A comprehensive Study of the Out of Field Non Target Dose Associated with 6 and 10 MV Flattened and Flattening Filter Free X Ray Beam in a True Beam Linear Accelerator.

AIM: To evaluate the out-of-field dose associated with flattened (FF) and flattening filter-free (FFF) 6 and 10 MV X-ray beams in a TrueBeam linear accelerator (Linac). MATERIALS AND METHODS: Measurements were taken in a slab phantom using the metal oxide semiconductor field effect transistor (MOSFET) detector at varying depths (dmax, 5 cm, and 10 cm) for clinically relevant field sizes and up to 30 cm from the field edges for 6 and 10 MV FF and FFF beams in TrueBeam Linac. Dose calculation accuracy of the analytic anisotropic algorithm (AAA) and Acuros algorithm was investigated in the out-of-field region. Similarly, the out-of-field dose associated with volumetric modulated arc therapy (VMAT) head-and-neck plan delivered to a body phantom was evaluated. RESULTS: The out-of-field dose for both FF and FFF photon beams (6 and 10 MV) decreased with increasing distance from the field boundary and size. Furthermore, regardless of FF in the field, higher-energy photon beams were associated with lower out-of-field dose. Both algorithms underestimated the dose in the out-of-field region, with AAA failing to calculate the out-of-field dose at 15 cm from the field edge and Acuros failing to calculate out-of-field radiation at 20 cm. At 5 cm from the field edge, an average of 50% underestimation was observed, and at 10 cm, an average of 60% underestimation was observed for both FF and FFF (6 and 10 MV) beams. The VMAT head-and-neck plan performed with the FFF beam resulted in a lower out-of-field dose than the FF beam for a comparable dose distribution. CONCLUSION: Compared with flattened beams, the FFF modes on TrueBeam Linac exhibited a clinically relevant reduction in the out-of-field dose. Further dosimetric studies are warranted to determine the significant benefit of FFF beams across different cancer sites.

Comparative study of concurrent conventional chemoradiotherapy versus hypofractionated chemoradiotherapy in newly diagnosed glioblastoma multiforme postoperative patients.

Purpose: To assess the treatment response and toxicity profile among two groups of newly diagnosed glioblastoma multiforme (GBM) postoperative patients receiving conventional radiotherapy (RT) versus hypofractionated RT with concurrent temozolomide (TMZ) in both. Materials and Methods: A total of 50 patients randomly allotted into two arms (25 in each). Dose received 60 Gy (2 Gy/#) in conventional fractionation RT versus 50 Gy (2.5 Gy/#) in hypofractionated RT with concurrent TMZ 75 mg/m2 orally daily in both arms, respectively. Follow-up was done at 1, 3, 6, and 12 months after completion of treatment to evaluate toxicities, treatment response, and progression-free survival (PFS). Results: All patients were well tolerated with treatment; no major adverse effects were monitored in two arms. There was no statistical significant difference in treatment response, which was found 64% versus 60% in arm A and arm B, respectively, at 3 months of follow-up (P = 0.768). Toxicity profiles were also noted similar in both arms. The 6-month PFS was 84% and 80% in arm A and arm B, respectively (P = 0.71) and 12-month PFS was 60% and 52% in arm A and arm B, respectively (P = 0.69). Conclusion: Among the patients followed, this study showed that hypofractionated RT regimen was not inferior to conventional RT regimen.

Interfraction variations in doses at OARs during three-dimensional high dose rate brachytherapy planning of cervix cancer.

Objective: The American Brachytherapy (BT) Society recommends that BT must be included as a component of the definitive radiation therapy for cervical carcinoma because recurrences and complications are decreased when BT is used in addition to external beam radiotherapy. The aim of this study is to quantify the interfraction dose variations (VARacts) during high dose rate (HDR) BT, the effect of variation in dose in terms of excess "unrecognized" dose to OAR and to conclude the reason of the variation in reference of applicator position/geometry versus deformation of the organ at risk (OAR) concerned. Materials and Methods: Total 30 patients of carcinoma cervix, biopsy proven, between June 2018 and May 2019, were taken for the study. All patients were treated with external beam radiation therapy to a dose of 50 Gy in 25 fractions over 5 weeks, followed by three fractions of HDR intracavitary brachytherapy (ICBT) (7.5 Gy to point A in each fraction) by two-dimensional (2D) X-ray-based planning. Before treatment in the first and last fraction of BT, computed tomography (CT) scan was done for every patient. Then, a 3D-based planning was performed with CT images on our HDR Plus software with image sequence option. VARact was calculated. Rigid image registration of consecutive fraction images was used for quantification of the hypothetical variation in dose (VARhypo) arising exclusively due to changes in applicator placement and geometry. Results: The mean contoured rectal volumes for the first and third fractions were 41.49 cc and 44.72 cc, respectively, while the respective volumes for bladder were 9.33 cc and 9.35 cc cm. These differences were statistically insignificant (P value: 0.263 and 0.919 for rectum and bladder, respectively). The mean equivalent dose in 2 Gy fraction (EQD2) bladder D2cc was 5.68 Gy and 5.79 Gy in the first and third fraction ICBT, respectively. The mean EQD2 for the rectal D2cc was 11.63 Gy and 12.85 Gy in the first and third fraction ICBT, respectively. None of the patients had an actual cumulative EQD2 more than 90 Gy for bladder, but 36.66% of the patients had a rectal dose exceeding the tolerance (75 Gy). Regression plots showed that VARhypo alone could predict about 42.2% of the VARact in the rectum and 19.2% of the VARact in the bladder. Thus, the remaining variation was due to the organ deformation-related dose variations between the two fractions. Conclusions: There were no statistically significant variations in the volumes or doses of OAR between the two fractions. However, a significant proportion of patients may have a higher dose to the OAR in the third fraction in the absence of individualized planning. This increase is likely to be more detrimental where higher doses per fraction are used. Variations in OAR doses may be caused by organ deformation and/or changes in applicator placement/geometry.

Triple combination of palliative oral metronomic chemotherapy in recurrent and metastatic epithelial ovarian cancer: A retrospective study.

Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post-treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan-Meier analyses were performed. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35-80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) was 0-1 in 28 patients and 2-3 in 12 patients. The best clinical response rate post-oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow-up was 6.4 months (4.5-9.2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade-I/II mucositis. Grade-III/IV mucositis were observed in 9 (22.5%) patients. Thirty-seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well-tolerated regime with good symptomatic control and low-moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade-III/IV thrombocytopenia.

A plan comparison study between rapid arc and conventional intensity-modulated radiation treatment plans in nasopharyngeal carcinoma patients.

Introduction: Head and neck cancers are one of the common malignancies in Indian population. It's entity, nasopharyngeal carcinoma is among the aggressive malignancies with its location and spread near very critical structures. Thus requires a highly conformal radiotherapy delivery techniques. Purpose: The aim of the study is to dosimetrically evaluate and to compare Intensity modulated radiation therapy (IMRT) plans and RAPID ARC plans for irradiation of nasopharyngeal carcinoma. Material and Method: A retrospective study is done on 10 nasopharyngeal carcinoma patients, who were treated with Radiotherapy at ATRCTRI Bikaner. Radiotherapy was delivered by IMRT technique (Total of 70 Gy in 33 fractions). Same patients are now planned on Rapid arc technique. Dosimetric comparison is done in terms of PTV coverage, OAR dose, conformity index, homogeneity index. Result: PTV coverage is similar with both the plans. Homogeneity index is higher for IMRT plans 0.119+/- 0.020 compared to 0.104 +/- 0.018 for Rapid arc plans (statistically significant).The Rapid arc plans achieved slightly better conformity 1.018+/-0.09, whereas 1.105+/-0.12 for IMRT plans. Rapid arc achieved better results for OAR, statistically significant for Brainstem (54.4 +/-10.4 Gy for IMRT and 49.7+/-4.2 Gy for Rapid Arc, Lens (Left lens and Right lens received 10.55+/-5.8 Gy and 9.44+/-9.08 by IMRT and 6.12+/-6.1 Gy and 5.45+/-6.05 Gy for Rapid Arc), optic nerves (Right and Left optic nerve received 34.36 and 35.01 Gy for IMRT plans and 30.06 and 30.05 Gy for Rapid Arc plans. However the gains are statistically insignificant for spinal cord and vestibulocochlear nerve. No major difference found for Right and left parotid between both the arms. Conclusions: Rapid Arc is better technique compared to IMRT for Nasopharyngeal carcinoma treatment, that provides better dose conformity, more homogeneous coverage and OAR sparing. However study is retrospective and has lesser patients, thus requires prospective study with more number of patients along with comparison of clinical outcome.

Comparative study of induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone in locally advanced head and neck cancer.

Objective: Concurrent chemoradiotherapy (CTRT) is the standard treatment for patients with unresectable, nonmetastatic Locally advanced squamous cell cancer of head and neck (LASCCHN). The aim of this study to compare the efficacy and toxicity of induction chemotherapy (ICT) followed by CTRT versus standard CTRT alone in patients with LASCCHN. Materials and Methods: Between January 2017 and September 2017, 100 patients with LASCCHN (Stage III and IV) were randomly assigned to two arms: 50 patients in each. Arm A treated by standard CTRT alone (a total 66 Gy in 33fr 2 Gy/# administered daily 5 days/week with 3 weekly inj. cisplatin 100 mg/m2 divided in two days) and Arm B received two cycles of ICT (TPF - inj. paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 divided in 2 days and inj. 5FU 1 gm/m2 iv d1 and d2 ) followed by same CTRT. Assessment was done weekly during RT and 1, 3, 6, 12, and 18 months posttreatment for treatment response, toxicities, and progression-free survival (PFS). Results: Total response was observed 79.1% and 82.1% in Arm A and Arm B, respectively (P = 0.705) at 6-8 weeks after the completion of treatment. Acute toxicities were significantly higher in ICT arm. The 18 months PFS was 57% versus 55% in Arm A and Arm B, respectively (x2 = 0.039, P = 0.8414). Conclusion: Among the patients followed, this study failed to show benefit of ICT-CTRT over CTRT alone in patients of LASCCHN.

Comparison of two schedules of hypo-fractionated radiotherapy in locally advanced head-and-neck cancers.

Aim: In India, more than 70% patients present as locally advanced head-and-neck cancers (LAHNC), with poor performance status and are suitable candidates for palliative radiotherapy (RT) aimed at symptom relief. This prospective study aims to compare two different short course hypo-fractionated RT regimens in patients of LAHNC at a regional cancer centre of north-west India. Materials and Methods: A total of 70 patients of LAHNC were randomized to receive palliative RT in two groups of 35 each. Group A received 30 Gy/10# over 2 weeks and Group B received 20 Gy/5# over 1 week. Baseline symptoms of pain, dysphagia, insomnia, dysphonia, bleeding, fungation, and dyspnea were assessed before the start of study. The first assessment for toxicities, subjective and objective response was done at the conclusion of RT and then after 4-6 weeks. Results: Out of total 70 patients, 71% were males and 29% were females with a median age of 54 years. The most common sites were oropharynx (39%) followed by larynx (24%), oral cavity (20%), and hypopharynx (17%). Nearly 60% of the patients in both groups presented in stage IV and 40% in stage III. At conclusion of RT and at 4-6 weeks follow-up, both groups showed similar results in terms of symptom palliation, objective response, and acute toxicities. Group B showed higher incidence of Grade III and above mucositis (P = 0.027). Median overall survival was found to be 5.9 months (range 1-15 months) in group A and 6.1 months (range 1-18 months) in Group B. Conclusion: Hypo-fractionated RT promises to effectively relieve symptoms in LAHNC and reduces the need of analgesics and hospital visits. Furthermore, a shorter overall treatment time is beneficial at high volume centers and is also welcomed by patients with shorter life expectancy.

Survival pattern in cervical cancer patients in North West India: A tertiary care center study.

Background: Cervical cancer is most common malignancy of female reproductive system worldwide. As per GLOBOCAN 2020, there are 604,127 (6.5%) new cases of cervical cancer in the world, among women it is fourth most common and eighth most common in both sexes. In India,there are 123,907 total new cervical cancer cases (18.3% in female sex whereas 9.4% in both sexes). There are several etiological factors and the most significant is due to persistent infection of specific human papilloma virus (HPV) strains,particularly type 16 and 18 which are most common. Screening and early detection is likely to improve mortality and incidence also. Aims and Objectives: The objective of this retrospective study was to determine the survival rates of cervical cancer and its associated factors in North-West region. Materials and Methods: A total of 520 newly diagnosed cases of cervical cancer were enrolled at Acharya Tulsi Regional Cancer Treatment and Research Centre, Bikaner from January 1, 2014 to December 31, 2014 were included in this study. The main source of information was patient's medical records from which the data were abstracted and cases were followed up for next five years periodically from the date of diagnosis to access their survival status. Results: Kaplan Meier analyses were conducted to identify overall survival and median survival time. Among 520 cases, 130 (25%) had lost to follow up so excluded from the study and the study sample was about 390 patients. The median survival time for cervical cancer in this study was 60 (32-60) months and the overall survival rates at 1, 3 and 5 years were 93.07%, 72.3% and 54.9% respectively. Education, use of oral contraceptive pills (OCP), tobacco chewing ( good survival in tobacco non-chewers) and staging were significantly associated with survival. Conclusion: The 1, 3 and 5 year survival rates for cervical cancer were found to be 93.07%, 72.3% and 54.9% respectively. Various factors determining survival rates were potentially modifiable. Early diagnosis and prevention strategies are keys to obtain better outcomes.

Role of maintenance paclitaxel in epithelial ovarian cancer: An affordable option for poor resources countries (a Regional Cancer Institute study).

Purpose: The purpose of the study is to assess the benefits of maintenance chemotherapy (CT) in epithelial ovarian cancer with CT and surgery. The primary and secondary endpoints of the study were progression-free survival (PFS) and overall survival (OS), respectively. Patients and Methods: Three hundred patients with ovarian cancer (registered between January 2012 and December 2013) received 6 cycles of 3 weekly CT (injection paclitaxel 175 mg/m2 + injection carboplatin 6 AUC) and surgery. After 4 weeks of completion of the above treatment, patients were assessed for response with radiological imaging and serum CA125. Then, these patients were randomly allotted in two arms; 150 patients in Arm A received 6 cycles of single agent, 3 weekly injection paclitaxel 175 mg/m2 as maintenance therapy while 150 patients in Arm B, were on observation. The follow-up was done at 1 month, then 3 monthly in the 1st year and 6 monthly in the 2nd year to evaluate PFS and annually up to 5 years for OS. Results: The PFS at 1 and 2 years was 91% and 80% in study arm and 65% and 50% in control arm; the differences were statistically significant (P = 0.010). The 5-year overall survival was 43% versus 38% in study and control arms, respectively (P = 0.410) and 5-year PFS was 28% versus 18% (P = 0.039) in maintenance and observation arm, respectively. Except for peripheral neuropathy, there was no statistically significant difference in toxicities between the two arms. Conclusion: The study suggests that 6 cycles of single-agent paclitaxel maintenance therapy significantly prolongs the duration of PFS and better trends toward OS, though a large study is needed to come to a conclusion.

Clinical impact of extended field radiation therapy in Stage III carcinoma cervix versus conventional field techniques: A comparative study.

Aim: The aim of the study was to examine tumor control and clinical outcomes of extended field irradiation and compare it with those treated with conventional field in same disease profile and also to determine toxicities associated with radiation treatment. Methods: This study included 50 biopsy-proven and registered International Federation of Gynecology and Obstetrics Stage III cases of carcinoma cervix treated with concurrent computed tomography (injection cisplatin 40 mg/m2 weekly) + external beam radiotherapy (EBRT) upto 50 Gy + high-dose-rate intracavitary brachytherapy (ICBT) (22.5 Gy). Twenty-five patients were randomized to each arm. Arm A: Conventional field EBRT 50 Gy with concurrent weekly chemotherapy followed by ICBT. Arm B: Extended field EBRT 50 Gy with concurrent weekly chemotherapy followed by ICBT. Results: At 12-month follow-up, 43 patients (86%) had attained CR. Overall, seven patients (14%) were in noncomplete response (CR) group (non-CR = patients with partial response, stable disease, or progressive disease). The non-CR rate was 16% for Arm A and 20% for Arm B. Among seven patients of non-CR group, six had local disease and one had failure at distant site. Five (10%) patients died in this study, 2 (8%) in Arm A and 3 (12%) patients in Arm B. Residual disease was seen in 2 (4%) patients. Grade III diarrhea was seen in eight patients (16%), 3 in Arm A (12%) and 5 in Arm B (20%). Fifteen patients (30%) developed Grade III skin toxicity. Seven patients in Arm A (28%) and 8 patients (32%) in Arm B developed Grade III toxicity. Twenty-five (50%) cases presented with varying stages of vaginal adhesions and stenosis. Conclusion: Majority of patients achieved CR with minimal acute and late toxicities with similar results in both arms. No patient had pelvic or para-aortic metastasis until recent follow-up.

Hypofractionated radiotherapy versus conventional radiotherapy in early glottic cancer T1-2N0M0: A randomized study.

OBJECTIVE: Glottic cancer has an excellent probability of cure. The early glottic cancer is usually treated by radiotherapy with different fractionation schedules. The aim of this study was to compare conventional versus hypofractionated radiotherapy with respect to overall survival and disease-free survival. MATERIALS AND METHODS: A total of fifty patients with T1-2N0M0 glottic cancer with no previous treatment history were prospectively randomized into two arms. In Arm A (Study), patients received a total of 55 Gy in 20# at 2.75 Gy/#, 5 days a week. In Arm B (Control), patients received a total of 66 Gy in 33# at 2 Gy/#, 5 days a week. Disease response was evaluated by the WHO criteria at the end of treatment, then at 1, 2, and 3 months to complete their 6-month follow-up. Overall survival and disease-free survival were evaluated at 1, 2, and 3 years. RESULTS: Overall, 100% of patients in the study arm and 96% of patients in the control arm had complete response after 6 months. Overall survival rates at 1, 2, and 3 years were 96%, 96%, and 88%, respectively, in the study arm, while in the control arm, these values were 92%, 84%, and 80%, respectively, and the difference was not statistically significant (P > 0.05). Disease-free survival at 3 years was 88% in the study arm and 80% in the control arm. CONCLUSION: The study suggests that hypofractionated regimen may be better in local control and symptomatic relief with the added advantage of shorter treatment time, which offers better patient compliance and advantageous in busy setups where there is heavy patient load.

Combination of quercetin and 2-methoxyestradiol inhibits epithelial-mesenchymal transition in PC-3 cell line via Wnt signaling pathway.

AIM: We have previously reported that quercetin (Qu) regulates epithelial-mesenchymal transition (EMT) by modulating Wnt signaling components. In this study, we investigated the synergistic effect of Qu and 2-methoxyestradiol (2-ME) and the role of Wnt signaling components in regulating EMT in PC-3 cells. MATERIALS & METHODS: EMT was induced by treating PC-3 cells with TGF-ß, followed by evaluation of expression of EMT markers and Wnt signaling proteins in naive, induced and after exposing induced cells to Qu and 2-ME at both gene and protein level by real-time PCR (RT-PCR) and western blot, respectively. RESULTS: Qu and 2-ME synergistically downregulated mesenchymal markers with simultaneous upregulation of epithelial markers. Wnt signaling proteins expression was also downregulated by Qu and 2-ME in TGF-ß-induced EMT in PC-3 cells. CONCLUSION: Thus, combination therapy of Qu and 2-ME could be a new promising therapeutic approach for the treatment of prostate cancer.

In-silico identification of frequently mutated genes and their co-enriched metabolic pathways associated with Prostate cancer progression.

Prostate cancer (PCa) has emerged as a significant health burden in men globally. Several genetic anomalies such as mutations and also epigenetic aberrations are responsible for the heterogeneity of this disease. This study identified the 20 most frequently mutated genes reported in PCa based on literature and database survey. Further gene ontology and functional enrichment analysis were conducted to determine their co-modulated molecular and biological pathways. A protein-protein interaction network was used for the identification of hub genes. These hub genes identified were then subjected to survival analysis. The prognostic values of these identified genes were investigated using GEPIA and HPA. Gene Ontology analysis of the identified genes depicted that these genes significantly contributed to the cell cycle, apoptosis, angiogenesis and TGF-ß receptor signalling. Further, the research showed that high expressions of identified mutated genes led to a reduction in the long-term survival of PCa patients, which was supported by immunohistochemical and mRNA expression level data. Our results suggest that identified panel of mutated genes viz., CTNNB1, TP53, ATM, AR and KMT2D play crucial roles in the onset and progression of PCa, thereby providing candidate diagnostic markers for PCa for individualised treatment in the future.

A Comparative Study Of Concurrent Chemo-Radiotherapy With or Without Neoadjuvant Chemotherapy in Treatment of Locally Advanced Non Small Cell Lung Cancer.

INTRODUCTION: The standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiotherapy. This study was undertaken to evaluate whether induction chemotherapy along with concurrent chemoradiotherapy would result in better tumor control, improved symptom control and any variation in toxicity as compared to concurrent chemoradiotherapy alone. PATIENTS AND METHODS: Between February 2015 to September 2016, 25 patients each were randomized to control group, in which they received concurrent chemoradiotherapy with weekly cisplatin 40 mg/m2 intravenous, during chest radiotherapy of 66Gy in 33 fractions for 6.5 weeks, and study group, in which patients received three cycles of induction chemotherapy with Cisplatin 75 mg/m2and Paclitaxel 175 mg/m2administered every 21 days followed by identical chemoradiotherapy. RESULTS: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, histology, grade, and stage. At 6thmonth follow-up, complete response was seen in 6 patients in control arm and 7 patients in study arm (?2 = 1.603, p = 0.205) and partial response was seen in 13 and 12 patients in control and study arms respectively (?2 = 1.932, p = 0.165). Symptom control of cough, hemoptysis, chest pain and dyspnoea were also similar in both groups. DISCUSSION: In our study, no difference in treatment outcome with respect to the two groups was observed, which was similar to studies which have been conducted previously. Radiation is a good modality for symptom control of cough, hemoptysis, chest pain and dyspnoea. In toxicities, pneumonitis and hematological toxicity was slightly higher in study group even at 6th month follow up. CONCLUSION: Slight increase in toxicity with no added benefit in locoregional tumor control and symptom regression, was seen in patients receiving induction chemotherapy followed by chemoradiotherapy. Concurrent chemoradiotherapy alone can thus be used as only modality of treatment in unresectable stage III NSCLC.

Neo-adjuvant chemotherapy followed by either continuous hyper-fractionated accelerated radiation therapy week-end less or conventional chemo-radiotherapy in locally advanced NSCLC-A randomised prospective single institute study.

CONTEXT: Better locoregional control and increased overall survival by continuous hyper fractionated accelerated radiotherapy have been shown in unresectable nonsmall cell lung carcinoma (NSCLC). Dose escalation and neoadjuvant chemotherapy (NACT) along with continuous hyperfractionated accelerated radiotherapy week end-less (CHARTWEL) were also tried for improved survival. In this present study, we compared the results of NACT followed by CHARTWEL against NACT followed by conventional concurrent chemo-radiation therapy. AIMS: The aim of this study is to compare the locoregional control and toxicities in NSCLC Stage IIIA and B in both arms. SETTINGS AND DESIGN: Randomized, prospective single-institutional study with a study population comprising all locally advanced unresectable NSCLC patients enrolled in 2014 at our institute. SUBJECTS AND METHODS: All enrolled patients were randomized into two arms-CHARTWEL and concomitant chemo-radiotherapy (CCRT), after three weeks of the fourth cycle of NACT. In CHARTWEL arm 30 patients received two-dimensional radiotherapy (RT) 58.5 Gy/39 fr/2.5 weeks while in CCRT arm 30 received 66 Gy/33 fr/6.5 weeks. Disease response was evaluated at 6 months and toxicity assessment during and after treatment completion. Data were analyzed using tools such as percentage, mean, Chi-square test and P value. Chi-square and P value was calculated by statistical online software (http://quantpsy.org). RESULTS: 28% of patients in study arm and 20% in control arm had complete response at 6 months after RT. Locoregional disease control was observed in 44% in study arm and 32% in control arm of patients. There was no statistical difference in grades of toxicities or overall survival (OS)/disease-free survival except persistent esophagitis Grade III seen in two patients of study arm. CONCLUSIONS: Study suggests that CHARTWEL in combination with NACT is an effective strategy to treat patients with locally advanced lung cancer with the advantage of a smaller dose and shorter duration. Although large multivariate studies still needed.

LHRH-conjugated, PEGylated, poly-lactide-co-glycolide nanocapsules for targeted delivery of combinational chemotherapeutic drugs Docetaxel and Quercetin for prostate cancer.

One of the major challenges in effective cancer chemotherapy is the severe systemic cytotoxicities of anticancer drugs on healthy tissues. The present study reports chemically modified polymeric nanocapsules (NCs) encapsulating combination of chemotherapeutic drugs Docetaxel (DTX) and Quercetin (QU) for its active targeting to prostate cancer (PCa). The active targeting was achieved by conjugating Luteinizing-hormone-releasing hormone (LHRH) ligand to poly-lactide-co-glycolide (PLGA) using polyethylene glycol (PEG) as a spacer. The structure of the conjugates was characterized and confirmed using 1H NMR and ATR-FTIR. The drug encapsulated NCs showed a homogenous size distribution with their size ranging between 120 and 150 nm, and exhibited a negative zeta potential in the range of -20 to -40 mV. The in vitro release studies highlighted the sustained drug release pattern from the respective NCs; while the PEG coating to polymeric NCs provided serum stability to the NCs. The in vitro biological evaluation of the NCs was conducted using PC-3 and LNCaP cell lines. The results of the cellular uptake studies showed a significantly higher untake of the LHRH targeted NCs, while the LHRH-targeted-PEGylated DTX: QU NCs exhibited higher caspase-3 activity. The cell viability assay results showed the enhanced cell inhibition activity of the combinatorial DTX: QU when compared to individual DTX. Further, higher cell cytotoxicity was achieved by LHRH-targeted DTX: QU NCs as compared to their free-form or non-targeted NCs. Finally, the results of in vivo tumor localization and in vivo antitumor activity studies complimented and upheld the in vitro results, demonstrating the beneficial role of PLGA-PEG-LHRH NCs encapsulating combination of DTX and QU in combating prostate cancer (PCa).

Clinical and dosimetric impact of adaptive intensity-modulated radiotherapy in locally advanced head-and-neck cancer.

BACKGROUND: Radiotherapy in head-and-neck cancer (HNC) is a challenging task, and the anatomical alterations occurring during the course of intensity-modulated radiotherapy (IMRT) can be compensated by adaptive radiotherapy (ART) which utilizes repeat computed tomography (CT) scans during the treatment course for replanning. In this study, the clinical and dosimetric benefits of ART were compared with the conventional IMRT. MATERIALS AND METHODS: Sixty patients with locally advanced HNC were randomized into two arms to receive IMRT up to a curative dose of 70 Gy with concurrent weekly chemotherapy and were prospectively analyzed between March 2018 and March 2019. Repeat CT scan was acquired after the 3rd week of radiation. Patients in the study arm underwent replanning, whereas those in the control arm continued with the first IMRT plan. Assessment was done weekly till the end of treatment and at 1, 3, and 6 months post IMRT for disease response and toxicities. Tumor volume reduction rate (TVRR) and dose reduction to organs at risk were also recorded. RESULTS: Complete response was observed in 90% and 96.7% patients in the control and study arms, respectively, at the end of 6 months. Insignificant differences were found between the two arms in terms of toxicities. Xerostomia was statistically significantly higher in the control arm at 6 months (P = 0.01). TVRR was found to be 31.85%. Dose to spinal cord, ipsilateral, and contralateral parotid reduced by 4.3%, 6%, and 2.2%, respectively, with ART. CONCLUSION: Mid-treatment adaptive replanning can help in better target coverage and minimize toxicities in HNC patients.

A Comparative Study of Uninterrupted Treatment by Radiotherapy versus Standard Gap Correction after Interruptions in Oropharyngeal Cancer.

BACKGROUND: Radiation is an important modality in the treatment of cancer. The longer course of treatment, favors stem cells repopulation, increasing the bulk of stem cells that have to be obliterated. So overall treatment time increases, the chances of local cure by radiotherapy decreases. Primary aim of study is to test the efficacy of radiation treatment after standard correction in unplanned interruption. MATERIAL AND METHOD: 105 patients of head and neck cancer (Oropharynx) with ECOG performance score = 2, with squamous cell carcinoma histopathology and with stage III and IVa were enrolled and 95 patients have completed treatment. Patients were planned for Concurrent chemo-radiotherapy with Cisplatin 40mg/m2 with EBRT (66Gy/33#/2Gy/#) treatment completed in 6.5 weeks. During the treatment the patients were grouped into uninterrupted arm (48) and interrupted arm with standard correction (47). RESULTS: The enrolled patients mean age: 50 years, males 76.8%, stage IVa disease 50.7%, ECOG performance status (0/1: 67.9%). The complete response (CR) in uninterrupted arm was 64.5% and CR in interrupted arm with standard correction was 61.7% at 6 months (X2= 1.883, p value=0.169). While considering alone Stage IV cases, had found that the locally advanced cases of uninterrupted arm have significant better response (X2= 5.90, p value=0.015). The quality of life was slightly poor, but was statistically insignificant in interrupted arm. CONCLUSION: The study concludes that patients with advanced stage (i.e. IVa) have significantly poor treatment outcomes even the standard correction once treatment is interrupted. While the patient treated with gap correction also have similar outcomes in form of disease-free survival and overall survival at 3 years compared to uninterrupted arm.

Acute treatment-related toxicity in elderly patients with good performance status compared to young patients in locally advanced esophageal carcinoma treated by definitive chemoradiation: A retrospective comparative study.

INTRODUCTION: The benefit of definitive chemoradiotherapy (CRT) in elderly patients with locally advanced esophageal cancer is not well established. We perform a single institutional retrospective study of CRT in terms of toxicity in elderly patients (age more than 60 years) as compared with young cohort (age <60 years) in locally advanced nonmetastatic esophageal cancer. PATIENTS AND METHODS: A total 145 of patients, 79 in young age (Group A) and 66 patients of elder age (Group B) with Stage II and III squamous cell carcinoma of the esophagus with ECOG PS of 0-1, who had undergone definitive CRT at our institute from January 2015 to November 2018 were selected for this analysis. Chemotherapy was cisplatin (40 mg/m2) given concurrently on weekly basis with radiotherapy (RT). Total prescribed dose of RT was 50.4 Gy at the rate of 1.8 Gy per fraction. Median age was 40 years (25-60 years) and 65 years (60-75 years) in young and elderly group, respectively. Follow-up is done at median of 28 months (1-48 months) after treatment. RESULTS: Acute Grade 2-3 esophagitis was seen in 48.10% in young cohort, while it was 60.6% in older group. Grade 2-3 nausea and vomiting was seen in 32.91% in young age patients, while it was 45.5% in elder patients. No statistically significant difference is seen in acute treatment-related toxicity in young and elderly group. CONCLUSION: Our conclusion is that patients with adequate functional status should not be excluded from curative CRT based on age alone.

Quantitative SWATH-Based Proteomic Profiling for Identification of Mechanism-Driven Diagnostic Biomarkers Conferring in the Progression of Metastatic Prostate Cancer.

Prostate cancer (PCa), the most frequently diagnosed malignancy in men is associated with significant mortality and morbidity. Therefore, demand exists for the identification of potential biomarkers for patient stratification according to prognostic risks and the mechanisms involved in cancer development and progression to avoid over/under treatment of patients and prevent relapse. Quantitative proteomic mass spectrometry profiling and gene enrichment analysis of TGF-ß induced-EMT in human Prostate androgen-dependent (LNCaP) and androgen-independent (PC-3) adenocarcinoma cell lines was performed to investigate proteomics involved in Prostate carcinogenesis and their effect onto the survival of PCa patients. Amongst 1,795 proteins, which were analyzed, 474 proteins were significantly deregulated. These proteins contributed to apoptosis, gluconeogenesis, transcriptional regulation, RNA splicing, cell cycle, and MAPK cascade and hence indicating the crucial roles of these proteins in PCa initiation and progression. We have identified a panel of six proteins viz., GOT1, HNRNPA2B1, MAPK1, PAK2, UBE2N, and YWHAB, which contribute to cancer development, and the transition of PCa from androgen dependent to independent stages. The prognostic values of identified proteins were evaluated using UALCAN, GEPIA, and HPA datasets. The results demonstrate the utility of SWATH-LC-MS/MS for understanding the proteomics involved in EMT transition of PCa and identification of clinically relevant proteomic biomarkers.