Dose Escalation Versus Standard in Laryngopharyngeal Cancers

The primary objective of the study is to establish the safety of using a moderate escalation of radiotherapy dose in advanced/poor prognosis OPC and LH cancers receiving curative radiotherapy. The study will also explore the efficacy (improvement in complete response rates at 2 years) of dose escalation in intermediate and high risk OPC and LH cancers patients.

Sex

All

Minimum age

18 Years

LH Inclusion Criteria ALL of the following inclusion criteria must be met

* Histologically confirmed squamous cell cancer of the larynx or hypopharynx
* Radiotherapy with concomitant chemotherapy as primary therapy
* Induction chemotherapy is permitted
* TNM Stage T3-4, N0-3, M0 or T1/2 with N2-3 disease (Stage III or IV a/b) disease
* WHO performance status of 0 or 1
* Creatinine clearance of more than 50ml/min
* All patients must be suitable to attend regular follow up

OPC inclusion criteria ALL of the following inclusion criteria must be met

* Histologically confirmed squamous cell cancer of the oropharynx
* Radiotherapy with concomitant chemotherapy as primary therapy
* Induction chemotherapy is permitted
* WHO performance status of 0 or 1
* Creatinine clearance of more than 50ml/min
* All patients must be suitable to attend regular follow up
* And any of the stage of disease as seen below HPV (p16) negative: TNM Stage T2-T4, any N stage, M0 disease HPV (p16) Positive: more than 10 pack year history and N2b or N3 disease

LH Exclusion Criteria The patient is ineligible if ANYONE of the following exclusion criteria is met

* Previous radiotherapy to the head and neck region
* Previous malignancy except non-melanoma skin cancer and early stage cancer in remission for at least 5 years following treatment
* Previous or concurrent illness, which in the investigator's opinion would interfere with either completion of therapy or follow-up
* Pre-existing previous speech or swallowing problems unrelated to the diagnosis of cancer
* Patients with locally advanced LH tumours where organ preservation is unrealistic
* Patients with metastatic carcinoma

OPC Exclusion Criteria The patient is ineligible if ANYONE of the following exclusion criteria is met

* Previous radiotherapy to the head and neck region
* Previous malignancy except non-melanoma skin cancer and early stage cancer in remission for at least 5 years following treatment
* Previous or concurrent illness, which in the investigator's opinion would interfere with either completion of therapy or follow-up
* Pre-existing previous speech or swallowing problems unrelated to the diagnosis of cancer
* Patients with locally advanced LH or OPC tumours where organ preservation is unrealistic
* Patients with metastatic carcinoma
* Low risk OPC: HPV p16 positive T1-2 with N0-N2a disease or less than 10 pack year history

• BACKGROUNDKapil U, Singh P, Bahadur S, Dwivedi SN, Singh R, Shukla N. Assessment of risk factors in laryngeal cancer in India: a case-control study. Asian Pac J Cancer Prev. 2005 Apr-Jun;6(2):202-7. PMID 16101334
• BACKGROUNDAng KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7. PMID 20530316
• BACKGROUNDChatterjee S, Willis N, Locks SM, Mott JH, Kelly CG. Dosimetric and radiobiological comparison of helical tomotherapy, forward-planned intensity-modulated radiotherapy and two-phase conformal plans for radical radiotherapy treatment of head and neck squamous cell carcinomas. Br J Radiol. 2011 Dec;84(1008):1083-90. doi: 10.1259/bjr/53812025. PMID 22101580
• RESULTGuerrero Urbano T, Clark CH, Hansen VN, Adams EJ, A'Hern R, Miles EA, McNair H, Bidmead M, Warrington AP, Dearnaley DP, Harrington KJ, Nutting CM. A phase I study of dose-escalated chemoradiation with accelerated intensity modulated radiotherapy in locally advanced head and neck cancer. Radiother Oncol. 2007 Oct;85(1):36-41. doi: 10.1016/j.radonc.2007.07.011. Epub 2007 Aug 20. PMID 17709149
• RESULTOvergaard J, Hansen HS, Specht L, Overgaard M, Grau C, Andersen E, Bentzen J, Bastholt L, Hansen O, Johansen J, Andersen L, Evensen JF. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet. 2003 Sep 20;362(9388):933-40. doi: 10.1016/s0140-6736(03)14361-9. PMID 14511925
• RESULTFu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, Garden AS, Ridge JA, Cooper JS, Ang KK. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000 Aug 1;48(1):7-16. doi: 10.1016/s0360-3016(00)00663-5.