Importance of dose intensity in neuro-oncology clinical trials: summary report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium.
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Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of primary CNS lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed. (+info)
Small cell lung cancer with a brain metastasis controlled for 5 years: a case report.
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We report a case of small cell lung cancer whose initial presentation was a solitary brain metastasis. On chest radiography the primary tumor was unclear and only detected by bronchofiberscopy. A small single pulmonary metastasis was noted in the right lower lobe. Subtotal resection and external irradiation were applied to the brain tumor and external irradiation was applied to the lung. Concurrently one course of systemic chemotherapy was administered. The tumors in the brain and lung had disappeared by the end of the treatment. The patient has been alive and well for 5 years without recurrence. (+info)
Late effects in long-term survivors of ALL in childhood: experiences from the SPOG late effects study.
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With the use of more intensive regimens including prophylactic CNS treatment, the prognosis of children with ALL has dramatically improved over the last three decades. The aim of this cross-sectional, nationwide study was to comprehensively assess long-term toxicity in ALL survivors, with special attention given to neuropsychological morbidity, and to look for possible differences in cognitive outcome between children having received prophylactic cranial irradiation and those not having received it. Between 1994 and 1996, long-term survivors of ALL were assessed in a multi-center setting according to a standardized protocol which included, besides usual clinical and laboratory investigations, a comprehensive endocrine work-up. Additionally, children having received anthracyclines were checked for possible late cardio-toxicity with echocardiography and ECG. Intellectual performance was evaluated with standardized neuropsychological tests (age-adapted versions of the Wechsler test). One-hundred and fifty patients were eligible for the study. The median age at diagnosis was 5 years and at evaluation 16 years, for a median follow-up of 10 years. Thirty-five patients had cranial irradiation as part of the prophylactic CNS treatment. One-hundred and forty (93%) of the 150 eligible patients were completely evaluated in terms of global long-term toxicity: 117 (83%) long-term survivors had no (n = 61) or only minimal (n = 56) late toxicity; 19 (14%) suffered from moderate impairments; 4 (3%) showed severe somatic or neuropsychological sequelae. Intellectual performance could be assessed in 147 (98%) of the 150 eligible patients. The mean global, verbal and non-verbal IQs (103, 105 and 101 respectively) of the ALL survivors as a group were comparable with those found in the general population. The results of the comparison between children having and those not having received prophylactic cranial irradiation showed: 1) significantly higher scores in chemotherapy-only treated patients, both for the global and the verbal performances; 2) significantly poorer results in specific items of the Wechsler test (short-term verbal memory, arithmetics, concentration/speed of processing) in irradiated children. These findings which show the deleterious role of cranial irradiation correlate well with many other reports found in the literature. However, they could have been influenced by the significantly longer time interval observed between therapy and evaluation in our irradiated patients. Prospective studies are needed to further characterize the potential neuropsychological hazards of chemotherapy and their evolution over time. (+info)
Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis.
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PURPOSE: A systematic review of the literature was carried out to determine the role of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC). METHODS: To be eligible, full published trials needed to deal with SCLC and to have randomly assigned patients to receive PCI or not. Trials quality was assessed by two scores (Chalmers and ELCWP). RESULTS: Twelve randomised trials (1547 patients) were found to be eligible. Five evaluated the role of PCI in SCLC patients who had complete response (CR) after chemotherapy. Brain CT scan was done in the work-up in five studies and brain scintigraphy in six. Chalmers and ELCWP scores are well correlated (p < 0.001), with respective median scores of 32.6 and 38.8 %. This meta-analysis based on the available published data reveals a decrease of brain metastases incidence (hazard ratio (HR): 0.48; 95 % confidence interval (CI): 0.39 - 0.60) for all the studies and an improvement of survival (HR: 0.82; 95 % CI: 0.71 - 0.96) in patients in CR in favour of the PCI arm. Unfortunately, long-term neurotoxicity was not adequately described. CONCLUSIONS: PCI decreases brain metastases incidence and improves survival in CR SCLC patients but these effects were obtained in patients who had no systematic neuropsychological and brain imagery assessments. The long-term toxicity has not been prospectively evaluated. If PCI can be recommended in patients with SCLC and CR documented by a work-up including brain CT scan, data are lacking to generalise its use to any CR situations. (+info)
Hyperbaric oxygen therapy and mandibular osteoradionecrosis: a retrospective study and analysis of treatment outcomes.
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BACKGROUND: Hyperbaric oxygen (HBO) therapy is recognized as an adjunctive treatment for osteoradionecrosis (ORN). It may also be used prophylactically in patients who require dental extractions and are at high risk for developing ORN. This article reviews the treatment outcomes of patients treated with HBO therapy at the Toronto General Hospital from 1985 to 1997. MATERIALS AND METHODS: A total of 297 charts of patients treated with HBO were reviewed. Criteria assessed included age of patient, gender, original diagnosis, radiation dose, time between radiation treatment and onset of ORN, presence or absence of fracture, orocutaneous fistula, pain, history of a precipitating event triggering ORN, medical status, HBO therapy (total oxygen time, number of dives), method of treatment of ORN and follow-up period. Minimum patient follow-up time for inclusion in the study was 6 months. RESULTS: Adequate information to meet the inclusion criteria was obtained for 75 patients. Group A (51 patients) had been treated for overt ORN with HBO alone, HBO with sequestrectomy, or HBO with sequestrectomy and reconstruction. Group B (24 patients at risk for developing ORN) had been treated with HBO prophylactically for dental extractions. In group A, only 3 patients (5.9%) failed to show improvement. In group B, only one patient (4.2%) had complications during healing. CONCLUSIONS: Encouraging results were achieved when HBO was used in the 2 groups described above. This paper supports existing literature on the potential benefit of HBO as a prophylactic agent and adjunctive treatment of ORN. (+info)
Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study.
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PURPOSE: To investigate the intellectual outcomes of children with medulloblastomas/primitive neuroectodermal tumors (MB/PNET) treated with reduced-dose craniospinal radiotherapy (RT) plus adjuvant chemotherapy. PATIENTS AND METHODS: Forty-three children with average-risk posterior fossa MB/PNETs underwent longitudinal intelligence testing. All had been treated with a reduced-dose craniospinal RT regimen (23.4 Gy to the neuraxis, 32.4-Gy boost to the posterior fossa) and adjuvant chemotherapy. RESULTS: The estimated rate of change from baseline was significant for Full Scale Intelligence Quotient (FSIQ), Verbal IQ (VIQ), and Nonverbal IQ (NVIQ) (P <.001 for all three outcomes). The rate of change was estimated to be -4.3 FSIQ points per year, -4.2 VIQ points per year, and -4.0 NVIQ points per year. Females were more subject to VIQ decline than were males (P =.008), and young children (< 7 years of age) were more negatively affected than were older children, with a significant decline in NVIQ (P =.016). Finally, patients with higher baseline evaluations suffered greater declines in IQ than did those with lower baseline scores. CONCLUSION: This study represents the largest series of patients with average-risk MB/PNETs treated with a combination of reduced-dose RT and adjuvant chemotherapy whose intellectual development has been followed prospectively. Intellectual loss was substantial but suggestive of some degree of intellectual preservation compared with effects associated with conventional RT doses. However, this conclusion remains provisional, pending further research. (+info)
Hypothalamic-pituitary-ovarian dysfunction after prepubertal chemotherapy and cranial irradiation for acute leukaemia.
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BACKGROUND: We assessed adult hypothalamic-pituitary-ovarian function following treatment with chemotherapy and cranial irradiation for childhood acute lymphoblastic leukaemia. METHODS: The patients (n = 12) had median age at diagnosis of 4.7 years, and at assessment of 20.8 years. They collected a daily urine sample over two to five consecutive menstrual cycles (total of 41 cycles) for analysis of LH and steroid excretion. Blood sampling and ovarian ultrasound examination was performed in the early follicular phase. Sixteen healthy women with regular menstrual cycles were recruited as controls. RESULTS: Urinary LH excretion was significantly lower in patients throughout the cycle, particularly during the LH surge (P < 0.0001). The length of the luteal phase was significantly shorter in patients than in normal controls (12.2 +/- 0.3 versus 13.6 +/- 0.4 days, P = 0.01) with a high prevalence of short (< or =11 days) luteal phases (15/39 cycles). Luteal phase pregnanediol excretion was slightly but not significantly lower. Follicular and luteal phase excretion of oestrone was lower in patients than in controls (P = 0.01). Early follicular phase plasma oestradiol was also lower in the patient group (P = 0.032) although LH, FSH, inhibin A and B concentrations were similar. CONCLUSIONS: These data indicate that treatment for childhood leukaemia results in subtle ovulatory disorder in some patients, probably related to cranial irradiation. Follow-up of these women is required to detect any effect on reproductive potential. (+info)
Preliminary results of conformal radiation therapy for medulloblastoma.
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Radiation therapy for medulloblastoma consists of postoperative irradiation of the intracranial and spinal subarachnoid volume with an additional boost to the primary site of disease in the posterior fossa. The entire posterior fossa is usually included in the boost volume. Conformal radiation therapy techniques may be used to boost the primary site alone and substantially reduce the dose received by normal tissues, including the supratentorial brain, the middle and inner ear, and the hypothalamus. Using these techniques to irradiate only the tumor bed or residual tumor and not the entire posterior fossa represents a new paradigm in the treatment of medulloblastoma. In this study, we examine the use of conformal radiation therapy in the treatment of 14 patients with medulloblastoma. These patients were treated with multiple static, individually shaped, noncoplanar beams directed at the primary site after craniospinal irradiation. Excluding two patients who had previously received irradiation to the posterior fossa, the mean dose delivered to the primary site was 5715 cGy. Among the medulloblastoma patients (n = 10) who received immediate postoperative radiation therapy, no failures have occurred with a median follow-up of 42 months (range from 30 to 54 months). To demonstrate the differences in the distribution of dose to normal tissues when comparing conventional and conformal techniques, dose-volume histograms of the total brain, middle and inner ear, hypothalamus, and temporal lobe were created and presented for an example case. The neurologic, neuroendocrine, and neurocognitive outcome for patients with medulloblastoma may be influenced with the use of conformal radiation therapy. The use of these techniques should be formally tested in prospective studies of rigorously staged patients with failure rate monitoring. (+info)