The integration of irradiation and surgery as the treatment for selected cancers.

Combinations of radiation therapy with surgery originated when the surgeon thought he had transected cancer. Unrealistic expectations, however, plagued these combinations until it was appreciated that the dose required to eradicate a given cancerous mass varied primarily with its volume and the associated oxygen tension of its cells. This helped to establish the rationale for combining irradiation and surgery and enabled the radiation therapist to more closely tailor dose needs to each specific clinical problem. Tailoring of dose remains crude. Our greatest errors continue to be attributable to poor definition of tumor extent and the underestimation of residual tumor volume. We need more precise information from the surgeon and pathologist along with greater knowledge of patterns of spread. To the degree that such added information becomes available, we have the means to increase loco-regional control rates.

High-dose reirradiation of head and neck cancer with curative intent.

PURPOSE: This study evaluates the response of new or recurrent head and neck cancers and the response of associated normal tissues to high dose reirradiation with curative intent. METHODS AND MATERIALS: From 1964 to 1991, 15 patients with in-field new second head and neck cancers and 85 patients with recurrent head and neck cancers have had high-dose reirradiation that overlapped with previously irradiated volumes. Reirradiation was given only to patients with no more than apparent minimal clinical radiation effects from the first radiation course. The reirradiation consisted of external beam only in 82 patients, external beam plus intracavitary or interstitial implant irradiation in 14 patients, and interstitial implant irradiation only in four patients. The combined overlapping dose from both the initial and subsequent irradiation (including brachytherapy) was 69-89 Gy in 14 patients, 90-99 Gy in 15 patients, 100-119 Gy in 27 patients, and 120 Gy or greater in 44 patients. Four patients had areas of overlap that received greater than 180 Gy. RESULTS: The actuarial 5-year survival was 37% for patients with new second primary cancers and 17% for patients with recurrent cancers. Loco-regional tumor control was achieved in 60% of the patients with new tumors and in 27% of the patients with recurrent tumors. Nine of the 100 patients developed severe adverse normal tissue effects from the reirradiation. CONCLUSION: High-dose reirradiation of head and neck cancers can be successful curative treatment in a significant proportion of patients. It is associated with substantial but acceptable risks in properly selected patients.

Bone metastasis: review and critical analysis of random allocation trials of local field treatment.

PURPOSE: Compare and contrast reports of random allocation clinical trials of local field radiation therapy of metastases to bone to determine the techniques producing the best results (frequency, magnitude, and duration of benefit), and relate these to the goals of complete relief of pain and prevention of disability for the remaining life of the patient. METHODS AND MATERIALS: Review all published reports of random allocation clinical trials, and perform a systematic analysis of the processes and outcomes of the several trial reports. RESULTS: All trials were performed on selected populations of patients with symptomatic metastases and most studies included widely diverse groups with regard to: (a) site of primary tumor, (b) location, extent, size, and nature of metastases, (c) duration of survival after treatment All trial reports lack sufficient detail for full and complete analysis. Much collected information is not now available for reanalysis and many important data sets were apparently never collected. Several of the variations in patient and tumor characteristics were found to be much more important than treatment dose in the outcome results. Treatment planning and delivery techniques were unsophisticated and probably resulted in a systematic delivery of less than the assigned dose to some metastases. In general the use and benefit of retreatment was greater in those patients who initially received lower doses but the basis and dose of retreatment was not documented. Follow-up of patients was varied with a large proportion of surviving patients lost to follow-up in several studies. The greatest difference in the reports is the method of calculation of results. The applicability of Kaplan-Meier actuarial analysis, censoring the lost and dead patients, as used in studies with loss to follow-up of a large number of patients is questionable. The censoring involved is "informative" (the processes of loss relate to the outcome) and not acceptable since it results in artificial elevation of the frequency of response. Overall, higher dose fractionated treatment regimens produced a better frequency, magnitude, and duration of response than lower dose single-fraction regimens. Relapse after initial response was frequent. The "median duration of relief" was much shorter than the "median duration of survival" post-treatment. Thus the "net pain relief" is far less than the goal of pain relief for the total duration of life after treatment. CONCLUSIONS: The pain relief obtained in all studies is poor and our care practices need to be improved. Many patients never achieved complete relief and for most who did, the duration of relief was much less than their period of survival after treatment. Higher dose, fractionated treatments produced a greater frequency, magnitude, and duration of response with an improved "net pain relief." Additional trials with selection of comparable cases, good definition of extent of disease, exemplary treatment, and complete follow-up are required.

Squamous cell carcinoma of the pharyngeal walls treated with radiotherapy.

PURPOSE: To assess the impact of fractionation schedule, chemotherapy, and tumor location on local control and survival in patients treated with definitive irradiation for carcinoma of the pharyngeal walls. METHODS AND MATERIALS: Between May 1971 and December 1991, 74 patients with previously untreated squamous cell carcinoma of the pharyngeal walls (excluding nasopharynx, tonsil, and pyriform sinus) were treated with radical megavoltage irradiation with or without chemotherapy at Oregon Health Sciences University. RESULTS: Two-year local control rates by stage were: T1: 100%, T2: 55%, T3: 31%, and T4: 29% . Twice-a-day irradiation improved local control rates as compared with once-a-day irradiation for patients with Stage T3 lesions, with 5 out of 7 (71.4%) vs. 4 out of 19 (21%) patients controlled at 2 years (p = 0.015). No improvement was seen in 2-year local control of all stages when chemotherapy was used in conjunction with once-a-day fractionation; however, six of eight patients (75%) treated with twice-a-day irradiation combined with either induction or concurrent chemotherapy had local control. The 2-year local control rate of 100% (6 out of 6) for the group of patients treated with concurrent chemotherapy and b.i.d. irradiation (all with Stage T3 and T4 tumors) is a dramatic improvement over the 2-year local control rate of 30% (10 out of 33) for our entire group of patients with Stage T3 and T4 tumors. Local control rates did not differ by tumor location on the pharyngeal walls. Adjusted disease-specific survival rates by stage were: 1: 100%, II: 85%, III: 58%, IV: 40%. Overall survival rates by stage were: I: 75%, II: 67%, III: 33%, IV: 30%. CONCLUSION: We advocate radical irradiation as the primary therapy for pharyngeal wall carcinomas with the use of twice-a-day fractionation for Stages T2-T4. Our preliminary results with concurrent chemotherapy and b.i.d. irradiation for advanced T3 and T4 tumors appear to be comparable to reported results with hyperfractionated radiation alone. The relative contribution of chemotherapy to b.i.d. irradiation cannot be determined from this small retrospective series; however, in view of the relatively poor results for patients with advanced stage disease, we feel this treatment combination deserves further investigation.

Elective irradiation of the lower cervical region in patients at high risk for recurrent cancer at the tracheal stoma.

The results of treatment for recurrent cancer at the tracheal stoma have been poor. From 1971 to 1976, elective postoperative irradiation of the neck was given to 26 high-risk patients with carcinoma of the larynx and hypopharynx. None of the 22 patients whose stomas were irradiated developed stomal or peristomal recurrence, while 2 of the 4 patients whose stomas were shielded had stomal recurrence. Elective irradiation of the tracheal stoma was effective in preventing stomal recurrence; we recommend inclusion of the stomal area in preoperative or postoperative irradiation to the lower cervical region for high-risk patients.

Pre-estrogen breast irradiation for patients with carcinoma of the prostate: a critical review.

We studied 38 patients with prostatic cancer who received breast irradiation before oral estrogen administration. Our data are combined with those from other institutions to determine the effectiveness of pre-estrogen breast irradiation in minimizing gynecomastia and/or pain. Based on our review the incidence of estrogen-induced breast changes is 70%. Irradiation given before estrogen administration can prevent or minimize these changes in 89.3% of the treated patients. Histologic changes of gynecomastia are reviewed and recommendations for optimum radiation therapy technique are included.

External irradiation in the management of stage II endometrial carcinoma.

Twenty-nine patients with stage II endometrial carcinoma were reviewed and the possible risk factors involved in state II disease are presented. Twenty-four patients received external irradiation as part of their treatment with or without intracavitary or intravaginal radium and/or TAH BSO. The 5-year actuarial survival in our series was 81.4%. The data showed that preoperative external irradiation can be effectively administered without undue complication. A strong argument against the traditional use of preoperative intracavitary radium is presented. Preoperative external irradiation administered with a 4-field box technique to deliver a minimum dose of 5000 rad in 5--6 weeks to all the structures at risk is the recommended treatment for stage II endometrial carcinoma.

High-dose fractionated radiation therapy for select patients with brain metastases.

Four patients with metastases to the brain were treated by high-dose fractionated radiation therapy. In all four cases, a complete response and prolonged disease-free survival could be documented. Unlike the standard therapy for such patients (i.e., craniotomy and postoperative irradiation), high-dose fractionated radiation therapy carries no operative risk and can encompass multiple brain metastases and metastases in deep or critical intracranial sites.