Palliation of pelvic and head and neck cancer with paclitaxel and a novel radiotherapy regimen.

PURPOSE: In patients with advanced malignancies, local palliation is undertaken if the patient is not a candidate for aggressive intervention. We developed a prospective study using the same radiotherapy schedule as the Radiation Therapy Oncology Group (RTOG) 85-02 with the addition of the radiosensitizer paclitaxel to evaluate its effect on the tumor response rate, palliation of symptoms, and toxicity. METHODS: Twenty subjects with advanced pelvic or head and neck cancer were enrolled after signing an informed consent. Paclitaxel 60 mg/m(2) was administered 1 hour prior to the first day of each radiation cycle. Radiation therapy was delivered in 2 daily fractions of 3.7 Gy for 2 days every 3 weeks for three cycles (total dose 44.4 Gy). This radiotherapy schedule is referred to as "Quad Shot'' at our institution. RESULTS: Nineteen patients had adequate follow-up data and were considered evaluable. Five patients had a complete response (CR) and 13 patients had a partial response (PR) with symptomatic improvement for a response rate of 94.7%. One patient only had a minimal response. Seventeen patients (89.5%) had palliation of their presenting symptom(s). Eight patients had effective palliative benefit lasting more than 6 months. Two patients experienced a grade 2 allergic reaction to paclitaxel, one of them received the last cycle of treatment with cisplatin obtaining a CR. No late toxicities have been observed. CONCLUSIONS: This palliative schedule has been shown to provide good tumor response and palliation of symptoms. The toxicity profile remains low with the addition of paclitaxel. Further investigation is warranted in a larger trial. Palliation of symptoms resulted in improved quality of life for this group of patients.

Predicting patients at low probability of requiring postmastectomy radiation therapy.

BACKGROUND: Postmastectomy radiation therapy (PMRT) is recommended for patients with four or more positive lymph nodes (LN+). Given the ramifications of PMRT for immediate reconstruction, we sought to create a model using preoperative and intraoperative factors to predict which patients with a positive sentinel lymph node will have less than four LN+. METHODS: The database from a prospective multicenter study of 4,131 patients was used for this analysis. Patients with one to three positive sentinel lymph nodes (SLN) and tumors < 5 cm (n = 1,133) in size were randomly divided into a training set (n = 580) and a test set (n = 553). Multivariate logistic regression was used on the training set to create a prediction rule that was subsequently validated in the test set. RESULTS: Median patient age was 57 (range, 27-100) years, and median tumor size was 2.0 (range, 0.2-4.8) cm. In the training set, factors associated with having four or more LN+ on multivariate analysis were: tumor size [odds ratio (OR) = 2.087; 95% confidence interval (CI): 1.307-3.333, P = 0.002), number of positive SLN (P < 0.0005), and proportion of positive SLN (OR = 3.602; 95% CI: 2.100-6.179, P < 0.005). A predictive model was established with a point assigned to each positive SLN, T2 (vs. T1), and if proportion of positive SLN was > 50%, for a maximum of five points. In both the training and test sets, patients with one point had a low probability of having four or more LN+ (3.8% and 3.3%, respectively). CONCLUSION: Tumor size, number of positive SLN, and the proportion of positive SLN influence whether patients will have four or more LN+. A simple model can predict the probability of requiring PMRT.

The relationship of radiation pneumonitis to treated lung volume in breast conservation therapy.

Breast conservation therapy has become a common modality for therapy of early stage breast cancer. Most studies of primary lung irradiation correlate the risk of pneumonitis with the volume of lung treated. It is proposed that the lung volume treated during tangential radiation of the intact breast may be calculated from a measurement of the central lung distance. Central lung distance is the distance from the chest wall to the edge of the field at the central axis. This study examines whether the incidence of radiation pneumonitis indeed correlates with the lung volume treated as calculated from a measurement of the central lung distance. From January 1, 1985, through December 31, 1998, 353 patients were treated with breast conservation therapy at the University of Louisville. The charts were reviewed for any evidence of clinically significant radiation pneumonitis. The treatment films were obtained and the central lung distance ascertained. Four cases of radiation pneumonitis were identified. Three of these occurred after tangential radiation and one occurred in a retreatment field after bone marrow transplant. The overall rate of radiation pneumonitis was 1.2%. A central lung distance of less than 3 cm was found in 78.3% of patients and 21.7% had a central lung distance of three or greater. There was no correlation between central lung distance and the risk of radiation pneumonitis. Breast conservation therapy is a well-tolerated modality for treatment of early stage breast cancer. The incidence of radiation pneumonitis is very low and is usually associated with other factors in addition to the tangential field lung volume.

Hodgkin's lymphoma in adults--clinical features.

One hundred (100) patients were treated in the Department of Radiation Oncology, James Graham Brown Cancer Center, University of Louisville School of Medicine, from 1980-1994. All patients were evaluated and staged according to the accepted guidelines at the treatment times. All patients were followed on a strict follow-up schedule for the outcome of treatment including late effects. The age range was 18 years-77 years. The age groupings are described in Table 1. Eighty-one percent (81%) of the patients were 40 years of age or younger. Nineteen percent (19%) of the patients were older and this was similar to the reported bimodal pattern in Hodgkin's disease. Fifty-eight percent (58%) of the patients were female and the rest were male. Eighty-eight percent (88%) of the patients were Caucasian as depicted in Table 2. Majority of the patients (64) presented with mass in the neck. Some of the patients presented with one or more symptoms and signs. The details of the presentation features are shown in Table 3. Thirty-one percent (31%) of the patients presented with one or more of the 'B' symptoms as described by Cotswolds Staging Classification for Hodgkin's Disease. These include fever (temperature >38 degrees C), drenching night sweats, and unexplained loss of >10% body weight within the preceding 6 months. Appropriate staging included complete physical examination, blood studies, and imaging studies such as plain chest x-rays, lymphangiograms, CT scans, gallium scans, etc. Forty-eight percent (48%) of the patients had staging laparotomy with lymph node sampling, splenectomy, and liver biopsies. The staging was done according to Ann Arbor Staging Classification. Forty-four percent (44%) of the patients were in Stage IIA group and the rest are shown in Table 4. Of the sites of involvement, neck (82 patients) and mediastinum (79 patients) were the common sites. Other sites of involvement are described in Table 5. Many patients had more than one site of involvement. Thirty-three percent (33%) of the patients had bulky mediastinal disease. This was defined based on the ratio of the width of the lesion to the transverse diameter of the chest. The most common histological subtype was nodular sclerosing (73%). This would explain the gender variation in this group of patients. The histological classification was done according to the Rye Classification (Table 6).

Pediatric Hodgkin's disease.

Thirty-two patients were treated in this Department from 1981-1992. The median age was 14 years (range 4 years to 17 years). There are 6 patients (19%) below the age of 10 years, 16 patients (50%) between 11 years to 15 years, and 10 patients (31%) above 16 years. Twenty-three patients (72%) are male and 9 patients (28%) are female. Thirty-one patients (97%) are white, and 1 patient (3%) is Afro-American. The stages of the patients are: Stage I--7 patients, Stage II--12 patients, Stage III--9 patients, and Stage IV--4 patients. Twenty-one patients (66%) in the early period of the study were staged surgically by staging laparotomy. The most common sites are: neck (84%), mediastinum (66%), and para-aortic lymph nodes (22%). Twenty-five patients (78%) have nodular sclerosing type, 5 patients (16%) have mixed cellularity, and 2 patients (6%) have lymphocytic predominant type. Eight patients (25%) were treated with radiation alone and 24 patients (75%) were treated with a combination of chemotherapy and radiation. Of the radiation group, 5 patients were treated with mantle field; 2 patients with mantle, para-aortic node and splenic pedicles; and 1 patient with mini-mantle field. The treatment was given with 4 or 6 mv photon, and the median dose was 36 Gray (range 32-40 Gy). Of the combination group, 11 patients were treated with ABVD (doxorubicin + bleomycin + vinbastine + dacarbazine), 10 patients with ABVD/MOPP (MOPP: mechlorethamine + vincristine + procarbazine + prednisone) and 3 patients with MOPP alone. The median irradiation dose in the combination group was 25 Gy (range 21 Gy-36 Gy). All the patients in this group were treated to the involved site with custom blocks. Three patients were lost for follow-up because of transfers out-of-state and could not be located. All patients in Stages I and II are alive without any evidence of disease at the last follow-up. One patient with Stage III disease developed a second cancer (PNET: primitive neuroectodermal tumor) 111 months after combination treatment and has died. One Stage IV patient has died with Hodgkin's disease 28 months after treatment with combination therapy. All other patients are followed closely along with the primary physicians and consultants.

Matched-control retrospective study of the acute and late complications in patients with collagen vascular diseases treated with radiation therapy.

BACKGROUND: Controversy surrounds the potential complication rate of patients with collagen vascular diseases (CVD) after radiation. We assess the acute and late complications (based on Radiation Therapy Oncology Group criteria) by a matched-control retrospective study. PATIRNTS/METHODS: The charts of 12,000 patients treated with radiation therapy at the University of Louisville from 1982 to 2001 were reviewed for CVD. A total of 38 patients with documented CVD were compared with a matched-control group of 38 patients without CVD. Median follow-up for patients with CVD was 35 months. The patients were matched on the basis of site treated, age, dose, date of treatment, sex, treatment goal, follow-up, tumor site and histology, therapeutic technique, and general treatment method. The patients with CVD included 21 patients with systemic lupus erythematosus (55%), two with scleroderma (5%), four with Raynaud's phenomena (11%), three with fibromyalgia (8%), three with polymyalgia rheumatica (8%), three with Sjögren's syndrome (8%), and two with polymyositis-dermatomyositis (5%). Twenty-nine patients received curative doses, and nine patients received palliative doses. RESULTS: No difference was observed in the incidence of acute or late complications between the two groups. For CVD and matched-control patients receiving curative doses, the incidence of acute reaction for grade II was 49% versus 58% and for grade III was 7% versus 7%, respectively. The incidence of late reactions for patients with CVD and the matched control patients for grade I was 3% versus 7%, for grade II was 7% versus 3%, and for grade III was 7% versus 7%, respectively. The patients treated with palliation had a similar incidence of acute reaction in the CVD and the matched-control groups. No patients in the CVD or matched-control group had fatal complications. Only patients with scleroderma had a slight increase in acute and late complications. CONCLUSION: This is the largest matched-control study thus far in the literature. In the comparison between the patients with CVD and the matched-control patients, there was no significant difference in the incidence of acute or late complication. However, there was a higher incidence of radiation complications in patients with scleroderma. Importantly, no fatal complication was noted in any of the patients with CVD.

A phase III comparison of radiation therapy with or without recombinant beta-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04).

PURPOSE: The results of Phase I/II data testing beta-interferon with radiation therapy in a non-small-cell lung cancer population were promising. Based on these data, the Radiation Therapy Oncology Group (RTOG) initiated a Phase III trial to test the efficacy of beta-interferon in poor-risk patients with Stages IIIA and IIIB non-small-cell lung carcinoma. METHODS: Between September 1994 and March 1998, 123 patients were accrued to this trial. Enrolled patients were not eligible for other chemoradiation studies within the RTOG. Eligibility criteria included histologically confirmed Stage IIIA or IIIB non-small-cell lung cancer (according to American Joint Committee on Cancer) considered clinically inoperable or unresectable at the time of surgery. Patients were required to have a Karnofsky performance status 50-70 or >70 and at least 5% weight loss over the preceding 3 months. Betaseron (recombinant human interferon beta(ser), rHuIFN-beta(ser),) was the chosen preparation of beta-interferon. The patients randomized to the investigational arm received 16 x 10(6) IU of Betaseron by i.v. bolus given 3 days a week (Monday-Wednesday) on Weeks 1, 3, and 5. The Betaseron was given 30 minutes before radiation therapy for a total of nine doses. Irradiation was delivered at 2 Gy per fraction, 5 days a week, for a total of 60 Gy over 6 weeks and was identical for both arms. The primary end point of the trial was overall survival with local control as a secondary end point. Toxicities occurring within 90 days of therapy completion were defined as acute. RESULTS: The median follow-up was 4 years (range: 2.5-6 years) for surviving patients. Seventy-six percent of all patients completed beta-interferon. Toxicity was the primary reason for noncompliance. Radiotherapy (RT) compliance was excellent in the RT-alone arm, with 94% completing therapy, compared to 82% in the beta-interferon arm (p = 0.0475). Grade 3 and 4 acute toxicities were higher on the beta-interferon arm (p = 0.0249). Grade 3 and 4 acute toxicities were primarily related to lung (n = 8) and esophagus (n = 7). No Grade 4 or 5 late toxicities were seen for patients in the radiation-alone arm. However, three patients on the beta-interferon arm experienced Grade 4 toxicity, and one patient died. The 1-year survival rate for the RT-alone arm was 44% with a median survival time of 9.5 months. The 1-year survival on the beta-interferon arm was 42% with a median survival of 10.3 months. There was no statistical difference in survival times (p = 0.66). CONCLUSIONS: This multicenter, controlled Phase III trial failed to confirm the efficacy of Betaseron in patients receiving definitive radiotherapy for locally advanced, nonmetastatic non-small-cell lung cancer. The use of beta-interferon led to greater rates of both acute and late treatment-related toxicity. The RTOG continues to investigate other biologic modifiers that may provide a nontoxic alternative for this poor-risk population.