A prospective randomized comparison of radiation therapy plus lonidamine versus radiation therapy plus placebo as initial treatment of clinically localized but nonresectable nonsmall cell lung cancer.

PURPOSE: By means of a multicenter, prospective randomized, placebo-controlled study, to assess the impact of adding the radiation-enhancing agent lonidamine to standard "curative-intent" radiation therapy upon overall survival, progression-free survival, and local progression-free survival of patients with clinically localized but nonresectable nonsmall cell lung cancer. METHODS AND MATERIALS: Lonidamine, or the lonidamine-placebo, was administered at a dose of 265 mg/m2 in three divided daily doses. Drug therapy began 2 days prior to the initiation of radiation therapy and continued until progression of disease mandated a change in therapy. The radiation therapy dose was 55-60 Gy, at a daily dose of 1.8 Gy and five treatments per week. Patients with clinical Stage II or III nonsmall cell lung cancer were stratified within the treatment center, and within two histologic strata: epidermoid vs. other nonsmall cell cancers. RESULTS: A total of 310 patients were enlisted on study, 152 on the placebo arm and 158 on the lonidamine arm. The median survival durations were 326 days and 392 days for the placebo and lonidamine-treated groups respectively, p = 0.41 for a comparison of the survival curves. Median progression-free survival and median local progression-free survival durations were 197 days and 341 days for placebo + radiation therapy vs. 230 days and 300 days for lonidamine + radiation therapy; p-values for the respective curves were 0.75 and 0.42. Although there were proportionately more lonidamine-treated patients than placebo-treated patients demonstrating continued local control in excess of 12 months, the numbers of patients still at risk after 24 months were too small for meaningful statistical analysis. CONCLUSION: This multicenter Phase III study failed to demonstrate a significant advantage in the lonidamine-treated population in overally patient survival, in progression-free survival, or in the median duration of local control.

Increased chronic bowel complications with split-course pelvic irradiation.

PURPOSE: To assess the possible impact of various treatment factors including split-course versus continuous course treatment on the incidence of chronic bowel complications in patients receiving adjuvant pelvic radiotherapy. METHODS AND MATERIALS: A retrospective review was performed of records of 153 patients treated with adjuvant external beam pelvic radiation therapy without brachytherapy for endometrial and colorectal carcinomas. Continuous course radiotherapy was administered in 91 patients (59%) and 62 patients (41%) received split course treatment with a planned 2 week mid-treatment break. Mean pelvic dose and daily fraction size were 51.4 and 1.71 Gray, respectively. Multiple patient and treatment variables were assessed for their possible relationship to chronic bowel complications. Univariate and multivariate statistical analyses were carried out. RESULTS: Twenty-seven patients (18%) developed chronic bowel complications at a median interval of 12 months after radiotherapy. Of all factors analyzed, only the use of split course technique was associated with a significantly higher rate of chronic bowel injury and decreased complication-free survival (p = 0.009). CONCLUSION: This study supports earlier suggestions that the use of split course rather than continuous course pelvic radiotherapy can increase late intestinal complication rates. Possible pathophysiologic mechanisms are discussed.

Impact of bone density corrections on target dose delivered to the prostate with 4 MV, 6 MV, 10 MV, and 18 MV photons.

Doses for definitive prostate irradiation have been derived empirically using low-energy megavoltage equipment without availability of bone density corrections. With their increased availability, higher energy photons are being used more frequently because of their improved depth of penetration. Although inhomogeneity corrections lead to greater accuracy of dose delivery, the clinical utility of corrections in the pelvis is unclear. This study evaluates the effect of bone density on the dose delivered with respect to the photon energy employed. Contours and volumes for 10 patients were taken from computed tomography scans at the center of the prostate gland. Treatment plans for bilateral prostate arc fields were run on the Capintec Treatment Planning System for 4, 6, 10, and 18 MV photon energies. The monitor units needed to deliver 6500 cGy to isocenter without bone correction were used for calculations, both with and without bone correction using the equivalent path length algorithm. The median dose to the isocenter was 6500 cGy for all energies without bone correction. The median doses using the uncorrected monitor units for the 4 MV, 6 MV, 10 MV, and 18 MV photon beams corrected for bone density were 6033, 6062, 6166, and 6228 cGy, respectively. The variance in target doses observed in our patient sample was +/- 2.3%, +/- 2.2%, +/- 1.7%, and +/- 1.4%, respectively, for the 4 MV, 6 MV, 10 MV, and 18 MV beams with bone correction. The increased density of bone in the pelvis does alter the actual dose to the prostate from external beam treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Interstitial reirradiation for recurrent gynecologic malignancies: results and analysis of prognostic factors.

Thirteen patients with recurrent or new primary gynecologic malignancies after previous radiation therapy (RT) underwent interstitial reirradiation (IRI) from July 1986 through December 1990. Mean and median ages were 63 and 70 years, respectively. Mean and median implanted volumes were 14.3 and 12 cc, respectively. Overall, 9/13 (69%) had complete responses to IRI and 6 (46%) continue to have no evidence of disease (NED) 24-71 months later (median follow-up, 59 months). Of 7 patients with recurrent cervical or new primary vaginal carcinoma, 5 (71%) remain free of disease 27-71 months (median, 58 months) after IRI. Of 6 patients with recurrent endometrial carcinomas, only 1 (16%) continues with NED 24 months after IRI. Patients with NED after IRI had a median disease-free interval prior to IRI of 100 months compared to 6 months in patients failing IRI. Trends toward improved outcomes were observed in squamous vs adenocarcinoma, smaller tumor volumes, higher implant doses, and vaginal wall/suburethra vs vaginal cuff location. One possible complication, a rectovaginal fistula, developed in the presence of recurrent cervical cancer 22 months after IRI. Interstitial reirradiation is an effective treatment for selected patients with recurrent gynecologic malignancies after previous RT. Advantages of IRI over radical surgery include its potential to preserve organ structure and function and its applicability to patients with medical contraindications to salvage surgery. Furthermore, since subsequent exenterative surgery should not be compromised in patients failing IRI, a policy of IRI as initial treatment may be justified for patients in whom the potential for morbidity is limited.

An immunohistochemical study of perianal Paget's disease. Possible origins and clinical implications.

The histogenesis of perianal Paget's disease is controversial. A clinical and pathologic study was done of a patient with a history of adenocarcinoma of the rectum for whom a subsequent diagnosis of perianal Paget's disease was the sole manifestation of recurrent rectal cancer. Immunohistochemical techniques were used to compare and contrast the original rectal adenocarcinoma with the subsequent perianal skin recurrence confined to the epidermis. Both the rectal adenocarcinoma and the Paget's cells were positive for cytokeratin, epithelial membrane antigen, B72.3, and carcinoembryonic antigen and negative for gross cystic disease fluid protein-15, Leu-M1, CA 125, and S-100 protein. These findings, their relevance to the histogenesis of perianal Paget's disease, and the possible clinical implications are discussed.

Radiation tolerance of the cervical spinal cord.

The incidence of permanent injury to the spinal cord as a complication of radiation therapy generally correlates positively with total radiation dosage. However, several reports in the literature have indicated that fraction size is also an important factor in the development or nondevelopment of late injuries in normal tissue. To determine the effect of fraction size on the incidence of radiation-induced spinal cord injuries, we reviewed 144 cases of head and neck cancer treated at our institution between 1971 and 1980 with radiation greater than 5600 cGy to a portion of the cervical spinal cord. Most of these patients received greater than or equal to 6000 cGy, with fraction sizes ranging from 133 cGy to 200 cGy. Fifty-three of the 144 patients have been followed up for 2 years or more. Nearly half of these (26 patients) received greater than 6000 cGy with fraction sizes of 133 cGy to 180 cGy. Only 1 of the 53 (1.9%) has sustained permanent spinal cord injury; 20 months after completion of radiation treatments he developed Brown-Séquard syndrome. Our experience suggests that radiation injuries to the spinal cord correlate not only with total radiation dosage, but also with fraction size; low fraction sizes appear to decrease the incidence of such injuries.

Recurrent meningioma.

Single meningiomas are histologically classified as benign tumors, but clearly malignant types have been encountered. The standard mode of management is total macroscopic removal with excision of the dural attachment and abnormal bone, if there is any. Despite this aggressive surgery, recurrence rates of approximately 9% have been reported with the removal of benign tumors, and the rate is much higher with the removal of malignant meningiomas. Recurrence most frequently occurs at the original tumor site and is most often explained by incomplete removal, which, in turn, is a function of the anatomic location of the tumor. Less common are regional recurrences, which may be explained on the basis of the multicentric origin of meningiomas. This theory may also explain the rare entity, "multiple meningioma." This article documents an unexpected regional recurrence of meningioma. The pertinent literature is reviewed.

Metastatic carcinoma of the neck from an unknown primary.

From 1974 to 1984, 31 patients with metastatic carcinoma to the neck from an unknown primary were treated with radiation therapy. On review, three groups were identified based on presentation and treatment. Group I consists of 19 patients treated with curative intent. They all presented with cervical adenopathy, 11 patients with N1 disease, 2 with Stage N2A disease, 1 with Stage N2B disease, 4 with N3A disease, and 1 with unknown stage. The majority of patients were treated with portals encompassing the nasopharynx, oropharynx, hypopharynx, and neck to a dose of 5000 rad followed by boosts of 1000-1500 rad. The overall 2-year NED survival in this group was 63% (12/19). The most significant prognostic factor was the stage of the metastatic nodes. The NED survival rate for the 14 patients with Stage N1 and N2 was 86% (12/14). Histology of the lesions was not an important factor in the outcome. In Group II there are six patients who received palliative treatment because of large, fixed, cervical nodes. Three of these patients (50%) died within 2 months of completion of treatment. Group III consists of six patients who presented with supraclavicular adenopathy. All had persistent or recurrent disease within 19 months. We have concluded that in patients with metastatic carcinoma to the cervical nodes from an unknown primary, radiation therapy to the neck and suspected areas of primary disease may play an important role in cure, particularly in early stage disease.