Acute and long-term effects on limb function of combined modality limb sparing therapy for extremity soft tissue sarcoma.

A retrospective review is presented on 145 patients who underwent limb-sparing surgery and radiation therapy (with or without adjuvant chemotherapy) for their primary soft tissue sarcomas of the extremities on protocol between 1975 and 1986. The focus on our analysis was the acute and long term toxicity of treatment on limb function. The most common acute complication was skin reaction, occurring in 52 patients (36%). Long term (occurring after more than 1 year following all treatment) treatment complications in the extremity were as follows: bone fracture = 6%; contracture = 20%; pain requiring narcotics = 7%; edema greater than 2+ = 19%; moderate to severe decrease in range of motion = 32%; moderate to severe decrease in manual muscle strength = 20%; orthotic device required = 9%; cane or crutch required = 7%; chronic infection = 9%; and tissue induration = 57%. Three amputations for treatment complications were required. Inclusion of more than 50% of the joint in the radiation portal was associated with a higher frequency of contracture. High nominal standard dose (greater than 1760 rets, greater than 63 Gy at 1.8 Gy per fraction) resulted in more painful limbs as well as limbs with increased edema, decreased manual muscle strength, decreased range of motion, and skin telangiectasias. Edema was more often noted in patients with a longer radiation portal (greater than 35 cm), as was tissue induration. Chronic ulcer or infection was more frequently seen in patients with lower extremity tumors and when more than 75% of the extremity diameter was irradiated. Although chemotherapy given concurrent with radiation therapy was associated with a higher number of acute skin reactions, this did not appear to translate into increased long term morbidity. The percentage of patients ambulating without assistive devices and with mild or no pain was 84%. Careful attention to the techniques of radiation therapy may have a significant impact on minimizing acute and long term complications of limb sparing treatment for extremity soft tissue sarcoma.

A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides.

Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.

Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience.

CLM developed in 60 of 526 patients (11%) with SCLC seen at the NCI between August 1969 and June 1980. Life table analysis revealed an overall 25% risk of CLM at 3 years. CLM was diagnosed during all phases of the patients' clinical course, but the majority (83%) were cases diagnosed at the time of progressive systemic disease. Univariate log rank analysis indicated that pretreatment factors associated with the development of CLM included: involvement of the brain, spinal cord, bone marrow, liver or bone; extensive disease; and male sex. Patients who did not obtain a complete response to systemic therapy were at greater risk of developing CLM than complete responders. Multivariate analysis of these factors indicated that liver metastases were most strongly associated with the time to development of CLM, followed in order of importance by bone and CNS metastases. Patients usually presented with signs and symptoms reflecting involvement of multiple areas of the neuraxis including the cerebrum, cranial nerves and spinal cord; 51 of the 60 patients had intracerebral metastases and 27 had spinal cord lesions during their clinical course. Autopsy features including focal or diffuse involvement of the leptomeninges with infiltration of the Virchow-Robin spaces were similar to meningeal lymphoma and leukemia, except that CLM was rarely the sole manifestation of CNS tumor. Median survival following the diagnosis of CLM was 7 weeks. However, most deaths were attributed to systemic disease, and treatment with intrathecal chemotherapy and irradiation often provided palliation. With the increased awareness of this complication, an antemortem diagnosis increased from 39% prior to 1977, to 88% of patients after 1977.

Combined modality therapy of Hodgkin's disease: a report on the Stanford Trials.

A total of 440 previously untreated patients with Hodgkin's disease have been treated on randomized clinical trials at Stanford University, testing the value of combined modality therapy. A group of 244 patients with stages I, II and III were treated between 1968 with radiotherapy alone or combined with adjuvant MOPP chemotherapy. The adjuvant MOPP significantly improves the initial freedom from relapse (FFR) duration but improvement in survival is only minimal and not yet significant. The ability to induce a second durable remission after initial treatment failure results in freedom from second relapse rates (FF2dR) which more closely parallel survival figures than FFR. Adjuvant MOPP cannot yet be recommended as a routine adjuvant in the radiation maanagement of Hodgkin's disease. A pilot trial of the role of radiation therapy in the chemotherapy management of stage IV patients does not indicate an advantage of the irradiation. Preliminary analyses of new treatment programs in 163 patients with all stages of disease treated between 1974--1977 indicate improved survival and FFR rates, the majority of patients receiving combined modality therapy. Only three patients have died and nine patients have relapsed during the three year period of these new trials.

Hematologic neoplasia in patients treated for Hodgkin's disease.

We studied 680 patients with Hodgkin's disease, treated at Stanford University Medical Center from July 1, 1968, through December 31, 1975, to determine the risk of development of hematologic neoplasia. Six cases of leukemia occurred in patients in clinical remission, one 7 1/2 years after diagnosis. Two additional cases occurred in patients with active Hodgkin's disease. No cases were seen in 320 patients treated with radiotherapy alone or in 30 treated with chemotherapy alone. A single case of subacute leukemia occurred in a patient treated initially with radiation therapy and colloidal gold. The actuarial probability of development of leukemia at five and seven years is 1.5 and 2.0 per cent for the entire group and 2.9 and 3.9 per cent for the 330 patients treated with combined radiation and chemotherapy. The medium survival after diagnosis is four months, with no patient living beyond six months.

Role of radiation therapy in combination with chemotherapy in extensive oat cell cancer of the lung: a randomized study.

After 3 months of chemotherapy with procarbazine, vincristine, cyclophosphamide, and CCNU, patients with extensive oat cell carcinoma of the lung were randomly allocated to receive 3000 rads of involved-field irradiation and further chemotherapy or to continue with chemotherapy only. In addition, all patients received 3000 rads of prophylactic whole-brain irradiation. The addition of involved-field radiation, as given in this trial, not only failed to improve survival but was unable to alter the pattern of sites of initial relapse. There were no cases of extension to the brain in 31 consecutive patients who received prophylactic whole-brain irradiation. This was in strong contrast to a preceding trial in which six cases of brain extension occurred among 19 patients who did not receive prophylactic whole-brain irradiation.

Combined modality treatment for oat cell carcinoma of the lung: a randomized trial 1,2,3.

Twenty-three patients with oat cell cancer of the lung were randomized to receive chemotherapy with POCC (procarbazine, 100 mg/m2/day orally, Days 1-14; vincristine, 2 mg iv, Days 1 and 8; cyclophosphamide, 600 mg/m2 iv, Days 1 and 8; and CCNU, 60 mg/m2 orally, Day 1) or COM (cyclophosphamide, 2000 mg/m2 iv, Day 1; vincristine, 2 mg iv, Day 1; and methotrexate, 30 mg/m2 iv, Day 15). After two to three cycles of chemotherapy, all patients were to receive radiotherapy to initially involved sites and then have chemotherapy continued. Patients treated with POCC had a median survival of 14 months vs 10 months for those treated with COM (P = 0.055). Eight of 15 first sites of relapse were intrathoracic and five of these eight had received radiotherapy to that site. Six central nervous system (CNS) failures were evenly divided between the two chemotherapy programs. Thus, the CNS penetration of procarbazine and CCNU in the POCC combination did not prevent CNS relapse. All future patients will receive prophylactic brain radiotherapy.

Bladder cancer: results of radiation therapy in 384 patients.

Between 1957 and 1972, 384 patients with bladder cancers were treated initially with megavoltage radiation therapy. Actuarial five-year survival ranged from 35 to 42% for Stages A and B1 tumors, and was 35, 22 and 7%, respectively, for Stages B2, C and D carcinomas. Approximately 30-40% of deeply invasive tumors confined to the bladder can be controlled with radiation therapy alone, directed solely to the bladder itself.