Evaluation of bromodeoxyuridine in glioblastoma multiforme: a Northern California Cancer Center Phase II study.

In a study activated in 1983 and closed in 1987, the Brain Tumor Research Center of the University of California and the Northern California Cancer Center evaluated the effect of bromodeoxyuridine in the treatment of glioblastoma multiforme. A total of 160 patients were evaluable of 173 entered. Patients were to receive a bromodeoxyuridine infusion of 0.8 g/m2 daily over 24 hours for 4 days of each of 6 weeks of radiotherapy directed to the tumor plus a margin delivering a total of 60 Gy. Eligibility requirements included Karnofsky performance status greater than or equal to 70, biopsy or resection and central pathology review by one of the authors. Following radiotherapy patients were to receive chemotherapy with procarbazine, CCNU, and vincristine for 1 year. Median survival was 55.7 weeks and time to failure, 34.5 weeks for the evaluable group of 160 patients. In a univariate analysis the variables that influence survival and time to failure were: age, Karnofsky performance status, bromodeoxyuridine dose and the delivery of at least one procarbazine, CCNU, and vincristine cycle following radiotherapy. In multivariate analysis, age, Karnofsky performance status, and bromodeoxyuridine dose remain significant for time to failure; age and Karnofsky performance status remain significant for survival.

Amyloid tumor of the spleen.

An unusual case of amyloid tumor of the spleen that developed in a patient with malignant lymphoma is reported. A splenectomy performed for a persistent splenic lesion after an otherwise complete response to chemotherapy revealed the amyloid tumor. To our knowledge, amyloid tumor has not been previously described in the spleen.

Extraadrenal myelolipoma.

A rare case of presacral myelolipoma surgically resected from a 72-year-old woman, who also had megaloblastic anemia and brest carcinoma, is described and compared with mass-forming extramedullary hematopoiesis, and other reported cases of extra-adrenal myelolipoma. Extra-adrenal myelolipoma should be morphologically differentiated from mass-forming extra medullary hematopoiesis. The former is encapsulated or well-circumscribed, is composed of fat cells, and has normal marrow hematopoietic elements. The latter lacks circumscription, and fat is not an integral component of the process. Clinically, myelolipoma is usually asymptomatic, and shows no consistent associated disease process, while mass-forming extramedullary hematopoiesis is usually symptomatic, and is associated with myeloproliferative disorders, hemolytic anemia, or severe skeletal diseases.

Peritoneal carcinomatosis after prophylactic oophorectomy in familial ovarian cancer syndrome.

A woman who was at high risk for ovarian cancer because of a strongly positive family history underwent prophylactic oophorectomy, but subsequently developed and died of intraabdominal carcinomatosis. One small focus of adenocarcinoma was found on the ovarian surface in serial sections performed retrospectively on the resected ovaries. This case study emphasizes the importance of thorough histologic examination for familial ovarian cancer syndrome, including serial sectioning of the specimens removed in prophylactic oophorectomy.

Long-term palliation of pulmonary artery sarcoma by radical excision and adjuvant therapy.

The case of an extensive pulmonary artery sarcoma managed by radical excision and homograft reconstruction followed by aggressive chemotherapy and irradiation with prolonged survival is presented. Pulmonary artery sarcomas are reviewed with emphasis on the diagnosis and management of these usually fatal tumors.

Carcinosarcoma of renal pelvis.

A new case of carcinosarcoma of the renal pelvis is reported and the literature reviewed. This tumor occurs in patients over sixty years of age. Three patients died of the disease in one year, and 2 showed six-month and two-year disease-free survival after nephrectomy.

Malignant mesothelioma of tunica vaginalis testis.

A case of biphasic malignant mesothelioma of the tunica vaginalis occurring in a sixty-four-year-old man is described. The tumor metastasized widely and led to the patient's death two and one-half years after diagnosis. Review of the literature revealed 7 cases of malignant mesothelioma of tunica vaginalis. These tumors appeared highly aggressive with early onset of metastasis. Histologically, the tumors may be epithelial, fibrous, or biphasic. In contrast to the benign variants of mesotheliomas, these tumors often show significant nuclear atypia, mitotic activity, and invasion of the epididymis, spermatic cord, lymphatic spaces, or the fibrous tissue of the tunica.

Hodgkin's disease complicating lymphomatoid papulosis.

A patient with a 14-year history of lymphomatoid papulosis developed localized subcutaneous lymphoma with morphologic features of Hodgkin's disease at the age of 46 years. The lymphoma was clinically atypical in that it remained localized in the subcutis for 10 years before involvement of lymph nodes occurred. A review of the literature indicates that patients with lymphomatoid papulosis, especially those with plaque or nodular lesions in addition to papular lesions, are given to develop malignant lymphomas of various histologic types.

Peritoneal papillary serous carcinoma with long-term survival.

Three cases of peritoneal papillary serous carcinoma with a complete response to chemotherapy and long-term disease free survival are reported. All three patients presented with multifocal or diffuse peritoneal involvement. Microscopic ovarian serosal surface involvement was demonstrated in two cases. The ovaries were uninvolved in one case. All patients were treated with combination chemotherapy consisting of Adriamycin (doxorubicin) and cisplatin, with or without cytoxan. All three patients survived for 5 years or longer with no clinical evidence of persistent or recurrent tumor.

Clinical potential of synchronous radiotherapy and chemotherapy for advanced squamous cell carcinoma.

The equivocal results of past treatment regimens in which concurrent radiotherapy and chemotherapy were used may have resulted from a lack of site-specific active drugs that were also true radiation sensitizers. This report demonstrates an experience with 3 chemotherapeutic agents, 5-fluorouracil, cisplatin, and mitomycin, given simultaneously with radiation for locally advanced squamous cell carcinomas of such diverse sites as the anal canal, cervix, and esophagus. Early results show that the toxicity of these combination regimens is generally acceptable and indicate that such synchronous combination treatments may be superior in local control and survival to radiotherapy alone.

Hodgkin's disease involving the urinary bladder diagnosed by urinary cytology: a case report.

A unique case of lymphocyte depletion Hodgkin's disease of the urinary bladder in a 91-year-old woman was diagnosed by exfoliative cytology on a single passed urine specimen. Subsequent bladder biopsy confirmed the diagnosis. Retrospectively, it was ascertained that the patient had had a previous diagnosis of Hodgkin's disease based on biopsy of a cervical lymph node ten years previously. This is the first case to be reported in which the presence of Reed Sternberg cells in a cytologic preparation of the urine led to the diagnosis of Hodgkin's disease with involvement of the bladder.

Angiosarcoma in postsurgical lymphedema. An unusual occurrence in a man.

A 63-year-old man underwent partial left axillary node dissection for metastatic melanoma of unknown primary. Lymphedema of his left upper extremity developed after surgery. Eight years later, extensive cutaneous angiosarcoma developed in the edematous limb. The occurrence of cutaneous angiosarcoma in postsurgical lymphedema is extremely rare in men; to our knowledge, our case is the fifth such case thus far reported.

Ewing's sarcoma of the phalangeal bone.

A rare case of Ewing's sarcoma of the toe bone is described and compared with three cases of phalangeal Ewing's sarcoma. The lesion in two cases was initially treated as infection and the diagnosis was delayed for several months. Roentgenographic and aspiration cytology examinations in cases with clinically unresolving infection of the hands and feet may prevent delayed diagnosis. Radical surgery alone may be curative if no metastases are found preoperatively in careful clinical investigations.

Hodgkin's disease complicating neuronal ceroid-lipofuscinosis.

This article reports the previously undescribed occurrence of Hodgkin's disease in a child with neuronal ceroid-lipofuscinosis.

Malignant interstitial cell tumor of the testis.

A case of malignant interstitial cell tumor of the testis is reported and the literature is reviewed. Malignant interstitial cell tumors occur exclusively in adults. Gynecomastia was noted in 12% of the cases. Elevated plasma levels or increased urinary excretion of estrogen, 17-ketosteroid, or testosterone were demonstrated in 64% of the patients. Vessel invasion, which occurred in 74% of the patients, appears to be the only reliable histologic feature for predicting malignant behavior. There is no proved sensitivity to radiation or chemotherapeutic regimens in patients with disseminated tumor. Once the diagnosis of malignancy is histologically established, inguinal and retroperitoneal lymph node dissections, even in the absence of clinical evidence of metastasis, may be beneficial in providing early staging of the tumor and, perhaps, in preventing subsequent lymphatic spread.

Definitive combined modality therapy of carcinoma of the anus. A report of 30 cases including results of salvage therapy in patients with residual disease.

Thirty patients with epidermoid carcinoma of the anus, ranging in age from 40 to 89 years, were treated with combined chemotherapy (CT) and radiation therapy (RT) in lieu of abdominoperineal resection. Two courses of 5-FU (1000 mg/m2/day X four days) by continuous infusion and mitomycin-C (10-15 mg/m2 IV bolus on day 1 of each course) were given 3 to 4 weeks apart simultaneously, with whole pelvis RT to 4140 to 4500 cGy. Twenty-one of 28 patients had T3-T4 primaries and ten had positive nodes (N1). Two of the 30 patients were treated for local recurrence following surgical excision and one was treated immediately after local excision. Twenty-six of the 30 patients attained biopsy-confirmed complete remission. Four of the 30 patients demonstrated residual disease at completion of therapy but all subsequently achieved complete remission with additional nonsurgical treatment. One patient, initially treated for local recurrence following excision failed locally at four years and was salvaged with chemotherapy followed by abdominoperineal resection. No patient has experienced distant failure. Twenty-seven of 30 patients were alive and disease free after 9 to 76 months of follow-up and three died, disease-free, of unrelated causes. Acute toxicities were mild and did not necessitate interruption of treatment. A brisk perineal reaction and diarrhea were noted in all patients. Late complications were unusual. All patients were treated in a community-based, private practice setting. The authors conclude that combined CT-RT, as employed herein, represents a first-line curative treatment for the majority of patients with epidermoid anal carcinoma. For patients who demonstrate residual disease following this therapy, salvage regimens such as 5-FU infusion and cisplatin, or sequential MTX-5-FU-Leucovorin with additional synchronous RT should be employed before resorting to radical surgery.

Radiotherapy alone and chemoradiation for nonmetastatic esophageal carcinoma. A critical review of chemoradiation.

Sixty-five patients with nonmetastatic (Stages I, II, and III) esophageal cancer (EC) were treated with radiotherapy (RT) alone (56.00 to 61.00 Gy in 6 to 7 weeks) or synchronous combinations of radiotherapy and chemotherapy (RT-CT). RT-CT consisted of 41.40 to 50.40 Gy in 4.5 to 8 weeks with continuous infusion 5-fluorouracil 5-FU (1000 mg/m2/d for 4 days in weeks 1, 4, and 8), mitomycin C (10 mg/m2 intravenously [IV] in weeks 1 and 8), cisplatin (75 mg/m2 IV in week 4). Maintenance CT consisted of methotrexate (200 mg/m2 IV), leucovorin (10 mg/m2 orally every 6 hours for 5 doses), and 5-FU (600 mg/m2 IV) in weeks 10, 12, and 14. Thirty-five patients treated by RT alone (Group A) were comparable in terms of age, sex, AJC staging, histologic condition, and location of primary with 30 patients treated by RT-CT (Group B). In Group A (range, 2- to 144+ months), two patients (42 and 144 months) are alive and well. In Group B (range, 2- to 59+ months), 12 patients (7 to 59 months) are alive and well. Median survival in Group A is 8 months, compared with 15 months for patients achieving a complete response (CR) in Group B. Patients in Group B achieved a 77% CR rate by endoscopy-biopsy, whereas 30% of the patients in Group A achieved a CR (P = 0.0001). The recurrence rates at the primary site/regional nodes were 77% and 27% in Groups A and B, respectively (P = 0.0001). The incidences of distant metastases were 29% and 20%, respectively (P = 0.423). In Group A, the 1-year and 2-year cumulative survival rates were 27% and 13%, respectively. In Group B, the cumulative survival rates were 53% at 1 year and 29% at 2 years (P = 0.023). Aside from reversible myelotoxicity, the incidences of pulmonary fibrosis, esophagitis, and fistulae formation were less frequent in the combined technique treatment group. A compilation of reported chemoradiation protocols for EC indicates consistently improved 1-year and 2-year survival rates, compared with surgical and RT series. The key to further improvement in the treatment of EC appears to lie in increasing the biologic response (RT fractionation and endocavitary RT) and optimal use of multiple effective CT agents with nonadditive toxicities.

Definitive nonsurgical therapy of epithelial malignancies of the anal canal. A report of 12 cases.

Twelve patients with epidermoid carcinoma of the anal region ranging in age from 40-89 years were treated with combined chemotherapy (CT) and radiotherapy (RT) in lieu of abdominal-perineal resection. Ten patients received no prior treatment and two patients were treated for local recurrence following limited surgical excision. Two courses of 5-FU infusion and mitomycin C were given 3-4 weeks apart simultaneously with whole pelvis RT to 3000-4140 rad. One patient received an additional tumor volume dose of 3094 rad by interstitial Iridium implant and one patient received an orthovoltage boost of 1000 rad to the anal ring. All patients completed treatment. Complete regression of the anal mass occurred in all patients. Biopsies of the anal region performed after completion of therapy revealed no evidence of residual cancer. Ten of the 12 patients are alive without evidence of disease 4-24 months (median, 14 months) after completion of treatment. Two patients have died seven months after treatment of unrelated causes and were tumor-free at autopsy. All patients developed proctitis, diarrhea, and moist perineal desquamation which resolved by four weeks posttreatment. Based on their experience and that of others recently reported, the authors conclude that the described CT-RT protocol offers a definitive alternative to surgery of epidermoid cancer of the anal region.

Overexpression of p53 protein and outcome of patients treated with chemoradiation for carcinoma of the anal canal: a report of randomized trial RTOG 87-04. Radiation Therapy Oncology Group.

BACKGROUND: Despite encouraging results with chemoradiation as the primary means of managing carcinoma of the anal canal, approximately 20% of patients will develop a local recurrence. This study examined the prognostic significance of p53 nuclear protein overexpression in the pretreatment biopsies of patients treated with chemoradiation for epidermoid carcinoma of the anal canal. METHODS: All patients were treated in a prospective, randomized Radiation Therapy Oncology Group trial (RTOG 87-04) in which radiotherapy to the pelvis was compared with concurrent 5-fluorouracil (5-FU) or 5-FU and mitomycin-C. Formalin fixed, paraffin embedded blocks or unstained slides from the pretreatment biopsies of 64 patients were obtained from referring institutions and evaluated immunohistochemically with the polyclonal p53 antibody CM-1. A multivariate analysis was conducted to analyze overexpression of p53 in terms of locoregional control, no evidence of disease (NED), and overall survival. RESULTS: p53 protein was overexpressed in 48.4% of the cases. Although not statistically significant, there was a trend for patients whose tumors overexpressed p53 to have inferior locoregional control (52% vs. 72%, P = 0.13), NED survival (52% vs. 68%, P = 0.27), and absolute survival (58% vs. 78%, P = 0.14). Of all the pretreatment factors analyzed, only International Union Against Cancer stage was predictive of outcome in multivariate analysis. Among those patients whose tumors overexpressed p53, there was a trend toward improved outcome in the arm that received 5-FU and mitomycin-C compared with the arm that received 5-FU only. CONCLUSIONS: Overexpression of the p53 protein may be associated with inferior outcome for patients managed with definitive chemoradiation for epidermoid carcinoma of the anal canal.