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Purpose: This population-based study describes the treatment of early glottic cancer in Ontario, Canada and assesses whether treatment variations were associated with treatment effectiveness., Methods and Materials: We studied 491 T1N0 and 213 T2N0 patients. Data abstracted from charts included age, sex, stage, treatment details, disease control, and survival., Results: The total dose ranged from 50 to 70 Gy, and the daily dose ranged from 1.9 to 2.8 Gy. In 90%, treatment duration was between 25 and 50 days. Field sizes, field reductions, beam arrangement, and beam energy varied. Late treatment breaks occurred in 13.6% of T1N0 and 27.1% of T2N0 cases. Local control was comparable to other reports for T1N0 (82% at 5 years), but was only 63.2% in T2N0. Variables associated with local failure in T1N0 were age less than 49 years (relative risk [RR], 3.21; 95% confidence interval [CI], 1.49-6.90) and >3 treatment interruption days (RR, 2.43; 95% CI, 1.00-5.91). In T2N0, these were field reduction (RR, 2.33; 95% CI, 1.23-4.42) and late treatment breaks (RR, 2.19; 95% CI, 1.09-4.41)., Conclusion: Some aspects of treatment for early glottic cancer were associated with worse local control. Problems with protracted treatment are of particular concern, underscoring the need for randomized studies to intensify radiotherapy.

Purpose: To determine whether prevention of hyposalivation after curative radiotherapy (RT) to the head and neck improves patients' quality of life (QOL)., Methods and Materials: Patients were to receive at least 50 Gy to 50% of the volume of the major salivary glands, provide unstimulated and stimulated saliva samples, and complete the University of Washington head-and-neck QOL tool before RT and 3 and 6 months after RT. Patients were randomized to receive pilocarpine 5 mg or placebo q.i.d., Results: A total of 249 patients was randomized between March 1998 and January 2000. Of these, 214 were eligible for QOL analysis. Patients were evenly distributed between arms by race, gender, tobacco use, tumor site, T stage (50% T2-T3), and salivary function. A Karnofsky performance status of 90% was more common in the pilocarpine arm. Twenty percent of the patients on the pilocarpine arm and 29% of the patients on the placebo arm were taking nutritional supplements. The placebo arm patients had greater mouth pain and chewing difficulties. Compliance for the QOL tool at 3 and 6 months was 65% and 50%, respectively. Despite statistically significant (p = 0.047 and p = 0.049, respectively) preservation of salivary function in the pilocarpine arm, patients on the pilocarpine arm reported difficulties with swallowing (75%), activity (80%), hyposalivation (64%), and taste (81%). No difference was noted between arms at 3 months in mucositis scores, with both arms demonstrating increased requirement for oral nutrients., Conclusion: Objective prevention of hyposalivation did not affect patients' assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT.

Purpose: To determine the prognosis of new patients with T1-4N0-1B0M0 mycosis fungoides treated with total skin electron beam radiation., Methods and Materials: 25 consecutive patients received 30 Gy with 3 or 4 MeV electrons in 1977-1980; 121 received 35 Gy with 4 MeV in 1980-1992. Response rates, relapse-free survival, and overall and cause-specific survivals were assessed by explicit criteria. The relationships of T, N, gender, age, and radiation technique to prognosis were investigated by regression statistics., Results: The average age was 55 years and the male:female ratio was 1:4. Forty-four percent were T1N0 and 34% were T2N0. The overall complete response rate was 82%, and lower T status, more radiation, and female gender were independently and positively associated with response. Median follow-up was 5.2 years. T1 patients who entered remission had a higher relapse-free survival compared to T2 through T4 patients. Thirty-four percent of T1 patients remained relapse-free at 6 years, compared to fewer than 20% of T2-4 patients. For all 146 patients the median overall survival was not reached at 15 years. Only 8 of 29 deaths were related to mycosis fungoides and these were significantly associated with higher T. The 54 T1N0 patients who had 35 Gy had a 10-year mycosis fungoides-specific survival of 100%., Conclusion: Total skin electron beam radiation gives good results with T1N0B0M0 disease. T3-4 disease is less likely to respond, it relapses more quickly, and it implies a poorer survival, but radiation offers palliation. T2 responds like T1, but relapses like T3-4. T2 also implies an intermediate survival. These results have implications for staging, informed consent, optimizing radiation treatment, and clinical trials.

Purpose: The probability of treatment resistant cells developing in a tumor, such as small cell lung cancer (SCLC) which has a rapid cell cycle time, is a function of the number of tumor cells present and of time. Theoretically, the development of resistance to chemotherapy and radiotherapy should be minimized by using all treatment modalities early in the treatment program., Methods and Materials: The importance of the timing of loco-regional radiotherapy was assessed in a multi-institution randomized study. Three hundred and eight patients with limited small cell lung cancer (LSCLC) were given three cycles of cyclophosphamide, doxorubicin and vincristine alternating with three cycles of etoposide and cisplatin. In addition, patients were randomized to receive locoregional radiotherapy: 40 Gy in 15 fractions in 3 weeks with treatment planning techniques to limit the spinal cord dose to be < or = 35 Gy either with the first cycle (early) or with the sixth cycle of chemotherapy (late). Responding patients received prophylactic brain irradiation (25 Gy in 10 fractions in 2 weeks) after completion of locoregional radiotherapy and chemotherapy., Results: 96% of the 155 eligible patients allocated to the "early" arm and 87% of the 153 allocated to the "late" arm received locoregional radiotherapy; 26 patients did not receive locoregional radiotherapy. The mean field sizes were similar in both arms. The mean radiation doses were significantly less in the "early" arm (p = 0.0319 Wilcoxon rank sum test). Any differences in the frequency of toxicities were minor. All patients have been followed for at least 2 years and the median follow up is 4 years. 64% had a complete response in the "early" arm compared with 56% in the "late" arm (p = 0.137). Survival was measured from the start of chemotherapy. There was a significant improvement in survival in the "early" arm; median survival was 21.2 months compared with 16.0 months in the "late" arm (p = .008 log rank test). Survival at 2, 3, and 4 years was 40%, 32%, and 25%, respectively, for the "early" arm and 33%, 22%, and 15% for the "late" arm. There were 232 (75%) recurrences among those patients whose disease recurred. The proportion who had local recurrence within the radiation field was 41% and 39% for "early" and "late" treatment arms respectively. The proportion of brain metastases in the "late" arm (28%) was significantly higher than in the "early" arm (18%) p = .0425 Fishers' exact test., Conclusion: We conclude that early administration of locoregional radiotherapy in a combined modality treatment is superior to late consolidative locoregional radiotherapy in limited small cell lung cancer.

The optimization of radiotherapy for the treatment of malignant mesothelioma highlights many of the currently outstanding problems in clinical radiation physics. The experimental investigation of an intuitively attractive irradiation technique with combined photon and electron beams using a specially constructed phantom has established that, due to the penetration in low density material of both primary electrons and those secondary to photon irradiation, the normal lung tissue is not spared to any significant degree by such a technique. Furthermore, great care needs to be exercised in the treatment planning calculations for this approach if absolute dosimetry errors as large as 50% are to be avoided.

There are sound radiobiologic and suggestive clinical rationale for superfractionating the radiotherapeutic regimens employed for the therapy of rapidly growing malignancies. Oat cell carcinoma of the bronchus is such a tumor. We report our experience combining aggressive systemic combination chemotherapy with superfractionated radiotherapy for the treatment of "limited" oat cell carcinoma of the bronchus. Overall, patient tolerance was satisfactory and a complete remission rate of 74% was achieved. It remains to be proven, in a prospective randomized fashion, whether this approach is superior to current conventional management.

Forty-two patients, with a variety of advanced pelvic malignancies, have been treated with a hypofractionated radiotherapy regimen. The most common schedule was 30 Gy in three fractions at monthly intervals. This has provided effective palliation with acceptable morbidity in the select patient group treated. The results in advanced rectal and ovarian tumors were particularly encouraging. The most effective dose/fraction and interfraction interval is, at present, under active investigation within our institution.

Twenty-four patients with chordoma who received one or more courses of megavoltage radiation therapy following biopsy or incomplete resection were reviewed. The uncorrected survival rate at five years was 62%, and at 10 years was 28%, but most patients had clinically detectable residual chordoma present at the time of death or last follow-up. The duration of symptomatic improvement following irradiation ranged from a few months to 18 years, median 3.5 years. Detailed dose-time and symptomatic response data for 56 patients from this series and from the literature who were treated by conventional daily fractionated megavoltage irradiation show no convincing evidence that symptomatic relief is more likely after high doses than after total doses of only 4000 to 5500 cGy. Patients are rarely cured of chordoma by partial tumor resection and conventional radiation. Four patients received multiple fractions of 100 cGy each day either as retreatment for recurrence, or as initial treatment. Symptomatic responses, and decreases in the size of tumor masses, were seen following total doses ranging from 2000 cGy/20 fractions/5 days/4 X 3 hourly fractions each day to 4000 cGy/40 fractions/12 days/4 X 3 hourly fractions each day. The short duration of follow-up in these patients prevents comparison with conventional fractionation. However, this technique presents one possible new approach for the treatment of chordoma.