Radiation Deintensification Possible For Select Oropharyngeal Carcinoma Patients

Phase II trial results support the further evaluation of radiation de-escalation in certain subgroups of patients with human papillomavirus-associated oropharyngeal carcinoma

medwireNews: Reduced-dose intensity-modulated radiation therapy (IMRT) could be considered for patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) who achieve a complete clinical response after induction chemotherapy, research suggests.

Researcher Barbara Burtness, from Yale University School of Medicine in New Haven, Connecticut, USA, and co-authors explain that chemoradiation therapy leads to high cure rates in patients with HPV-associated OPSCC, “but causes long-term toxicity and may represent overtreatment of some patients.” They propose that certain patients, selected using responsiveness to induction chemotherapy, could undergo radiation deintensification to help minimise acute and late toxicity.

In the phase II trial, 80 patients with newly diagnosed, operable, stage III or IV OPSCC that was positive for p16 or HPV16 received three cycles of induction chemotherapy with cisplatin, paclitaxel and cetuximab.

Of these, 56 (70%) achieved a complete clinical response at the primary site, defined as the complete disappearance of the primary lesion on manual and endoscopic evaluation, and 51 went on to receive 54 Gy of radiation with concurrent weekly cetuximab. Study participants who did not achieve a complete response at the primary site or nodes were given 69.3 Gy of radiation, also alongside weekly cetuximab.

Among these patients who received reduced-dose radiation, the progression-free survival (PFS) and overall survival (OS) rates at 2 years were 80% and 94%, respectively, which the investigators say are comparable to previously reported rates.

They also found a beneficial effect of reduced-dose IMRT on patient-reported outcomes as assessed by the Vanderbilt Head and Neck Symptom Survey version 2. Compared with study participants who received high-dose IMRT, a significantly smaller proportion of those given low-dose IMRT had difficulty swallowing solids (40 vs 89%) or impaired nutrition (10 vs 44%) at 12 months post-treatment.

“This finding provides justification for further study of radiation deintensification but requires validation in a larger comparative trial”, the team writes in the Journal of Clinical Oncology.

Barbara Burtness et al believe that “[p]atient selection will be critical to optimal implementation of this strategy in future trials” because of observed differences in response according to baseline tumour and patient characteristics.

Specifically, a post hoc analysis showed that patients with low-volume disease (ie, T1–T3, N1–N2b) and minimal smoking history (≤10 pack–years) had higher 2-year PFS and OS rates than their counterparts with high-volume disease (ie, T4, N2c) and a greater than 10 pack–year smoking history, at 96% versus 71% and 96% versus 91%, respectively.

Reference

Marur S, Li S, Cmelak AJ, et al. E1308: Phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx— ECOG-ACRIN cancer research group. J Clin Oncol; Advance online publication 28 December 2016 doi:10.1200/JCO.2016.68.3300

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