Mark E. Alden, MD #{149} Robert C. O’Reilly, MD #{149} Alan Topham, BA #{149} L. Dale Lowry, MD Harvey Brodovsky, MD #{149} Walter J. Curran, Jr. MD Elapsed Radiation Therapy Treatment Time as a Predictor ofSurvival in Patients with Advanced Head and Neck Cancer Who Receive Chemotherapy and Radiation Therapy’ Index terms: Head and neck neoplasms, 20.37 #{149}Head and neck neoplasms, therapeutic radiology, 20.1299, 20.37 #{149} Therapeutic radiology Abbreviations: RTOG = Radiation Therapy Oncology Group, VBM = z’inblastine sulfate, bleomy- cm sulfate, and methotrexate. Radiology 1996; 201:675-680 From the Bodine Center for Cancer Treatment, ThomasJefferson University Hospital, 111 5 11th St, Philadelphia, PA 19107. From the 1995 RSNA scientific assembly. Received December 5, 1995; re- vision requested February 5, 1996; revision received July 26; accepted August 5. Address reprint re- quests to W.J.C. ‘ RSNA, 1996 675 PURPOSE: To determine whether elapsed radiation therapy treatment time relates to survival in patients with head and neck cancer treated sequentially with chemotherapy and radiation therapy. MATERIALS AND METHODS: From 1981 to 1988, 76 adult patients with bulky stage II-IV head and neck can- cer received induction chemotherapy (fluorouracil and cisplatin). Those with a complete or partial response (n = 46) received full-dose definitive radiation therapy (range, 64.0-77.5 Gy; median, 70 Gy). Those with less than a partial response (n = 21) un- derwent surgery and postoperative radiation therapy (n 15), palliative radiation therapy (n = 4), or pallia- tive chemotherapy (n = 2). Nine pa- tients refused to undergo radiation therapy after induction chemother- apy. RESULTS: The 5-year overall sur- vival rates were as follows: 32% in all patients, 38% in patients who under- went chemotherapy and radiation therapy, and 27% in patients who un- derwent chemotherapy, surgery, and radiation therapy. The number of days between radiation therapy treat- ments was highly predictive of over- all survival. In the groups with treat- ments less than 55 days apart, 56-65 days apart, and more than 66 days apart, the 5-year survival rates were 56%, 46%, and 15%, respectively (P = .02). CONCLUSION: The time between radiation therapy treatments is strongly predictive of survival in pa- tients undergoing sequential chemo- therapy and radiation therapy. The use of induction chemotherapy does not negate the need to avoid treat- ment interruptions during definitive radiation therapy. T HERE were more than 39,000 non- cutaneous head and neck can- cens diagnosed in the United States in 1995 (1), and more than 50% of pa- tients had advanced-stage disease at presentation. Approximately two- thirds of these patients were referred for radiation therapy for definitive treatment of small lesions, postopera- tive treatment of large lesions, or or- gan-preserving treatment of advanced- stage disease. The cancer control rate for radiation therapy alone is approxi- mately 80%-90% in patients with stage I or II disease and 20%-30% in patients with stage III or IV disease. This rate varies considerably depend- ing on tumor site and stage. In aggre- gate, approximately 52% of patients will survive 5 years. When treatment-related factors have been evaluated for their influ- ence on tumor control in patients with stage III or IV tumors, the time elapsed from initiation to completion of radiation treatment has been in- versely correlated with patient sun- vival (2-8). This has not been broadly shown to be true in patients with early-stage disease. Chemotherapy is one approach for improving the outcome (local control, survival, and organ preservation) in patients with stage III or IV disease. It can be delivered in sequence with or concurrently with radiation therapy. If it is delivered concurrently, there is a risk of increased toxicity, treatment breaks in the delivery of radiation therapy, and, therefore, an increase in the time between radiation treat- ments. If chemotherapy is delivered before radiation therapy, there are risks that (a) patients will be more de- bilitated and unable to sustain a full course of radiation therapy without substantial treatment breaks or that (b) induction chemotherapy may cause an acceleration in tumor clono- genic doubling time, which makes short radiation treatment breaks more important. The goals of this study were to document the frequency of radiation therapy treatment delays in an insti- tutional experience with induction chemotherapy and definitive radia- tion therapy and to compare elapsed radiation therapy treatment time with tumor control (survival) in patients who receive sequential chemotherapy and radiation therapy. MATERIALS AND METHODS From 1981 through 1988, an institutional organ preservation study was conducted in patients with previously untreated ad- vanced-stage squamous cell carcinoma of the head and neck. The single treatment arm consisted of induction chemotherapy followed by definitive radiation therapy. Patients were selected for this program on the basis of their inability or refusal to un- dergo surgery. Multispecialty pretreat- ment evaluation was conducted by an oto- laryngologist (L.D.L.), a medical oncologist