A B S T R A C T PurposeTo report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients and MethodsPatients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. ResultsFive hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P ϭ .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P ϭ .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P ϭ .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P ϭ .0050) and over RT alone (P Ͻ .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P ϭ .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). ConclusionThese 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.

A B S T R A C T PurposeTo investigate the feasibility of intensity-modulated radiation therapy (IMRT) with or without chemotherapy, and to assess toxicities, failure patterns, and survivals in patients with nasopharyngeal carcinoma (NPC). Patients and MethodsRadiation consisted of 70 Gy given to the planning target volumes of primary tumor plus any Nϩ disease and 59.4 Gy given to subclinical disease, delivered over 33 treatment days. Patients with stage T2b or greater or with Nϩ disease also received concurrent cisplatin (100 mg/m 2 ) on days 1, 22, and 43 followed by adjuvant cisplatin (80 mg/m 2 ) on day 1; fluorouracil (1,000 mg/m 2 /d) on days 1 through 4 administered every 4 weeks for three cycles. Tumor, clinical status, and acute/late toxicities were assessed. The primary objective was to test the transportability of IMRT to a multi-institutional setting. February 2003 and November 2005, 68 patients with stages I through IVB NPC (of which 93.8% were WHO types 2 and 3) were enrolled. Prescribed IMRT (target delineation) was given to 83.8%, whereas 64.9% received chemotherapy per protocol. The estimated 2-year local progression-free (PF), regional PF, locoregional PF, and distant metastasis-free rates were 92.6%, 90.8%, 89.3%, and 84.7%, respectively. The estimated 2-year PF and overall survivals were 72.7% and 80.2%, respectively. Acute grade 4 mucositis occurred in 4.4%, and the worst late grade 3 toxicities were as follows: esophagus, 4.7%; mucous membranes, 3.1%; and xerostomia, 3.1%. The rate of grade 2 xerostomia at 1 year from start of IMRT was 13.5%. Only two patients complained of grade 3 xerostomia, and none had grade 4 xerostomia. Results Between ConclusionIt was feasible to transport IMRT with or without chemotherapy in the treatment of NPC to a multi-institutional setting with 90% LRPF rate reproducing excellent reports from single institutions. Minimal grade 3 and lack of grade 4 xerostomia were encouraging.