Concomitant cisplatin/5-FU infusion and radiotherapy in advanced head and neck cancer: 8-year analysis of results.

BACKGROUND: The purpose of this study was to analyze long-term follow-up of a single institution's experience with a regimen of concomitant cisplatin/fluorouracil (5-FU) infusion and radiation given every other week. This analysis was stimulated by results of a randomized trial showing superiority for this regimen over induction cisplatin/5-FU chemotherapy followed by radiotherapy, especially in regional disease control. METHODS: All patients with stage III/IV disease who were referred by surgeons for nonoperative therapy and had a follow-up of at least 2 years were included. Concomitant chemoradiotherapy was administered days 1-5 of a 2-week treatment cycle, for a total of 7 cycles, with cisplatin 60 mg/m2 day 1, 5-FU 800 mg/m2 given over 24 hours days 1-5, and radiation 2 Gy days 1-5. RESULTS: Seventy-eight patients with stage III (n = 16) or IV (n = 62) were treated and followed for a median of 8 years. Six patients died during treatment, of aspiration pneumonia, sudden death, gastrointestinal bleeding, and stroke. When assessed 6 weeks after the end of treatment, 45 patients (63%) had no clinical evidence of disease, whereas 27 (37%) still had some persistent abnormality. However, 17 of these "partial responders" have not recurred. In all, 24 patients (31%) have recurred or progressed, 13 at the primary site, 5 after 3 years. None of 16 stage III and 24 (39%) of 62 stage IV patients ever progressed. Tongue and glottic larynx did best, with only 1 of 22 patients ever failing (none locally). Supraglottic and oral cavity cancers other than tongue had the worst failure rates. Nineteen patients (24%) died of other causes (DOC), tumor-free. Patients who DOC correlated strongly with T stage (p < .002) but not with N stage or with AJC stage. The 5-year progression-free survival was 60% (confidence interval [CI] = 49% to 72%), and overall survival was 43% (CI = 33% to 56%). CONCLUSIONS: Disease control for this advanced head and neck cancer population was excellent. This regimen was especially effective in advanced tongue and glottic cancers and all stage III disease sites. Advanced supraglottic and hypopharynx cancers are problematic. These, and especially T4 lesions, are associated with high DOC rates, possibly in part related to swallowing malfunction. Nevertheless, the long-term survival without surgical intervention was high with this regimen.

Integration of surgery in multimodality therapy for esophageal cancer.

BACKGROUND: While adding chemotherapy to radiation for the treatment of esophageal cancers has been shown to be beneficial, surgery usually follows treatment or is omitted. In either case, regional control remains problematic. The purpose of this study was to test the feasibility of using chemotherapy and radiation following surgery in the treatment of of esophageal cancer and to assess the impact of this approach on regional control and survival. PATIENTS AND METHODS: Twenty-five patients with esophageal cancer were treated in a phase I pilot protocol consisting of initial esophagectomy with gastroesophagostomy and subsequent combined chemotherapy and radiation. Chemotherapy consisted of cisplatin given on day 1 and 5-fluorouracil (FU) on days 1-5 by continuous infusion. Radiation therapy was administered in varying fractionation schedules of once or twice daily concomitantly with the chemotherapy. Treatment was repeated every other week for two to four cycles. Median follow-up was 42 months. RESULTS: Acute toxicities (mucositis and cytopenias) were common but not worse than grade 3. Higher doses of 50 Gy with 2 Gy b.i.d. hyperfractionation caused late complications in four of 10 patients, (two lethal). Control of local disease for all patients was excellent with only two known and two possible local recurrences (16%) but distant metastases were common (46%). Disease-free survival was 58 and 30% at 1 and 2 years, respectively. Survival was 58 and 32% at 1 and 2 years, respectively (median survival, 19 months). CONCLUSION: The local control rate and survival were better than those in our historical experience with cisplatin and 5-FU chemotherapy and radiation given prior to surgery. A dose-fractionation schedule of < 2 Gy up to a total of 50 Gy b.i.d. is recommended to avoid late adverse effects. The role of surgery will be defined by randomized studies. Better systemic therapy is needed to impact on systemic failure.

Delaying the initiation of intact breast irradiation for patients with lymph node positive breast cancer increases the risk of local recurrence.

BACKGROUND: The impact of delaying irradiation to the intact breast for patients receiving chemotherapy for lymph node positive breast cancer is controversial. METHODS: From 1974 to 1989, 474 patients underwent lumpectomy and intact breast irradiation for early stage invasive breast cancer. Chemotherapy was administered to 84 patients (1 patient with bilateral breast cancer) because of positive axillary lymph nodes. Time from definitive breast surgery (lumpectomy or reexcision) to the initiation of breast irradiation was 21-314 days, with a median of 124 days. Forty-two patients began receiving radiation therapy before 120 days (early) and 42 more than 120 days after surgery (delayed). In the early group, cyclophosphamide/methotrexate/5-fluorouracil (CMF) was administered to 32 patients, doxorubicin, cyclophosphamide or cyclophosphamide, doxorubicin, 5-fluorouracil (AC or CAF) to 6 patients, and other regimens to 4 patients; in the delayed group, CMF was given to 29 patients, CAF to 12 patients, and L-PAM/5-fluorouracil to 1 patient. RESULTS: Median follow-up was 62 months. There was one breast recurrence in the early group, compared with six in the patients receiving delayed irradiation. The actuarial relapse rates for these groups at 5 years were 2% and 14%, respectively (P = 0.05). Survival and distant disease free survival were not significantly different between the two groups. CONCLUSIONS: Delays in the initiation of irradiation are associated with increased risk of relapse in the breast. When possible, the interval between definitive breast surgery (lumpectomy or reexcision) and the initiation of radiation therapy should be fewer than 120 days.

Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy?

PURPOSE: Multicentric cancer is present in a large proportion of mastectomies performed as treatment of breast cancer; it has been considered a contraindication to breast conservation. METHODS AND MATERIALS: We reviewed the records of our patients with Stage I or II breast cancer treated with breast conserving surgery and radiation therapy over a 13-year period. Twenty-seven patients had two or more nodules of grossly visible cancer separated by histologically normal breast tissue. All patients had grossly negative margins of excision; however, four patients had microscopically positive margins. Nine patients had positive axillary nodes. All patients received radiation therapy to the breast postoperatively, with a median dose of 50.4 Gy in 28 fractions; 11 patients also received a boost dose of 6-20 Gy to the tumor bed. Eleven patients were given adjuvant chemotherapy and one patient was given adjuvant tamoxifen. RESULTS: With a median follow-up of 53 months, only one patient has relapsed in the breast (3.7%); that patient relapsed in multiple distant sites at the same time. Three patients have died of disseminated disease; the actuarial survival and disease-free survival rates at 4 years are 89%. CONCLUSION: Breast conservation may be considered for patients with multicentric breast cancer discovered at the time of histologic examination. For patients with multicentric disease detected prior to surgery, breast conserving therapy may be appropriate as long as: (1) all clinically and radiographically apparent abnormalities are removed, (2) clear margins of resection are achieved, and (3) there is no extensive intraductal component.

Long-term results of curative irradiation in pathologically staged IA and IIA Hodgkin disease.

One hundred seventy-six patients with pathologically staged IA and IIA Hodgkin disease (HD) treated with irradiation alone were evaluated for long-term survival and freedom from relapse (FFR). Most of the patients received treatment to mantle and paraaortic fields; chemotherapy was not given except as salvage therapy. For pathologically staged IA disease, the 5-, 10-, and 15-year survival rates were 94%; the corresponding FFR rates were 96%, 93%, and 93%. For pathologically staged IIA disease, respective survival rates were 93%, 89%, and 80%, with FFR rates of 86%, 84%, and 84%. Twenty-one patients (12%) had relapse of HD; salvage therapy was successful in 11 of these patients. Pelvic recurrence was uncommon (three of 176 cases [2%]). No patient developed leukemia, and only two patients developed second malignancies (lung cancer in both cases). The authors conclude that radiation therapy is effective in treatment of early-stage HD.