Background: Currently available clinical information regarding management of posterior uveal melanomas complicated by nodular extrascleral extension is inadequate to determine the role, if any, for plaque radiotherapy in such patients.Methods: The authors performed a retrospective descriptive study of eight patients with a choroidal or ciliochoroidal melanoma complicated by nodular extrascleral extension who were treated by surgical excision of the extrascleral nodule followed immediately by plaque radiotherapy of the intraocular tumour. The calculated volume of the extrascleral nodule was greater than I mm 3 but less than 1000 mm(3) in all cases, and the intraocular tumour was deemed treatable by plaque radiotherapy in all patients.Results: Four of the eight patients died during available follow-up, three from metastatic melanoma and one from a second cancer. The median length of follow-up for the four surviving patients was 10.1 years. The actuarial 5-year and 10-year all-cause death rates were 37.5% and 53.1% respectively. One of the eight patients experienced local intraocular tumour relapse following plaque therapy and underwent secondary enucleation. None of the patients experienced orbital tumour recurrence or underwent secondary orbital exenteration.Interpretation: Our results coupled with previously published results from another centre suggest that plaque radiotherapy may be an effective local treatment for selected patients with choroidal or ciliochoroidal melanoma complicated by nodular extrascleral extension. The fact that none of the patients in this series or in the previously reported series experienced orbital recurrence following plaque radiotherapy or required secondary orbital exenteration suggests that plaque therapy may be better than enucleation alone in terms of these end points. These results should not be extrapolated, of course, to patients with massive extrascleral tumour extension or a choroidal or ciliochoroidal melanoma too large for plaque radiotherapy.

Bilateral synchronous breast cancer appears to have a worse prognosis than comparable unilateral breast cancer. HER-2/neu expression in bilateral breast cancer has not been reported. The purpose of this study was to review the characteristics of patients with bilateral synchronous breast cancer and to report the incidence of HER-2/neu overexpression. Between 1984 and 1998, 58 patients were diagnosed with bilateral synchronous breast cancer (defined as both cancers diagnosed within 3 months). The paraffin blocks from both breast specimens were available and immunostained in 21 patients. Of 42 breast specimens, there were 31 invasive carcinomas and 11 noninvasive carcinomas. Of the 21 paired specimens immunostained for HER-2/neu, 11 were invasive cancers in both breasts, nine were invasive cancers in one breast and noninvasive cancers in the other breast, and one was noninvasive cancers in both breasts. Of the 31 invasive carcinomas, HER-2/neu was overexpressed (2–3+) in 22 (71%) and negative (0–1+) in nine (29%). In contrast, 35 of 101 (34.7%) consecutive unilateral invasive breast cancer specimens from our institution overexpressed HER-2/neu. The difference in HER-2/neu overexpression between patients with bilateral synchronous breast cancer and unilateral breast cancer (22/31 v.s. 35/101) was statistically significant (chi square = 11.3, p   <  0.001). In cases where both breasts had invasive carcinoma, HER-2/neu overexpression could be either in one (six patients) or both breasts (four patients). The increased mortality of patients with bilateral synchronous breast cancer may be due to the higher incidence of HER-2/neu overexpression.

The erbB2 receptor tyrosine kinase and the CD44 transmembrane glycoprotein interact with one another in numerous cell types. This interaction helps to maintain erbB2 activity that contributes to tumor progression. We investigated whether CD44 and erbB2 similarly interact in endometrial carcinomas in vitro and in situ. In contrast to other carcinomas, CD44 did not colocalize with erbB2 in any of the 51 cases of endometrial cancer analyzed. CD44 also did not coimmunoprecipitate or colocalize with erbB2 in two endometrial carcinoma cell lines. We propose that the lack of CD44-erbB2 interactions may reduce the contribution of erbB2 to endometrial carcinoma progression.

Background. A two-week elective clerkship in clinical oncology is offered tu third-year medical students. Methods. Two students at a time participated in the rotation and spent time with attendings in a one-to-one setting in outpatient clinics in the cancer specialties. The students also attended multidisciplinary tumor boards. Grand rounds, peer review conferences, and problem-case conferences were attended by the students as well. The students met with an attending for one-hour, twice-per-week to discuss pertinent oncologic cases and problems. The exposure to clinical oncology for two weeks is intended to educate the students relative to the presentation, evaluation, treatment, prognosis, and follow-up for a variety of cancers. Results. The rotation has been highly successful as measured by its popularity and by consistently high course evaluations from the medical students. Conclusion. The overall quality of the learning experience for the rotation has been rated by the students as the highest among all courses in their four-year curriculum.

This is the first clinical case report of a thoracic invasive thymoma metastatic to the ovary with disease noted in the entire abdomen including the pelvis 5 1/2 years after initial diagnosis. The involved areas of metastases include the distal ileum, peritoneal and serosal surfaces (including the surface of the distal colon, bladder, and pelvis), and the surface of the right ovary. The patient survived 13 years after her initial diagnosis and 7 1/2 years after discovery of her metastases. Thymomas are rare tumors but comprise the most common primary tumor of the anterior mediastinum. Extrathoracic metastases of malignant thymomas are also rare, and the literature reports that the most common sites for metastases are the liver, lung, lymph nodes, and bone. Extrathoracic disease is associated with a poor prognosis. The average time of survival after the diagnosis of metastases is 1.5 years.

PURPOSE:To compare sequential methotrexate (M) and fluorouracil (F) (M-->F) with surgery (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-13) and cyclophosphamide (C), M, and F with M-->F (NSABP B-19), in patients with estrogen receptor (ER)-negative tumors and negative axillary nodes. PATIENTS AND METHODS:A total of 760 patients were randomized to B-13; 1,095 patients with the same eligibility requirements were randomized to B-19. Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were determined using life-table estimates. RESULTS:A significant benefit in overall DFS (74% v 59%; P < .001) was demonstrated at 8 years in all B-13 patients who received M-->F (69% v 56% [P = .006] in those or= 50 years). A survival advantage was evident in older patients (89% v 80%; P = .03). In B-19, through 5 years, an overall DFS advantage (82% v 73%; P < .001) and a borderline survival advantage (88% v 85%; P = .06) were evident with CMF. The DFS (84% v 72%; P < .001) and survival (89% v 84%; P = .04) benefits from CMF were greater in women aged F or CMF after lumpectomy and breast irradiation resulted in a low probability of ipsilateral breast tumor recurrence (IBTR). In B-13, the frequency of IBTR was 2.6% following M-->F versus 13.4% in women treated by lumpectomy; it was 0.6% following CMF in B-19. Toxicity >or= grade 3 was more frequent among CMF patients in B-19. The age-related difference in CMF benefit was not related to amount of drug received. CONCLUSION:M-->F and CMF are effective for node-negative patients with ER-negative tumors. The incidence of local-regional or distant metastases and IBTR decreased after either therapy. The benefit from either therapy was evident in all patients, but the CMF advantage was greater in those F may be used in patients with medical problems that would preclude CMF administration.

Purpose: Sinonasal undifferentiated carcinoma (SNUG) is a rare and aggressive malignancy of the paranasal sinuses and nasal cavity. Of the few reported series, most indicate a dismal prognosis. In this report, the clinical presentation, histopathologic criteria used for diagnosis, mode of treatment, and outcome are evaluated in seven patients with SNUG.Materials and Methods: Seven patients with SNUG treated at the University of Cincinnati between 1983 and 1993 were analyzed retrospectively.Results: Most of the patients presented with extensive local disease, and two patients also had cervical metastases. AII except one were treated using a multimodality approach. Four of the seven patients died of disease (DOD), with a mean survival of only 11.5 months following treatment. Inability to eradicate local disease was responsible for treatment failure in all cases. Three patients have achieved short-term control of disease following combined therapy, but one is at high risk for recurrence.Conclusion: SNUG was associated with an overall poor prognosis in our series despite aggressive treatment. Control of local disease was the central therapeutic consideration. Intensive multimodality therapy is recommended for all patients with SNUG. Copyright (C) 1996 by W.B. Saunders Company.

BACKGROUND:Preoperative radiation with sensitizing doxorubicin has been popularized in the treatment of high grade sarcoma of the extremity. A multiinstitutional experience with this protocol that was initiated by the Southeastern Cancer Study Group in 1984 and maintained in three institutions was updated by the authors.METHODS:Patients with biopsied sarcoma had intraarterial infusion with doxorubicin hydrochloride (Adriamycin) 30 mg/24 hrs x 3 days and were allocated by the institution to receive radiation 30-35 Gy in 10 fractions or 46 Gy in 23-25 fractions followed by resection. Surgery was performed within 10 days or 30 days depending on the radiation dose. Postoperative chemotherapy was administered to 31 patients.RESULTS:Of 66 patients, 32 were female and 34 were male. The median age was 46 years (range, 14-77 years); 73% had lower and 27% had upper extremity tumors. There were 55 soft-tissue and 9 malignant bone tumors. Common types were malignant fibrous histiocytoma 20%; liposarcoma, 17%; synovial sarcoma 18%; and 14% were osteosarcoma. American Joint Committee on Cancer stages were: I, IIB (17%), IIIA/B (59%), and IIIC/4A (24%). Limb salvage surgery was performed on 60 patients including radical resection in 21 with extensive tumors, wide local excision in 30, and limited excision in 2 patients. Primary amputation was performed on four patients and delayed amputation in two because of wound complications. Three patients had pulmonary metastasectomy in conjunction with primary surgery (2 are long term survivors > 5 years). There were no postoperative deaths, but wound complications occurred in 41% of the patients. Overall survival and disease free survival at 5 years was 59 and 49%. One patient (1.5%) had local recurrence 9 years after resection of an extensive synovial sarcoma of the shoulder. This was resected with limb salvage techniques. Among 23 patients who failed primarily in the lung, the median survival was 7 months with 4 surviving more than 5 years, after demonstration of the pulmonary metastases. Multivariant analysis of prognostic factors showed that extent of disease and stage correlated with disease free survival, whereas only extent of surgical resection correlated with overall surgical survival.CONCLUSION:Combined therapy for extremity sarcoma in a multicenter setting using preoperative radiation with sensitizing chemotherapy and adequate resection was associated with an excellent local control rate (98.5%) and reasonable long term tumor control, although distant metastases continued to be a major challenge.

BACKGROUND:The incidence of cancers after renal transplantation is significantly higher than in populations that have not undergone transplantation. The authors report a group of renal transplant patients from the University of Cincinnati who had cancer develop; the focus is on the patients' clinical course.METHODS:Since 1968, 876 renal transplantations have been performed for a variety of causes of end stage renal disease. Charts of transplant patients who had neoplasms were reviewed.RESULTS:Forty-four patients had epithelial skin cancers, and 36 had nonskin cancers or melanoma. No correlations could be established between disease course and type of immunosuppressive agent, type of disease for which transplantation was required, or type of renal allograft donor. The skin cancers demonstrated a propensity for multifocality: 22 of the 44 patients had multiple separate lesions develop. Of the patients with cancer not of the skin, six were treated surgically for carcinoma in situ, and none have experienced disease recurrence. Of 11 patients treated for early invasive disease, 6 are disease-free, 3 died of intercurrent disease, and 2 died of progressive disease 11 and 13 months, respectively, after disease diagnosis. Nineteen patients had advanced disease, and only 1 is alive and disease-free. Sixteen died of progressive disease at a median of 1 month from the time of diagnosis, and 2 died of intercurrent disease within 1 week of diagnosis.CONCLUSIONS:The natural history of cancers developing in renal transplant patients often is more aggressive than would be expected in patients who have not undergone transplants. The immunosuppression induced to allow viability of the renal allograft may allow tumor cells to thrive.

Symptomatic local failure following thoracic irradiation for bronchogenic carcinoma presents a clinical challenge to the Radiation Oncologist. We retrospectively evaluated the efficiency of reirradiation with external beam radiation of 30 patients. The median dose of initial irradiation was 6,000 cGy in 6 weeks. The median time following initial irradiation to recurrence was 12 months. The median dose of retreatment was 3,030 cGy in 3 weeks. Of the symptomatic patients, 88% and 70% subjectively responded to initial irradiation and to reirradiation, respectively. Retreatment toxicity included radiation esophagitis (6 patients), dry desquamation (4 patients), and symptomatic radiation pneumonitis (1 patient). Based on this study, doses of external beam radiation in the range of 2,000-3,000 cGy in 2 to 3 weeks appear safe and effective in reirradiating recurrent bronchogenic carcinoma.

The purpose of this retrospective study is to identify prostate cancer patients who would benefit from pelvic nodes irradiation (whole pelvis) as opposed to the small-field irradiation to the prostate only. Between 1975 and 1983, 126 patients were treated by whole pelvis (4,600-5,000 cGY) with prostate boost (2,000 cGY) radiation (WP + P). Median follow-up was six years and six months. Comparison was made with historic control of 116 patients irradiated at the same institutions between 1971 and 1977 by small field to the prostate (P) to a dose of 7,000-7,500 cGY. There was a significant five-year survival improvement in the current WP + P radiation in Stage C (72% vs 40%, p = 0.0004) and Stage B (92% vs 70%, p = 0.025) but not in Stage A2 patients. However, WP + P radiation significantly improved disease-free survival (DFS) in only well and moderately but not in poorly differentiated carcinoma with a combined well and moderately differentiated five-year DFS of 63 percent compared with the 45 percent in P radiation (p = 0.0228). Local tumor control was significantly improved in WP + P radiation in only Stage C cancers with their local recurrence rate 16 percent as compared with the 34 percent in P radiation (p = 0.0172). Although acute radiation reactions were more frequent in WP + P than P radiation (61% vs 41%, p = 0.0022), chronic radiation morbidity in both series were similar. Thus, whole pelvis with prostate boost radiation should be utilized in Stage B and Stage C cancers as this has shown to increase the survival of the patient without increasing chronic radiation morbidity.

A rare case of embryonal sarcoma of the liver in a 28-year-old man is reported. The patient was treated preoperatively with a combination of chemotherapy and radiation therapy. Complete surgical resection, 4.5 months after diagnosis, consisted of a left hepatic lobectomy. No viable tumor was found in the operative specimen. The patient was disease-free 20 months postoperatively.

The goals of this ongoing Phase III study of adjuvant local hyperthermia with radiotherapy were to evaluate how tumor control and normal tissue complications were related to patient and treatment variables. Canine veterinary patients with localized malignancies were stratified by histology and anatomic site and randomized into three groups. All patients received radiotherapy (60CO) in 3.5 Gy fractions given Mon-Wed-Fri to 14 treatments (49 Gy). One group received radiotherapy alone while the others also received microwave-induced hyperthermia (44°C) for 30 minutes once each week. Hyperthermia followed radiotherapy and was given to one group immediately and delayed 4–5 hours in the other. Adjuvant hyperthermia resulted in a significant (p < .05) increase in complete response rate, reduction in the frequency of non-responders, and increased persistant local control relative to radiotherapy alone. Hyperthermia increased the complete response rate regardless of histology, site, or volume and with the current sample size control was significantly (p < .05) greater for sarcomas, tumors of the trunk and extremities, and those with volumes < 10 cc. Quantitative clinical assessment of the acute response of skin and oral mucosa idicated that hyperthermia significantly enhanced these acute reactions, which required roughly twice the healing time observed with radiotherapy alone. Quantitative histologic scoring of changes seen between pre- and post-therapy skin biopsies indicated that a treatment induced decline in the frequency of dermal blood vessels, sebaceous glands, and hair follicles was enhanced by adjuvant hyperthermia, particularly in the late response evaluation interval. The probability of tumor control and adverse normal tissue responses correlated with several measures of thermal dose. Thermal doses in excess of 120 equivalent minutes at 43°C correlated positively with increased skin reactions and negatively with the complete response rate, and these trends were usually evident during the animals' first treatment.