Correlation of PD-L1 expression with toxicities and response in oropharyngeal cancers treated with definitive chemoradiotherapy.

Introduction: The programmed death receptor ligand 1 (PD-L1) is a cell-surface glycoprotein expressed in tumour cells (TCs) and is also upregulated in tumour infiltrating lymphocytes. The effect of PD-L1 expression on TCs and tumour-infiltrating lymphocytes (TILs) on acute radiation toxicity and response in oropharyngeal squamous cell carcinoma treated with concurrent chemoradiotherapy is less known. Material and methods: Squamous cell carcinoma of oropharynx with stage II-IVA (AJCC 8th) were recruited in this prospective observational study. Definitive radiation therapy (RT) of 70 Gray in 35 fractions at 2 Gray per fraction, 5 fractions a week in 2 phases was delivered with concurrent chemotherapy (cisplatin 40 mg/m2 weekly). Patients were assessed weekly for acute toxicities with Radiation Therapy Oncology Group criteria. Response assessment was done at 3 months post RT according to World Health Organization response assessment criteria. The programmed death receptor ligand 1 expression in TCs and TILs was correlated with acute toxicity and survival. Results: Of 51 patients, 20 (39.2%) had PD-L1 expression in TCs and 18 (35.3%) in TILs. Patients with PD-L1 expression in TCs had fewer grade ≥ 3 oral mucositis (25% vs. 58%; p = 0.02) and grade ≥ 3 dysphagia (25% vs. 55%; p = 0.046). The programmed death receptor ligand 1-tumour infiltrating lymphocytes positives had lower ≥ 3 grade oral mucositis (22% vs. 58%; p = 0.02) and ≥ 3 grade dysphagia (17% vs. 58%; p = 0.007). Two-year overall and progression-free survival rate for the PD-L1-tumour-positive vs. PD-L1-tumour-negative group was not different (p > 0.5). Conclusions: Positive PD-L1 expression is associated with fewer acute radiation toxicities, and this could be used as a potential biomarker.

Prospective evaluation of definitive chemoradiotherapy with volumetric modulated arc therapy in patients with muscle invasive carcinoma of urinary bladder.

INTRODUCTION: Concurrent chemoradiotherapy (CTRT) remains one of the treatment options in patients with muscle invasive bladder cancer (MIBC) unwilling/unsuitable for radical surgery. We evaluated the role of volumetric modulated arc therapy (VMAT) in MIBC patients treated with definitive CTRT. MATERIAL AND METHODS: 25 patients of histologically proven transitional cell MIBC (T2-T4a, N0, M0) unwilling/unsuitable for radical surgery (after maximal transurethral resection of bladder tumour) were recruited in this prospective study. Primary clinical target volume (CTV) consisted of the gross tumour and whole bladder. Primary planning target volume (PTV) and nodal PTV were prescribed 60 Gy and 54 Gy (both in 30 fractions). Concurrent chemotherapy was cisplatin (40 mg/m2) weekly. Acute toxicities were assessed as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Survival estimates were done from the date of registration using the Kaplan-Meier method. RESULTS: Median age was 70 years (37-80 years). Median overall treatment time was 45 days (44-51). Median number of chemotherapy cycles was 5 (range 3-6). 5 (20%) and 4 (16%) patients respectively suffered from acute grade ≥ 2 gastrointestinal and grade ≥ 2 genitourinary toxicities during treatment. One patient each had grade 3 anaemia and neutropenia. At a median follow-up of 34 months (10-45 months), 3-year progression-free survival and overall survival were 65.6% and 81.2% respectively. 3-year distant metastasis-free survival was 90.5%. Bladder preservation rate at 3 years was 68%. CONCLUSIONS: Definitive CTRT with VMAT is well tolerated in patients with MIBC unsuitable for surgery and yields decent survival and bladder preservation outcome.

Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (>50 Gy) with or without chemotherapy.

PURPOSE: Benzydamine is recommended for prophylaxis of oral mucositis (OM) in head and neck cancer (HNC) patients for radiation doses (<50 Gy). This study evaluates role of benzydamine for higher radiation doses (>50 Gy) with or without chemotherapy. METHODS: One hundred twenty patients of HNC with planned radiation doses of ≥60 Gy were randomized to group A (control radiotherapy alone), group B (study radiotherapy alone), group C (control chemoradiotherapy), or to group D (study chemoradiotherapy). Groups A and C were advised saline mouth rinses, and in groups B and D, additional benzydamine rinses (0.15%) were advised. Mucositis grading was done with both WHO (WHO-M) and CTCAE (CTC-M) version 4.0 (common terminology criteria for adverse events) weekly. RESULTS: Patient characteristics are presented in the table. Patients in group B had lesser grade 3 WHO-M and CTC-M as compared to group A, 62.1 vs. 36.4% (p = 0.038) and 51.7 vs. 27.3% (p = 0.043), respectively. The rates of Ryle's tube feeding (RTF), intravenous fluid supplementation (IVF), and hospitalization were also lesser in group B as compared to A, 34.5 vs. 21.2% (p = 0.18), 27.6 vs. 9.1% (p = 0.06), and 6.9 vs. 0% (p = 0.21), respectively. WHO-M and CTC-M in groups C and D were not statistically different, 64.3 vs. 43.3% (p = 0.091) and 53.6% vs. 43.3% (p = 0.30), respectively. The rates of RTF, IVF, and hospitalization were all lesser but p > 0.05. CONCLUSION: Benzydamine significantly reduces OM even at doses >50 Gy in HNC patients. Its role in patients receiving concurrent chemotherapy further needs to be evaluated.

Primary Small Cell Neuroendocrine Carcinoma of nasopharynx with metastatic cervical lymph nodes: an exceedingly rare entity with review of literature.

Small cell neuroendocrine carcinoma of nasopharynx is extremely rare and displays aggressive nature with a poor prognosis. Neuroendocrine tumours rarely arise from the head and neck region and pose a diagnostic and management challenge. In English literature, only 16 cases of primary small cell neuroendocrine carcinoma of nasopharynx have been reported so far; and to the best of our knowledge, this is the seventeenth case and second in the younger age group. Here, we report the case of an adolescent male patient who presented with nasal blockage, repeated episodes of epistaxis and neck swellings. After proper diagnostic workup, the diagnosis of small cell neuroendocrine carcinoma of nasopharynx was made. The patient was treated with chemotherapy, followed by radiotherapy. Imaging investigation executed after the end of the treatment exhibited complete remission of the disease. The patient is kept under active surveillance with no signs of relapse at present.

Neuroendocrine tumor of the gall bladder: A rare case report with review of literature.

Neuroendocrine tumor of the gall bladder is an extremely rare malignancy, accounting for only 0.2% of all neuroendocrine tumors. Gall Bladder-Neuroendocrine Tumors (GB-NETs) are mainly diagnosed on histological examination of GB samples after cholecystectomy or after any biliary pathology surgery since it is very difficult to diagnose based on imaging. The overall outcome of gallbladder NET is worse than the adenocarcinoma of the gallbladder. No focused approach towards its treatment is available in literature due to its rarity. We share our experience of gall bladder NET in a 37-year-old female who was successfully managed at our institution.

Dosimetric Comparision of Coplanar versus Noncoplanar Volumetric Modulated Arc Therapy for Treatment of Bilateral Breast Cancers.

Introduction: The purpose of this study was to compare the dosimetric parameters of volumetric modulated arc therapy (VMAT) treatment plans using coplanar and noncoplanar beams in patients with bilateral breast cancer/s (BBCs) in terms of organ at risk sparing and target volume coverage. The hypothesis was to test whether VMAT with noncoplanar beams can result in lesser dose delivery to critical organs such as heart and lung, which will result in lesser overall toxicity. Materials and Methods: Data of nine BBC cases treated at our hospital were retrieved. Computed tomography simulation data of these cases was used to generate noncoplanar VMAT plans and the parameters were compared with standard VMAT coplanar plans. Contouring was done using radiation therapy oncology group guidelines. Forty-five Gray in 25 fractions was planned followed by 10 Gy in five fractions boost in breast conservation cases. Results: No significant difference in planning target volume (PTV) coverage was found for the right breast/chestwall (P = 0.940), left breast/chestwall (P = 0.872), and in the total PTV (P = 0.929). Noncoplanar beams resulted in better cardiac sparing in terms of Dmean heart. The difference in mean dose was >1 Gy (8.80 ± 0.28 - 7.28 ± 0.33, P < 0.001). The Dmean, V20 and V30 values for total lung slightly favor noncoplanar beams, although there was no statistically significant difference. The average monitor units (MUs) were similar for coplanar plans (1515 MU) and noncoplanar plans (1455 MU), but the overall treatment time was higher in noncoplanar plans due to more complex setup and beam arrangement. For noncoplanar VMAT plans, the mean conformity index was slightly better although the homogeneity indices were similar. Conclusion: VMAT plans with noncoplanar beam arrangements had significant dosimetric advantages in terms of sparing of critical organs, that is Dmean of heart doses with almost equivalent lung doses and equally good target coverage. Larger studies with clinical implications need to be considered to validate this data.

Combination of image-guided IMRT and IGBT in locally advanced carcinoma cervix: Prospective evaluation of toxicities and clinical outcomes from a tertiary cancer center in India.

Purpose: We aimed to assess the toxicity profile and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with a combination of image-guided intensity-modulated radiation therapy (IG-IMRT) and image-guided brachytherapy (IGBT). Material and methods: 25 LACC patients were recruited in this single-arm prospective study. Whole pelvis IG-IMRT was delivered (45 Gy with simultaneously integrated nodal boost of 55 Gy in 25 fractions), with concurrent weekly cisplatin (40 mg/m2). Patients received IGBT of 7 Gy each in 4 fractions to high-risk clinical target volume (HR-CTV). First fraction was done under MRI, and subsequent fractions were performed under CT guidance. Primary endpoint was acute toxicity, and secondary endpoints were 2-year loco-regional control and late toxicity. Results: The median age was 52 years, and FIGO 2018 stage distribution was IIA2, IIB, IIIB, and IIIC1 in 12%, 40%, 20%, and 28% patients, respectively. All patients received concurrent chemotherapy with median number of 5 cycles (range, 4-5 cycles). Grade 1 and 2 diarrhea, and grade 1 cystitis was reported in 4 (16%), 3 (12%), and 2 (8%) patients, respectively. Grade 1 and 2 anemia, and grade 1 and 2 dermatitis were observed in 3 (12%) and 2 (8%), and 3 (12%) and 3 (12%) patients, respectively. No patient reported grade 3-4 acute toxicity. At median follow-up of 29.5 months (range, 25-37 months), late grade 1 bladder toxicity was observed in 1 (4%) patient. Loco-regional control at 1 and 2 years were 96% and 92%, respectively. Conclusions: The combination of IG-IMRT and IGBT yielded excellent outcomes in terms of acute toxicity and loco-regional control.

Retrospective analysis of clinical outcome of 100 inoperable oral cavity carcinoma treated with definitive concurrent chemoradiotherapy with or without induction chemotherapy.

Objectives: The management of inoperable oral cavity squamous cell carcinoma (OC-SCC) is onerous. We aimed to retrospectively analyse the outcome of our cohort of inoperable OC-SCC treated with definitive concurrent chemoradiotherapy (CTRT) with or without induction chemotherapy (IC). Methods: Data of 100 patients (January 2017 to May 2022) of histopathologically proven inoperable OC-SCC treated with definitive CTRT with weekly cisplatin 40 mg/m2 were retrieved from our departmental archives. Radiotherapy (RT) was delivered with three-dimensional conformal plan (66-70 Gy). Toxicities were evaluated using acute morbidity scoring criteria of Radiation Therapy Oncology Group. The response was evaluated as per WHO criteria. Progression free survival (PFS) was calculated from the date of the start of treatment (IC/CTRT) using Kaplan Meier method. Results: Median age was 45 years (range 30-80 years). The primary site was oral tongue (59%), retro-molar trigon (15%), buccal mucosa (15%) and others (11%). The stage was III: IVA: IVB in 16:70:14 patients respectively. 72% patients received IC (platinum ± 5 FU ± taxane). Grade 3 skin toxicity, oral mucositis and dysphagia was noted in 13 (13%), 19 (19%) and 13 (13%) patients respectively. The median follow-up duration was 30.5 months (range 6-62 months). Complete response (CR), partial response, progressive disease and death at the time of the last follow-up were 49%, 25%, 15% and 11% respectively. 2-year PFS rate was 49.5%. Stage III patients had a higher CR rate (81.2% versus 42.8%; p = 0.0051) and higher 2-year PFS (81.2% versus 46.4%; p = 0.0056) in comparison to stage IV patients. Conclusion: Inoperable patients of OC-SCC treated with definitive CTRT with or without IC yielded CR in approximately half of patients with acceptable toxicity profiles.

Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image guided-IMRT in locally advanced rectal cancers.

Purpose: To analyse the safety and efficacy of neoadjuvant chemoradiation (NACRT) with dose-escalated image-guided intensity modulated radiation therapy (IG-IMRT) in locally advanced (T3/4; T1-4N1-2) rectal cancers (LARCs). Materials and methods: Twenty patients with the diagnosis of LARC were recruited in this prospective interventional single-arm study treated by IG-IMRT with 45 Gray (Gy) in 25 fractions to elective nodal volumes and 55 Gy in 25 fractions to the gross primary and nodal disease with concurrent capecitabine 825 mg/m2 twice daily on radiotherapy days. Patients underwent total mesorectal excision 6-8 weeks post completion of NACRT followed by adjuvant chemotherapy (Capecitabine and oxaliplatin every 3 weekly for 6-8 cycles). Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Clinical T stage was T3:T4 in 19:1 and clinical N0:N1: N2 in 2:7:11 patients, respectively. With a median follow up of 21.2 months (13.8-25.6 months), 18 of 20 (90%) patients received the full course of treatment. Tumour and nodal downstaging was achieved in 78% and 84% of patients, respectively. pCR and overall complete response (defined as pCR and near CR) was achieved in 22.2% and 44.4% of patients, respectively. 2 (10%) patients completed NACRT, and achieved complete clinical response but refused surgery. Adjuvant chemotherapy course was completed by 17/18 (94.5%) patients. Grade 3 toxicities were observed in 2 (10%) patients during NACRT. All patients were disease-free at the time of the last follow up. Conclusion: Dose-escalation of NACRT therapy with IG-IMRT in LARC patients offers decent rates of pCR and overall response with excellent LRC and acceptable toxicities.

Toxicities and clinical outcome of adjuvant dysphagia optimized versus standard intensity-modulated radiotherapy for post-operative oral cavity cancers: A prospective comparative study.

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.

Role of p53 and p73 genes polymorphisms in susceptibility to esophageal cancer: a case control study in a northern Indian population.

Genetic variants in p53 and in its homologue p73 may modulate Esophageal Cancer (EC) risk because they are supposed to influence cell cycle progression, apoptosis and DNA repair. Therefore, we aimed to evaluate the association of p53 intron3 16 bp duplication and p73 G4C14-to-A4T14 polymorphisms with susceptibility to EC in a northern Indian population in 255 EC patients and 255 age and sex matched healthy controls. We found that p53 intron3 16 bp duplication polymorphism was not associated with EC and its clinical characteristics. However, p73 G4C14-to-A4T14 polymorphism was associated with significant higher risk of EC (OR = 1.74, 95% CI = 1.16-2.60, P = 0.007) in an allele dose-dependent manner (P(trend) = 0.0047). Stratification of subjects on the basis of clinical characteristics showed that p73 AT genotype carriers were at significant increased risk of developing esophageal squamous cell carcinoma (OR = 1.78, 95% CI = 1.18-2.67, P = 0.006) at middle third tumor location (OR = 1.87, 95% CI = 1.18-2.97, P = 0.007) with lymph node metastasis (OR = 1.77, 95% CI = 1.04-3.02, P = 0.035). No interaction with environmental risk factors was observed with any of the studied polymorphisms. In summary, p73 G4C14-to-A4T14 polymorphism but not the p53 intron3 16 bp duplication polymorphism is associated with EC and its clinical characteristics in northern Indian population.

Dynamics of cell-free DNA in predicting response in adult diffuse glioma on chemoradiotherapy.

BACKGROUND: Adult diffuse glioma (ADG) is a heterogeneous primary brain tumor with a variable prognosis and treatment response. Tissue biomarkers and molecular genetic profiling form an integral part of diagnosis and prognostication. However, obtaining tissue in inoperable locations and diagnosis of recurrence can be an issue. Cell-free DNA (cfDNA) may help to meet these challenges in the management of ADG. OBJECTIVES: The study aimed to serially quantify cfDNA in ADG on chemoradiation and to correlate mutational profiling of the cfDNA with biopsy. MATERIAL AND METHODS: The study group comprised of histopathological confirmed ADG (n = 50), including grade II, III and IV glioma, and controls (n = 25). Serum cfDNA was extracted using ChargeSwitch gDNA 1 mL Serum Kit (Invitrogen, USA) and quantified using SYBR based quantitative polymerase chain reaction (qPCR). Next-generation sequencing (NGS) was performed in 07 pre-operative and 05 post-operative cfDNA and tumor biopsy DNA on an Ion personal genome machine (IonPGM) with an in-house designed NGS panel (including TP53, ATRX, and IDH1 and IDH2). RESULTS: In patients with ADG, the pre-radiotherapy cfDNA level was significantly higher (Median; 113.46 ng/mL) than normal controls (Median; 74.37 ng/mL), (p = 0.048). Non-responders had significantly higher cfDNA levels (Median; 184.4 ng/mL), than responders (Median; 68.12 ng/mL), (p = 0.023). TP53 gene mutation was most common in both pre-operative and post-operative cfDNA samples. CONCLUSION: Pre-radiotherapy cfDNA levels are associated with clinical outcomes independent of other prognostic factors. Targeted NGS in pre-operative cfDNA matches the results of IHC analysis with high concordance, and it may be helpful in inoperable cases or ADG recurrence.

Long term outcome and late toxicity Of SIB-IMRT in definitive management of head and neck cancers in patients not suitable for chemo-radiotherapy.

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.

Treatment Pattern and Outcomes in Verrucous Carcinoma of Oral Cavity: A Single Institutional Retrospective Analysis from a Tertiary Cancer Center and Review of Literature.

Verrucous carcinoma (VC) is a locally invasive uncommon histopathological variant of oral squamous cell cancer. There is paucity of literature regarding control rates in these cases. We intend to report the outcomes in terms of administered treatment and control rates. 28 patients of oral cavity verrucous carcinomas treated at our institute from March 2014 to December 2018 were reviewed retrospectively. Demographic profile, histopathological features and clinical outcomes were analyzed. Statistical analysis was performed with SPSS for Mac (version 23.0). Median age was 54 years (range 31-75) with M:F ratio of 25:3. Buccal mucosa was the most common site. All patients underwent surgical resection except one. Of these, 24 had neck dissection; 12 had supra-omohyoid neck dissection, eleven had modified neck dissection and one patient underwent radical neck dissection. Three patients had their histology upgraded to squamous cell carcinomas in the post-operative histopathology. The post-operative staging was as follows: 21% stage I and 35% stage II. One patient opted for non-surgical approach and received radical concurrent chemoradiotherapy. Median follow up was 12 months (range 6-36). Two patients had local failures and one had a regional failure. No distant metastasis was found. There was one death. 14-Months survival rate was 92%. Estimated 18 month loco-regional control rate was 92%. Curative surgical resection remains the cornerstone for VC of oral cavity. Any change of histopathology post-operatively to squamous cell carcinoma is a poor prognostic sign and needs appropriate adjuvant treatment.

Role of survivin gene promoter polymorphism (-31G>C) in susceptibility and survival of esophageal cancer in northern India.

BACKGROUND AND AIM: Survivin is an upregulated inhibitor of apoptosis protein in esophageal cancer (EC), and a promoter region polymorphism (-31G>C) in the survivin gene has been reported as a modulator of gene expression. We aim to explore the role of survivin -31G>C polymorphism in susceptibility and survival of EC patients in northern Indian population. MATERIALS AND METHODS: A case-control study was performed in 500 subjects (250 EC patients and 250 controls), and genotyping was done by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. RESULTS: Survivin CC genotype was found to be significantly associated with EC susceptibility [odds ratio (OR) = 2.29; 95% confidence interval (CI) = 1.27-4.14; P = 0.006], particularly in males (OR = 4.91; 95% CI = 2.19-11.02; P = 0.0001) having squamous cell carcinoma (SCC) histopathology (OR = 2.4; 95% CI = 1.36-4.21; P = 0.002) at middle third esophagus location (OR = 2.60; 95% CI = 1.40-4.82; P = 0.002). Patients carrying CC genotype were found to have higher susceptibility to lymph node metastasis (OR = 2.82; 95% CI = 1.46-5.48; P = 0.002). However, on survival analysis, no prognostic role of survivin -31G>C polymorphism was detected. In case-only analysis, no gene-environment interaction was observed. CONCLUSION: Survivin promoter region polymorphism (-31G>C) is associated with susceptibility and clinical characteristics but not prognosis of esophageal cancer in northern Indian population.

Evaluation of MTHFR677C>T polymorphism in prediction and prognosis of esophageal squamous cell carcinoma: a case-control study in a northern Indian population.

Early diagnosis and better prognosis of esophageal squamous cell carcinoma (ESCC) is still a challenge. Besides environmental risk factors, nutritional deficiencies have an established role in pathogenesis of ESCC. Folate deficiency and functional polymorphisms in folate metabolizing genes such as methylene tetrahydrofolate reductase (MTHFR) 677C>T may have oncogenic role through disruption of normal DNA methylation pattern, synthesis, and impaired DNA repair. MTHFR677C>T or A222V (rs1801133) polymorphism has conflicting role in susceptibility to ESCC among different populations. Thus, we aimed to study the role of MTHFR677C>T polymorphism in susceptibility, survival, and interaction with environmental risk factors in ESCC patients from a northern Indian population. A case control study was performed in 208 ESCC incident cases (including 114 follow-up cases) and 223 healthy controls, and genotyping was done by PCR-RFLP. Our results show no significant association of MTHFR677C>T polymorphism with ESCC, tumor locations, or gender of subjects. However, we found a trend of decreased risk of ESCC due to interaction of MTHFR677CT genotype with smoking and alcohol intake. Kaplan Meier, and Cox regression survival analysis showed no prognostic impact of MTHFR677C>T polymorphism in ESCC patients. In conclusion, MTHFR677C>T polymorphism does not seem to have significant role either in susceptibility or survival of ESCC in a northern Indian population.

Correlation of Molecular Markers in High Grade Gliomas with Response to Chemo-Radiation.

BACKGROUND: The standard of care in high grade glioma (HGG) is maximal safe surgical resection followed by adjuvant radiotherapy (RT) with/without chemotherapy. For anaplastic gliomas, studies have shown use of procarbazine, lomustine, vincristine (PCV) improves overall survival (OS) and progression free survival (PFS). Currently, there is substantial evidence that molecular markers strongly predict prognosis and response to treatment. METHODS: Between January 2016 to January 2018, 42 patients were accrued and followed up till April 2019. The primary end points were to correlate molecular markers with response to therapy in terms of OS and PFS in HGG. The secondary end point was to evaluate frequency of 1p/19q codeletion, IDH 1 mutation, ATRX deletion and p53 in HGG patients. RESULTS: The median age was 46 years (range 18-67) with M:F ratio 30:12. The frequency of IDH1 mutation,1p/19q codeletion, p53 mutation and ATRX mutation were 42.8%, 16.6%, 42.8% and 14.2% respectively. All the seven patients with 1p/19q codeletion had IDH1 mutation. Median follow up was 22 months. The 20-months PFS for different mutations were as follows; IDH1-mutated vs wild type: 53.6% vs 29.8%; p-0.035, 1p/19q codeleted vs non-codeleted: 85.7% vs 62.3%; p-0.011, p53 wild type vs mutated 32.1% vs 35.6%; p-0.035 and ATRX lost vs retained: 55.6% vs 53.3%; p- 0.369. The 20-months OS for IDH1 mutated vs wild type: 82.4% vs 30.6%; p-0.014, 1p/19q codeleted vs non-codeleted: 85.7% vs 65.8%; p-0.104, p53 wild-type vs mutated 45.5% vs 73.9%; p-0.036 and ATRX lost vs retained: 100% vs 60.3%; p-0.087. CONCLUSION: Codeletion of 1p/19q with IDH1 mutation in HGG is associated with a significantly favourable PFS. However, larger studies with longer follow up are required to evaluate OS and PFS in all the molecular subgroups.

Patterns of failure and clinical outcomes of post-operative buccal mucosa cancers treated with adjuvant ipsilateral radiotherapy.

PURPOSE: Adjuvant radiotherapy (RT) in buccal mucosa cancers is guided by histopathological factors. The decision to treat ipsilateral or bilateral draining lymph node is on physician discretion and guidelines do not have a defined indication regarding this. We aimed to analyze the failure patterns and survival in buccal mucosa cancers treated with adjuvant ipsilateral RT. MATERIALS AND METHODS: One hundred sixteen cases of post-operative buccal mucosa cancers-pT3 or more, node positive, close margins (1-5 mm), lymphovascular invasion positive, perineural invasion positive, depth of invasion >4 mm-treated with RT to primary and ipsilateral nodes from May 2013 to May 2019 were retrospectively analyzed. Patients were treated to a dose of 60-66 Gy (44 Gy in the first phase and a coned down boost of 16-22 Gy in the second phase) with three-dimensional conformal radiotherapy on a linear accelerator. Primary end point was to assess control rates and secondary end point was to evaluate the overall survival (OS) and disease-free survival (DFS) outcomes. RESULTS: Median age was 46 years with male; female ratio of 110:6. The edition of the American Joint Committee on Cancer stage distributions were I (3.4%), II (34.4%), III (24.1%), and IV (37.9%). At a median follow-up of 22 months, crude rates of local failure, regional failure, and contralateral neck failure were 9.4%, 10.3%, and 3.4%, respectively. The 2-year contralateral neck control rate was 94.9%. Pathological positive node portended poorer OS (86.6% vs. 68.6%; p = 0.015) and DFS (86.5% vs. 74.9%; p = 0.01). CONCLUSION: Incidence of contralateral recurrence with ipsilateral irradiation in buccal mucosa cancers is low with descent survival outcomes, particularly in node negative cases.

Evaluation of purely accelerated six fractions per week radiotherapy in postoperative oral cavity squamous cell carcinoma.

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.

Synchronous Cervical Minimal Deviation Adenocarcinoma, Gastric Type Adenocarcinoma and Lobular Endocervical Glandular Hyperplasia Along with STIL in Peutz-Jeghers Syndrome: Eliciting Oncogenesis Pathways.

We describe an unusual case of a Peutz-Jeghers syndrome associated with a composite synchronous cervical neoplasia comprising precursor "lobular endocervical glandular hyperplasia (LEGH)", "minimal deviation adenocarcinoma (MDA)" and "gastric-type adenocarcinoma (GTA)" along with a serous tubal intraepithelial lesion (STIL) in the right fallopian tube. A 24-year-old woman presented with a white mucoid discharge and bleeding per vaginum for one year. Histopathological evaluation showed MDA & GTA in FIGO grade III with pelvic lymph node metastasis despite a deceptively bland tumour morphology and low Ki-67 index, indicating an aggressive tumour course and poor prognosis. Diagnostic marker profile in the cervix showed gastric type mucin and positive expression of CK-7, CK-20 (patchy), CEA, and negative CDX-2, p16, ER and PR. Further an attempt at eliciting the oncogenesis pathway in view of the p16 and HPV negative nature of the gastric type cervical adenocarcinoma showed negativity for p53 but activation of cyclin D1. Growth factors including Her2 and EGFR were negative while VEGFR was over-expressed. She was treated by radical hysterectomy and pelvic radiation. She was free from recurrence at the 12-month follow-up. This is a first-time report of a STIL in the fallopian tube which was validated by a unilateral mutant type p53 expression and increased Ki67 index, associated with synchronous gastric type adenocarcinoma of the cervix in all stages of evolution.