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Background: We prospectively assessed acute and late toxicity in post‐operative oral cavity squamous cell carcinoma (PO‐OCSCC) treated with adjuvant dysphagia optimized intensity‐modulated radiotherapy (Do‐IMRT) versus standard IMRT (S‐IMRT). Material and methods: Fifty‐six patients of PO‐SCC without indications of concurrent chemotherapy were alternatively allocated to adjuvant Do‐IMRT (n = 28) versus S‐IMRT (n = 28) arms. High‐ and low‐risk planning target volume received 60 and 54 Gy, respectively, in 30 fractions over 6 weeks. Dysphagia aspiration‐related structures (DARS) were contoured in both arms. While dosimetric constraints were given in Do‐IMRT arm, doses to DARS were only observed without dose constraints in S‐IMRT arm. Acute and late toxicity were assessed by common terminology criteria for adverse events (CTCAE) v5.0 and RTOG criteria, respectively. Results: The primary site of disease was buccal mucosa (64% vs. 53%) and oral tongue (21% vs. 32%), in Do‐IMRT and S‐IMRT, respectively. The mean doses to DARS was significantly less with Do‐IMRT (all p < 0.001) as compared to S‐IMRT. Median follow‐up was 24.2 months. Grade ≥2 oral pain was less in the Do‐IMRT arm (50% vs. 78.6%, p = 0.05). Grade ≥2 late dysphagia at 2 years were significantly less in Do‐IMRT arm (0% vs. 17.9%, p = 0.016). Two‐year locoregional control was 89.2% in Do‐IMRT and 78.5% in S‐IMRT (p = 0.261). Conclusion: DARS can be spared in PO‐OCSCC patients treated with Do‐IMRT without compromising coverage of the target volumes. Limiting doses to DARS leads to lesser acute and late toxicity without compromising locoregional control. [ABSTRACT FROM AUTHOR]

Objective: To evaluate efficacy and late toxicity of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) in definitive management of head-and-neck cancers.Methods: In this prospective interventional study, histological proven squamous cell carcinoma of oropharynx, hypopharynx, or larynx with stage T1-3 N0-3 M0 who were not candidates for concurrent chemotherapy were treated with IMRT-SIB with radical intent. Doses prescribed for IMRT-SIB to meet the clinical needs of nodal volumes were either SIB-66 schedule 66 Gray (Gy) prescribed to high risk (HR) planned target volume (PTV), 60 (Gy) to intermediate risk (IR) PTV and 54 Gy to low risk (LR) PTV in 30 fractions or SIB-70 schedule 70 Gy to PTV-HR, 59.4 Gy to PTV-IR and 56 Gy to PTV-LR in 33 fractions.Result: Forty-five patients were included. Forty-two patients were treated with SIB-66 schedule and three patients with SIB-70 schedule. The median follow-up period was 21 (6-68) months. There was residual disease in three patients. Recurrence was observed in 24 patients. Most recurrences were in HR volume (n = 19) and three patients had distant failure. Estimated 2-year locoregional control, disease-free survival, and overall survival were 55.55%, 49.7%, and 51.1%, respectively. Grade 3 late skin toxicity, subcutaneous fibrosis, and xerostomia were observed in three patients.Conclusions: Efficacy and late toxicity of IMRT-SIB observed in our study suggest it as a suitable treatment option for patients who are not fit for chemoradiation. [ABSTRACT FROM AUTHOR]

To investigate the role of interaction of tobacco metabolizing polymorphic cytochrome P450s (CYPs) and glutathione S‐transferase M1 (GSTM1) with environmental risk factors in modifying the susceptibility to head and neck squamous cell carcinoma (HNSCC), a case–control study with 1250 proven cases of HNSCC and equal number of healthy controls was planned. A small but significant increase in the risk to HNSCC (1–2 fold) in the cases with variant genotypes of CYPs (1A1 or 1B1 or 2E1) increased several folds (up to 13 fold) in regular tobacco or alcohol users. This several fold increase in risk could be due to more than multiplicative interaction observed between the risk genotypes of CYPs and tobacco or alcohol. A synergistic effect was also observed between tobacco as well as alcohol users among cases with risk genotypes of CYPs and GSTM1 that resulted in a further increase in risk (up to 29 fold) to HNSCC. Interestingly, the increase in the risk in tobacco users among cases with variant genotypes of CYPs or a combination of CYPs & GSTM1 (−) was associated with a higher mRNA expression of CYPs when compared to nontobacco users in controls with wild type of genotypes of CYPs & GSTM1. The data suggest that the interaction of genetic and environmental risk factors leads to increased expression of CYPs which may increase the levels of tobacco‐derived carcinogens thereby modifying the risk to HNSCC. [ABSTRACT FROM AUTHOR]

The present case–control study consisting of 1300 cases of head and neck squamous cell carcinoma (HNSCC) and the equal number of controls aimed to investigate the association of functionally important polymorphisms in cytochrome P4502A6 (CYP2A6*1B, CYP2A6*4C, CYP2A6*9‐rs28399433) with HNSCC and the treatment response in cases receiving a combination of chemotherapy/radiotherapy (CT/RT). A significant decrease in risk to HNSCC was observed in the cases with deletion (CYP2A6*4B and CYP2A6*4C) or reduced activity genotypes (CYP2A6*9) of CYP2A6. This risk to HNSCC was further reduced significantly in tobacco users among the cases when compared to nontobacco users among the cases. The risk was also reduced to a slightly greater extent in alcohol users among the cases when compared to nonalcohol users among the cases. In contrast with decreased risk to HNSCC, almost half of the cases with variant genotypes of CYP2A6 (CYP2A6*1A/*4C+*1B/*4C+*4C/*4C and *9/*9) did not respond to the treatment. Likewise, the survival rate in cases receiving the treatment, after 55 months of follow‐up was significantly lower in cases with deletion (6.3%) or reduced activity (11.9%) allele than in the cases with common alleles (41%). The present study has shown that CYP2A6 polymorphism significantly reduces the risk to HNSCC. Our data further suggested that CYP2A6 polymorphism may worsen the treatment outcome in the cases receiving CT/RT. [ABSTRACT FROM AUTHOR]

Objectives: Randomized controlled trials have shown improved loco‐regional control (LRC) and disease‐free survival (DFS) by modest acceleration using six fractions per‐week radiotherapy (RT) as compared to conventional fractionation in patients of head and neck squamous cell carcinoma. We aimed to evaluate the role of pure modestly accelerated fractionated radiotherapy (PM‐ART) using six fractions per‐week in patients of postoperative oral cavity squamous cell carcinoma (OCSCC). Materials and Methods: Between May 2015 and July 2016, 40 OCSCC patients with ≥ 1 indication of RT were treated with adjuvant PM‐ART, 60 Gray in 30 fractions over 5 weeks by three‐dimensional conformal technique on a linear accelerator with a sixth 2 Gray fraction on Saturday using same fields. Primary endpoint was to assess acute toxicity, which was reviewed weekly during RT using Radiation Therapy Oncology Group criteria. Results: Maximal grade 3 oral mucositis, pharynx/esophageal toxicity, and skin toxicity were seen in 77.5%, 25%, and 17.5%, respectively. Two patients had grade 4 mucositis. 47.5% were on tube feeding during RT. All the patients were taken off Ryle's tube within 4 weeks of RT completion. The median RT completion duration was 36 days. Three patients had treatment interruptions. With a median follow‐up of 21.2 months, the 2‐year LRC, DFS, and overall survival rates were 87.5%, 83.5%, and 85%, respectively. There were two distant failures. Conclusion: PM‐ART is feasible and tolerable. The high acute mucositis rates did not result in increased consequential late toxicity. [ABSTRACT FROM AUTHOR]

Context: Tongue is a three dimensional structure and assessment of accurate tumor extent is important for surgical planning. Various imaging modalities are used to assess the dimensions and depth of tumor like MRI, CECT, and clinical examination with doubtful accuracy. Aim: To evaluate tumor thickness in three dimensions on MRI and whether it correlates well with final histopathology so as to assess its reliability in staging and planning treatment. Material and Methods: Fifty patients with biopsy proven squamous cell carcinoma of the tongue who were planned for surgery and willing to participate in the study were included. These patients underwent MRI to analyse tumor thickness and extent of tumor spread in three planes and it is correlated with final histopathology to assess the reliability of MRI in preoperative assessment. Setting and Design: This is a prospective study, conducted at a tertiary care hospital and research centre. Correlation and linear regression analysis were used to study the relationship between tumor dimensions in MRI and correlated with the results on final histopathology. Result: In this prospective study, we studied fifty cases of carcinoma tongue of which 38 were males and 12 were females. Mean age was 49 years. The tumor thickness on MRI correlated well with final histopathology and most values fell below the 1:1 (x=y) line of agreement. Also, depth of invasion on histopathology was correlated with MRI which also related well to the histopathology taking into account the shrinkage. Conclusion: There was a significant correlation between the MRI T staging and final histopathology and it is found that MRI findings and depth correlated well with final histopathology taking into account the shrinkage factor. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms have been reported in several cytochrome P450 (CYP) genes, including CYP1B1 which metabolically activates procarcinogens present in tobacco to carcinogenic intermediates. This study used a case-control approach in North Indian population to determine associations between genetic variants in CYP1B1 and risk of Head and Neck Squamous Cell Carcinoma (HNSCC). We examined the genotype and haplotype frequencies at various single-nucleotide polymorphisms (SNPs), including SNPs previously reported in the promoter region and intron 1 of CYP1B1 in Caucasians. Using cycle sequencing, 9 SNPs were identified in the promoter region, intron 1, and exons 2 and 3. Haplotype analysis revealed that 5 SNPs (those in the promoter region, intron, and Arg48Gly and Ala119Ser in exon 2) were in strong linkage disequilibrium (LD). Cases with the T-A-T-G-T haplotype were significantly associated with increased risk of HNSCC. Interestingly, qRT-PCR studies revealed a significant increase in mRNA expression of CYP1B1 in peripheral blood isolated from cases with the T-A-T-G-T haplotype compared with cases with the C-G-C-C-G haplotype, and in cases compared to controls for both main haplotypes. The data thus provide evidence that CYP1B1 haplotypes could be more effective in predicting HNSCC risk. Environ. Mol. Mutagen. 58:443-450, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: With conformal radiotherapy techniques, acute and late toxicities can be reduced because of better dose conformity and reduced doses to normal tissue. With Intensity Modulated Radiation Therapy (IMRT) further dose escalation is possible and one of the methods is IMRT with simultaneous integrated boost (IMRT-SIB).Aim: To evaluate feasibility, toxicity patterns and loco-regional control rates of IMRT-SIB technique in head and neck cancer patients who are not suitable candidates for concurrent chemoradiation.Study Design: Prospective study of 30 patients treated with IMRT-SIB technique and evaluation of clinical results.Method and Materials: 30 patients received definitive treatment using IMRT-SIB without concurrent chemotherapy. Patients were monitored during and after treatment for toxicity using the Radiation Therapy Oncology group (RTOG) criteria. Analysis of acute and late toxicity and early efficacy is presented.Results: The median treatment duration was 42days (range 41-43days). Overall, maximum acute Grade 3 toxicity of mucositis, skin, pharynx/esophageal toxicity and laryngeal were 56.66%, 30%, 26.67%, and 6.67% respectively at treatment completion. None of the patients had Grade 4 acute toxicity. No haematological toxicity was seen. Overall, grade 2 late toxicities were 7% (subcutaneous toxicity) and 13.3% (Xerostomia). Loco regional control rate at a median follow up of 13months was 86%.Conclusion: IMRT-SIB is a safe and acceptable treatment option for patients of head and neck squamous cell carcinoma unsuitable for definitive chemo-radiotherapy. [ABSTRACT FROM AUTHOR]

Circulating free DNA (cfDNA) is in use for the non-invasive diagnosis of tumors. Methylation of tumor suppressor genes (TSGs) is an early event in carcinogenesis and may serve as tumor biomarker. We have investigated cfDNA integrity and methylation of tumor suppressor genes P16, DAPK and RASSF1A in serum cfDNA of oropharyngeal squamous cell carcinoma (OPSCC) comparing paired serum and tumor tissue samples to evaluate their diagnostic use. Prospective case-control study, paired serum and tissue samples from 56 OPSCC, and 15 normal controls (NC). Sybr green Quantitate real time PCR was used for cfDNA quantification through amplification ALU 115 and 247 fragments. Promoter methylation of was analyzed in paired samples using methylation specific PCR. There was significantly high cfDNA integrity in OPSCC compared to normal control (p = < 0.0001). The cfDNA integrity values were significantly higher and associated with nodal status (p = 0.016). The AUC for cfDNA integrity was 0.967. The P16 , DAPK and RASSF1 promoters were significantly hypermethylated in serum of OPSCC compared to NC with high concordance in tissue (up to 96.55 %). The gene promoter methylation of P16 was associated with smoking (p = 0.030), RASSF1A with stage (p = 0.011). The combination of ALU115 with cfDNA integrity and combination of gene methylation increases diagnostic sensitivity. In followup samples the cfDNA change was not different. Liquid biopsy approach including cfDNA integrity, methylation profiling in cfDNA, in combination or separately can assist in the diagnosis of OPSCC along with radio diagnostic scan. Serum changes represent changes in tissue with very high concordance. [ABSTRACT FROM AUTHOR]