Oral cavity adjuvant therapy (OCAT) -a phase III, randomized controlled trial of surgery followed by conventional RT (5 fr/wk) versus concurrent CT-RT versus accelerated RT (6fr/wk) in locally advanced, resectable, squamous cell carcinoma of oral cavity.

BACKGROUND: Limited data exists regarding the impact of intensification of adjuvant therapy in resected Oral Cavity Squamous Cell Carcinomas (OCSCC) with adverse prognostic features on histopathology. PATIENTS AND METHODS: This was a three-arm phase III, randomised trial including patients with resected advanced OCSCC. Randomisation was done in a 1:1:1 ratio: Arm-A- standard adjuvant radiation therapy (RT) 60Gy/30 fractions over 6 weeks versus Arm-B-concurrent chemoradiation versus Arm-C-accelerated radiation therapy (6 d a week). The trial was powered to detect an absolute difference of 10% in 5-year Locoregional Control (LRC). RESULTS: The trial was conducted between June 2005 and March 2013. Majority of the patients were males, had T3-T4 disease, had N2-N3 nodal status and had Extra-Capsular Extension (ECE) in nodes. The median follow-up was 95.9 months. There was no difference between the three arms (A versus B versus C) for 10-year locoregional control (LRC): 60.2% versus 61.4% versus 65.7%, p = 0.57; disease free survival (DFS): 37.4% versus 43.9% versus 39.6%, p = 0.40; or Overall Survival (OS): 39.7% versus 46.6% versus 40.4%, p = 0.40. There was no benefit of intensification with either modality in patients with any single adverse pathological factor. A benefit of intensification could be seen in patients with a combination of high-risk features: T3-T4 primary tumours with N2-N3 nodes along with ECE for DFS (Arm B versus Arm A HR) = 0.53, Arm C versus Arm A HR = 0.63) and OS (Arm B versus Arm A HR = 0.58, Arm C versus Arm A HR = 0.60). CONCLUSIONS: All optimally resected OCSCC with adverse features did not benefit from intensification of adjuvant therapy. Only a cohort of patients with a combination of high-risk features are likely candidates for intensification. CLINICAL TRIAL REGISTRATION: NCT00193843.

Evaluation of quantitative imaging parameters in head and neck squamous cell carcinoma.

BACKGROUND: Functional imaging such as 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT), 18F-fluoro-misonidazole (F-MISO)-PET/CT, and diffusion-weighted magnetic resonance imaging (DW-MRI) can assess complex biological phenomena in tumors reflecting underlying disease biology. The aim of this prospective observational study was to correlate quantitative imaging parameters derived from pretreatment biological imaging such as FDG-PET/CT, F-MISO-PET/CT, and DW-MRI with each other and with clinical outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive radio(chemo)therapy. METHODS: Twenty patients with pharyngo-laryngeal cancers underwent pretreatment biological imaging. Gross tumor volume (GTV) was delineated on axial planning CT (GTVCT). Quantitative FDG-PET/CT parameters included maximum, mean, minimum standardized uptake values (SUVmax-FDG, SUVmean-FDG, SUVmin-FDG); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). F-MISO-PET/CT parameters included hypoxic tumor volume (HTV); maximum, mean, minimum SUV; and fractional hypoxic volume (FHV). Mean apparent diffusion coefficient (ADCmean) was derived from DW-MRI. RESULTS: There was moderately strong positive correlation (r=0.616, P=0.005) between GTVCT and MTV. HTV derived from F-MISO-PET/CT at 3-hours (HTV3hrs-F-MISO) showed strong positive correlation with GTVCT (r=0.753, P<0.0001) and MTV (r=0.796, P<0.0001) respectively. ADCmean showed strong positive correlations with SUVmean-5hrs-F-MISO (r=0.713, P=0.021) and SUVmin-5hrs-F-MISO (r=0.731, P=0.016) respectively. A moderate negative correlation (r=-0.500, P=0.049) was observed between ADCmean and MTV. At a median follow up of 44 months, the 5-year Kaplan-Meier estimates of loco-regional control, disease-free survival, and overall survival were 53%, 43%, and 40% respectively. Larger volume of primary tumor (GTVCT>22cc and MTV>7.9cc) and increasing hypoxia (HTV3hr-F-MSO>4.9cc) were associated with worse outcomes. CONCLUSIONS: Functional imaging represents an attractive and non-invasive modality to assess complex biological phenomena in solid tumors. Larger tumor volume and increasing hypoxia emerged as putative prognostic imaging biomarkers in HNSCC.

Clozapine and cancer treatment: Adding to the experience and evidence.

The judiciousness of the use of clozapine in patients with schizophrenia in clinical practice is brought to an even sharper focus when it has to be used in combination with other agents that cause myelosuppression, for example, chemotherapy and radiation treatment. There are a few references till date illustrating the combination of clozapine and chemotherapy and/or radiation therapy. To the best of our knowledge, such a case has not been reported from India. We report the case of a 39-year-old gentleman with a diagnosis of schizophrenia, remaining psychiatrically stable on clozapine, who underwent combination treatment of chemotherapy and radiotherapy for the treatment of cancer of the tongue in a tertiary care oncology centre in India.

Toxicity with radiotherapy for oral cancers and its management: a practical approach.

Radiotherapy-induced damage in the oral mucosa is the result of the deleterious effects of radiation, not only on the oral mucosa itself but also on the skin, adjacent salivary glands, bone, dentition, and masticatory apparatus. From basic skin care to dental and oral health maintenance, several ointments and lotions, oral and parenteral medications, biological response modifiers, cytoprotective drugs, newer radiation techniques and surgery have been introduced to combat and more importantly to prevent the development of these complications. Radiotherapy-induced oral complications involve complex and dynamic pathobiological processes. This in the immediate- and long-term course lowers the quality of life and predisposes patients to serious clinical disorders. Here, we focus on these oral complications of radiotherapy, highlight preventive and therapeutic developments, and review the current treatment options available for these disorders.