Hyperbaric oxygen as radiation sensitizer for locally advanced squamous cell carcinoma of the oropharynx : A Phase I dose-escalation study
Menée sur 12 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade III-IV (M0), cette étude évalue la faisabilité d'un traitement combinant oxygène hyperbare, radiothérapie avec modulation d'intensité et chimiothérapie par cisplatine
Purpose : Hyperbaric oxygen (HBO) has promise as a radiosensitizer in squamous cell carcinoma of the head-and-neck (SCCHN), but older studies using large fractions and treatment volumes showed excess toxicity. This dose-escalation study explored the feasibility of HBO treatments immediately prior to intensity-modulated radiation therapy (IMRT) in conjunction with cisplatinum chemotherapy. Methods : Eligible patients presented with SCCHN (stage III-IV (M0)), life expectancy > 6 months, KPS >= 70. Enrollees received IMRT, 70 Gy in 35 fractions over 7 weeks with weekly cisplatinum. Patients received HBO – 100% oxygen, 2.4 atmospheres absolute for 30 minutes – twice a week initially. Subsequent patients were escalated to three and then five times a week. IMRT began within 15 minutes after HBO. Patients were followed for 2 years post-RT with quality-of-life (QOL) questionnaires (PSS-HN and FACT-HN), and for 5+ years for local recurrence (LR), distant metastases (DM), disease-specific survival (DSS), and overall survival (OS). Results : Twelve subjects enrolled from three centers. Two withdrew during RT and one within 14 weeks after RT. The remaining 9 had primary oropharyngeal disease and were Stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and RT was 8.5 minutes with 2 of 231 administrations delivered beyond 15 minutes (0.5%). Per protocol analysis showed a clinical complete response (CR) in 7, and a pathologic CR without tumor in salvage neck dissections in 2. With minimum follow-up of 61 months, per protocol 5-year OS was 100%, LR 0%, and DM 11%. Patient-reported outcomes for QOL (FACT-HN) were comparable to published results for chemo-RT without HBO. Conclusion : While acknowledging the study’s small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation.