320 I. J, Rad ia t ion O n c o l o g y • B i o l o g y • Phys ics V o l u m e 42 , N u m b e r 1 S u p p l e m e n t , 1998

2185 A PHASE 1 - 1I STUDY OF ACCELERATED RADIOTHERAPY WITH DELAYED CONCOMITANT BOOST IN LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK.

R. MacKenzie, J. Balogh, R. Choo, E. Franssen

Toronto- Sunnybrook Regional Cancer Centre ( TSRCC ), University of Toronto, Toronto, Ontario.

Purpose: To determine the toxicity, maximal tolerated dose ( MTD ) and response rate of an accelerated radiotherapy regimen delivered over 5 weeks in patients with locally advanced squamous cell carcinoma of the head and neck ( SCCHN ).

Materials and Methods: 35 patients with untreated T3T4NM 0 or TN 2 (>3cm) N 3 squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx were entered on study between 01/94 and 10/97. The initial target volume encompassing documented tumor and potential sites of microscopic spread was treated with conventional daily fractions. A small field boost covering gross disease was added as a second daily fraction during the last 2 weeks of the 5 week schedule. Morning and afternoon treatments were separated by a minimum of 6 hours. The fraction size was increased in a classical dose escalation strategy from 180 cGy to 200 cGy to deliver total doses ranging between 63 Gy and 67 Gy. Toxicity was scored weekly until the peak reactions subsided. Patients were assessed for response at monthly intervals until complete response or progression. Complete responders were followed every 3 months. Living patients have been followed for a median of 16 months with a range of 4 - 38 months.

Results: P~ase I : 4 patients were entered at Level 1 (63 Gy), 9 at Level 2 (65 Gy) and 8 at Level 3 (67 Gy). One patient was withdrawn at Level 2 because of unstable angina and one at Level 3 because of uncontrolled diabetes. RTOG grade 3 mucositis, dermatitis or both was documented in 2 (50%), 5 (63%) and 7 (100%) patients at Levels 1, 2 and 3 respectively. No patient developed grade 4 toxicity. The median interval to resolution of grade 3 toxicities was 6 weeks with a range of 4 - 21 weeks. The time to recovery did not correlate with dose. 3 patients required hospitalization for nutritional support and 2 for management of acute complications. One patient at Level 3 died at home 5 weeks post-treatment of unknown causes. 65 Gy ( Level 2 ) was chosen as the MTD. Phase 11 : 13 of 14 additional patients were evaluable for response bringing the total of evaluable patients entered at level 2 up to 21. A

complete response was documented in 15 (71%). Radiotherapy controlled disease above the clavicles in 13 (62%). 3 of 5 patients with uncontrolled disease and 3 of 4 patients with relapsing local-regional disease underwent salvage surgery. No patient suffered a major post- operative complication. Ultimate local-regional control was achieved in 16 (76%). The disease-free, overall and cause-specific survival of all patients entered at level 2 was 62%, 79% and 84% at 1 year and 52%, 79% and 84% at 2 years. Late complications have been documented in 3 patients ( trismus, chronic mucosal ulcer and soft tissue necrosis ).

Conclusions: A 5 week course of accelerated radiotherapy based on a delayed concomitant boost can deliver 65 Gy with acceptable toxicity. encouraging rates of complete response and local-regional control, and no compromise of salvage surgery in patients with locally advanced SCCHN. The regimen is worthy of further study in a Phase III trial.

2186 PLANNED N E C K DISSECTION AS AN ADJUNCT TO THE MANAGEMENT OF PATIENTS WITH ADVANCED N E C K

DISEASE TREATED WITH DEFINITIVE RADIOTHERAPY

Kailash Narayan, MD ÷, Christopher H. Crane, MD*, Stephen Kleid, MD ̂ , Peter Hughes ÷, MD, and Lester Peters, MD +

The Peter MacCallum Cancer Institute Departments of Radiation Ontology +, and Head and Neck Surgery ̂ , Melbourne, Australia and the University of Virginia Department o f Therapeutic Radiation and Oncology*, Charlottesville, VA

Purpose/Objective- Management of patients with head and neck carcinoma and advanced nodal disease is controversial. The purpose of this analysis was to evaluate the efficacy and toxicity of definitive radiotherapy followed by neck dissection in patients with bulky neck disease.

Materials and Methods- The records of 52 patients who were treated between 1989 and 1995 were reviewed. All had advanced neck disease with one or more nodes > 3cm in maximum diameter. All patients were stage IV. The most common primary site was the oropharynx (56%). Sixty percent of patients had either T2 or T3 primaries and 94% had N2 or N3 neck disease. Treatment consisted of definitive radiotherapy to the primary and involved neck sites using various fractionation protocols followed by modified radical or radical neck dissection after confirmation of a complete response at the primary site. The median follow-up for living patients was 56 months (range 32-97)

Results- Five-year actuarial rates of neck and primary control were 84% and 79%, respectively. Two patients failed in the contralateral unirradiated neck yielding an in-field neck control rate of 88%. There was only one in-field neck failure in the 28 patients with pathologically negative neck dissections. Of the 24 patients with tumor in the resected neck specimen, 6 recurred in the neck. Ten of these 24 patients are currently alive and free of disease (5) or died free of disease (5). Ten patients relapsed at the primary site and there were eight distant relapses. A total of 22 patients relapsed at one or more sites and none was salvaged. Five-year actuarial relapse-free survival was 57%, and overall survival was 35%. There were ten significant treatment-related complications following neck dissection. (19.2%).

Conclusions- Planned neck dissection provides excellent regional control at the cost of significant but acceptable morbidity in patients with advanced neck disease who are treated primarily with radical radiotherapy. However in many patients the neck dissection is either unnecessary (no residual tumor) or futile (unsalvageable disease relapse outside the dissected neck). More reliable ways o f evaluating neck, primary and distant sites for the presence of disease prior to neck dissection are needed to optimize the utility of adjunctive surgery in these patients.