Target volume coverage in clinically designed radiotherapy plan of post-mastectomy adjuvant radiotherapy of breast cancer patients in comparison with radiation therapy oncology group-based contoured plan: A dosimetric study.

Objective: Conventional field radiotherapy based on anatomical landmarks has been the traditional treatment for breast cancer. Having proven efficacy, it is still the current standard of treatment. The Radiation Therapy Oncology Group (RTOG) has published guidelines for contouring target volumes in postmastectomy patients. The impact of this guideline in the current clinical practice is less known; hence, we have analyzed dose-volume histograms (DVHs) for these plans and compared them with the proposed treatment plans to treat RTOG-defined targets. Subjects and Methods: RTOG consensus definitions were used to contour the target volumes in 20 previously treated postmastectomy patients. The prescription was 42.4 Gy in 16 fractions. DVHs were generated from clinically designed plans that had actually been delivered to each patient. For comparing dose to target volumes, new plans were generated with the goal of covering 95% of volume to 90% of prescribed dose. Results: In RTOG contoured Group, coverage improved for the supraclavicular (V90 = 83 vs. 94.9%, P < 0.05) and chest wall (V90 = 89.8 vs. 95.2%, P < 0.05). Axillary nodal coverage improved for Level-1(V90 = 80.35 vs. 96.40%, P < 0.05), Level-II (V90 = 85.93 vs. 97.09%, P < 0.05) and Level III (V90 = 86.67 vs. 98.6%, P < 0.05). The dose to the ipsilateral lung is increased (V20 = 23.87 vs. 28.73%, P < 0.05). Low dose to heart is increased in left-sided cases (V5 = 14.52 vs. 16.72%, P < 0.05) while same in right-sided cases. Conclusions: The study shows that radiotherapy using the RTOG consensus guidelines improves coverage to target volumes with a nonsignificant increase in normal organ dose compared to that based on anatomical landmarks.

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.

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.

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.

Evaluation of XRCC1 Gene Polymorphism as a Biomarker in Head and Neck Cancer Patients Undergoing Chemoradiation Therapy.

PURPOSE: We evaluated the correlation of the x-ray repair cross complementing gene 1 (XRCC1) Arg194Trp polymorphism with clinical outcomes in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation therapy (CCRT). METHODS AND MATERIALS: In this prospective cohort study, we included 101 patients with HNSCC (oral cavity, pharynx, and larynx) who were aged ≥ 18 years, had stage III to IVB disease, had a Karnofsky Performance Status ≥ 80, and were deemed fit for CCRT. DNA extraction was done through polymerase chain reaction, and the genotypes of XRCC1 polymorphism were detected using designed restriction fragment length polymorphism. The genetic polymorphisms were classified into wild and polymorphic variants (Arg194Trp CT and TT). Radiation therapy was delivered with conventional parallel opposed lateral and low anterior neck fields with concurrent weekly cisplatin, 35 mg/m2. Acute toxicity was graded per Radiation Therapy Oncology Group criteria, and treatment response was assessed per World Health Organization criteria. Overall survival and progression-free survival (PFS) were estimated using the Kaplan-Meier method. RESULTS: Of the patients, 62 had the wild type and 39 had polymorphic variants. Patients with polymorphic variants had higher rates of grade > 2 oral mucositis, with 35.8% versus 16.0% (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.13-7.46; P = .023); dermatitis, with 30.7% versus 8.0% (OR, 5.076; 95% CI, 1.62-15.8; P = .003); and laryngeal toxicity, with 25.6% versus 6.4% (OR, 5; 95% CI, 1.44-17.54; P = .006). Complete response rates in polymorphic versus wild variants were 76.9% versus 56.0% (P = .209). At a median follow-up of 21 months, the 2-year PFS and overall survival rates for patients with polymorphic versus wild variants were 57.0% versus 42.2% (P = .077) and 73.0% versus 55.5% (P = .143), respectively. CONCLUSIONS: Polymorphic variant XRCC1 HNSCC patients treated with CCRT have significantly increased acute radiation morbidities and may have a trend toward better PFS in comparison with the wild variant.

Prospective evaluation of Intensity Modulated Radiation Therapy with Simultaneous Integrated Boost (IMRT-SIB) in head and neck squamous cell carcinoma in patients not suitable for chemo-radiotherapy.

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.

Non-small cell lung cancer presenting with choroidal metastasis as first sign and showing good response to chemotherapy alone: a case report.

INTRODUCTION: Metastatic tumors are the most common intra-ocular malignancies and choroid is by far the most common site for intra-ocular malignancies. Multiple foci are usually involved, and bilateral involvement is frequently seen. The primary sites for choroidal metastasis in decreasing order and by gender are: breast, lung, unknown primary, gastrointestinal and pancreas, skin melanoma and other rare sources in females, and lung, unknown primary, gastrointestinal and pancreas, prostate, kidney, skin melanoma and other rare sources in males. Available treatment options are external beam radiotherapy and plaque radiotherapy, while new methods like surgical resection, transpupillary thermotherapy and intravitreal chemotherapy offer promises for the future. The use of chemotherapy alone for choroidal metastases is not widely reported. CASE PRESENTATION: We report the case of a 50-year-old Indian man who had a unilateral solitary lesion in his right eye. He was found to have an adenocarcinoma of the lung with choroidal metastasis as the first presenting sign. There were no findings of metastasis involving his contralateral eye. He was administered chemotherapy based on gemcitabine and carboplatin. He had significant progressive subjective and objective improvement since his first chemotherapy. His current best corrected visual acuity is 20/60 after three cycles of chemotherapy. CONCLUSIONS: Chemotherapy alone can be used as an effective mode of treatment in patients who have primary tumors that respond to chemotherapy.

Fractal characterization of brain lesions in CT images.

Fractal Dimension (FD) is a parameter used widely for classification, analysis, and pattern recognition of images. In this work we explore the quantification of CT (computed tomography) lesions of the brain by using fractal theory. Five brain lesions, which are portions of CT images of diseased brains, are used for the study. These lesions exhibit self-similarity over a chosen range of scales, and are broadly characterized by their fractal dimensions.