C. Ronald Kersh

Curative radiotherapy in non-small cell carcinoma of the lung.

Recent reports suggest radiotherapy administered to the 5000-6000 cGy level can result in significant long-term survival in non-small cell carcinoma of the lung. This is particularly true for many cases that are technically operable but for medical or other reasons thoracotomy cannot be performed. Such patients drawn from Southern Appalachia where the principal industry is coal mining are the subject of this report. In this region coal miners pneumoconiosis (black lung) is common as well as other chronic respiratory disorders resulting in poor tolerance for surgery. Three hundred and eleven cases of non-small cell carcinoma were irradiated during the 4 years of 1980 through 1983. This group consisted of 77 patients with clinical Stage T1, T2, T3 all N0, M0 tumors, the majority of which were technically operable but upon whom no thoracotomy was performed because of medical reasons or patient refusal. All are available for 5-year study. Each of these patients was uniformly irradiated to 6000 cGy target dose in 30 fractions over 6 weeks using standard techniques. Absolute or crude survival in these 77 patients is as follows: 1 year, 57%; 2 year, 36%; 3 year, 21%; 4 year, 17%; and 5 year, 17%. Comparison with reported surgical series treated for cure show little difference in survival up to 2 years. Thereafter, the survival curves diverge with radiotherapy patients dying at a somewhat higher rate although by 4 years both survival curves slope similarly. A possible explanation for this difference is the advantage thoracotomy offers in early case selection allowing exclusion of advance cases from surgical reports whereas radiotherapy must include patients with occult local metastasis not identifiable on clinical grounds. This experience, among other reports include evidence that radiotherapy can result in long-term survival or cure with minimal morbidity in lung cancer patients in whom surgery carries excessive risk.

Concomitant 5-fluorouracil, Mitomycin-C, and radiotherapy for advanced gynecologic malignancies

Advanced gynecologic neoplasms continue to pose major therapeutic problems; 22,500 deaths were estimated for 1987. Between December 1983 and October 1985, there were 25 patients evaluated at our institution who on joint evaluation by the radiation oncologist and gynecologic oncologists were found to have extensive disease not amenable to standard therapy. Patients were to be treated by a combined modality approach with Mitomycin-C and 5-Fluorouracil given concomitantly with radiotherapy. Nineteen patients were treated definitively and six patients were treated with palliative intent (24 primary, 1 recurrent). The patients ranged in age from 27 to 90 years with a mean of 57.3 and a median of 57. Primary sites at presentation were: cervix--14 patients, vagina--7 patients, and vulva--4 patients. The initial FIGO stages at time of the initial diagnosis were: Stage I--1 (recurrent), Stage II--4, Stage III--15, and Stage IV--5. Chemotherapy consisted of 5-fluorouracil 1 gm/m2 given continuous infusion for 4 days with Mitomycin-C 10 mg/m2 IV push on day 1. Radiation therapy was started on day 1. Only 2 of 25 patients (8%) required chemotherapy reductions. All 25 patients received mega-voltage irradiation. The external beam dose range was 2000-6500 cGy and 14/25 patients received intracavitary or interstitial therapy. In the definitive patient group, there was no reduction in the therapeutic dose. Only four patients underwent surgical therapy. With a minimum follow-up of 8 months and a median follow-up of 28 months, the survival for the entire population was 56%. Fourteen of the 19 patients (74%) treated definitively are surviving with 12 patients having no evidence of disease. Survival by site in the definitive therapy group was cervix--70%, vulva--100%, and vagina--66%. The overall response rate was 84% at 3 and 9 months (3 months; CR--36%, PR--48%, and 9 months; CR--60%, PR--24%). There were no local recurrences in the 12 patients who achieved a complete response. Three patients died of metastatic disease alone and the overall local control was 60%. Evaluation of therapeutic side effects was performed. Hematologic analysis by the Southeastern Oncology Group criteria showed neutropenia in 14 patients (1--life-threatening, 2--severe, and 11 patients--mild/moderate) and thrombocytopenia was observed in 11 patients (all mild or moderate). All hematologic complications resolved. Acute complications did not appear increased except for the addition of mild oral mucositis (12 patients). Six patients demonstrated late effects with only 2 patients felt to have severe complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Primary central nervous system germ cell tumors. Effect of histologic confirmation on radiotherapy.

Primary malignant intracranial germ cell tumors are rare lesions responsible for only 0.5% of all central nervous system (CNS) malignancy. With stereotactic localization these lesions can be safely biopsied, and histologic confirmation will affect the ultimate prognosis. This report is a multi‐institutional retrospective analysis of 33 patients diagnosed with a primary CNS germ cell tumor. Tumors in 14 patients (42%) were histologically confirmed (13 germinoma and one embryonal cell carcinoma); 19 patients were treated with a presumptive diagnosis. All patients were irradiated with a dose range of 3950 cGy to 6000 cGy to the primary lesions. Eight patients received craniospinal irradiation, and 25 patients were locally treated. The 5‐year actuarial survival for the entire population was 64%. The survival rate in patients with histologic confirmation was 79% versus 53% in the unbiopsied population. Radiation doses greater than 5000 cGy, radiotherapy volume, and age were prognostic factors in determining survival.

Definitive Radiotherapy in the Management of Stage I and II Carcinomas of the Glottis

Definitive radiotherapy for early glottic carcinoma continues to offer excellent control and the advantage of voice preservation. In the 13 years from January 1972 through December 1984, there were 187 patients diagnosed with squamous cell carcinoma of the glottis at the University of Virginia Medical Center. One hundred forty-eight patients were treated with definitive radiotherapy as the initial management. The 3-year disease-free survival for the irradiated population was 93.6% in stage I and 75.5% in stage II. Twenty patients had recurrences following radiotherapy, and 13 of 20 were successfully surgically salvaged for an overall determinate survival of 100% in stage I and 85.7% in stage II at 3 years. These statistics are comparable to those from our previous 16-year review of 147 patients from 1956 through 1971. Factors of prognostic significance were persistent hoarseness after radiotherapy, impaired cord mobility, subglottic extension, and multiple sites of involvement in stage I. We conclude that definitive radiotherapy offers excellent survival and that a majority of the small number of treatment failures can be managed with surgical salvage.

A phase I-II trial of multimodality management of bulky gynecologic malignancy: Combined chemoradiosensitization and radiotherapy

Between December 1983 and December 1987, there were 44 patients with bulky, nonresectable squamous cell carcinomas of the gynecologic tract (cervix, 36; vagina, eight) who were treated with concomitant chemotherapy and radiotherapy. Chemotherapy consisted of 5‐fluorouracil (5‐FU) 1 g/m2 given by continuous intravenous infusion on days 1 through 4 and mitomycin C 10 mg/m2 given intravenously on day 1. External‐beam irradiation was started on day 1 with a total calculated dose of 5000 cGy in 25 fractions employed. This was followed by brachytherapy. With a mean follow‐up of 30.3 months and a median of 28 months, local control has been achieved in 32 of 44 patients (73%). The overall response rate was 88% (3‐month partial response, 43%; 3‐month complete response, 45%; 8‐month partial response, 15%; 8‐month complete response, 73%). Analysis of complications by Radiation Therapy Oncology Group (RTOG) criteria did not demonstrate an increase in acute or late complications.

Primary malignant extragonadal germ cell tumors. An analysis of the effect of radiotherapy

A retrospective analysis was performed on all patients diagnosed with biopsy‐proven extragonadal germ cell tumors at the University of Virginia (Charlottesville, VA), The Medical University of South Carolina (Charleston, SC), the Bethesda Naval Hospital (Bethesda MD. ), and The Medical College of Virginia (Richmond, VA) for the time period of January 1965 to December 1984. A total of 54 patients were treated with the initial sites of presentation observed: mediastinum, 26; central nervous system, 14; retroperitoneum, eight; and sacrococcygeal region, six. Megavoltage irradiation was used in 44 patients with a dose range of 2400 to 5580 cGy (mean, 4213 cGy). With a minimum follow‐up of 4.0 years and a mean follow‐up of 10.8 years, the 5‐year actuarial survival for the entire population was 57.8%. Local control was achieved in 26 of 44 (59%) of the irradiated population. Factors of prognostic significance included histologic type at presentation, site of presentation, and radiation doses greater than or equal to 4000 cGy. Radiotherapy appears to be an effective modality in patients with extragonadal seminomas; however, the non‐seminomatous tumors do not appear to be as radioresponsiye.

Whole abdominal radiotherapy following cytoreductive surgery and chemotherapy in ovarian carcinoma

Persistent or recurrent disease following surgery and chemotherapy in ovarian carcinoma remains a major therapeutic dilemma. Between January 1980 and December 1985, there were 26 patients who had previously undergone cytoreductive surgery and chemotherapy and were treated with external beam radiotherapy. Twenty-one of these patients had been treated with platinum-adriamycin-cytoxan (PAC) regimen and 5 were treated with other combinations. Surgical reevaluation was performed in 21 of the 26 patients and only 4/21 (19%) patients were free of disease. All 26 patients were irradiated with a planned dose of 2500 cGy/100 cGy/day or 2280 cGy/120 cGy/day to the whole abdomen and a final calculated dose to the pelvis of 4500 cGy. Initial evaluation showed a 3-year actuarial survival rate of 51% and a disease-free survival rate of 42%. Follow-up analysis yields survivals of 45 and 35%, respectively. Severe gastrointestinal complications were observed in 3/26 patients and all hematologic complications resolved. Variables of prognostic significance were chemotherapy tolerance, grade, and volume of residual disease. We conclude that a proportion of patients with disease following cytoreductive surgery and chemotherapy may be salvaged with abdominopelvic irradiation.

Prognostic value of vocal cord fixation with respect to treatment in cancers of the supraglottis and pyriform sinus

Vocal cord fixation in supraglottic and pyriform sinus cancers has, in the past, precluded management by radiotherapy alone. Ninety‐eight patients were reviewed to determine the prognostic effect of vocal cord fixation. The predictive value of cord mobility status after 50 Gy was evaluated with respect to treatment modality.

Concomitant 5-flurouracil and mitomycin-C with radiotherapy in the primary management of advanced gynecologic malignancy

Advanced gynecologic neoplasms continue to pose major therapeutic problems with an esti, mated 22,500 deaths in 1987. Between December 1983 and October 1985, there were 25 patients evaluated at the University of Virginia Medical Center who on joint evaluation by the radiation oncologist and gynecologic oncologist were felt to have extensive disease not ameniable to standard therapy. A combined modality approach with Mitomycin-C and 5-Flurouracil given concomitantly with radiotherapy was analyzed. Nineteen patients were treated definitively and six patients were treated with palliative intent (24 primary, 1 recurrent). The patients ranged in age from 27 to 90 years with a mean of 57.3 and a median of 57. Primary sites at presentation were: cervix-14 patients, vagina-7 patients, and vulva-4 patients. The initial FIG0 staqes at time of the initial diacrnosis were: -(recurrent), Stage 11-5, Stage III-13, and Stage IVz5. Stase I-l