TORPEdO

The number of cases of cancers arising from the tonsil and back of the tongue is rising worldwide. Even when this type of cancer is large or has spread to lymph nodes in the neck (called locally advanced cancer), it usually responds well to treatment and most people are cured. However, treatment with radiotherapy combined with chemotherapy can cause severe side effects during treatment. In the long-term this has the potential for significant harmful impact on quality of life. 

This study includes patients with locally advanced cancers of the tonsil and back of the tongue. It will focus on whether proton beam therapy (a newer form of radiotherapy) can reduce side effects and improve patient-reported quality of life compared with standard radiotherapy (called intensity-modulated radiotherapy). 

Proton beam therapy can be directed more precisely than standard radiotherapy. This reduces the amount of normal tissue receiving radiation that isn’t wanted. We know from international use of proton beam therapy (e.g. the USA) that it is a safe treatment and is thought to cause less damage to normal tissues. 

About 183 patients will take part in the study. Approximately 122 (two thirds) patients will receive proton beam therapy at an NHS proton centre in Manchester or London. The other 61 (one third) patients will receive intensity-modulated radiotherapy at their recruiting cancer centre. The NHS will provide accommodation for the duration of treatment for patients receiving protons and additional funding has been obtained for patient/carer travel costs. Patients will be asked to complete quality of life questionnaires at baseline, during treatment and during 5 years of clinical follow-up, in keeping with routine practice. There are also optional translational studies that patients will be asked to take part in. 

Inclusion Criteria:

1. Histologically confirmed oropharyngeal squamous cell carcinoma. 

2. HPV positive TNM8: T1-2 N1-2 (excluding T1-2 with a single ipsilateral node < 3cm), T3-4 N0-2 

3. HPV negative TNM 8: T1N2, T2N1-N2, T3-4N0-2 

4.  Local MDT decision for concurrent chemoradiotherapy with bilateral neck treatment. 

5. Age > = 18 years. 

6. WHO performance status 0-1. 

7. Adequate renal function, glomerular filtration rate (GFR) > 60ml/min calculated using Cockcroft-Gault formula 

8. Adequate cognitive ability (in the opinion of the local PI) to complete PRO assessments. 

9. Willingness to comply with the protocol, including travel to the proton centre for IMPT treatment. 

10. Written informed consent. 

Exclusion Criteria:

1. Feeding tube insertion required for nutrition due to dysphagia prior to treatment [Note: patients who have prophylactic feeding tube insertion, with or without tube use to top up nutrition prior to starting treatment, remain eligible for the study]. 

2. N3 disease. 

3. Upfront neck dissection.

4. Use of induction chemotherapy. 

5. Previous head and neck radiotherapy. 

6. Major surgery within 6 months of trial entry. 

7. Permanent pacemaker or implantable cardioverter defibrillator. 

8. Any invasive malignancy within previous 2 years (other than non melanomatous skin carcinoma or cervical carcinoma in situ).

9. Previous or concurrent illness (e.g., active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis), which in the investigator’s opinion would interfere with completion of therapy, trial assessments or follow up. 

10.  Pregnancy; lactating women or women of childbearing potential unwilling or unable to use adequate non-hormonal contraception (male patients should also use contraception if sexually active); 

11.  Pre-existing speech or swallowing problems unrelated to the diagnosis of cancer. For patients taking part in the optional DW-MRI study at The Christie Hospital the following additional exclusion criteria apply: 

12.  Any contra-indication to MRI scanning, including metallic heart valve replacement, permanent pacemaker, implantable cardiac defibrillator, non-MRI compatible metal implants, neuro-stimulators. 

13.  A history of allergy / reaction to Gadolinium contrast. 

Research Nurse: Iram Asif (iram.asif@elht.nhs.uk) 

Administrator: Oncology Research Team