NACT Mandible study

Patients with resectable oral cancers requiring upfront segmental resection of the mandible fulfilling the inclusion criteria will be included in the study. patient will be randomized to one of the two groups.

Arm 1 – Standard of care – Surgical resection as decided in the tumor board. – Adjuvant therapy: High risk patients- (extra capsular spread, Positive cut margins) will receive adjuvant concurrent chemo radiotherapy. Other adverse features – Adjuvant radiotherapy. Radiotherapy- Conventional radiotherapy 50 Gy/25# for node negative and 60 Gy/ 30# for node positive, five days a week. Chemotherapy – Single agent cisplatin 40 mg/m2 , weekly, 6 cycles

Arm 2 –Two drug (TP) or Three drug (TPF) Neoadjuvant chemotherapy: Three weekly based on patient’s eligibility. Patients will be admitted for administration of chemotherapy. It will be administered via central venous access. Second cycle will be repeated after 3 weeks. T – Docetaxel 75mg/m2 Day 1 P – Cisplatin 75mg/m2 Day 1 F – 5FU 750mg/m2 Day 1-5 All patients will receive GCSF following chemotherapy.

Safety evaluation will be done at every visit for the patients during the time patients is on chemotherapy. The toxicity will recorded as per common terminology criteria for toxicity (CTCAE) version 4.03.

Efficacy evaluation will be done clinically at each routine visit. Any patient who has clinically progressive disease will be considered for early surgery. Radiological evaluation will be done at the end of the second cycle. Contrast enhanced computed tomography scan will be done for radiological response assessment. Patients will be reevaluated at the end of 2nd cycle in the tumor board. Decision to do surgery or to give 3rd cycle will be taken in tumor board. Patients will undergo surgery after 21-35 days following completion of last dose of chemotherapy. Extent of surgery will be determined by the extent of residual disease by the operating surgeon. In case of complete response decision between surgery versus chemo radiotherapy will be decided in the tumor board. All patients who undergo conservative surgery will receive adjuvant chemo-radiotherapy. Those undergoing segmental mandibulectomy will receive adjuvant therapy as mandated by the histopathological characteristics. Radiotherapy – Conventional radiotherapy 50 Gy/25# for node negative and 60 Gy/ 30# for node positive, five days a week. Chemotherapy – Single agent cisplatin 40 mg/m2, weekly, 6 cycles.

Response to chemotherapy: Evaluation will be done by RECIST criteria 1.1. Complete response: Disappearance of all lesions. Partial response (PR): At least a 30% decrease in the sum of diameters of lesions. Progressive Disease (PD): At least a 20% increase in the sum of diameters of one or more lesions, or appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD Toxicities

All patients who receive even one cycle will be assessed for toxicity with NCI – common terminology criteria for toxicity (CTCAE) version 4.03.

Quality of life evaluation - Quality of life will be assessed using EORTC-QLC-C30 and EORTC-H&N 35 questionnaire. Questionnaire will be served prior to NACT, after completion of NACT, post surgery 3 months after completion of adjuvant treatment (1st Follow up), 6 months, 1 year, 2 year, 3year, 4year and at 5 years in Arm 2. In Arm 1 QOL questionnaire will be served before surgery, post surgery 3 months after completion of adjuvant treatment (1st Follow up), 6 months, 1 year, 2 year, 3year, 4year and at 5 years. Quality of life questionnaire will be filled by the patients.

Patient may be benefited with mandible preservation with less radical surgery with reduced treatment related toxicity in the intervention arm. This will have a major functional and cosmetic impact.