Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method.

PURPOSE: To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT). METHODS AND MATERIALS: An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone. RESULTS: Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26-83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone. CONCLUSION: In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.

Effects of advanced nursing care on quality of life and cost outcomes of women diagnosed with breast cancer.

PURPOSE/OBJECTIVES: To evaluate quality of life (QOL) and cost outcomes of advanced practice nurses' (APNs') interventions with women diagnosed with breast cancer. DESIGN: Randomized clinical trial. SETTING: Integrated healthcare system in a midwestern suburban community. SAMPLE: 210 women with newly diagnosed breast cancer with an age range of 30-85 years. METHODS: The control group (n = 104) received standard medical care. The intervention group (n = 106) received standard care plus APN interventions based on Brooten's cost-quality model and the Oncology Nursing Society's standards of advanced practice in oncology nursing QOL was measured using the Functional Assessment of Cancer Therapy, Mishel Uncertainty in Illness Scale and Profile of Mood States at seven intervals over two years. Information about costs (charges and reimbursement) was collected through billing systems. MAIN RESEARCH VARIABLES: Uncertainty, mood states, well-being, charges, and reimbursement. FINDINGS: Uncertainty decreased significantly more from baseline in the intervention versus control group at one, three, and six months after diagnosis (p = 0.001, 0.026, and 0.011, respectively), with the strongest effect on subscales of complexity, inconsistency, and unpredictability. Unmarried women and women with no family history of breast cancer benefited from nurse interventions in mood states and well-being. No significant cost differences were found. CONCLUSIONS: APN interventions improved some QOL indicators but did not raise or lower costs. IMPLICATIONS FOR NURSING PRACTICE: The first six months after breast cancer diagnosis is a critical time during which APN interventions can improve QOL outcomes. More research is necessary to define cost-effective interventions.

Purchasing oncology services. Kerr L. White Institute/American Cancer Society Task Force on Purchasing Oncology Services.

BACKGROUND: A multidisciplinary panel representing various stakeholders in the health care delivery and oncology services marketplace was convened to develop specific criteria for healthcare purchasers to consider when evaluating the structures and processes of health plans. These rank ordered criteria also can be used by oncologic service providers and health plan designers as a yardstick for the services they offer. METHODS: A multidisciplinary 31-member Task Force was assembled by the Kerr L. White Institute and the American Cancer Society in March 1997. Task Force members were selected for their ability to offer expert insight as purchasers, suppliers, policymakers, consumers, or stakeholders in the health care marketplace. A preference-weighted majority voting rule was used to identify the three most important recommendations of the 10 that were generated through a modified Delphi technique. To test the practicality of the top three recommendations, leaders of large managed care organizations (MCOs) were surveyed; the results of this survey then were compared with the results of the Task Force survey. RESULTS: The three most important recommendations from the Task Force were that health plans provide access to: 1) comprehensive cancer care, 2) preventive and screening services, and 3) second opinions and treatment options supported by scientific evidence. The difference between the responses of the Task Force and the MCOs was that MCOs placed the highest importance on evidence-based decision-making, with their next three rankings coinciding with those identified by the Task Force. CONCLUSIONS: The value of these summary recommendations will be realized through their use by both purchasers and suppliers to influence the structure and content of the delivery of oncologic services.

Prognostic factors after conservative surgery and radiation therapy for early stage breast cancer.

A retrospective review was conducted of all early-stage breast cancer patients treated with breast-conservation surgery plus radiation therapy (BCS/RT) to determine mortality and recurrence rates and to evaluate prognostic factors for these outcomes. Between 1982 and 1988, 121 patients with stages I and II breast cancer were treated with BCS/RT at our institution. Most of the patients (83%) had re-excision of the initial biopsy site and at final surgical evaluation, only 4 patients had positive margins (3.2%). Median follow-up was 89.7 months. Cox proportional hazards regression models were used to select prognostic factors significant for breast cancer-specific mortality, overall disease recurrence, and local recurrence. Breast cancer survival rates were 92% at 5 years and 83% at 10 years. Prognostic factors predicting breast cancer mortality included positive lymph nodes (relative risk=.9; 95% confidence interval, 1.2,12.2) and a higher grade (relative risk=1.9; 95% confidence interval, 1.1,3.3). For disease recurrence, prognostic factors included positive nodes (relative risk=2.6; 95% confidence interval, 1.2, 5.5), and a negative progesterone-receptor status (relative risk=0.3; 95% confidence interval, 0.2, 0.8). Local recurrence rates were 2.5% at 5 years and 14% at 10 years. No prognostic factors were significant for local recurrence; however, most patients had negative margins after surgery.

Stereotactic radiosurgery in pediatric patients.

Although stereotactic radiosurgery has been studied extensively in adults, the data demonstrating its efficacy in children is limited. Medical records were reviewed to identify the indications for and outcomes of patients treated with this modality. Linear accelerator-based radiosurgery was used to treat 11 recurrent brain tumors and one posterior fossa arteriovenous malformation over 3 years. The mean and median age of those treated was 10 and 8 years, respectively (range 1-20 years). Patients received 700 to 3,000 cGy delivered to the 50-90% isodose line in a single fraction. The mean and median follow-up was 15 and 17 months, respectively. Three of the four children with malignant disease died 6 to 9 months after treatment. One patient died of recurrence outside the treatment field. Another child died of complications related to radiation injury, and the third died of disease progression. All children with low-grade tumors remain alive without complications. Six of eight (75%) children exhibit substantial radiographic reductions in tumor size. The child with a vascular malformation has been followed for 26 months, without hemorrhage and with a radiographically proved decrease in size. Our series suggests that radiosurgery has limited usefulness in malignant disease. Therapeutic response is influenced by lesion size and/or location. Stereotactic radiosurgery appears to be effective in children with low-grade intracranial tumors or arteriovenous malformations. Further experience is required to establish the role and long term side effects of radiosurgery in pediatric patients.

Stereotactic radiosurgery for recurrent malignant gliomas.

PURPOSE: To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas. PATIENTS AND METHODS: We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA). RESULTS: The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury. CONCLUSION: Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.

Neuropsychological effects of cranial radiation: current knowledge and future directions.

Radiation is an invaluable therapeutic tool in the treatment of cancer, with well-established palliative and curative efficacy. As patient survival has improved, attention has focused on long-range treatment side effects. One such adverse effect, neuropsychological impairment, is incompletely understood. Much of the extant research has been directed at childhood leukemia survivors treated with low-dose whole-brain radiation. Less is known about the effects of high-dose focal or whole-brain radiation used in the treatment of brain lesions. This article reviews the scientific literature in this area, with greatest emphasis on methodologically rigorous studies. Research design considerations are discussed. Review findings suggest that low-dose whole-brain radiation (18 to 24 Gy) in children is associated with mild delayed IQ decline, with more substantial deficits occurring in children treated at a young age. A high incidence of learning disabilities and academic failure is observed in this population and may be caused by poor attention and memory rather than low intellectual level. Children who receive higher dose radiation for treatment of brain tumors experience more pronounced cognitive decline. At higher doses, whole-brain radiation, in particular, is linked to deleterious cognitive outcomes. Remarkably little is known about cognitive outcomes in irradiated adults. Preliminary findings indicate that certain cognitive functions, including memory, may be more vulnerable to decline than others. Suggestions for future research are proposed.

The in vitro radiosensitization of human glioblastoma with pentoxifylline.

There is evidence that pentoxifylline may be both a radioprotector of normal tissue and a radiosensitizer of tumor cells. This article reviews this evidence and then describes our own laboratory study to determine whether pentoxifylline is a radiosensitizer of human glioblastoma cells in vitro. Human glioblastoma multiforme cells (SNB19 cell line) were irradiated in vitro with and without pentoxifylline. Regression of the log ratios (quotient of surviving colonies) revealed greater tumor cell kill in the PTX group, and the difference increased as the radiation dose increased (p < 0.01 at the 750 and 1000 cGY doses). Before the hypothesis that PTX is a radiosensitizer of hypoxic tumor cells can be confirmed or denied, it must be determined if the agent also has a separate mechanism of tumoricidal activity. Whereas in vivo models allow the well-documented rheologic, immunologic and oxygen-related effects of PTX to be active simultaneously, the in vitro model described herein excludes the effects of such systemic actions and focuses on mechanisms at the cellular or subcellular level. These data suggest there exists such a mechanism of tumoricidal activity of PTX that has not been previously identified.

Photodynamic therapy for chest wall recurrence in breast cancer.

Photodynamic therapy is the use of a sensitizer (dihematoporphyrin ethers) which is preferentially retained in tumor cells and activated by subsequent light delivery resulting in a selective tumoricidal effect. Between 1986 and 1989, we treated 20 patients with photodynamic therapy for chest wall recurrence of breast cancer. Responses were seen (20% complete response, 45% partial response, 35% no response), but the duration of response was short (average 2.5 months). Complications, in decreasing frequency, included pain, ecchymoses, blistering, ulceration and necrosis in the area of tumor involvement on the chest wall. One patient required skin flap reconstruction for full thickness necrosis. A limitation to this mode of therapy is that the sensitizer currently used is activated by light at a wavelength of 630 nm. This light can penetrate to a tissue depth of only 0.5 to 1.0 cm; thus, deeper disease cannot be treated. Future research must focus on the development of a clinically useful photosensitizer that can be activated by light at longer wavelengths and thereby achieve deeper tissue penetration. This would greatly expand the patient population for which this therapy is useful.

Spontaneous regression of squamous cell lung carcinoma with adrenal metastasis.

A 61-year-old man was found to have squamous cell carcinoma of the left hilum with metastasis to the left adrenal gland documented by needle aspiration. About two years later, the primary tumor is not detectable, and the adrenal gland is of normal size on follow-up computerized tomography. To our knowledge, this is the first documented case of spontaneous regression of squamous cell carcinoma of the lung with adrenal metastasis.

Knee flexion contractures in myelodysplasia.

From 1976 to 1982, 12 children with myelodysplasia had surgery at our institution for knee flexion contractures (21 affected knees). Follow-up was a minimum of 18 months and averaged 47 months. Soft tissue lengthening of the hamstring tendons and release of the posterior capsule with or without femoral osteotomy yielded uniformly excellent results; femoral osteotomy alone produced 40% unsatisfactory results. Based on these data, we no longer recommend osteotomy alone as an effective treatment for fixed knee flexion contractures in children with myelodysplasia.