFS) and overall survival(OS) was 75% and 76%, respectively. Concurrent chemotherapy alone or in combination with induction chemotherapy using three-drug regimens showed better survival compared to those treated by radiation alone. On multivariate analysis, factors found to be adversely affecting OS and PFS were lymph node (LN) size of more than 2 cm, non-squamous histology, overall treatment time(OTT) of more than 12 weeks and use of non three-drug chemotherapy regimen. CONCLUSION: Subtotal hysterectomy results in a higher incidence of local recurrence of disease. Factors that impair the outcome in this sub-group of patients are gross lymphadenopathy, non-squamous histology and prolong OTT.

Areca nut and smokeless tobacco exposure induces micronucleus, other nuclear abnormalities and cytotoxicity in early chick embryo.

Areca nut (AN) and smokeless tobacco (SLT) are indiscriminately consumed among the populations of Southeast and South Asian countries, even by women during the gestational period. This study aimed to investigate the genotoxic and cytotoxic potentials of AN and Sadagura (SG), a unique homemade SLT preparation, alone and in combination in early chick embryos. Fertile white leghorn chicken eggs were randomly divided into five treatment groups: vehicle control, positive control (Mitomycin C, 20 µg/egg), AN, SG, and AN+SG. AN, SG, and AN+SG were given at dosages of 0.125, 0.25, and 0.5 mg/egg. The hen's egg test for micronucleus induction (HET-MN) was performed in chick embryos to evaluate the genotoxic potential of the test agents. Furthermore, the cytotoxic potential was assessed by studying erythroblast cell populations and the polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs) ratio. Our results indicated a significant increase (p < .001) in MN frequency and other nuclear abnormalities, suggesting the potential of AN and SG to cause genotoxicity. Also, AN and SG exposure alone and in combination considerably altered the erythroblast cell population (%) and the PCE to NCE ratio in all the treatment periods. Our findings established the genotoxic and cytotoxic potential of both AN and SG alone and in combination during early embryonic development in the chick embryo.

Neem-based products as potential eco-friendly mosquito control agents over conventional eco-toxic chemical pesticides-A review.

Mosquitoes cause serious health hazards for millions of people across the globe by acting as vectors of deadly communicable diseases like malaria, filariasis, dengue and yellow fever. Use of conventional chemical insecticides to control mosquito vectors has led to the development of biological resistance in them along with adverse environmental consequences. In this light, the recent years have witnessed enormous efforts of researchers to develop eco-friendly and cost-effective alternatives with special emphasis on plant-derived mosquitocidal compounds. Neem oil, derived from neem seeds (Azadirachta indica A. Juss, Meliaceae), has been proved to be an excellent candidate against a wide range of vectors of medical and veterinary importance including mosquitoes. It is environment-friendly, and target-specific at the same time. The active ingredients of neem oil include limonoids like azadirachtin A, nimbin, salannin and numerous other substances that are still waiting to be discovered. Of these, azadirachtin has been shown to be very effective and is mainly responsible for its toxic effects. The quality of the neem oil depends on its azadirachtin content which, in turn, depends on its manufacturing process. Neem oil can be used directly or as nanoemulsions or nanoparticles or even in the form of effervescent tablets. When added to natural breeding habitat waters they exert their mosquitocidal effects by acting as ovicides, larvicides, pupicides and/or oviposition repellents. The effects are generated by impairing the physiological pathways of the immature stages of mosquitoes or directly by causing physical deformities that impede their development. Neem oil when used directly has certain disadvantages mainly related to its disintegration under atmospheric conditions rendering it ineffective. However, many of its formulations have been reported to remain stable under environmental conditions retaining its efficiency for a long time. Similarly, neem seed cake has also been found to be effective against the mosquito vectors. The greatest advantage is that the target species do not develop resistance against neem-based products mainly because of the innumerable number of chemicals present in neem and their combinations. This makes neem-based products highly potential yet unexplored candidates of mosquito control agents. The current review helps to elucidate the roles of neem oil and its various derivatives on mosquito vectors of public health concern.

Percutaneous high-dose-rate interstitial brachytherapy for non-resectable, chemo resistant malignant lesion of lung and liver.

PURPOSE: To explore the feasibility and efficacy of interstitial brachytherapy application for nonresectable and chemo-resistant malignant liver and lung lesions. MATERIALS AND METHODS: Percutaneous high-dose-rate interstitial brachytherapy (HDR ISBT) was applied in nine lesions of seven middle-aged patients with advanced carcinoma (five patients with liver lesion and two patients with lung lesion). All patients were surgically ineligible. All patients had already received systemic chemotherapy. Under computed tomography (CT) guidance (for lung lesion) or ultrasonography (USG) guidance (for liver lesion), a single stainless steel brachytherapy needle was inserted percutaneously in patients with lesion size ≤4 centimeter (cm) and multiple needles were inserted in patients of lesion size >4cm. A single dose of 15 Gy to 20 Gy with HDR ISBT was prescribed at the periphery of the lesion. The needles were removed just after treatment. Patients were kept under observation for 24 h after treatment. RESULTS: The median size of the lesion was 6.5 cm. In all the cases of liver lesion, more than 75% shrinkage of tumor volume in follow-up at 6 mo was observed. It was more than 50% for lung lesion. None of the patients had developed significant complications as on the median follow up period of 15 mo (ranges 3-27 mo). CONCLUSIONS: Percutaneous CT-guided high-dose-rate interstitial brachytherapy is a minimally invasive, safe, and feasible treatment option with minimal complication for inoperable, chemo resistant, advanced cancers with encouraging treatment outcomes.

Clinico-epidemiological profile and treatment outcome in adolescents and young patients of rectal cancer attending a tertiary cancer center.

INTRODUCTION: The incidence of colorectal cancer in young adults is on an increasing trend. It is observed that this subgroup of patients has an aggressive disease and carries a poorer prognosis compared to its older counterpart. This study aimed to analyze the incidence, treatment outcome, and prognostic factors in adolescents and young adults with rectal cancer attending a tertiary cancer center in North India. MATERIALS AND METHODS: We retrospectively analyzed 50 patients of histologically proven rectal cancer, aged up to 30 years, treated at our center between 2015 and 2019. The clinical, demographic, and pathological parameters were studied in all these patients. Kaplan-Meier survival analysis was used to find out survival. Univariate analysis was performed to assess prognostic factors. RESULTS: The incidence was 26.4% at our center with a median age of 28 years. Bleeding per rectum was the commonest complaint. Most of them had signet ring cell histology (26%). The median overall survival was 16 months. Survival was significantly better in patients having bleeding per rectum as an initial complaint (P = 0.009), absence of lymphovascular invasion (LVI) (P = 0.005), and perineural invasion (PNI) (P = 0.002), who received complete planned treatment compared to patients who could not receive either of the modality (P < 0.001). Patients who did not receive radiotherapy (RT) had the worst outcomes compared to those who received RT in any form. RT dose of 50.4 Gy was found to be superior as compared to other schedules. There was no significant difference in survival with gender, tumor stage, grade, type of surgery, or chemotherapy regimen. CONCLUSION: The majority of patients presented in an advanced stage. Therefore, bleeding per rectum should be properly and timely investigated in all these young patients. Early detection and complete treatment are paramount to improving the outcome.

Evaluation of survival outcomes and prognostic factors of carcinoma anal canal at a tertiary cancer center.

CONTEXT: Concurrent chemoradiotherapy is considered a standard of care for patients with carcinoma anal canal. Being an unusual malignancy, there is limited Indian data regarding survival outcomes and prognostic factors. AIM: To evaluate survival outcomes and associated prognostic factors in patients with carcinoma anal canal treated with radical intent. METHODS AND MATERIAL: Patients with squamous cell carcinoma of the anal canal, treated with radical intent between 2015 and 2019 were included in the study. Data regarding the baseline characteristics of the patients and treatment outcomes were collected and analyzed. Survival rates were estimated using Kaplan-Meier method. To determine survival difference between the groups, log-rank test was used. Multivariate analyses were performed with Cox proportional hazard models and P value < 0.05 was considered significant. RESULTS: Forty-two patients were identified after applying suitable eligibility criteria. The median age was 55 years (range: 26-80 years).The median follow-up duration was 23.5 months (range: 1.9-51.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and locoregional (LRC) were 78.5%, 53.1%, and 66.4%, respectively. On multivariate analysis, inferior DFS was significantly affected by lack of concurrent chemotherapy (CT) (hazard ratio [HR], 11.50; 95% confidence interval [CI], 1.92-68.78; P = 0.007) and radiotherapy (RT) dose of 45 Gy or less (HR, 35.96; 95% CI, 6.32-204.56; P = 0.000). CONCLUSION: For patients of carcinoma anal canal, concurrent CT and RT dose are independent prognostic factors influencing DFS.

A prospective randomized comparison of simultaneous integrated boost with sequential boost intensity-modulated radiotherapy in locally advanced head and neck cancer.

Purpose: A comparison of simultaneous integrated boost (SIB) with sequential boost (SEQ) using intensity-modulated radiotherapy along with concurrent cisplatin in locally advanced head and neck cancer (HNC) was made with regard to their survival outcomes and toxicity profile. Materials and Methods: A total of 34 patients were enrolled between October 2016 and March 2019. They were randomized into two arms, SIB and SEQB. All patients were treated with 6 MV photon beam on Linear Accelerator with weekly concurrent cisplatin at 35 mg/m2. Overall survival (OS) and disease-free survival (DFS) were the primary end points and acute and late toxicities were the secondary end points. Results: The median follow-up period was 40.6 and 37.3 months for SIB and SEQB, respectively. At the end of 5 years, the median OS was 40.6 and 37.3 months (P = 0.947) and the median DFS was 35.1 and 37.3 months in the SIB and SEQB arms, respectively (P = 0.991). Complete response at 3 months was 64.7% and 76.5% and partial response was 23.5% and 17.6%, whereas progressive disease was 11.8% and 5.9% in SIB and SEQB arms, respectively. Acute dermatitis, mucositis, dysphagia, and salivary gland toxicities were higher in the SIB arm compared to the SEQB arm. Conclusion: SIB and SEQ arms were comparable in terms of OS and DFS. However, the acute toxicities were higher in the SIB arm, although the difference was not significant, compared to the SEQB arm.

Development and validation of an indigenous, radiobiological model-based tumor control probability and normal tissue complication probability estimation software for routine plan evaluation in clinics.

Purpose: Development and validation of a simple and convenient computational program in MATLAB environment for estimating the tumor control probability (TCP) and the normal tissue complication probability (NTCP), as a decision support system for routine plan evaluation. Materials and Methods: We developed an in-house software using MATLAB 2016b (Mathworks) for estimating TCP and NTCP named as RBMODELV1. The program contains Niemierko free equivalent uniform dose (EUD) program code provided in authors research article. For rest of radiobiological (RB) models in the software separate coding is performed. The program accepts cumulative dose-volume histogram file in (.txt) format containing two columns dose and volume. A set of two RB parameters were prepared, default and user-dependent in excel sheet named as RBDATA. We cross-validated results of RBMODELV1 software with BioSuite software for Poisson's TCP model and Lyman-Kutcher-Burman (LKB) model. A set of total 20 patient's data of head and neck site took under study and respective TCP and NTCP calculated by all the RB models and compared. Results: This is the first study in which we tried to establish correlation between the mean doses (EUD) received by parallel structure (parotid gland and oral cavity) and predicted percentage of NTCP values. It is found that mean dose in the range of 35-40 Gy for parotid gland can result in more than 50% NTCP predicted by all four RB models. Similarly oral cavity receiving mean dose in the range of 53-58 Gy can results in more than 35% NTCP predicted by all the four models. There is <3% variation observed between TCP calculated by BioSuite and RBMODELV1 software and <4% variation observed between predicted NTCP for parotid gland and oral cavity OAR from LKB model by both the software. Conclusion: We created simple software RBMODELV1 which can be used as a research tool as well as decision support system.

Testing Equality of Multiple Population Means under Contaminated Normal Model Using the Density Power Divergence.

This paper considers the problem of comparing several means under the one-way Analysis of Variance (ANOVA) setup. In ANOVA, outliers and heavy-tailed error distribution can seriously hinder the treatment effect, leading to false positive or false negative test results. We propose a robust test of ANOVA using an M-estimator based on the density power divergence. Compared with the existing robust and non-robust approaches, the proposed testing procedure is less affected by data contamination and improves the analysis. The asymptotic properties of the proposed test are derived under some regularity conditions. The finite-sample performance of the proposed test is examined via a series of Monte-Carlo experiments and two empirical data examples-bone marrow transplant dataset and glucose level dataset. The results produced by the proposed testing procedure are favorably compared with the classical ANOVA and robust tests based on Huber's M-estimator and Tukey's MM-estimator.

Influence of adjuvant therapy on pattern of failure and survival in curatively resected gallbladder carcinoma.

PURPOSE: The study was done to evaluate the role of adjuvant therapy in curatively resected Stage II and III gallbladder carcinoma (GBC). MATERIALS AND METHODS: This was a retrospective analysis of patients of GBC registered between 2008 and 2017 in outpatient department of a tertiary cancer hospital in India. Patients who had any of the following adjuvant treatment after radical surgery: (a) external beam radiotherapy (RT) alone, (b) chemotherapy (CT) alone, and (c) RT with CT (CRT) were considered for the study. RESULTS: A total of fifty patients could meet the selection criteria. It was seen that seven patients were treated with RT, 20 with CT, and 23 with CRT. Median follow-up for patients who were alive was 26.7 months. Nineteen patients had locoregional failure while eight had distant failure. Patients treated with CRT had a significantly better mean overall survival compared to those treated with RT or CT (44.0 months, 12.5 months, and 15.1 months, respectively; P = 0.003). Similarly, mean disease-free survival was superior in CRT arm compared to RT and CT arms (43.6 months, 9.6 months, and 12.4 months, respectively; P = 0.002). CONCLUSIONS: Adjuvant CRT had better survival outcome compared to patients treated with either RT or CT with Stage II and III disease after curative cholecystectomy.

Dose optimization comparison study of inverse planning simulated annealing [IPSA] and hybrid inverse planning optimization [HIPO] in interstitial brachytherapy of head and neck cancer.

PURPOSE: This study was a retrospective dose optimization comparison of two commercially available inverse planning algorithms, the inverse planning simulated annealing (IPSA) and hybrid inverse planning optimization (HIPO) for head and neck cancer interstitial brachytherapy. MATERIALS AND METHODS: Seven patients with head and neck cancer were selected (4 with tongue cancer, 2 with buccal mucosa cancer and 1 with carcinoma lip) who were previously treated with interstitial brachytherapy using a flexible nylon tube catheter and graphical optimization/geometric optimization technique. All seven patients were retrospectively re-planned using both IPSA as well as HIPO algorithms available in the Oncentra Brachytherapy Treatment Planning System (TPS) version V4.5.3.30. The dosimetric parameters [PTV-V100, V150, V200, D90; mandible-D2cc, parotid-D2cc, conformity index (CI), dose homogeneity index (HI), overdose volume index (ODI)] were chosen for evaluation in compliance with the objective function and organ at risk dose constraints. RESULTS: Using the paired sample T test in chosen parameters (PTV-V100, V150, V200, D90; mandible-D2cc, CI, HI, ODI both the inverse planning algorithms), it was found that IPSA and HIPO were comparable. CONCLUSIONS: Even though both IPSA and HIPO are largely comparable in most of the dosimetric parameters for inverse planning in brachytherapy of head and neck cancers, differences in the algorithms can be exploited to improve certain parameters in specific situations such as D2cc parotid.