The present study is designed as a two arm randomized trial to evaluate the impact of accelerated radiotherapy delivered by image guided radiotherapy with rapid arc technique in carcinoma nasopharynx. The study will evaluate a pure acceleration schedule of 6 fractions per week with concurrent chemotherapy and without any radiotherapy dose escalation.The control arm will receive standard chemoradiotherapy using image guided radiotherapy with rapid arc technique.

The study is designed as a two arm prospective randomized controlled trial which will be carried out in the Department of Radiotherapy and Otolaryngology at PGIMER, Chandigarh.

Inclusion criteria

1. Histopathologically proven non keratinizing nasopharangeal cancers.
2. Karnofsky performance status more than 70
3. Stage T3-4, N0-3 patients (as per AJCC 8th edition).
4. Patients willing for informed consent and regular follow up

Exclusion Criteria

1. Keratinizing squamous cell carcinoma
2. Age >70 years
3. Patients who have received previous chemoradiotherapy.
4. Patients with uncontrolled co- morbid conditions like hypertension , diabetes or any renal impairment

Randomization Patients will be randomized into the two study groups using computer generated randomization table given below.Total number of patients to be recruited will be 120 and will be divided into • Study Group A (N= 60): Accelerated Chemoradiotherapy followed by 3 cycles of Adjuvant chemotherapy. Patients will be treated with radiotherapy for 6 days per week from Monday to Saturday

• Control Group B (N=60) : Concurrent Chemoradiotherapy followed by 3 cycles adjuvant chemotherapy. Patients will be treated with radiotherapy for 5 days per week from Monday to Friday.

Treatment Protocol Clinical evaluation All patients enrolled in the study will undergo a full clinical examination including a complete head and neck check up Investigations All patients enrolled in the study will undergo the following investigations

1. Complete Haemogram, Liver Function test & Kidney Function Tests, Blood Sugar
2. Chest X Ray PA View
3. X Ray Soft tissue neck
4. ECG
5. CECT Head and Neck/ Contrast enhanced MRI head and neck
6. Biopsy from primary tumor and FNAC from neck nodes

RADIOTHERAPY Chemoradiotherapy treatment protocol For radiotherapy planning patients will be immobilized using S type thermoplastic cast & will undergo a planning CT scan with 3mm slice thickness. The images will be transferred to Eclipse treatment planning system. All patients will be planned with 6MV photons using 4 arcs with SIB Rapid Arc technique using the dose prescription given below.

PTV70: 70 Gy in 33 fractions PTV59.4 : 59.4 Gy in 33 fractions PTV50.4: 54 Gy in 33fractions Concurrent chemotherapy will be given using Cisplatin injection 40mg/m.sq weekly or 100mg/m.sq 3 weekly along with radiotherapy in both the groups. Patients will undergo will undergo a repeat treatment planning CT scan at the 16th radiotherapy fraction and will be evaluated for adaptive re-planning.

CHEMOTHERAPY Concurrent : Inj. CDDP 100mg/m2 D1 q 3weekly along with XRT

Adjuvant:

Inj. CDDP 80mg/ m2 D1 q 3 weekly x 3 cycles Inj. 5- FU 1gm/ m2 D1-4

Patients weight will be monitored weekly during treatment.patients will be reviewed at 16th fraction of treatment. Patients with a weight loss more than 10 % or a decrease of neck diameter by more than 10% will be evaluated for need for adaptive re-planning.Where indicated patients will be replanned .

Toxicity & Response Evaluation Patients will be evlautaed weekly for dermatological, mucositis,Dysphagia, haemtological ,gastrointestinal & constitutional toxicity using Common Terminology Criteria for adverse effects (CTCAE v3). Overall Response will be evaluated at end of treatment using Response evaluation criteria for solid Tumors (RECIST ).

Follow up All patients included in the study will be followed up 2 monthly intervals during the first year, at 3 monthly intervals during the 2-3 years and 6 monthly intervals thereafter. At each visit a full clinical examination, toxicity grading and disease status will be evaluated.

Statistics Assuming a significance level of 0.05 and power of 80% a minimum of 110 patients need to be recruited to detect a difference of about 25% in failure free survival including a drop out rate of 10%.For statistical analysis data will be entered into SPSSv 20.Treatment toxicity will be compared between the treatment groups using independent 't' test. Pearson correlation test and logistic regression analysis will be used to evaluate prognostic variables.Survival analysis will be done using Kaplan Meir analysis. A p value <0.05 will be considered as statistically significant.

Inclusion Criteria:

1. Histopathologically proven non keratinizing nasopharangeal cancers.
2. Karnofsky performance status more than 70
3. Stage T3-4, N0-3 patients (as per AJCC 8th edition).
4. Patients willing for informed consent and regular follow up

Exclusion Criteria:

1. Keratinizing squamous cell carcinoma
2. Age >70 years
3. Patients who have received previous chemoradiotherapy.
4. Patients with uncontrolled co- morbid conditions like hypertension , diabetes or any renal impairment