Increased radiosensitivity of normal tissue fibroblasts in patients with acquired immunodeficiency syndrome (AIDS) and with Kaposi's sarcoma.

Fibroblasts cultured from skin biopsies of patients with AIDS and Kaposi's sarcoma were found to be more radiosensitive than fibroblasts from non-HIV-infected-sources. This supports clinical observations of overt sensitivity to radiotherapy in some AIDS patients with Kaposi's sarcoma.

Primary central nervous system lymphoma in AIDS. Results of radiation therapy.

Primary central nervous system (CNS) lymphoma is one of the clinical presentations of the acquired immune deficiency syndrome (AIDS). Ten patients had biopsy-proven high-grade lymphomas that were confirmed by further staging as limited to the CNS. All ten patients received cranial irradiation (total dose, 2200 to 5000 cGy). Six patients demonstrated complete response (CR) of the intracranial masses at the time of repeat computed tomography (CT) scan, whereas one attained a partial response (PR). Two of the CR patients died of multiple opportunistic infections, two experienced relapse of lymphoma, and died at 7 and 16 months from diagnosis, and two were alive without evidence of disease at 8 and 14 months from diagnosis. The median survival of the whole group was 5.5 months (range, 2 to 16 months). Patients with AIDS-related primary CNS lymphoma may respond to radiation treatment; however, response duration is usually short, and survival is influenced by refractory disease or systemic opportunistic infections.

Radiation therapy for acquired immunodeficiency syndrome-related Kaposi's sarcoma.

Twenty-four patients with acquired immunodeficiency syndrome (AIDS) received 80 courses of radiation therapy for Kaposi's sarcoma (KS). Pain and other symptoms due to mass effects were well controlled, but KS lesions often persisted in irradiated sites. Acute radiation toxicity to doses of approximately 2,000 cGy in ten fractions to the oral cavity and/or the foot were significant and may limit the dose and the efficacy of radiotherapy in patients with the epidemic form of KS.

Magnetic resonance imaging of bone after radiation.

Magnetic resonance imaging (MRI) was performed in 22 patients at various times (0-3) years) following radiation therapy to the spine. T1 and T2 weighted images were obtained at 0.5 Tesla. Increased signal was seen after 800-6000 rads (8-60 Gy). Marrow effects corresponded to radiation ports. Recurrent tumor was clearly separated from fatty replacement. This was much better seen on T1 weighted images. Five patients that had MRI during their course of radiotherapy (XRT) did not have increased signal on T1 images of the bone marrow. The earliest fatty marrow change was seen nine days following completion of 3000 rads (30 Gy) XRT over one month's duration. One patient who received 800 rads (8 Gy) to the upper thoracic spine for eosinophilic granuloma had no radiation effects on MRI when imaged 16 days following completion of XRT given over five days. Fatty marrow change was seen in this patient on MRI six months later. MRI was particularly useful in defining the extent of prior radiation effects when repeat therapy was needed.

Treatment of carcinoma of the skin with bone and/or cartilage involvement.

From 1956 to 1978, 23 patients with stage T4 carcinoma of the skin of the head and neck were treated with radiotherapy (RT). There were nine patients with cancer of the skin of the nose, eight with tumors of the pinna, and six with lesions of the eyelids. Basal cell carcinoma (BCC) was seen in 61%, squamous cell carcinoma (SCC) in 26%, and 13% of patients had tumors with BCC and SCC features. The majority of patients had large tumors. Less than one-third of patients had smaller lesions, whereas three patients had intermediate-size tumors (greater than 2 cm to less than or equal to 5 cm). Of the 23 patients treated, nine had prior surgical therapy and recurrent or persistent tumor. The remaining 14 patients had no prior therapy. RT was given up to an average total dose of 55 Gy. The 5-year actuarial tumor control rate was 80%. Of the 23 patients treated, four had recurrent tumors. There were no recurrences among the 14 BCC patients, whereas there were four recurrences among the nine SCC and mixed histology patients. Of the four patients who had tumor recurrence, one was salvaged by subsequent radical surgery and three died of their tumor. No serious complications were observed in this group of 23 patients. There was no cartilage, bone, or soft-tissue necrosis noted. RT is a good treatment option and it may be treatment of choice in patients with BCC and SCC of the skin with cartilage or bone involvement. It provides an excellent chance of tumor control, good cosmesis, preservation of function, and a low incidence of complications.

Solitary plasmacytoma of bone: treatment, progression, and survival.

Twenty patients with solitary plasmacytoma of bone were treated by radiation therapy. Local control was achieved in 19 and most patients developed systemic myeloma. To evaluate disease progression, 65 patients, including 45 from published series, were analyzed. Younger patients seemed less likely to progress (P = .06), but other clinical characteristics including site of involvement and paraprotein status did not influence progression. After dissemination, patients had a clinical course similar to patients with stage I myeloma, with a median survival of 47 months. Overall, patients with solitary plasmacytoma of bone had an indolent course of disease, with a median survival of 10.7 years and a 5-, 10-, and 20-year survival of 75%, 52%, and 37%, respectively.

Treatment results and patterns of failure in 646 patients with carcinoma of the eyelids, pinna, and nose.

From 1956 to 1978, 646 patients were treated with radiotherapy for carcinoma of the nose (350 patients, 54 percent), eyelids (159 patients, 25 percent), pinna (93 patients, 14 percent), and skin adjacent to the lip (44 patients, 7 percent). The histologic distribution was 72 percent basal cell carcinoma, 18 percent squamous cell carcinoma, and 10 percent mixed basal and squamous cell features. Tumors less than 2 cm in diameter were found in 602 patients (93 percent), whereas 44 patients (7 percent) had larger tumors. Tumor involvement of cartilage and bone was seen in 23 patients at the time of diagnosis. The 5, 10, and 20 year control rates were 99 percent, 98 percent, and 98 percent, respectively, for 502 tumors less than 2 cm in diameter. This compared favorably with control rates of 92 percent at 5 years and 79 percent at 10 years for tumors from 2 to 5 cm in diameter and 60 percent at 5 years and 53 percent at 8 years for 12 patients with massive tumors (p less than 0.0001). The histologic characteristics of the lesion had a strong influence on tumor control (p less than 0.02). Of the patients with cartilage or bone invasion, tumor was controlled in 19 (83 percent). Of these 19 patients, 11 had no evidence of disease for 3 years or more. Of all 646 patients treated, failure was seen in 60 (9 percent). It correlated well with the size of the lesion, being 7 percent for tumors of less than 2 cm and 50 percent for tumors of greater than 5 cm. Of the 60 patients in whom treatment failed, 48 (80 percent) had prior definitive therapy. Radiotherapy was an efficient modality to control operative failures; however, it was not as efficient at control in patients in whom previous radiotherapy failed. Operation was the treatment of choice to salvage patients in whom radiotherapy failed. Of the patients in whom retreatment failed, 10 were known to have died from skin cancer, and an additional 6 patients were presumed to have died from the cancer. This study has demonstrated a good control rate and good cosmetic results for small tumors of the eyelids, pinna, and nose. In addition, a good control rate was obtained in patients with cartilage and bone involvement. Treatment of massive tumors should involve planned operative resection with adjuvant radiotherapy.

Neurologic dysfunction in patients treated for small cell carcinoma of the lung: a clinical and radiological study.

The neurologic dysfunction in 7 patients treated for small cell carcinoma (SCC) of the lung by combination chemotherapy and prophylactic brain irradiation was evaluated. The disease appeared to be a diffuse encephalopathy frequently affecting the higher cortical functions. Five out of seven patients had progressive dysfunction leading to death in 1 to 26 months; one patient had stabilization of symptoms followed by death in 21 months, probably from the neurologic disease as well as SCC; one patient's symptoms improved. The clinical course of the neurologic disorder seemed different from the known reactions to brain irradiation and from the other neurologic syndromes associated with lung cancer. The relative contributions of cranial irradiation and treatment with chemotherapeutic agents in producing the neurotoxicity are not known. Computed tomographic (CT) brain scans done after the onset of symptoms did not show any focal signs or necrosis. However, there was a suggestion of progressive increase in intracranial fluid volume on the scans. The incidence of the disorder, 10.2% among a group of 49 patients, suggests the need for prospective studies to evaluate the problem.

Doxorubicin cardiac toxicity manifesting seven years after treatment. Case report and review.

This report describes a patient treated for lymphoma who had development of doxorubicin (Adriamycin) cardiotoxicity proved by endomyocardial biopsy seven years after treatment. Doxorubicin cardiotoxicity is reviewed with emphasis on the implications of the long latency period for anthracycline cardiotoxicity in patients treated with this widely used antineoplastic agent.

Chemotherapy of small-cell carcinoma of lung: a randomized comparison of alternating and sequential combination chemotherapy programs.

One hundred forty-seven eligible patients with small-cell carcinoma of the lung (SCCL) have been randomized to receive alternating (A) or sequential (S) combination chemotherapy. Initial treatment was with three cycles of VAM (A) or two cycles of POCC (S). VAM consists of VP16-213 200 mg/m2 intravenously (IV) day 1, Adriamycin (Adria Laboratories, Columbus, Ohio) 50 mg/m2 IV day 1, and methotrexate 30 mg/m2 IV day 1 repeated at 21-day intervals. POCC consists of cyclophosphamide 600 mg/m2 IV days 1 and 8, vincristine 1.5 mg/m2 (maximum, 2 mg) IV days 1 and 8, CCNU 60 mg/m2 po day 1, and procarbazine 100 mg/m2 po days 2 through 15. After initial treatment, all patients received whole brain radiation therapy (3,000 rad/10 fractions/2 wk). Patients with limited disease in addition received irradiation encompassing the tumor, hilar, mediastinal, and supraclavicular regions (5,000 rad/25 fractions/5 wk). After radiation, patients on arm A received POCC alternating with VAM; patients on arm S received POCC until progression when they were to be treated with VAM. The alternating arm was superior with respect to rate of complete remission (CR), median disease-free survival (MDFS), and median survival (MS). The advantage of alternating therapy was not as clearly demonstrated in the limited disease groups when interposition of involved field radiation delayed the initiation of the alternating schedule. In limited disease alone, comparing arm A with arm S, no statistically significant differences were noted. The CR rate was 42% v 54%, MDFS was 14 v 10 months, and MS was 16 v 10 months. In extensive disease, the CR rate was 44% v 20% (P = .03), MDFS was 6 v 4 months (P = .003), and MS was 10 v 7 months (P = .001). Improved treatment outcome in SCCL is achieved when combination chemotherapy regimens of similar effectiveness are administered in an alternating rather than sequential schedule.

Increased incidence of acute nonlymphocytic leukemia following therapy in patients with small cell carcinoma of the lung.

A group of 158 patients with small cell carcinoma of the lung were followed for 174.5 person-years of observation to determine the risk of acute leukemia. Three cases of acute nonlymphocytic leukemia were observed at 2.3, 2.7, and 3.0 years. The relative risk of developing leukemia was 316 (95% confidence limit, 76-818) and the actuarial risk was 25% +/- 13% at 3.1 years. The relative risk for leukemia was significantly increased in these patients (p less than 0.0001).

Extramedullary lesions in non-lymphocytic leukemia: results of radiation therapy.

Fifty-four courses of radiotherapy were given to 33 patients with symptomatic extramedullary involvement by non-lymphocytic leukemia. Among them were 23 cases of granulocytic sarcoma. Analysis of the treatment response showed that age, hematopathologic type and quality of irradiation did not influence the radiation response. However, a dose response relationship could be demonstrated with a statistically significant difference in response among the four groups of patients treated to total doses of less than 1000 rad, 1000-1999 rad, 2000-2999 rad, and greater than or equal to 3000 rad (p = 0.003). We suggest irradiating all extramedullary lesions to at least 1100 ret.

Diagnostic accuracies of clinical studies in patients with small cell carcinoma of the lung.

The diagnostic accuracy of clinical studies done in 38 patients with small cell carcinoma of the lung was analyzed by comparing the test results to autopsy findings. The chest radiograph was accurate in 31 of 38 patients (82%). The accuracy of the chest radiograph was higher in evaluating the lung parenchyma and mediastinum than in evaluating the hilum and pleura. Computerized tomographic brain scan was accurate in 11 of 12 patients. However, all the diagnostic studies used for assessing the liver, including physical examination, serum liver enzyme and bilirubin measurements, and radionuclide liver scan, were only moderately accurate. More accurate studies for detecting liver metastasis in patients with small cell carcinoma are needed.

Patterns of failure in small cell carcinoma of the lung.

The initial sites and frequencies of disease progression in 97 patients with small cell carcinoma of the lung treated in a Northern California Oncology protocol were analyzed. Among the extensive disease complete responders (25 patients), the chest was the most frequent initial relapse site (18 patients), followed by the liver (nine patients) and bone (six patients). For those patients who had a partial or no response to treatment, the chest was the most frequent site of persistent disease and the majority progressed in the chest initially. The addition of chest irradiation (5000 rad/5 weeks) to patients with limited disease significantly reduced the incidence of relapse (25%) and prolonged the disease-free interval in the chest in the complete responders, but did not affect the failure pattern in partial and nonresponders. All patients received prophylactic cranial irradiation and three limited disease patients (10%) and three extensive disease patients (4%) progressed in the brain.

Non-Hodgkin's lymphoma presenting as thyroid enlargement.

From 1969 to 1978, 11 patients with non-Hodgkin's lymphoma presenting as thyroid enlargement were evaluated and treated in the Division of Radiation Therapy at Stanford University Hospital. All patients were staged with lymphangiogram and bone marrow biopsy. Eight patients had Stage I-II disease and three patients had Stage III-IV disease. The histologic pattern of the biopsies was diffuse in nine cases, and eight cases were classified as histiocytic lymphoma. All eight patients with Stage I or II disease were treated with irradiation. There is an 83.3% survival at three years and a 75% relapse-free survival at two years. No instance of local recurrence was observed in this group of patients. The three patients with Stage III or IV disease were treated by either irradiation or chemotherapy. Two relapsed within one year and died with disease; the third remained free of disease for nine years before relapse and died with disease six months later. High dose regional irradiation is the recommended treatment for patients with Stage I-II lymphoma of the thyroid.