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Background The trial hypothesis was that, in a resource-constrained situation, short-course radiotherapy would improve treatment compliance compared with conventional chemoradiotherapy for locally advanced rectal cancer, without compromising oncological outcomes. Methods In this open-label RCT, patients with cT3, cT4 or node-positive non-metastatic rectal cancer were allocated randomly to 5 × 5 Gy radiotherapy and two cycles of XELOX (arm A) or chemoradiotherapy with concurrent capecitabine (arm B), followed by total mesorectal excision in both arms. All patients received a further six cycles of adjuvant chemotherapy with the XELOX regimen. The primary endpoint was treatment compliance, defined as the ability to complete planned treatment, including neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy to a dose of six cycles. Results Of 162 allocated patients, 140 were eligible for analysis: 69 in arm A and 71 in arm B. Compliance with planned treatment (primary endpoint) was greater in arm A (63 versus 41 per cent; P = 0.005). The incidence of acute toxicities of neoadjuvant therapy was similar (haematological: 28 versus 32 per cent, P = 0.533; gastrointestinal: 14 versus 21 per cent, P = 0.305; grade III–IV: 2 versus 4 per cent, P = 1.000). Delays in radiotherapy were less common in arm A (9 versus 45 per cent; P < 0.001), and overall times for completion of neoadjuvant treatment were shorter (P < 0.001). The rates of R0 resection (87 versus 90 per cent; P = 0.554), sphincter preservation (32 versus 35 per cent; P = 0.708), pathological complete response (12 versus 10 per cent; P = 0.740), and overall tumour downstaging (75 versus 75 per cent; P = 0.920) were similar. Downstaging of the primary tumour (ypT) was more common in arm A (P = 0.044). There was no difference in postoperative complications between trial arms (P = 0.838). Conclusion Reduced treatment delays and a higher rate of compliance were observed with treatment for short-course radiotherapy with consolidation chemotherapy, with no difference in early oncological surgical outcomes. In time- and resource-constrained rectal cancer units in developing countries, short-course radiotherapy should be the standard of care.

BACKGROUND To determine X-ray repair cross-complementing 1 gene (XRCC-1) Arg194Trp polymorphism as bio-predictor for clinical outcome in advanced laryngeal squamous cell carcinoma undergoing cisplatin-based chemoradiation (CRT). METHODS A total of 150 patients were enrolled in this prospective study. XRCC-1 Arg194Trp genotyping categorized patients as wild (C/C) and polymorphic (C/T or T/T). The primary endpoint was to assess acute radiation-induced toxicity (ARIT). RESULTS A significant correlation of skin (P- .04) and oral mucosal ARIT (P- .01) was noticed in the XRCC-1 polymorphic variant. A higher treatment response was noted in the polymorphic variant, and it shows a trend toward significance (P- .08). With 33 months of median follow-up, 2-year progression-free survival (PFS) and overall survival (OS) of wild vs polymorphic variant were 34.6% vs 46.9% (P- .066) and 50.6% vs 62.2% (P- .12). CONCLUSION XRCC-1 polymorphic variants have significantly higher grade of >2 ARIT and may have improved trend for treatment response and PFS.

Background: The aim of this study was to evaluate any association between CYP1A1 (T6235C and C4887A, A4889G) gene polymorphisms and the risk of oral pre-cancer and cancer. Methods: In the present study, 250 patients with oral pre-cancer and/or cancer and 250 healthy controls were genotyped for CYP1A1 T6235C, C4887A and A4889G polymorphisms by the PCR-RFLP method. Results: None of the CYP1A1 polymorphisms were associated with the risk of either oral cancer or pre cancer. Nor were any links with clinical parameters of oral cancer found. However, among the consumers of areca nut/pan masala the TC, CA and AG genotypes respectively for the CYP1A1 T6235C,C4887Aand A4889G polymorphisms were significantly more frequent in controls compared to cases (p values for cases vs. controls of 0.0032, 0.0019 and 0.0009, respectively). Similarly, compared to the haplotype TCA, TAG constituted by CYP1A1 T6235C and C4887A and A4889G was more common in controls (6.88%) than in cases (4.07%). Conclusion: Our results suggest that genotypes regarding CYP1A1 polymorphisms may modulate the risk of oral cancer and pre-cancer among the areca nut/pan masala consumers. The haplotype may also exert an influence in our north Indian population.

Background: The dosimetric parameters required in lung cancer radiation therapy are taken from a homogeneous water phantom; however, during treatment, the expected results are being affected because of its inhomogeneity. Therefore, it becomes necessary to quantify these deviations. Objective: The present study has been undertaken to find out inter- and intra- lung density variations and its dosimetric impact on lung cancer radiotherapy using Monte Carlo code FLUKA and PBC algorithms. Material and Methods: Density of 100 lungs was recorded from their CT images along with age. Then, after PDD calculated by FLUKA MC Code and PBC algorithm for virtual phantom having density 0.2 gm/cm3 and 0.4 gm/cm3 (density range obtained from CT images of 100 lungs) using Co-60 10 x10 cm2 beams were compared. Results: Average left and right lung densities were 0.275±0.387 and 0.270±0.383 respectively. The deviation in PBC calculated PDD were (+)216%, (+91%), (+)45%, (+)26.88%, (+)14%, (-)1%, (+)2%, (-)0.4%, (-)1%, (+)1%, (+)4%, (+)4.5% for 0.4 gm/cm3 and (+)311%, (+)177%, (+)118%, (+)90.95%, (+)72.23%, (+)55.83% ,(+)38.85%, (+)28.80%, (+)21.79%, (+)15.95%, (+)1.67%, (-) 2.13%, (+)1.27%, (+)0.35%, (-)1.79%, (-)2.75% for 0.2 gm/cm3 density mediums at depths of 1mm, 2mm, 3mm, 4mm, 5mm, 6 mm, 7 mm, 8mm, 9mm,10mm, 15mm, 30mm, 40mm, 50mm, 80mm and 100 mm, respectively. Conclusion: Large variations in inter- and intra- lung density were recorded. PBC overestimated the dose at air/lung interface as well as inside lung. The results of Monte Carlo simulation can be used to assess the performance of other treatment planning systems used in lung cancer radiotherapy.

Gallbladder cancer (CaGB) in the subcontinent belongs to low socioeconomic status, and at the time of diagnosis, a large number is unresectable or inoperable so the palliative treatment remains the only option. In the present study, attempt was made to see the effect and safety profile of single-agent oral capecitabine in inoperable CaGB in presence of low levels of jaundice post-single-catheter transhepatic external biliary drainage. In N = 35 of inoperable jaundiced CaGB, post-biliary drainage capecitabine in low dose was started when their total bilirubin levels fell to 10 mg% or below. Post-external drainage decreased bilirubin level to

Dasatinib, a second generation multi-target tyrosine kinase inhibitor (TKI) is active against many imatinib-resistant BCR-ABL mutant forms, Src, and c-Kit tyrosine kinases. While skin hypopigmentation is a well recognized adverse effect of first generation TKIs; it has rarely been reported with dasatinib. We report a rare case of diffuse cutaneous hypopigmentation and bilateral supercilliary madarosis induced by dasatinib. A 51 year-old Indian male with no co-morbidities and with history of chronic myelogenous leukaemia with complex variant of Philadelphia translocation and E 225 V mutation in P loop domain of bcr-abl transcript who was initiated on imatinib followed by dasatinib as a part of treatment. After 5 months of treatment with dasatinib, he developed supercilliary madarosis bilaterally. Cutaneous side effects may adversely affect patient’s quality of life and, therefore, require prompt attention to prevent long-term complications or suboptimal outcomes due to poor compliance.

Background: Lung cancer now constitutes the majority of all cancer diagnosis in the world. It has the most unfavourable prognosis accounting for the maximum number of cancer related deaths worldwide. The objective of this study was to study the complete profile of lung cancer. Prevalence of EGFR mutation in adenocarcinoma. Methods: 116 lung cancer patients were enrolled. They were subjected to diagnostic procedures like transthoracic FNAC/biopsy, bronchoscopy, thoracoscopy, closed pleural biopsy, lymph node FNAC/biopsy, besides routine blood and sputum examinations and CECT thorax. Data was analysed retrospectively after 1 year. Results: Most patients presented in the sixth decade. Mean duration of symptoms was 7.24 months. 62% patients were smokers, 54.3% were exposed to non-smoke tobacco, 18.9% to environmental tobacco smoke (ETS) and biomass fuel. Mass as the single radiological lesion was the most common radiological finding. Pleural effusion was seen in 51.7% patients and was more common in females. Liver (3.4%) and brain (5.9%) were the most common sites of metastasis. EGFR mutation was positive in 34.2% of adenocarcinoma. Exon 19 deletion was more common. ALK was positive in 1 patient. Maximum number of patients (70.7%) presented in stage 4. Transthoracic biopsy could diagnose 61.2% of all lung cancers. Adenocarcinoma was the most common diagnosis (60.3%) and was more common in females and non-smokers. Conclusions: Most patients present in an advanced stage. Adenocarcinoma now seems to be the most common histological subtype of lung cancer in India. EGFR mutation is common in the Indian population. Biomass fuel exposure is a significant risk factor in females. Bronchoscopy is the procedure of choice for diagnosing central tumours and transthoracic FNAC and Biopsy for peripheral tumours.

Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), but its prediction is difficult. Several authors aimed to establish radioresistant OSCC cell lines to identify genes with altered expression in response to radioresistance. The development of OSCC is a multistep carcinogenic process that includes activation of several oncogenes and inactivation of tumour suppressor genes. TGM-3 is a tumour suppressor gene and contributes to carcinogenesis process. The aim of this study was to estimate serum and tissue expression of TGM-3 and its correlation with clinico-pathological factors and overall survival in patients of OSCC undergoing chemo-radiotherapy. Tissue expression was observed in formalin fixed tissue biopsies of 96 cases of OSCC and 32 healthy controls were subjected to immunohistochemistry (IHC) by using antibody against TGM-3 and serum level was estimated by ELISA method. mRNA expression was determined by using Real-Time PCR. Patients were followed for 2 year for chemo radiotherapy response. In OSCC, 76.70% cases and in controls 90.62% were positive for TGM-3 IHC expression. TGM-3 expression was cytoplasmic and nuclear staining expressed in keratinized layer, stratum granulosum and stratum spinosum in controls and tumour cells. Mean serum TGM-3 in pre chemo-radiotherapy OSCC cases were 1304.83±573.55, post chemo-radiotherapy samples were 1530.64±669.33 and controls were 1869.16±1377.36, but difference was significant in pre chemo-radiotherapy samples as compared to controls (p

Introduction: Oral cancer accounts for approximately 2.1% of all cancers worldwide. In India, oral squamous cell carcinoma (OSCC) is the most common cancer with half a million new cases diagnosed every year. More than 50% of patients eventually develop local recurrence or metastasis usually within the first 2-years following completion of treatment. It is beneficial to analyze the prognostic significance of Cyclin D1, p53 and EGFR which are critical mediators in the pathogenesis of OSCC. The objective of this study was to assess the association of expression of these markers with recurrence and pattern of recurrence in OSCC patients undergoing chemoradiation. Materials and Methods: A Total 290 OSCC cases of locally advanced stage (III, IV) oral cancer with World Health Organization (W.H.O.) performance status of grade 0/1 in the year 2009–2012 were enrolled in the study. Treatment response was assessed according to W.H.O. criteria. Cyclin D1, EGFR and p53 expression in tumor tissue was estimated by immunohistochemical (IHC) method and quantified as percentage positive nuclei. Results: During the 2-years follow up, 56 (19.3%) patients recurred, out of which, 47 (83.9%) were locoregional and 9 (16.1%) distant sites. On correlating, χ2 test showed significant (P < 0.05 or P < 0.01 or P < 0.001) association of marker expressions (Cyclin D1, EGFR and p53) with recurrence. The strong positive expressions of all three markers showed significant association with early time of recurrence. The multivariate logistic regression analysis showed significant (P < 0.05 or P < 0.01 or P < 0.001) association of recurrence with primary site, differentiation, Cyclin D1 and p53 expressions indicating these as an independent predictors of recurrence in OSCC. The Cyclin D1, EGFR and p53 expressions also showed significant (P < 0.001) poor survivals (OS, DFS and RFS) in patients with positive/strong positive expressions than negative expression suggesting their prognosis in OSCC. Conclusion: Our results signifies that tumors over expressing Cyclin D1, EGFR and p53 are resistant to chemoradiation and are associated with increased risk of locoregional recurrence and metastasis in OSCC patients undergoing chemoradiation.

Metastasis to regional lymph nodes via lymphatic vessels plays a key role in oral cancer progression. Tumor lymphangiogenesis is known to promote lymphatic metastasis and vascular endothelial growth factor C and D are the critical activator of tumor lymphangiogenesis during the process of metastasis. In this study, we evaluated the correlation between pretreatment serum levels of VEGF-C&D in oral cancer and clinicopathological features in patients with oral cancer. Serum VEGF-C and sVEGF-D were measured by enzyme-linked immunoadsorbent assay (ELISA) on 98 patients with oral cancer, 49 cases with healthy normal controls. Serum VEGF-C and sVEGF-D levels were significantly higher in patients with oral cancer than in the normal healthy group (p < 0.001 and p = 0.001, respectively). Subgroup analysis showed that lymph node metastasis (p=0.001) and histological grading (p=0.05) were correlated with elevated level of VEGF-C. Elevated level of VEGF-D were associated with lymph node metastasis (p=0.001) only. Serum VEGF-C AUC was higher than the VEGF-D AUC in detecting lymph node metastasis. These results suggest that pretreatment serum levels of VEGF-C & VEGF-D reflect lymph node metastasis and advanced stage of oral cancer.

Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. It is one of the leading causes of death. Tobacco and alcohol consumption appears to be the major determinants of oral cancer.The literature search was carried out in NCBI Pubmed database using keywords "oral cancer", "risk factor", "epidemiology" and "patho*". Some basic information was also obtained from textbook and medical university websites.Several risk factors have been well characterized to be associated with oral cancer with substantial evidences. The development of oral cancer is a multistep process involving the accumulation of genetic and epigenetic alterations in key regulatory genes. Experimental pathological studies of oral cancer in animal models and direct molecular genetic analysis of oral cancer subjects in recent times have revealed a substantial amount of knowledge on specific gene alterations or other genetic mechanisms involved in initiation and subsequent progression.Considering known risk factors, oral cancer appears to be to a certain extent, a preventable disease. Recent development of molecular picture of pathoprogression and molecular genetic tools opens the avenue for easier diagnosis, better prognostication and efficient therapeutic management.

Objective The aim of the present study was to define the prognostic impact of nodal density (ND) and total tumor volume along with many other tumor, treatment and patient related variables using the late chemo-intensification treatment regimen with conventionally fractionated radiotherapy (70 Gy/7 weeks). Methods A total of 74 patients with Stage III and IV biopsy proven squamous cell carcinoma of oropharynx, hypopharynx and larynx were treated with this regimen. ND and total tumor volume was measured on high resolution CT scans for all the patients. Chemotherapy consisted of continuous infusion of 5 FU at 350 mg/m(2)/day and cisplatin as 1 h infusion at 10 mg/m(2)/day on days 1-5 of week 6 and 7 of radiotherapy. Results Grade III mucositis was present in 48 (64.9%) patients. Overall complete response rate was 77%. At 28 months, locoregional relapse-free survival (LRFS), overall survival (OS) and distant metastases-free survival (DMFS) was 70.8%, 66.9% and 81.9%, respectively. In the final multivariate Cox-regression model tumor stage, ND, primary site and nodal stage were independent variables predicting for LRFS. Similarly AJCC group staging, ND and total treatment volume were found to have significant impact, independently over LRFS. Conclusions There is tremendous variation in terms of ND and total tumor volume within AJCC nodal staging and tumor staging, respectively. ND had significant impact over LRFS and OS. Future phase III trial may need stratification on the basis of these variables.

Aims and Objectives: To evaluate the prognostic significance of cyclooxygenase-2 (COX-2) overexpression in oral squamous cell carcinoma (OSCC) patients undergoing chemoradiation therapy. Purpose of the study was to determine whether COX-2 could be used as a diagnostic and prognostic index in OSCC. Materials and Methods: Forty-four patients of SCC were included in the present study and immunohistochemical examination was done for COX-2 expression. Negative and

Metastatic tumours of the oral cavity are uncommon, they may occur in soft tissue as well as in bone in the oropharyngeal region. Owing to its rarity, metastatic tumours of the oral regions are a challenge to diagnose. We report a case of metastasis of the oral cavity, arising from uterine cervix mimicking as mucoepidermoid carcinoma. The metastatic lesions were noticed in the soft tissue of the lower buccal and gingival side of a oral cavity, in a 40-year-old woman with history of an adenosquamous carcinoma of uterine cervix treated by panhysterectomy.

Aim of study 1.To study the association of genetic polymorphism in Cyp 2D6 in patients of locally advanced head and neck cancer. 2. Try to assess a correlation between this polymorphism & response to treatment. Need of the study- To find out a possible genetic level explanation for the different response achieved in patients with similar histopathology, stage, exposure to carcinogen & ethinicity undergoing similar treatment. Material & method A study comprising of 150 patients & 150 controls was done to analyse the association between polymorphs of Cyp 450 2d6 with Head & neck cancer and treatment response (TPF- > CTRT). Two cycles of TPF(paclitaxel-175 mg/m2 D1,cisplatin 35 mg/m2 D2-D3 and 5Fu 1gm/m2 D1-D3 ) were given followed by radiotherapy with concurrent cisplatin (40 mg/m2).The response to the treatment was assessed clinically, radiologically & by laryngoscopy- post treatment .Genotyping of the blood samples was done. Analysis of the association between genetic polymorphisms and risk of HNSCC was estimated by calculating crude odds ratio (OR). A p-value of Results 1. Patients with Cyp 2D6*1 showed good response to the therapy given, while Cyp 2D6*4 and *10 were poor responders. Conclusion 1. There is a strong association of polymorphs of Cyp 2D6 (*4 &*10) with occurrence of head and neck cancer. 2. Response to treatment (TPF- > CT + RT) is polymorph graded. Our study, thus provides an insight in to the concept of “Right therapy to the right patient” & may also explain to the fact that why, only some people are more prone to develop head and neck cancer despite the usage of tobacco,alcohol by so many people. Disclosure All authors have declared no conflicts of interest.

Molecular targeted agents have lower hematological toxicity. However, specific side-effects such as allergic rashes, skin reactions and high cost limit their use. We report a case of 35-year-old male patient with carcinoma of left tonsil treated with concurrent cetuximab and radiotherapy. After four weeks of treatment, the patient developed sudden onset of pain in the left calf region radiating to the left foot. Doppler study of the left lower limb revealed complete thrombosis of superficial femoral, popliteal and proximal tibial arteries and veins and no flow in anterior tibial artery and lower posterior tibial artery. Emergency embolectomy was done. After 48 h of observation, no improvement was noted. A repeat Doppler examination showed similar finding. Ultimately a left lower limb amputation was done. We report simultaneous arterio-venous thrombosis associated with cetuximab-based chemoradiotherapy. Oncologists should be aware of this possible complication to undertake early intervention.