Cystosarcoma phyllodes. Effective therapy with cisplatin and etoposide chemotherapy.

Cystosarcoma phyllodes is an unusual breast neoplasm that rarely metastasizes. Most series report chemotherapy, radiation, and hormonal therapy to be ineffective. Three patients were treated with cisplatin and etoposide combination chemotherapy with effective palliation in two patients. Radiation therapy was effective in controlling symptomatic metastasis in all three patients. Hormonal therapy was ineffective in two patients despite the presence of positive hormone receptors. Chemotherapy and radiotherapy may be more effective in the treatment of this tumor than has been reported, although there is no apparent role for hormonal therapy. Functional hormone receptors are probably not present.

Cisplatin and etoposide: an effective treatment for refractory breast carcinoma.

Thirty-one patients with metastatic breast carcinoma refractory to standard hormonal and chemotherapy were treated with cisplatin 100 mg/m2 per course and etoposide 300 mg/m2 per course divided over 5 days. Courses were repeated at 3-6-week intervals, depending on the speed of recovery from myelosuppression. Of 29 evaluable patients, three had complete responses, eight had partial responses, eight had stable disease, and 10 had progressive disease. Nausea, emesis, anorexia, weakness, and easy fatigability were common but tolerable side effects. Myelosuppression was frequent and occasionally profound but there were no deaths from hemorrhage or infection. No significant renal toxicity was encountered. The combination of cisplatin and etoposide has sufficient antitumor activity with acceptable toxicity in heavily pretreated patients to justify its further study in breast cancer.

A phase I/II study of combined cisplatin and hyperthermia treatment for refractory malignancy.

Research in animal and human cell cultures has shown that some chemotherapeutic agents, cisplatin in particular, have cytotoxicity that is significantly potentiated at elevated temperatures. Concurrent administration of systemic cisplatin and local hyperthermia in human patients has not been previously reported. A phase I/II study was undertaken to assess the systemic and local toxicities and activity of concurrently administered local hyperthermia and systemic cisplatin in human tumours. Nine patients with histologically proven malignant tumours have been treated from March 1985 to July 1987. Their histologies were: breast, four; SCC of head and neck, two; SCC of skin, one; malignant melanoma, one; synovial cell sarcoma, one. Once-weekly hyperthermia was administered for 60 min by external microwave devices in an attempt to achieve minimum intratumoral temperatures of 42 degrees C. Plastic catheters were placed intratumorally under CT guidance for thermometry purposes. Cisplatin 40-60 mg/m2 was given over 60 min when steady-state heating was achieved. A total of 44 treatments are available for analysis. All nine patients had minimum intratumoral temperatures below the desired goal of 42 degrees C, and only two patients achieved average intratumoral temperatures of 42 degrees C or greater. Two of the responding patients sustained significant thermal injury consisting of blistering and necrosis. Three patients required transfusion and delay of weekly treatment because of anaemia and leukopenia. Four patients had partial response (PR) and one patient had minor response (MR) within the heated treatment volume. Three of these five patients experienced significant subjective palliation. This combination of treatment modalities can be delivered safely.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase II study of human lymphoblastoid interferon in patients with multiple myeloma.

Interferon has been reported to have activity in the treatment of multiple myeloma. We studied 24 myeloma patients treated with human lymphoblastoid interferon (Wellferon) by intramuscular injection twice weekly at an initial dose of 3 MU/M2 (three patients) or 15 MU/M2 (21 patients). One of 17 evaluable patients achieved a partial remission, three others were stable over a 16-week period of treatment, and 13 others had progressive disease. Subjective toxicity was frequent and substantial, particularly at the 15 MU dose level. Hematologic toxicity was mild and reversible. Two patients experienced acute renal failure. The low rate of response (6%) and substantial level of toxicity fail to support further exploration of these schedules of interferon as a single agent in myeloma.

Phase II evaluation of teniposide (VM-26) in metastatic breast carcinoma. A Southeastern Cancer Study Group trial.

The Southeastern Cancer Study Group performed a Phase II study of teniposide in previously treated patients with metastatic breast cancer. No responses were observed in 11 evaluable patients who received teniposide 60 mg/m2 by IV infusion for five consecutive days every three weeks. Toxicity was primarily gastrointestinal and hematologic and was frequently severe. This study demonstrated no therapeutic activity for teniposide when given in this dose and schedule to patients with heavily pretreated metastatic breast cancer.

Estrogen receptor determination by monoclonal antibody in fine needle aspiration breast cancer cytologies: a marker of hormone response.

A monoclonal antibody (H222) prepared against purified estrogen receptor has been demonstrated to be highly specific and sensitive in an immunohistochemical assay for the detection and quantification of estrogen receptor in human breast carcinoma biopsy specimens. To evaluate the clinical applicability of this assay in cytologic specimens, response to therapy in 12 patients with recurrent breast cancer was correlated with H222 antibody localization in specimens obtained by fine needle aspiration biopsy. All 7 patients with positive H222 responded to hormone therapy (1 complete and 3 partial remissions and 3 stable disease), while 1 of 5 patients with negative H222 responded (1 stable disease). This experience suggests a role for immunohistochemical estrogen receptor determinations in prediction of response to hormonal therapy in patients whose tumor is accessible only to aspiration biopsy. Special care in the handling and interpretation of specimens is essential to optimal application of this method.

Inflammatory breast carcinoma. Effective multimodal approach.

Twenty-two patients with inflammatory breast carcinoma received preoperative chemotherapy consisting of weekly administration of cyclophosphamide, doxorubicin hydrochloride, fluorouracil, and vincristine sulfate for six weeks. Postoperative therapy consisted of 22 weeks of biweekly administration of these drugs. Regional radiotherapeutic consolidation followed chemotherapy. Nineteen patients completed therapy. Twelve of these patients remain disease free (median, 15 months; range, four to 32 months). Median disease-free survival for all 22 patients is 13 months or more (range, zero to 32 months). Median overall survival is 18 months or more (range, one to 33 months). This regimen compares favorably with prolonged adjuvant and maintenance chemotherapy for inflammatory breast carcinoma.

Oligodendroglioma. An analysis of the value of radiation therapy.

The role of radiation therapy in the treatment of supratentorial oligodendrogliomas is controversial. To evaluate the role of radiation therapy, the Duke University Medical Center series was retrospectively analyzed. Clinical history, radiation dosages, and pathologic materials were reviewed. Seventy-one patients were identified as having histologically proven oligodendroglioma. Analysis of the patient population demonstrated it to be similar in all major parameters to other populations previously reported in the literature. Multivariate statistical analysis of the demographic, clinical and radiographic variables of these patients showed that a poorer prognosis was associated with persons of increased age (P = 0.052) and black persons (P = 0.014), and in those with papilledema (P = 0.07), hemiparesis (P = 0.001), intellectual deficits (P = 0.0002), and necrosis (P = 0.041). All patients had a surgical procedure as first treatment while 18 and three patients, respectively, underwent a second and third surgical procedure. Thirty-seven patients had a subsequent course of radiotherapy. Univariate and multivariate statistical analysis comparing the patients treated with surgery alone those treated with surgery plus radiotherapy revealed no significant population or prognostic differences between the groups. The median times until clinical deterioration were 39 versus 27 months, the median times until documented tumor recurrence were 27 versus 28 months and the median survival times were 4.5 versus 5.2 years, for nonirradiated versus irradiated patients. These data, from a large and rigidly evaluated population, demonstrated no statistically significant difference in the symptom-free interval, time until tumor recurrence, or survival between the groups nor did radiation appear beneficial to any subgroup evaluated. The results suggest the need for a prospective clinical trial to evaluate the true role of radiation therapy in the treatment of this tumor.

Breast cancer in the elderly.

Breast cancer is one of the most common serious health problems for elderly women. The study of age-related differences in breast cancer provides useful insights into its pathophysiology. New strategies for treatment, including adjuvant systemic therapy and less aggressive therapy for primary lesions, add new dimensions to a complex and variable disease.

Endometrial adenocarcinoma estrogen receptor content: association of clinicopathologic features with immunohistochemical analysis compared with standard biochemical methods.

Endometrial adenocarcinomas from 96 patients were studied for their biochemical estrogen receptor content as well as immunohistochemical localization of estrogen receptor. A well-characterized specific monoclonal antihuman estrogen receptor antibody (H222 sp gamma) as amplified by peroxidase/antiperoxidase techniques was used for immunohistologic localization. Immunohistochemical evaluation incorporated both the intensity and distribution of staining into a semiquantitative analysis (HSCORE). The total HSCORE was the sum of the relative contributions of the four histologic components: benign epithelium, malignant epithelium, stroma, and myometrium. These results were compared with clinicopathologic features of the tumors. Excellent sensitivity (91.5%) and specificity (93.1%) were observed for immunohistochemical analyses as compared with the biochemical analysis of estrogen receptor for these tissues. The cancer component HSCORE correlated better with grade than did the biochemical estrogen receptor determination. Correlation was also observed between surgical stage and estrogen receptor content. Decreasing biochemical estrogen receptor content predicted advanced surgical stage (p = 0.0003), as did the total HSCORE (p = 0.003); however, the HSCORE of the cancer component only did not correlate with advanced surgical stage (p = 0.11). Although immunohistochemical analyses predicted biologic differentiation better than did the biochemical technique, stage correlated better with biochemical estrogen receptor analysis and total HSCORE than did the cancer component HSCORE. The HSCORE of the cancer component may better predict biologic behavior and therefore identify cancers more likely to respond to hormonal therapy.

Histologic composition of endometrial carcinomas analyzed for steroid receptor content.

One hundred endometrial carcinoma specimens were analyzed for estrogen receptor content and histologic composition. Benign tissue elements were identified in the majority of tissue sections. Histologic control of endometrial carcinoma specimens submitted for steroid receptor analysis is critical, because biochemical assays of whole tissue homogenates cannot determine receptor localization among tissue components.

Does transurethral resection of the prostate promote metastatic disease?

Previously published data have suggested that transurethral resection of the prostate might promote the subsequent appearance of metastatic disease. To confirm or deny these observations 145 patients underwent radical prostatectomy, after having had the disease diagnosed either by transurethral resection of the prostate or transrectal needle biopsy. Of the 145 patients 6 were excluded from analysis since they had had transurethral resection of the prostate and transrectal needle biopsy. In 33 patients the disease was diagnosed by transurethral resection of the prostate only and in 106 it was diagnosed by transrectal needle biopsy only. The relative distribution of Gleason grade and the positive versus negative margins among the 2 populations were similar. Using time to first evidence of distant disease as the endpoint of the study no difference in failure rates could be detected between the 2 populations. It is concluded that transurethral resection of the prostate does not enhance the appearance of metastatic disease.

Clinicopathologic correlations in the oligodendroglioma.

To determine the prognostic significance of histologic variables in oligodendroglial neoplasms, the presence and degree of 15 such variables were correlated with postoperative survival rates in 71 patients. By univariate analysis, prognostically significant factors, in order of decreasing importance, were mitoses (log), necrosis, nuclear cytologic atypia, vascular hypertrophy, and vascular proliferation. When studied by stepwise regression, necrosis and the number of mitoses contained all of the prognostically useful information. When each of the five variables significant by univariate analysis was tested in the Cox model by adding a variable to the model containing the other four, necrosis was found to be the only independently significant variable. There were significant positive pairwise correlations between each of the five significant histologic variables except for cytologic atypia with necrosis. The only histologic variable with a significant association with older age was the number of mitoses. These results suggest that necrosis and, to a lesser extent, the mitotic count are features that, in the appropriate setting, can be used to identify the "anaplastic" oligodendroglioma.

Evaluation of transcutaneous oxygen tension monitoring during cosmetic surgery.

Transcutaneous oxygen monitoring during rhytidectomy surgery under local anesthesia was evaluated in 18 patients. Blood gas analysis of samples of arterial blood obtained from the superficial temporal arteries during rhytidectomy was compared with transcutaneous PO2 values. Simple linear regression analysis indicated that the transcutaneous PO2 correlates strongly with arterial PO2. Transcutaneous PO2 monitoring could be a reliable, inexpensive, and continuous method of assessing gradual or sudden changes in arterial PO2, provided the sensor is fastidiously maintained and properly applied, elements which are critical to relying on this particular device. However, this instrument has no advantages over the digital pulse oximeter.

Value of cyclophosphamide or melphalan as combined chemotherapy in hormonally unresponsive prostatic carcinoma.

This prospective randomized study in nonhormonally responsive adenocarcinoma of the prostate shows that response rates to melphalan vs cyclophosphamide groups were virtually identical.

Radical prostatectomy: anatomical predictors of success or failure.

A total of 143 patients underwent radical prostatectomy. Surgical specimens were evaluated with respect to local extent of disease, Gleason grade of the primary and relative nuclear roundness of the surgical specimen. The probability of disease control in the total population was 88 per cent at 5 years. Only 8 per cent of the patients who had disease confined to the specimen failed compared to 14 per cent of those who demonstrated extension outside of the surgical margins. The incidence of failure increased as a function of seminal vesicle involvement. Seminal vesicle involvement was greatest among patients with a Gleason grade greater than 7. Postoperative radiation did not offer any apparent advantage in patients with positive margins.

Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody.

Immunohistochemical localization of estrogen receptor (ER) using specific monoclonal anti-human estrogen receptor antibody, H222, with an immunoperoxidase technique was performed on fresh frozen tissue derived from 100 endometrial adenocarcinomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining. In all cases, H222 localized in the nucleus of target cells. A significant quantitative relationship was shown between histological score (H-Score) and the biochemical analysis of ER content in tissue homogenates (r = 0.65, P = 0.00001). Excellent sensitivity (92%) and specificity (93%) were observed for the comparison of H-Score to the biochemical assay. Significant ER localization was present in stromal and myometrial elements, component H-Score of which correlated weakly with component H-Scores of malignant epithelial elements. Divergent receptor localization in stromal and myometrial versus malignant epithelial elements suggests that biochemical assays of endometrial carcinoma specimens may not reflect cancer-relevant receptor content. The data presented here suggest that the immunoassay of ER using H222 monoclonal antibody provides additional histochemical information to complement conventional analyses of endometrial adenocarcinomas.

Medulloblastoma: the Duke University Medical Center experience.

We have reviewed the clinical experience in the treatment of medulloblastoma with radiotherapy at Duke University Medical Center. One hundred and twenty-seven patients treated between January 1, 1940 and December 31, 1983 were evaluated. The irradiation technique was reviewed and all irradiation doses were recalculated as minimum tumor doses in Gray (Gy). The mean follow-up was 24.4 years and the median follow-up was 26.5 years. The energy of the treatment machine was known in 102 cases. Sixty patients were treated with orthovoltage equipment and 42 patients were treated with megavoltage equipment. As a gross assessment of the impact of the details of radiotherapy treatment upon outcome, patients were grouped into excellent, good, fair, and poor treatment groups. Patients undergoing cranio-spinal axis (CSA) irradiation and receiving greater than or equal to 52 Gy to the posterior fossa and greater than or equal to 30 Gy to the clinically uninvolved remainder of the CSA were classified as having "excellent" technique. Patients undergoing CSA irradiation and receiving 40 to 52 Gy to the posterior fossa and greater than or equal to 20 Gy to the remainder of the CSA were classified as "good." Patients receiving 20 to 40 Gy to the posterior fossa and greater than or equal to 10 Gy to the spinal axis with or without prophylactic cranial irradiation were designated "fair." Any patient not fulfilling the above minimum criteria was categorized as "poor." The actuarial 5-year survival for the entire population was 33%. The 10-year survival was 21%. In 93 patients for whom records were detailed enough to allow categorization of treatment technique, 5-year actuarial survivals were: Excellent 37% (n = 17), Good 55% (n = 13), Fair 35% (n = 23), Poor 20% (n = 40). A complete surgical resection was not correlated with improved disease-free survival (DFS) in the excellent and good groups, but was correlated with an improved DFS in the fair and poor groups. The posterior fossa accounted for 62% of the failures in the 55 patients completing irradiation where the initial site of failure was known. An examination of patterns of failure in the spinal canal failed to demonstrate a dose response relationship above 10 Gy for spinal canal prophylactic irradiation. No patient developed recurrence beyond their period of risk as defined by "Collins' Law."(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation therapy in the management of neuroblastoma: the Duke University Medical Center experience 1967-1984.

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% (p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage II disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of computed axial tomography of the chest in staging patients with nonmetastatic gestational trophoblastic disease.

Thirty-nine women with nonmetastatic gestational trophoblastic disease as determined by conventional staging studies were prospectively evaluated with computed axial tomography (CAT) of the lungs. Sixteen patients (41%) had pulmonary micrometastases detected by CAT, which were not detected by routine chest x-ray. Eight patients (20.5%) had indeterminate scans, and only 15 patients (38%) had negative scans. Eight of 16 patients (50%) with pulmonary micrometastases failed initial therapy with methotrexate-folinic acid rescue while one of eight (12.5%) patients in the indeterminate group and one of 15 (6.7%) patients in the true nonmetastatic group failed initial therapy (P less than .006). All patients who failed methotrexate-folinic acid rescue ultimately achieved prolonged remission with actinomycin D. Time to remission was significantly decreased in patients without evidence of pulmonary micrometastases (P = .03), but the total number of courses of chemotherapy was not significantly different (P = .06). No life-threatening toxicity occurred. Pulmonary micrometastases detected by CAT but not chest x-ray are predictive of an increased risk of methotrexate-folinic acid therapy failure. Computed axial tomography of the lungs identifies a group of patients at high risk for failure of methotrexate-folinic acid rescue, and, therefore, may be indicated for routine staging of patients with otherwise nonmetastatic gestational trophoblastic disease.