Total skin electron irradiation in mycosis fungoides dose and fractionation considerations.

This study was undertaken to analyze the influence of total skin dose and dose-fractionation schedules on the response rate, survival and skin toxicity of patients with mycosis fungoides [MF] treated with total skin electron irradiation [TSEI]. From 1979 to 1992, 40 patients with MF were treated with TSEI using a modified Christie Hospital technique. Mean follow-up time was 48 months [median 20 months]. 37/40 patients completed TSEI; three died due to non-treatment-related conditions during therapy. 34/37 [92%] treated patients achieved complete remission [CR] and 16/40 [40%] are alive with no evidence of disease. Over the years, changes in dose-fractionation schedules were made and correlated with the pattern of CR and skin toxicity. The 5-year actuarial survival [Stanford staging] was 84% in Stages IA-IB [all Stage IA patients are alive] and 59% in Stage II. The probability of survival of Stage III-IV patients was 30% at 30 months. Late skin toxicity was mild to moderate in 60% and severe in 25% of patients. A reduction of the total dose and dose-per-fraction resulted in an acceptable CR rate and a significantly lower toxicity. TSEI is effective in early stage MF. Skin control and late skin toxicity seem to be dose-fractionation-schedule related. For the early stages, the optimal treatment schedule seems to be 24-30 Gy to the whole skin surface in 2.4-3.0 Gy fractions, given twice weekly over a period of four to six weeks. Total doses of 24-30 Gy at 2.4-3.0 Gy per fraction yielded comparable skin control rates with lower skin toxicity.

Radiation-induced tumors in irradiated stage I testicular seminoma: results of a 25-year follow-up (1968-1993).

BACKGROUND AND OBJECTIVES: Testicular seminoma is a very radiosensitive and curable cancer, with survival rates following radiation therapy within the range of 90-98% without apparent severe side effects. However, long-term survival following exposure to moderate-dose radiation therapy can result in radiation-induced tumors. METHODS: The incidence of radiation-induced tumors was determined in 81 irradiated stage I testicular seminoma patients treated at the Northern Israel Oncology Center (NIOC) from 1968 through 1993. RESULTS: Three (4%) patients developed second cancers within the high-dose volume. Indeed, those patients received a higher than usual dose to the para-aortic and pelvic regions. One patient, who developed inoperable pancreatic carcinoma, was treated with "hockey stick" field and mediastinal irradiation, plus, as a result of relapses, multiple cisplatin and VP-16 based regimens. CONCLUSIONS: The elimination of causative factors through lower total doses and field size reduction may reduce the, albeit very low, incidence of radiation-induced cancer in cured testicular seminoma.

Haptoglobin-related protein as a serum marker in malignant lymphoma.

A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin's lymphoma (n=58) and Hodgkin's disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430x10 u/ml, range 0-4000x10 ) were significantly higher than in the control group (median 68x10 u/ml, range 0-180x10 )(p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), "B" symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma.

Dexamethasone, etoposide, ifosfamide, and cisplatin as second-line therapy in patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND: This study analyzed the long term results of a combination of dexamethasone, etoposide, ifosfamide, and cisplatin (DVIP) used at the study center as standard second-line combination therapy in patients with aggressive non-Hodgkin's lymphoma (NHL) after prior exposure to doxorubicin. METHODS: All drugs were given intravenously for 4 consecutive days. The maximum daily doses of etoposide, ifosfamide, and cisplatin were 75 mg/m2, 1200 mg/m2, and 20 mg/m2, respectively. The dexamethasone dose was 20 mg twice daily. Cycles were repeated every 3 weeks. RESULTS: Fifty-six patients were included in the study. Partial response was noted in 18 patients (32%) and complete response (CR) in 18 patients (32%). Pretreatment factors that predicted CR were CR with prior therapy (CR in 17 of 34 in patients with a recurrence vs. 1 of 21 in patients with primary refractory NHL) and age (CR in 12 of 25 patients age < or = 65 years vs. 6 of 31 patients age > 65 years). Median time to treatment failure (TTF) and median survival were 11.5 months and 30 months, respectively, for patients with a CR and 3.5 months and 8 months, respectively, for all patients. Five patients (9%) remained disease free for > 24 months. By multivariate analysis, age was the only independent prognostic factor for TTF, whereas age, serum lactate dehydrogenase, and number of extranodal sites were independent predictors for survival. Myelosuppression (median granulocyte nadir and median platelet nadir of 350/mm3 and 77,000/mm3, respectively) was the major toxicity. There was one possible drug-related death associated with myelosuppression. CONCLUSIONS: DVIP is a relatively safe salvage combination therapy in patients with aggressive NHL. Response to first-line therapy and age are the most important predictors for prognosis after the administration of DVIP. This regimen is highly active in patients with recurrent NHL, but relatively ineffective in patients with primary refractory NHL.

Radiation-induced sarcoma following curative radiotherapy for testicular seminoma: case report and brief review of the literature.

We report a case of radiation-induced retroperitoneal leiomyosarcoma which developed 37 years after the patient received radiation therapy for testicular seminoma. The sarcoma originated within the para-aortic field, extensively involving neighboring organs, soft tissue and muscle tissues, and could be only partially resected. The absolute number of these secondary sarcomas is low, but the risk of developing such neoplasms calls for awareness in the long-term follow-up of cured seminoma patients.

Benign proliferative lesions mimicking recurrence of Hodgkin's disease.

Salvage treatment in patients with recurrent Hodgkin's disease is more effective when tumor burden is minimal. That is why more intensive follow-up strategies, including frequent imaging tests, have been recently developed for the detection of early relapse. However, as screening procedures become more sensitive, there is an increasing risk of false-positive results, demonstrating nonmalignant proliferative disorders. We describe three young patients who had lymphocyte-predominant or mixed-cellularity Hodgkin's disease and were in clinical complete remission for 2.5-3 years after a combined treatment with chemotherapy and radiation. Imaging tests revealed new gallium-avid lymphadenopathy in the chest in two cases. Pathologically enlarged pelvic lymph nodes were identified in another case, after a diagnosis of recurrent disease in axilla. Those findings were interpreted as relapse, and the patients underwent thoracotomy and laparotomy, respectively, for histologic confirmation. The results showed progressively transformed germinal centers and sarcoid-like lesions, two benign proliferative disorders. When patients with Hodgkin's disease in remission show new lymphadenopathy, even with positive gallium scan, it seems mandatory to obtain tissue for histologic examination, even through invasive procedures such as laparotomy and thoracotomy, to avoid wrong diagnosis and unnecessary treatment.

Diffuse lung uptake of Ga-67 after treatment of lymphoma: is it of clinical importance?

PURPOSE: To determine if diffuse lung uptake (DLU) of gallium-67 at scintigraphy in patients with lymphoma is indicative of lymphomatous involvement of the lungs. MATERIALS AND METHODS: Thirty-eight patients (24 male, 14 female; aged 15-76 years) with DLU were examined. The relation between DLU and lymphoma was investigated. Radiographic and computed tomographic findings and the persistence of Ga-67 uptake were investigated to detect lymphomatous involvement of the lungs. The relations between chemotherapy and radiation therapy, previous lung or heart disease, and DLU were also examined. RESULTS: DLU appeared only during or after chemotherapy. No clinical, radiologic, or follow-up evidence indicated that patients with DLU had active lymphomatous involvement of the lungs. The difference in survival between patients with persistent and patients with transient DLU was not statistically significant. No statistically significant correlation between DLU and any possible inductive factor was indicated at multivariate analysis. CONCLUSION: DLU after treatment does not indicate lymphomatous involvement of the lungs.

Intermediate and high-grade gastric non-Hodgkin's lymphoma: a prospective study of non-surgical treatment with primary chemotherapy, with or without radiotherapy.

The role of surgery as initial treatment in gastric lymphoma remains controversial. We have prospectively evaluated a stomach conservation strategy in histologically aggressive gastric lymphoma, using primary adriamycin-containing chemotherapy, followed by involved-field radiotherapy in patients with limited disease. Twenty-six patients (median age 69 years) were entered in this study; 15 had stage I disease, 7 had stage II disease and 4 had stage IV disease. The chemotherapy combinations were CHOP (18 patients) and ProMACE/MOPP (8 patients). Radiotherapy was given to 11 patients. Of the 24 patients evaluated for response, 18 (75%) achieved endoscopically-confirmed complete response and 4 (17%) partial response. During follow-up (median 22 months), none of the complete responders developed recurrent lymphoma. Gastric resection was performed in 1/26 patients who did not respond to primary chemotherapy. There were no cases of perforation, but three patients (12%) developed acute gastro-intestinal bleeding a few days after the onset of chemotherapy, one of whom required a surgical devascularization procedure. There was no treatment-related mortality. These data further support the non-surgical approach in histologically aggressive gastric lymphoma, using primary chemotherapy with or without radiation therapy.

Gallium-67 scintigraphy in lymphoma with bone involvement.

UNLABELLED: Both Hodgkin's and non-Hodgkin's lymphoma (NHL) may involve bone. Traditionally, 99mTc-MDP bone scintigraphy has been used to detect such involvement. In recent years, 67Ga scintigraphy has shown to be useful in monitoring treatment response in lymphoma. Although 99mTc-MDP has not been found particularly useful for monitoring bone response to cancer treatment, we were interested in whether 67Ga scintigraphy and SPECT could be used to monitor bone involvement with lymphoma. METHODS: Gallium-67 and 99mTc-MDP uptake were investigated in 20 patients with lymphoma involving the bone before treatment. Gallium-67 scans were done in 16 patients for monitoring response to treatment in the bone lesions. RESULTS: Gallium-67 studies diagnosed bone lesions in 19 of the 20 patients. Technetium-99m-MDP detected bone lesions in all patients investigated. In four patients, uptake by Ga-67 was more intense than 99mTc-MDP and in another four patients 99mTc-MDP uptake was more evident. Gallium-67, however, was useful in detecting other regions of involvement in 18 of the 19 patients with soft-tissue lymphoma lesions. Gallium-67 scintigraphy also correctly monitored bone response to treatment in all but one of the 16 patients who had 67Ga scintigraphy after completing therapy. CONCLUSION: Gallium-67 uptake by lymphoma involving the bone can be used to monitor osseous response to treatment.

Full dose CHOP chemotherapy in elderly patients with non-Hodgkin's lymphoma.

Twenty-eight previously untreated elderly patients (median age 73 years, range 65-88) with aggressive non-Hodgkin's lymphoma were treated with full-dose CHOP chemotherapy between 1989 and 1992. The median of the average relative dose intensity (ARDI) was calculated for the initial cycles needed to achieve a maximal response or to determine progression of disease (1-6 cycles, median 4), as well as for the whole treatment course. For patients aged 65-74, both ARDIs were 0.89. A comparable group of 36 elderly patients who received reduced doses of CHOP from the start, served as a historical control. There was an increase of 11% and 29% in the ARDIs of the full-dose CHOP as compared with the reduced CHOP, in the initial cycles and for the whole treatment course respectively. Grade III-IV leukopenia was the main toxicity observed in 57% of the patients, and 7 patients were hospitalized for fever and leukopenia. There was no treatment-related death. It is concluded that CHOP chemotherapy without initial dose reduction is feasible in patients aged 65-74 years, resulting in high actual dose intensity with a reasonable degree of toxicity.

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 patient's 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.

Total skin electron irradiation: efficacy in early mycosis fungoides.

The rare, indolent, but lethal malignancy, mycosis fungoides (MF), is amenable to durable remissions if treated topically at an early stage with nitrogen mustard, PUVA, or radiotherapy. A modification of conventional therapeutic irradiation which utilizes electron beams rather than photons, has been in use since 1951. This method, termed total skin electron irradiation (TSEI), has achieved consistently good CR rates (95-100%) at a variety of centres in the U.S.A., England, France, and Italy, despite troublesome differences in staging systems. In northern Israel we have treated 37 MF patients with TSEI during the past 13 years. All 21 of our early stage patients achieved CR, which is no longer regarded as an unusual result. However, most workers in the field acknowledge that issues of optimal dosing and curative potency remain unresolved.

Stage I-II low grade non-Hodgkin's lymphoma: prognostic factors and treatment results.

48 patients with stage I-II low-grade non-Hodgkin's lymphoma were treated by radiation and/or chemotherapy between 1970 and 1986. The histologic types were diffuse lymphocytic well differentiated, eleven patients; nodular lymphocytic poorly differentiated, 28 patients; nodular mixed, nine patients. Complete remission was obtained in 45 patients (94%). Overall survival was 83% and 68% at five and ten years, respectively. Five and ten-year relapse-free survival of complete responders was 71% and 57%, respectively. Univariate analysis of potential prognosticators showed the following to significantly increase the survival rate: one or two sites of disease (p less than 0.01), stage I (p less than 0.02), age less than 65 years (p less than 0.02), complete excision of tumor mass (p less than 0.03), and the use of radiotherapy (p less than 0.02). The extent of radiotherapy field did not affect survival. Multivariate analysis by the stepwise proportional hazards model of Cox showed that the use of radiotherapy was the factor which significantly produced better survival figures (p less than 0.03). It is concluded that two thirds of stage I-II low-grade lymphoma patients are potentially curable; radiotherapy plays a major role in the management.

[Spermatocytic seminoma of the testis].

During 1968-1988, 6 patients with Stage I spermatocytic seminoma were registered at this oncology center. They represent 7% of a total of 83 patients referred for testicular seminoma (mean age 41 years, range 30-75). All 6 underwent high inguinal orchiectomy and 5 received postoperative radiotherapy. 1 refused any postoperative treatment. In a mean follow-up of 64 months (range 25-204), 4 patients were alive with no evidence of disease, 1 had died of ischemic heart disease without evidence of recurrence of the seminoma, and 1 was lost to follow-up after no evidence of disease was found 90 months after radiotherapy. In the light of our experience and reports in the literature, spermatocytic seminoma has a very good prognosis, although metastatic potential cannot be ruled out. Decision as to treatment should be based mainly on the stage of the disease.

A simple method for determining breast and chest wall thickness.

When planning radiotherapy for primary breast cancer, it is essential to determine the thickness of the chest wall in mastectomized patients and of the intact breast in patients undergoing conservation therapy. A simple method, based on the use of the simulator, to determine breast and chest wall thickness is described.