Kristie J. Paris

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

BACKGROUNDControversy 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. PATIENTS/METHODSThe 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 Raynauds phenomena (11%), three with fibromyalgia (8%), three with polymyalgia rheumatica (8%), three with Sjögrens syndrome (8%), and two with polymyositis-dermatomyositis (5%). Twenty-nine patients received curative doses, and nine patients received palliative doses. RESULTSNo 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. CONCLUSIONThis 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 β-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.

Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies.

PURPOSE To assess palliation of advance head and neck malignancies with the use of rapid hyper fractionation studies similar to the RTOG 85-02. MATERIALS AND METHODS 37 patients with 39 lesions were entered into the non-randomized Phase I-II protocol, between 1984 and 1991. Previously untreated malignancies were present in 24 lesions, primary recurrent diseases in six patients, metastasis to the head and neck in five patients and skin primaries in the remaining two cases. At presentation 15 of 37 patients (or 17 of 39 lesions) were in operable due to poor medical status, eight patients were considered technically in operable due to extent of disease, 10 patients had distant metastasis and four patients refused surgery. The protocol uses twice a day fraction (370 cGy per fraction) for 2 consecutive days totalling 1,480 cGy per course. Three courses were given at 3-week intervals for a final tumor dose of 4,440 cGy in twelve fraction over 8-9 weeks. RESULTS Eleven of 39 lesions had complete response; 19 lesions had partial response; 4 lesions had no response; 3 lesions progressed under treatment. Response could not be assessed in two patients. The average survival after completion of therapy was 4.5 months ranging from 2 weeks to 31 months. Palliation was achieved in 33 of 39 lesions. The acute reactions were minimal and no late or long term complications were noted. CONCLUSION The absence of significant complications with reasonable response in the high rate of palliation suggests that this rapid hyper fractionation palliation study should be studied for further evaluation.

Recurrent Chondrosarcoma of the Cranial Base: A Durable Response to Ifosfamide-doxorubicin Chemotherapy

The case of a 46-year old woman with recurrent chondrosarcoma of the cranial base, refractory to neurosurgical intervention and external radiotherapy is reported. She received five cycles of systemic chemotherapy utilizing ifosfamide and doxorubicin which resulted in a durable clinical and radiographic response lasting 52+ months. A review of the management options for recurrent chondrosarcoma of the cranial base is also presented.

The Relationship of Radiation Pneumonitis to Treated Lung Volume in Breast Conservation Therapy

Abstract:  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.

Complications in the use of intra-abdominal 32P for ovarian carcinoma.

From 1982 through 1989, 94 patients at the University of Louisville with ovarian neoplasm had abdominal instillation of 15 mCi chromic 32P as part of their management. The timing of the 32P was immediately postoperative in 55 patients and delayed greater than 24 hr in 39 patients. This is an analysis of factors contributing to gastrointestinal (GI) complications. GI complications were graded according to RTOG guidelines. There was a total of 11 GI complications grade 3 or worse for an overall incidence of 12%. Factors analyzed include timing of 32P delivery, age, stage, number of previous surgeries, use of Hyskon at surgery, addition of external beam radiation, and subsequent use of chemotherapy. There were significantly fewer complications when 32P was given on the same day as surgery than when 32P administration was delayed more than 12 hr following surgery (4% vs 21%), P = 0.007. This difference held significance when adjusted for the number of previous surgeries, use of Hyskon, external beam radiation, and stage. None of the other factors had a significant effect on complication rate. There have been no incidences of contamination even though 32P instillation in the immediate post-operative period had increased risk of contamination due to wound leakage or reoperation. In our experience, the delivery of 32P in the immediate postoperative period resulted in a significant reduction in abdominal complications.

Results of irradiation in patients with high-grade gliomas evaluated by magnetic resonance imaging

Evidence shows that most high-grade gliomas are a diffuse process. Prior studies reported a median survival with surgery and postoperative radiotherapy of 8.6 months for glioblastoma multiforme (GBM) and 36.2 months for anaplastic astrocytoma (AA). Since MRI delineated the glioma better than CT scan, using MRI-based radiotherapy treatment planning allows for more precise treatment volumes. We retrospectively reviewed the records of the first 36 patients with malignant glioma, who had a presurgery MRI-based radiotherapy treatment planning. These patients were diagnosed between January 1986 and February 1991. Minimum follow up was 14 months and median survival was 15.4 months for GBM (7–42 months) and 27.4 months for AA (7–53 months). We feel that the trend for increased median survival in GBM (15.4 vs 8.6 months) is partly due to better definition of the tumor volume by using MRI. Larger studies are needed to confirm this finding.

Pediatric Astrocytomas: The Louisville Experience: 1978–1988

PurposeThe purpose of this study is to retrospectively analyze all pediatric patients with the diagnosis of astrocytoma treated either definitively or postopcratively in our department from 1978 through 1988. Grade, age. T-stage, tumor location, and extent of resection are individually analyzed as prognostic indicators of overall survival. Materials and MethodsPediatric astrocytoma patients (grades I-1V) diagnosed by CT-guided biopsy or surgical resection were assessed. Patients were treated with external beam radiotherapy to involved fields using 4− or 6-MV photons. Daily doses ranged from 1.5 to 2.0 Gy; total doses from 41.4 to 66 Gy. Treatment was given to 17 patients (9 male, 8 female), aged 18 years and younger: 11 patients had low-grade (I & II) astrocytoma with incomplete margins; 3 patients had anaplastic astrocytoma; and 3 patients had glioblastoma multi-forme. ResultsOverall survival at 140 months was 63%. Median follow-up of patients living NED was 69 months, with a range of 39–140 months. Nine of the eleven (82%) low-grade patients survived NED; I of 3 anaplastic patients is NED at 44 months follow-up; 1 died of intercurrent disease at 80 months; the third died of disease at 49 months. All three glioblastomas succumbed to local disease at 9, 15, and 27 months from diagnosis. Univariate analysis showed only grade to be prognostically significant (p < .03) in determining overall survival. ConclusionPostoperative radiotherapy for unresected or partially resected low-grade astrocytomas produces excellent local control. Higher grade astrocytomas require further investigational studies to improve survival and local control. Grade is prognostically significant with respect to overall survival.

Radiation therapy for pituitary adenomas : A retrospective study of the University of Louisville experience

A retrospective analysis of treatment outcome was performed on patients treated with radiation for pituitary adenomas at the University of Louisville from January 1988 to December 1992. The study population included 27 patients. Twenty received radiation as a component of their initial treatment while seven received radiation as part of their treatment for recurrent disease. Nineteen patients were treated with post-operative radiation, and eight were treated with radiation alone. Follow-up interval ranged from 1 month to 109 months, with a median of 28 months. All three patients with stage I disease were controlled with radiation alone (1/3) or combined surgery and postoperative radiation (2/3), whereas six of eight stage II patients had disease control following surgery and postoperative radiation. Both patients with stage III adenomas treated with radiation alone had local control, whereas local control was achieved in six of seven with post-operative radiation. Three of five patients with recurrent disease had local control with radiation alone, whereas both patients undergoing surgery and postoperative radiation had local control. This retrospective analysis supports previous findings that radiation therapy alone or combined with transphenoidal resection is effective in long-term control of pituitary adenomas. It further suggests that immediate radiation therapy may be superior to radiation for surgical or medical failures.

Suppository administration of chemotherapeutic drugs with concomitant radiation for rectal cancer

PURPOSE: Preoperative radiation with combined chemotherapy is effective in shrinking advanced rectal cancer locally and facilitating subsequent surgery. Suppository delivery of 5-fluorouracil is associated with less toxicity and higher rectal tissue concentrations than intravenous administration. This prompted us to evaluate suppository and intravenous administration of 5-fluorouracil and mitomycin C with concomitant radiation to determine associated toxicity. METHODS: Rectal, liver, lymph node, and lung tissue and systemic and portal blood were collected serially from male Sprague Dawley rats to determine drug concentrations following suppository or intravenous delivery of 5-fluorouracil or mitomycin C. Thirty-six animals were randomly assigned to treatment groups and received 5-fluorouracil suppositories, mitomycin C suppositories, or an equivalent intravenous dose of 5-fluorouracil or mitomycin C 30 minutes before radiation therapy. Before and 3, 6, 10, and 15 days following this treatment, blood was collected, colonoscopy was performed, and rectal tissue was harvested for histologic examination. RESULTS: Mitomycin C suppository was significantly less toxic compared with intravenous delivery, and higher rectal tissue concentrations were observed from 10 to 30 minutes (P< 0.05). Compared with intravenous 5-fluorouracil administration and radiation, 5-fluorouracil suppository and radiation resulted in additive myelosuppression at day 6 (P<0.05) with rapid recovery. CONCLUSIONS: 5-Fluorouracil and mitomycin C suppository delivery combined with radiation causes less systemic toxicity and is more effective than intravenous administration.