Carboplatin is effective therapy for young children with progressive optic pathway tumors: a Pediatric Oncology Group phase II study.

The Pediatric Oncology Group conducted a phase II study to evaluate the activity of carboplatin in children 5 years or younger with progressive optic pathway tumors (OPTs). Of the 51 patients accrued to this study, 1 was not eligible because the child was older than 6 years. Fifty patients were eligible and had either neuro-imaging or symptomatic evidence of progressive OPTs. Twenty-one of 50 had evidence of neurofibromatosis type I (NF-1). Therapy consisted of carboplatin 560 mg/m2 at 4-week intervals. Patients with stable disease or better after two courses were continued on therapy for 18 months or until progressive disease. Of the 50 eligible children, 39 had stable disease or better, and 34 completed the 18-month therapy. Our data are sufficient to conclude that the proportion of objective responses (complete, partial, or minor response or stable disease) exceeded 30% (P < 0.00001), and the approximate 95% confidence interval estimate of the objective response rate was 0.665 to 0.895. Twenty-one patients went off protocol because of progressive disease. Fifteen patients progressed during the 18-month therapy, and 6 patients progressed after completing therapy. Six children died with progressive disease. Major toxicities were neutropenia and thrombocytopenia, and 3 children experienced allergic reactions. Carboplatin is active and safe for the treatment of young children with progressive OPTs. The addition of other potentially active drugs may further increase the event-free survival for these children.

Breast conservation therapy for breast cancer treatment in Brown County.

The Northeast Wisconsin Cancer Registry and a patient survey was utilized to examine the use of breast conservation surgery in Brown County between 1991 and 1997 and the factors influencing patients' treatment decisions. In all patients, the rate of breast conservation rose from approximately 30% to 44% during that time period. The percent of all patients with stage 0, I or II breast cancer who were potential candidates for breast conservation based on their stage rose from 89% in 1991 to 96% in 1997. The percent of Stage I and Stage II patients who underwent breast conserving surgery rose from 29% in 1991 to 38% in 1997. There was a higher use of breast conserving surgery in younger women (approximately 50% in age 35 to 49 years old in 1997) compared to women older than 62 (33% in 1997). Breast conservation surgery was used in 47% of patients with AJCC T1 (primary tumors less than 2 cm) and in 25% of patients with T2 lesions (primary tumors 2 to 5 cm); and more often in node negative than in node positive patients (51% vs. 20%). A patient survey revealed that a majority of patients felt that their surgeon's recommendation was the most important influence in making their surgical decision and that their fear of cancer recurrence most strongly influenced their decision on a personal level. Fewer than half of the women were referred to a medical oncologist, radiation oncologist, plastic surgeon or second opinion surgeon prior to surgery. Breast conservative treatment is increasingly utilized in Northeastern Wisconsin and women depend on their surgeon to give them clear, complete, non-biased information balanced with emotional support during the time when they are asked to make the complex decision of the type of breast cancer surgery they desire.

Management of advanced squamous cell carcinomas of the maxillary sinus.

From 1970 to 1988, 41 cases of advanced maxillary sinus cancers were treated at the University of Kansas Medical Center. Local control for the 37 evaluable patients was achieved in 21 (57%). Local control by radiation therapy alone was achieved in ten of 19 (53%) patients compared with eight of 14 (57%) treated with a combination of surgery and radiation therapy. A dose greater than 6500 cGy correlated with better local control in patients treated with radiation therapy alone. Neck node failure occurred in three of 35 (8%) patients when not electively treated. Neck metastasis either at presentation or at a later stage reduced survival. The overall absolute survival for the entire group at 5 years was 35%. A combination of preoperative radiation therapy and surgery is recommended for patients with advanced-stage maxillary sinus cancer. Radiation therapy is an equally good alternative for those who are not surgical candidates or refuse surgery.

Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck.

We treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.

Local recurrence of soft tissue sarcoma following brachytherapy.

Twenty-five patients with soft tissue sarcomas were treated with Ir192 implants following wide local excision at our institution between 1982 and 1987. External beam radiotherapy was given in addition to the implant in a majority of patients. The median follow-up in these 25 patients is 36 months (12 to 75 months). Twenty patients have had no evidence of local recurrence following their primary treatment (FFR = 80%). A multivariate analysis using stepwise logistic regression was used to predict failure in 3 years or less. Potential predictors examined included age, sex, tumor location, primary versus recurrent disease, grade, histology, surgical margins, implant only versus implant plus external beam, and a ratio of the volume of tissue which received 65 Gy (TV65) to the tumor volume (TV), that is (TV65/TV). The single variable which was significantly associated with local failure by 3 years was a TV65/TV of less than one. Once this variable was entered into the analysis, no other factor proved statistically significant. Our data suggest that when attempting local control of soft tissue sarcomas with brachytherapy, the volume of tissue receiving 65 Gy (TV65) from both implant and external beam must exceed the volume of the excised lesion (TV). Since the volume of a tumor can be readily determined prior to surgical excision either by CT or MRI scanning, pre-planning of the implant volume could potentially reduce the rate of local failure.

Testicular neoplasms: seminoma.

From 1969 to 1984, 58 patients with a diagnosis of testicular seminoma were seen and treated at the University of Kansas Medical Center. The median age was 34 years (range of 20 to 62 years). The American Joint Committee on Cancer Staging System was followed: stage I (34 patients); stage II (6); stage III (8); and stage IV (10). Forty-two patients had typical seminoma, and 16 had anaplastic histology. Nine patients had elevated B subunit of human chorionic gonadotropin, and nine had a history of cryptorchidism. Fifty-six patients received radiation treatment, and seven received chemotherapy with or without radiation. The median follow-up was 7 years (range 3 to 16 years). The overall disease-free (absolute) survival according to stage was: stage I, 91% (100%); stage II, 66% (80%); stage III, 75% (85%); and stage IV, 50% (50%). There were no late complications. The survival for patients with anaplastic histology or with elevated B subunit of human chorionic gonadotropin was not significantly different from that of typical seminoma.

A phase I/II study of the use of Fluosol as an adjuvant to radiation therapy in the treatment of primary high-grade brain tumors.

The main objective of this study was to evaluate the safety and efficacy of a perfluorochemical emulsion, Fluosol, with short-term high inspired oxygen tension as an adjuvant to radiation therapy in the treatment of high-grade tumors of the brain. Radiation was delivered to the whole brain at 1.8 Gy per daily treatment for 5 weeks to a total dose of 45 Gy. The radiation portals were then reduced in size to encompass the known volume of tumor, as determined by the presurgical contrast-enhancing ring on computed tomography (CT), plus a 3-cm margin. An additional 10 treatments of 2 Gy each were given to the smaller volume, to bring the total tumor dose to 65 Gy in 7 weeks. This report describes the experience of the first 18 patients treated at the University of Kansas Medical Center on this study, whose median follow-up time from the date of surgery is 77 weeks (62-115 w). Immediately following Fluosol administration on a Monday, patients breathed 100% oxygen for at least 45 minutes prior to and throughout their radiation treatment. On each subsequent day of the weeks in which they received Fluosol, patients breathed 100% oxygen. Hematology and blood chemistries were also drawn prior to Fluosol treatment each Friday during treatment and at the 2-week, 3-month, and 6-month follow-up visits. The median age of the patients was 45 years (16-72); 13 patients were male and 15 carried the diagnosis of glioblastoma multiforme (3 had anaplastic astrocytoma). Two thirds of the patients had an initial allergic reaction to the Fluosol consisting of back pain, shortness of breath, and flushing, but all responded to 50-100 mg of Benadryl. During radiation therapy, all patients developed scalp erythema and complete alopecia by the end of 3 weeks, but no patient required a treatment rest. The serum levels of SGOT, SGPT, and alkaline phosphatase were examined before and throughout the Fluosol treatment and, by week 5, 11/18 of the patients had increased values of all three enzymes above the upper range of normal. These increases persisted through the end of treatment, but most values returned to essentially normal by the 3-month follow-up visit. We conclude that Fluosol, given in the manner described above, appears to be associated with minimal significant side effects and no changes could be detected in the white matter of any of the patients at the time of their magnetic resonance imaging study at 6 months follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Dosimetric analysis in brachytherapy of carcinoma of the cervix.

Brachytherapy plays an essential role in the definitive radiation treatment of cervical carcinoma. The dosimetry of intracavitary irradiation is complex in that the optimum doses that can be delivered are dictated not only by the volume and extent of tumor but also by the close vicinity of dose-limiting structures, such as the small and large intestines, rectum, and bladder. To facilitate understanding of the relationships between the various dosimetric parameters involved, a retrospective analysis of 50 randomly chosen intracavitary insertions with Cesium-137 in 41 patients performed at our institution between 1975 and 1985 was carried out. All 50 cases utilized Fletcher-Suit-Delcos applicators and only the insertions using three sources in the tandem and one in each of the ovoids were included in this analysis. Using the AP and lateral radiographs and the lymphatic trapezoid, the reference points were obtained and transferred digitally to the treatment planning computer, and computerized dosimetry performed. In addition to the specified reference points, points were added and modified to obtain more complete information. The doses at the specified points were normalized to the average dose at AT, a reference point 2 cm superior to external os and 2 cm lateral to the tandem, and expressed as a percentage. It was noted that the average dose at the closest bladder point was 103 +/- 41% of the dose at AT, the maximum rectal dose 77 +/- 29% of the dose at AT and the maximum small bowel dose 65 +/- 16% of that at AT. The analysis of percent contribution of various sources to different reference points revealed that the dose to point AT was equally contributed to by all sources; bladder and rectal doses were mainly contributed to by the lowermost uterine and ovoid sources. Our analysis may provide a model for optimizing brachytherapy in cervical carcinoma.