Primary treatment of Bartholin's gland carcinoma with radiation and chemoradiation: a report on ten consecutive cases.

We reviewed our experience with primary radiation therapy for Bartholin's gland carcinoma (BGC) as an alternative to traditional surgical treatment. A retrospective study reviewed records from the Cancer Data Registry and Research Patient Data Registry from 1986 to 2002. Charts of ten women identified with BGC were reviewed for demographic information, presenting symptoms, tumor characteristics, treatment modalities, and complications, as well as for recurrence and survival. The incidence of BGC was 2.13% of all invasive vulvar cancer cases at the Massachusetts General Hospital (MGH). Four patients presented with clinical stage I disease, one with stage II, three with stage III, and two with stage IV. The median age at diagnosis was 63.5 years. There were five squamous cell carcinomas, two adenoid cystic carcinomas, two mucinous adenocarcinomas, and one small-cell carcinoma. After a change in treatment policy in 1986 from primary surgery that had often required postoperative radiation therapy, ten consecutive patients were treated with primary radiotherapy or chemoradiation therapy. Treatment included teletherapy combined with a boost to the primary site, regional nodes and/or interstitial brachytherapy. Short-term complications were mild and well tolerated; one patient developed late radiation-associated pelvic fractures. Four tumors recurred with a mean time to recurrence of 31.2 months. The median follow-up was 87.2 months (45-142). Three- and 5-year survivals were 71.5% and 66%, comparable to outcomes after surgery and postoperative radiation therapy. We conclude that primary radiation or chemoradiation therapy offers an effective alternative to surgery in the treatment of BGC with preservation of genital function and low morbidity.

Intraoperative radiation therapy in the treatment of pelvic gynecologic malignancies: a review of fifteen cases.

OBJECTIVE: The aim of this study was to review the experience with intraoperative radiation therapy (IORT) in the treatment of gynecologic pelvic malignancies at the Massachusetts General Hospital. METHODS: From July 3, 1996, through July 28, 1999, 15 patients were treated with IORT for gynecologic malignancies in a dedicated IORT operating room suite at the Massachusetts General Hospital. Hospital medical records, radiation oncology records, and office charts were reviewed on all patients treated with IORT. IORT was given in the presence of positive surgical margins and where the doses needed for adjuvant postoperative external beam radiotherapy (EBRT) would exceed those tolerated by normal structures. One patient presented with primary disease and 14 with local or regional recurrence. Follow-up time ranged from 3 to 36 months. RESULTS: Treatment in conjunction with IORT included surgery only (7 patients); preoperative EBRT, preoperative brachytherapy, and surgery (1 patient); preoperative chemotherapy and surgery (2 patients); and surgery and postoperative chemotherapy (5 patients). IORT doses ranged from 10 to 22.5 Gy. At the completion of this review, 4 patients (26.6%) have died, 6 (40%) are alive and free of disease, and 5 (33%) are alive with disease persistence or relapse. Of the 10 patients with gross total resection, 5 are alive and free of disease. Of the 5 women with gross residual disease at the time of IORT, only 1 is alive and free of disease. CONCLUSIONS: The volume of residual disease prior to IORT may be an important prognostic indicator for disease relapse. Both local recurrence and distant metastasis were more common among patients with gross residual disease at the time of IORT. Our institutional experience with IORT further supports the importance of optimal surgical resection.

The role of intraoperative radiation therapy (IORT) in the treatment of locally advanced gynecologic malignancies.

The prognosis in women with locally advanced primary or recurrent gynecologic malignancies is rather poor. Doses of external beam radiation necessary to treat gross or microscopic recurrence among patients surgically treated or previously irradiated exceed what is tolerated by normal structures. In this group of patients, intraoperative radiation therapy (IORT) can be utilized to maximize local tumor control, minimizing the radiation exposure of dose-limiting surrounding structures. Review of the available literature indicates that IORT may improve long-term local control and overall survival in women with pelvic sidewall and/or para-aortic nodal recurrence. The most encouraging results have been reported in the cases of microscopic residual disease, following surgical debulking.

Predictors of recurrence in surgical stage II endometrial adenocarcinoma.

OBJECTIVE: A retrospective review of surgical stage II endometrial carcinoma was performed to evaluate clinical course, treatment, recurrence rate, and survival. METHODS: A list of patients with clinical and surgical stage II endometrial carcinoma was obtained through the tumor registry and from the pathology department from 1988 to 1996. Data were collected on all cases of patients with endometrial carcinoma meeting stage II criteria by FIGO surgical staging. Variables including stage, histology, grade, lymph vascular space invasion (LVI), type and extent of surgery, radiation type and amount, smoking, menstrual status, parity, and age were evaluated for their predictive ability of disease recurrence. Cox proportional hazard regression models were used to examine the potential predictors of time to relapse univariately and multivariately. RESULTS: Of patients identified, 65 underwent primary surgical staging. Only adenocarcinomas were included. Mean follow-up time was 4.7 years (range 0.2-9.6 years). Postoperative radiation was given to 85.7% of patients. There were 10 patients (15.4%) with recurrence of disease with a mean time to recurrence of 25 months. Five-year disease-specific survival was 93%. The only significant predictor of time to relapse was LVI (P = 0.002) in the multivariate analysis. CONCLUSION: This retrospective review suggests that primary surgery followed by postoperative radiation therapy gives excellent results in surgical stage II disease. LVI appears to be a strong predictor of disease recurrence regardless of postoperative radiation therapy. It is difficult to draw conclusions about the type and amount of radiation given because recurrence rate is so low; however, it is reasonable to continue adjuvant radiation especially in cases where LVI is identified.

Ureteral stricture as a late complication of radiotherapy for stage IB carcinoma of the uterine cervix.

BACKGROUND: Ureteral stricture is a rare late complication of curative radiotherapy for carcinoma of the cervix. A retrospective study was performed to determine the incidence and latency of radiation-induced ureteral stricture, to investigate possible contributing factors, and to compare the time course and presenting characteristics of ureteral compromise caused by late radiation injury or tumor recurrence. METHODS: The records of 1784 patients with FIGO stage IB carcinoma of the cervix treated with radiotherapy at The University of Texas M. D. Anderson Cancer Center between 1960 and 1989 were reviewed. The characteristics of patients who developed ureteral stricture as a first manifestation of recurrent disease or without evidence of pelvic recurrence were compared. The risk of ureteral compromise was calculated actuarially. RESULTS: There were 29 patients with severe radiation-induced ureteral stricture. The overall incidences of severe ureteral stenosis were 1.0, 1.2, 2.2, and 2.5% at 5, 10, 15, and 20 years, respectively, reflecting a continuous actuarial risk increase of approximately 0.15% per year. Four patients died of complications from bilateral ureteral stricture. Patients who were treated with centrally blocked external fields or who received more than two transvaginal radiation treatments were at increased risk for developing ureteral stenosis. The risk was similar for patients treated with radiation alone or followed by extrafascial hysterectomy. CONCLUSIONS: During the first 5 years after treatment, tumor recurrence is the most common cause of ureteral stricture in patients treated with radiotherapy for carcinoma of the cervix. However, radiation injury to the ureter, although rare, may not become apparent for many years, necessitating continued vigilance throughout the lives of these patients.

Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma.

PURPOSE: We investigated the possibility that a significant proportion of children with osteosarcoma harbor germline mutations of the p53 tumor suppressor gene and, therefore, this subgroup of pediatric cancer patients should be considered for large-scale predictive testing. PATIENTS AND METHODS: Genomic DNA extracted from peripheral-blood leukocytes from 235 unselected children with osteosarcoma from 33 institutions were screened for the presence of germline p53 mutations using constant denaturant gel electrophoresis (CDGE). Exons 5 through 8 were evaluated in all patients and exon 2 and exon 9 were analyzed in 59 and 95 patients, respectively. Those samples that showed aberrant migration on CDGE were sequenced or analyzed by restriction enzyme digestion of polymerase chain reaction (PCR) products to confirm the nature of the gene alteration. RESULTS: In 18 samples, CDGE showed fragments of the p53 gene with altered electrophoretic mobilities compared with wild-type p53. DNA sequencing showed that 11 samples had an identical, previously described polymorphism. The other seven contained heterozygous p53 mutations located in exon 5 (n = 3), exon 6 (n = 1), exon 7 (n = 1), and exon 8 (n = 2). Six alterations were missense mutations and one was a nonsense mutation. Three of these patients had first-degree relatives with cancer. One of these three kindreds had a family history consistent with Li-Fraumeni syndrome (LFS). CONCLUSION: We identified germline p53 mutations in seven of 235 (3.0%) children with osteosarcoma. Four of these mutations were found in patients who did not have first-degree relatives with cancer. Although genetic transmission of the altered p53 gene could not be tested in this survey because of how it was designed, it is possible that predictive testing for p53 mutations could identify unaffected relatives of gene carriers who also have a high risk for the development of cancer. This study provides evidence for the importance of considering children with osteosarcoma for predictive testing for germline p53 mutations.

Differential cholinergic influences on the immobility response in various strains of domestic fowl.

A series of five experiments examined the effects of two anticholinergic drugs, atropine and scopolamine, on the duration of tonic immobility (TI) and susceptibility to the TI response in both Production Red and White Leghorn chickens (Gallus gallus), in an attempt to resolve previous contradictory findings about the effects of cholinergic manipulations on tonic immobility. These two anticholinergic drugs significantly reduced the duration of TI and, therefore, supported the conclusion that cholinergic systems are involved with the immobility response. However, the effects of these drugs on TI differed depending on the age, strain, local population, and handling experience of the individual birds.

Amelioration of acute graft vs host disease due to minor histocompatibility antigens by in vivo administration of anti-interleukin 2 receptor antibody.

Lethal acute graft vs host disease (GVHD) elicited by minor histocompatibility antigens was studied in a murine model of bone marrow transplantation (B10.BR----CBA). The severity of GVHD was reduced by both clinical and histologic parameters when transplant recipients received injections of a monoclonal antibody directed against the interleukin 2 receptor. This study suggests that anti-interleukin 2 receptor antibodies may be useful in clinical marrow transplantation and provides additional evidence that monoclonal antibodies that block T cell function in vitro may be of therapeutic value in vivo.