Trial Evaluating Hypo-fractionated Accelerated Versus Conventional Fractionated Adjuvant RT in Head & Neck Malignancies

The HYPCON 3 Trial A Phase II/III Randomized Study Evaluating Hypo-fractionated Accelerated Versus Conventional Fractionated Adjuvant Radiation Therapy in Head and Neck Malignancies

Hypo-fractionated radiotherapy reduces the OTT (overall treatment time) which may in turn reduce rapid accelerated repopulation of clonogenic cells during waiting period after surgery. If this holds true, there is a potential to achieve better loco-regional control in with PORT for HNSCC. There is a strong radiobiological and economic rationale for delivery hypo-fractionated radiotherapy in HNSCC. The HYPCON III trial will be aimed to reduce the number of fractions by 50% (30 fr to 15 fr)

The current standard radiotherapy regimen for squamous cell carcinomas of the head and neck in the post operative setting is 60-66Gy in 30-33# delivered in 6 weeks with 5 fractions delivered per week. The aim of this study is to test whether a resource sparing, 3weeks, 15 fraction course of hypo-fractionated radiotherapy is non inferior to the conventional fractionation regimen delivering 30 fractions over6 weeks of post operative radiotherapy (PORT). Hypofractionation is already the standard of care in the treatment of cancers like breast cancer which has evolved from 50 Gy in 25 # to 40 Gy in 15# and finally to 26Gy in 5 # with similar tumor control rates and toxicity profiles.

Hypofractionation has shown promising results in prostate, lung cancer and CNS tumors. Hypofractionation has been initially explored in palliative setting for HNSCC. Unlike 2 dimensional RT deliver, recent past has seen a rapid evolution of RT delivery techniques like 3-dimensional conformal radiotherapy (3D CRT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), volumetric arc therapy (VMAT). It is now possible to spare adjoining critical organs at risk which make delivery of hypo-fractionated feasible for HNSCC. Recently, the IAEA multicentric trial in radical setting for HNSCC has proved equivalent results in term of both disease control and toxicity with delivery of hypo-fractionated RT. Shorter treatment time is more convenient to the patient. The reduction in the number of fractions required per patient will help in optimal unitization of radiotherapy resources, especially in a low/moderate income country like India where the burden of cancer hugely surpasses the resource availability. Hypo-fractionated schedules have potential to provide attractive cost benefits.

Inclusion Criteria:

• Patients with pT1-4 squamous cell carcinoma of oral cavity/ oropharynx/ larynx/ hypopharynx with any of the intermediate risk features:

  • Positive lymph node (s)
  • Perineural invasion
  • Lympho-vascular invasion
  • Close margins

• Age 18-80yrs

• ECOG performance status 0-1at time of surgery

• Informed consent

• Available FOR long term follow-up

Exclusion Criteria:

• High risk factors following resection: positive-margin(s)and/or extra nodal extension (ENE)
• pT1-2disease and no high-risk features (LVSI, PNI, Close margins,pN0)
• Patients receiving Neo-adjuvant or concurrent Chemotherapy
• Non-Squamous Histology
• Distant metastasis
• Synchronous or second primary malignancy outside of the oropharynx, oral cavity, larynx and hypopharynx
• Pregnant females or nursing mothers due to the probability of congenital anomalies and potential of this regimen to harm nursing infants.
• Prior Radiotherapy to head and neck region