Moshe Stein

The management of metastatic spinal cord compression: A radiotherapeutic success ceiling

PURPOSE In assessing the effectiveness of the management of metastatic spinal cord or cauda equina compression, we performed a retrospective analysis of 70 patients with this complication whom we treated from 1985 to 1989. METHODS AND MATERIALS The most frequent primary diagnoses in our series were carcinomas of unknown origin and of the breast, lymphoproliferative disease, lung cancer, and prostatic carcinoma. We used the Findlay classification to group all patients according to their pre-therapeutic functional motor status as Grade I (24 patients or 34%), Grade II (27, or 39%) or Grade III (19 or 27%). Treatment consisted of 30-45 Gy of irradiation (using two different schedules) together with high-dose dexamethasone; in only five cases was there surgical intervention. RESULTS We found that a powerful predictor of response to radiotherapy was the patients neurologic status (Findlay grade) at the time of diagnosis: 66% of previously ambulatory patients remained so, whereas 30% of non-ambulatory patients and only 16% of paraplegic patients regained the ability to walk. Another important predictor of response was primary tumor histology, with the most favorable responses to radiation therapy having been observed in lymphoproliferative diseases and in breast cancer, but with some response in other radiosensitive malignancies as well. CONCLUSION The similarity of our results to those of other centers leads us to conclude that a radiotherapeutic success ceiling of 80% may have been reached for Findlay Grade I patients with metastatic spinal cord compression. In view of this, we suggest that future therapeutic endeavour would be best directed toward early diagnosis of the condition.

Splenomegaly and solitary spleen metastasis in solid tumors

Metastasis to the spleen from various neoplasms is very rare. Most of the splenic metastases are found at autopsy, and are part of a widespread disease. Four patients had cervical cancer (1 patient), endometrial cancer (1 patient), lung carcinoma (1 patient), and malignant melanoma (1 patient). All patients had splenic involvement without pathologic evidence of lymph node metastasis, and all underwent splenectomy. Three of the four presented with painful splenomegaly. The time from diagnosis to the development of splenic metastasis varied from 20 to 24 months. Two of the four patients had postoperative radiotherapy, one patient received intraperitoneal chemotherapy, and the patient with the melanoma received adjuvant chemotherapy. The rarity of solitary spleen metastasis from solid tumors and the treatment modalities are discussed.

Mast cells in colorectal neoplasias and premalignant disorders

PURPOSE: Mast cells have recently been found to be well correlated with the prognosis of patients with rectal cancer. This work aimed to characterize the role of mast cells in colonic premalignant conditions. METHODS: Mast cells were quantified in various colonic disorders, particularly those with premalignant potential. Possible avenues of mast cell action were investigated using these tissue samples, by measuring basement membrane and collagen layer thickening. RESULTS: The mean number of mast cells in carcinoma sections was 0.967/0.9 mm2, in various colorectal neoplasias and related conditions it ranged from 1.36–3/0.9 mm2, and in normal histologic specimens it was 11.90/0.9 mm2. These data established statistically significant differences in mast cell numbers in the colonic disorders studied. The number of mast cells is greatest in the lamina propria level of the colon, a site often not examined because of the limited depth of samples obtained from endoscopic biopsies. CONCLUSIONS: Mast cell numbers were found to be correlated to the development from premalignancy to colonic malignancy. Mast cells may be useful as markers of colorectal neoplasia.

Involvement of the central nervous system by ovarian carcinoma

Ovarian carcinoma rarely metastasizes to the central nervous system (CNS). Of 110 patients with epithelial ovarian carcinoma treated at the Northern Israel Oncology Center between the years 1979 and 1985, only five (4.5%) had CNS involvement. The median age of the patients was 54.5 years. All of them had treatment with cisplatin and Adriamycin (doxorubicin). The median duration from diagnosis to the development of brain involvement was 17 months. The median survival time was 28 months from diagnosis of carcinoma and 2 months from diagnosis of CNS disease. The increased incidence of this kind of metastasis in patients achieving local control of their advanced disease suggests that a change in the pattern of metastatic spread or the prolonged survival permits occult CNS metastases to become apparent. A routine computerized axial tomography (CAT) scan of the brain should therefore be performed on patients with ovarian carcinoma with prolonged survival.

Postradiotherapy hypothyroidism: Radiation dose response and chemotherapeutic radiosensitization at less than 40 Gy

To analyze our experience with iatrogenic hypothyroidism, we prospectively followed 84 patients, seen from 1984 to 1990, who had been diagnosed with either Hodgkins disease (HD) or head and neck (H&N) carcinoma and subsequently treated with radiotherapy. Within these two diagnostic groups were subgroups whose treatment differed as to dose of therapeutic irradiation received or adjunctive use of chemotherapy. Approximately 50% of all patients and of each subgroup developed either clinical or subclinical hypothyroidism during follow‐up. However, among the HD patients who received irradiation plus chemotherapy, a dose‐response relationship below a threshold limit of dose received, probably 40 Gy, was observed.

The value of postoperative irradiation in renal cell cancer

This is a retrospective analysis of 147 evaluable patients, with histologically proven renal cell carcinoma, who were referred to our center between 1977 through 1988. All patients with disease limited to the kidney underwent nephrectomy. Post-operative megavoltage irradiation, with a median dose of 46 Gy, was given to 56 patients, using parallel opposing portals, or multiple field technique. Five and 10 year actuarial survivals in irradiated patients (Rt+) were 50 and 44%, respectively, and in non-irradiated patients (Rt-) 40 and 32%, respectively. The disease recurred locally in a total of 19 patients; 16 had tumor bed recurrence and three had scar recurrence. Local recurrence by stage was as follows: T2 N0M0: RT+ 0/17, RT- 2/28; T3 N0M0: RT+ 4/37 (10%), RT- 11/30 (37%) (p less than 0.05); T4 N0M0: RT+ 1/2, RT- 1/5. Two of the local recurrences in irradiated patients developed in a surgical scar which was not included in the treatment volume. Significant toxicity developed in three patients (5%). It is concluded that post-operative irradiation can reduce local recurrence rate in T3 N0M0 renal cell carcinoma. It is recommended that the surgical scar should always be included in the treatment volume and irradiated to a full dose.

Octreotide in the treatment of severe chemotherapy-induced diarrhea

BACKGROUND Chemotherapy-induced diarrhea (CID) is a common side effect of a number of chemotherapeutic agents. Conventional therapy for severe CID with opioids or loperamide is moderately effective. A prospective trial was conducted using octreotide acetate for treatment of severe CID refractory to loperamide. PATIENTS AND METHODS Thirty-two patients with grade 2 and 3 CID refractory to loperamide were treated with octreotide at a dosage of 100 microg subcutaneously 3x/day for three days followed by 50 microg 3x/day for three days. Previous chemotherapy consisted of regimens containing fluorouracil, leucovorin, CPT-11, cyclophosphamide, methotrexate and cisplatin. Primary tumors were colorectal (n = 23), gastric (n = 3), and other cancers (n = 6). RESULTS Complete resolution of diarrhea was obtained in 30 of 32 patients (94%); 5 within 24 hours, 14 within 48 hours, and 11 within 72 hours of treatment. Nineteen patients were treated as outpatients. Thirteen were hospitalized for a median of three days. Response was unaffected by age, gender, performance status, previous chemotherapy or primary tumor site. No side effects related to octreotide were observed. CONCLUSIONS Octreotide 100 microg subcutaneously 3x/day for three days is an effective, safe treatment for CID given primarily or as a second-line therapy after loperamide failure.

Postoperative irradiation in localized renal cell carcinoma: the Rambam Medical Center experience.

Objective This study evaluated the results of postoperative adjuvant radiotherapy in patients with localized renal cell carcinoma (RCC). Patients Eighty-six patients (median age, 60 years) with RCC treated by radical nephrectomy were evaluated for the efficacy of postoperative radiotherapy. Twenty-four percent of patients had stage T2, 35% T3a, 36% T3b and 5% T4 disease. Seventy-seven percent had clear cell carcinomas and 23% granular cell or spindle and mixed cell carcinomas. Radiotherapy was given to the renal bed and adjacent lymphatic basin at a median dose of 46 Gy. Results Thirty-two (37%) patients relapsed: 27 (84%) had systemic relapse only and five (16%) had local and systemic relapse; all patients of the latter group had stage T3b disease. The 10-year disease-free and overall survival was 40% and 42%, respectively. Tumor invasion of the renal vessels and stage of disease were correlated with survival. Side effects of radiotherapy were mainly gastrointestinal, but one patient who received right abdominal irradiation died because of liver failure. Conclusion The results of our study are comparable with those reported in the literature. Since postoperative irradiation did not improve the survival of patients with RCC and showed toxicity, it is not recommended.

Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma

One hundred and sixteen patients with advanced ovarian carcinoma, who underwent primary cytoreductive surgery, received 6-11 courses of chemotherapy by cis-platin (50 mg/m2) and adriamycin (50 mg/m2) every 21 days. This was followed by second look laparotomy in 66 patients with no clinical evidence of disease. Consolidation abdominal irradiation was administered to 43 patients. Two techniques of irradiation were employed: between 1980-1983 whole abdominal irradiation was used and patients were to receive 3000 cGy in 4 weeks (Schedule I). Due to myelosuppression only 13 of 26 patients (50%) completed the planned dose of radiation. Between 1983-1985 the target volume was divided into upper and lower parts. First, the lower abdomen received 3000 cGy in 3 weeks, and then the upper abdomen received the same dose (Schedule II). Sixteen of seventeen patients (94%) thus treated, completed the planned dose of radiation. The actuarial survival for all 116 patients was 28% of 5 years. Irradiated patients with negative second look laparotomy had a survival probability of 100% at 24 months. Irradiated patients with microscopic disease at second look operation had an actuarial 5-year survival of 66%. Patients with minimal residual disease at second look laparotomy, receiving consolidation abdominal irradiation, had an actuarial survival of 5% only at 36 months. It is concluded that consolidation radiotherapy is effective in patients with negative or microscopic residual disease at second-look laparotomy. In regard to bone marrow tolerance, split field technique of irradiation is preferred.

Primary Lymphoma of Bone – A Retrospective Study

Objective: This retrospective study describes our experience with the diagnosis, treatment, results and long-term follow-up of primary bone lymphoma (PBL). Patients and Methods: Nineteen patients diagnosed with PBL were reviewed. Seven patients presented with stage IE disease, four with stage IIE (regional lymphadenopathy), and eight with stage IV disease (disseminated bone involvement). Only one stage IV patient exhibited ‘B’ symptoms. The majority (72%) demonstrated diffuse, large cell, B-type lymphoma. All patients were treated with adriamycin-based chemotherapy and consolidation radiotherapy to the primary site (8 patients: early PBL) or the most bulky area (3 patients: stage IV PBL). Results: Ten stage IE/IIE patients are alive with no evidence of disease (NED) and only one died due to metastatic secondary lung cancer while with NED from his PBL. Eight stage IV patients are alive with NED. Median follow-up for all living patients: 77 months. Side effects were mild and did not necessitate delay in treatment. Conclusions: Our departmental policy of treating PBL patients with an anthracycline-based regimen and involved field radiotherapy proved to be successful in achieving excellent long-term, disease-free survival. Phase III randomized, controlled, clinical trials will determine the true role of consolidation radiotherapy in PBL, when considering severe late side effects, including radiation-induced bone tumors.