Feasibility of cranio-spinal axis radiation with the Hi-Art tomotherapy system.

BACKGROUND AND PURPOSE: Helical tomotherapy can eliminate the need for junction lines. The goal of this study is to evaluate tomotherapy in the delivery of CSA radiation and measurement of plan quality using physical parameters in comparing conventional (CSA-RT) and helical tomotherapy (CSA-TOMO) plans. PATIENTS AND METHODS: CSA-TOMO and CSA-RT plans were created for dosimetric comparison. Integral dose values were calculated. The ratios D50% (dose received by 50% of the organ at risk's volume) and D10% (dose received by 10% of the organ at risk's volume) were calculated representing large volumes and small volumes of organs at risk receiving significant dose. RESULTS: When considering D50% and D10%, CSA-TOMO has a dosimetric advantage over CSA-RT for most organs at risk. The body integral dose was higher for the CSA-TOMO plan by approximately 6.5%. CONCLUSIONS: Tomotherapy is a feasible alternative for treatment of CSA. Analysis shows that tomotherapy improves dose ratios over conventional radiation for most organs at risk. The impact of a small increase in whole body integral dose is unknown. Long-term follow-up will be needed to answer this question as others have argued of the possibility of increased risk of secondary malignancies due to delivery of radiotherapy with IMRT.     

West Nile virus encephalitis causing fatal CNS toxicity after hematopoietic stem cell transplantation

We describe here a patient who died of progressive CNS deterioration following allogeneic stem cell transplant with West Nile virus as the sole pathogen on the cerebrospinal fluid and brain tissue analysis. A 50-year-old male with Philadelphia chromosome-positive acute lymphocytic leukemia (ALL) underwent allogeneic PBSCT from his HLA identical sister. After engraftment, the patient developed fever with progressive and ultimately fatal neurological deterioration. Imaging studies of the brain including CT and MRI scans were remarkable for mild low attenuation lesions of the white matter. CSF analysis was negative for neoplastic cells, bacteria, AFB, CMV, HSV, fungal infections and leukemic relapse. However, serological analysis of both the serum and CSF was positive for West Nile virus-specific IgM antibodies. At autopsy, West Nile virus PCR and cultures were positive in the mid-brain tissue. Electron micrographs showed evidence of viral particles. Given the recent increase in the spread of West Nile virus infections and the increased susceptibility of BMT patients to infectious complications, West Nile virus encephalitis should be considered in patients undergoing transplantation.     

Reversible arrhythmias observed in patients treated with recombinant alpha2 interferon

Summary We have treated 25 patients, 7 with breast cancer and 18 with non-Hodgkin's lymphoma, with recombinant alpha₂ interferon. In 5 patients we observed cardiac arrhythmias that were unexpected and required treatment. No deaths have occured that we can attribute to interferon, though 1 patient had to be resuscitated. Age, prior cardiac disease, prior treatment with doxorubicin, and interferon dose appear to be predisposing factors for this toxicity.Supported by the Schering Corporation and Harper-Grace Hospitals     

Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age

The National Marrow Donor Program (NMDP) maintains a registry of approximately 4 million volunteer unrelated donors for patients in need of a stem cell transplant. When several comparably HLA-matched volunteers are identified for a patient, various criteria are used to select a donor. A retrospective analysis of 6978 bone marrow transplantations facilitated by the NMDP from 1987 to 1999 was conducted to study the effects of various donor characteristics on recipient outcome. The evaluation addressed possible effects of donor age, cytomegalovirus serologic status, ABO compatibility, race, sex, and parity on overall and disease-free survival, acute and chronic graft-versus-host disease (GVHD), engraftment, and relapse. Age was the only donor trait significantly associated with overall and disease-free survival. Five-year overall survival rates for recipients were 33%, 29%, and 25%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P =.0002). A similar effect was observed among HLA-mismatched cases (28%, 22%, and 19%, respectively). A race mismatch between recipient and donor did not affect outcome. The cumulative incidences of grade III or IV acute GVHD were 30%, 34%, and 34%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P =.005). The corresponding incidences of chronic GVHD at 2 years were 44%, 48%, and 49% (P = 0.02). Recipients with female donors who had undergone multiple pregnancies had a higher rate of chronic GVHD than recipients with male donors (54% versus 44%; P <.0001). The use of younger donors may lower the incidence of GVHD and improve survival after bone marrow transplantation. Age should be considered when selecting among comparably HLA-matched volunteer donors.     

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): Validation Study of the Thai Version

The objective of this study was to assess the psychometric properties of the Thai version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0. The questionnaire was completed by 310 cancer patients during their follow-up at 2 teaching hospital oncology clinics. About 70% of participants had advanced stage of cancer and 72% had been receiving chemotherapy. Cronbach’s α coefficients of the six scales were above 0.7, except for cognitive and social function scales. All test–retest reliability coefficients were high. Multitrait scaling analysis showed that all item-scale correlation coefficients met the standards of convergent and discriminant validity. Most scales and items could discriminate between subgroups of patients with different clinical status assessed with the Eastern Cooperative Oncology Group (ECOG) scale. The results suggested that the EORTC QLQ-C30 and the Functional Assessment of Cancer Therapy – General (FACT-G) measured different aspects of quality of life and should be independently used. Testing psychometric properties of the EORTC QLQ-C30 in heterogeneous diagnostic group yield similar results as found in homogeneous group. These results support that the EORTC QLQ-C30 (version 3.0) has proven to be a reliable and valid measure of the quality of life in Thai patients with various types of cancer.     

Evaluation of integral dose in cranio-spinal axis (CSA) irradiation with conventional and helical delivery

In cranio-spinal axis (CSA) irradiation, patients are usually treated in the prone position with junctions between cranial and spinal fields. Collimator angle and pedestal rotations are introduced to obtain coplanar alignment of the matched junction. Furthermore, daily moving junctions are commonly used to feather out the junctional dose as additional safeguards to avoid radiation myelopathy. Helical tomotherapy integrates linear accelerator and CT technology capable of delivering CSA treatment without geometric matches or feathering of junctions. The patient is treated with helical beams in the supine position. Since CSA is used mainly in the pediatric population, the potential increase in integral dose to structures or the whole body from linac- or tomotherapy-based IMRT raises concerns of increased rates of secondary malignancies. In this study, we will present an integral dose comparison between conventional CSA (3D) and helical delivery to the CSA (TOMO) utilizing the Tomotherapy Hi-ART system for three pediatric patients. Integral dose was calculated for organ at risk (OAR), two targets (PTV-BRAIN and PTV-SPINE), entire planning CT data set and to the healthy tissue (entire CT-DATA SET minus the PTV). Overall integral dose was 8% higher in the TOMO plans for Patients #1 and #3, but 2% lower in Patient #2. DVH analysis shows that TOMO plans give lower doses to larger volumes and higher doses to smaller volumes of tissue in all three cases. The advantages of the TOMO plans are minimization of matched junctions and better sparing of most OARs. With increased computational and memory power in the tomotherapy planning station, the excess integral dose to the healthy tissue can be re-distributed within the patient and in turn the total integral dose can be same or lower than in conventional delivery. The impact of a small increase in overall integral dose and the associated risks of secondary malignancies are unknown. Long-term follow-up is needed to answer this question.     

Long term follow‐up of allogeneic stem cell transplantation in patients with myelodysplastic syndromes using busulfan,cytosine arabinoside,and cyclophosphamide

We report here the 10‐year follow‐up of 86 patients who underwent allogeneic stem cell transplantation (ASCT) for myelodysplastic syndrome (MDS). All patients received the busulfan, cytosine arabinoside, and cyclophosphamide (BAC) preparative regimen which consisted of busulfan 16 mg/kg, cytosine arabinoside 8 g/m² IV, and cyclophosphamide 120 mg/kg IV. Fifty‐nine patients (69%) had de novo MDS; 26 (30%) had secondary MDS (treatment related), and one had a preceding aplastic anemia which progressed to MDS before transplant. Cytogenetics (80 patients) was classified as good (34%), intermediate (17%), or poor (42%). With a median follow‐up for survivors of 124 months, the 10‐year Kaplan‐Meier estimates for overall survival (OS) was 43% (95% confidence interval [CI]: 31–53%). Cumulative nonrelapse mortality (NRM) and relapse was 43% (95% CI: 32–54%) and 19% (95% CI: 11–27%), respectively. No patient relapsed after 2 years. In patients with RAEB‐T/AML, 10‐year relapse‐free survival (RFS), relapse, and NRM was 36%, 36%, and 27%, respectively. Younger age (P = 0.05), human leukocyte antigen (HLA) match (P = 0.002), good risk cytogenetics (P = 0.008), and having a related donor (P = 0.03) significantly improved overall and RFS in the multivariable analysis. The long‐term follow‐up of patients receiving the BAC regimen with ASCT in this study indicated durable relapse‐free and OS with acceptable toxicity in this group of patients with high‐risk features. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

Application of intensity-modulated radiation therapy for pediatric malignancies

Novel radiation therapy delivery techniques have moved very slowly in the field of pediatric oncology. Some collaborative groups allow new radiation therapy delivery techniques in their trials. In many instances, the option of using these techniques is not addressed. These newer techniques of radiation delivery have the potential to reduce the probability of the common late effects of radiation and at the same time, potentially improve upon control and survival. The purpose of this study is to show the feasibility of IMRT in pediatric patients. No treatment results or toxicities will be presented. Five patients with a variety of pediatric malignancies received intensity-modulated radiation therapy (IMRT) at our institution as part of their disease management. A rigid immobilization device was developed for each patient and a computed tomography (CT) simulation was performed in the treatment position. In 3 of the patients, magnetic resonance imaging (MRI) scans were coregistered with the planning CT to facilitate target and critical structure delineation. In all but 1 patient, coplanar beam arrangements were used in the IMRT planning process. All IMRT plans exhibited a high degree of conformality. Dose homogeneity inside the tumor and rapid dose falloff outside the target volume is characteristic of IMRT plans, which allows for improved normal tissue sparing. Dose distributions were obtained for all plans, as well as dose and volume relationship histograms, to evaluate the fitness of the plans. IMRT is a viable alternative to conventional treatment techniques for pediatric cancer patients. The improved dose distributions coupled with the ease of delivery of the IMRT fields make this technique very attractive, especially in view of the potential to increase local control and possibly improve on survival.