Radiation therapy improves CAR T cell activity in acute lymphoblastic leukemia.

Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 are approved for the treatment of various CD19+ hematological malignancies. While CAR T cells induce objective responses in a majority of patients, relapse frequently occurs upon loss of CD19 expression by neoplastic cells. Radiation therapy (RT) has been successfully employed to circumvent the loss of CAR targets in preclinical models of pancreatic cancer. At least in part, this reflects the ability of RT to elicit death receptor (DR) expression by malignant cells, enabling at least some degree of CAR-independent tumor killing. In a human model of CD19+ acute lymphoblastic leukemia (ALL), we also observed DR upregulation by RT, both in vitro and in vivo. Moreover, low-dose total body irradiation (LD-TBI) delivered to ALL-bearing mice prior to CAR T cell infusion considerably extended the overall survival benefit afforded by CAR T cells alone. Such an improved therapeutic activity was accompanied by a superior expansion of CAR T cells in vivo. These data encourage the initiation of clinical trials combining LD-TBI with CAR T cells in patients with hematological malignancies.

Effect of chemotherapy (with and without radiotherapy) on the intelligence of children and adolescents treated for acute lymphoblastic leukemia; a meta-analysis.

OBJECTIVE: This meta-analysis assesses cognitive functioning in children with acute lymphoblastic leukemia post-treatment who were treated with either chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). METHODS: The databases Pubmed and PsychInfo were searched between 1-1-2000 and 31-12-2021. Data were analyzed using Comprehensive Meta-Analysis (version 2). RESULTS: Mean weighted intelligence after treatment was 100.2 (number of studies n = 51, 95% CI: 98.8-101.5). For CT-only, it was 100.8 (95% CI: 99.5-102.2) and for CTRT 97.8 (95% CI: 95.9-100.2). Compared to recruited healthy controls, treated children had on average lower IQ scores (n = 23, mean difference -7.8, 95% CI: -10.7 to -5.0, p < 0.001). When looking only at studies using controls recruited from the patient's family, results remained significant (n = 5, mean difference -6.0, 95% CI: -8.6 to -3.5, p = 0.001). Meta-regressions aimed at identifying predictors of IQ after treatment failed to find an effect for sex or age. We could demonstrate an effect of time between diagnosis and IQ measurement for the CTRT treated patient (B = -0.26, 95% CI: -0.40 to -0.1, p = 0.002). CONCLUSIONS: IQ scores of patients treated with CT-only or CTRT treatment regimens did not differ from the normative population. However, compared to recruited control groups, patients showed lower mean IQ scores. The Flynn effect and/or selection effects may play a role in this discrepancy. Considering time since diagnosis may have a significant impact on IQ, at least in CTRT treated patients, long-term clinical follow-up of neurocognitive development may be prudent to detect possible (late) neurocognitive effects.

Phase I trial of myeloablative conditioning with 3-day total marrow and lymphoid irradiation for leukemia.

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study.

Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.7%) (p = 0.017). An early CNS relapse-< 12 months from diagnosis-was observed in 41 patients. In multivariate analysis, risk factors for early CNS relapse included T-cell phenotype (p = <0.001), hyperleucocytosis >100 × 109 /L (p<0.001) and male gender (p = 0.015). Treatment was heterogeneous, including chemotherapy, radiotherapy, intrathecal therapy and novel agents. A complete remission (CR) was obtained in 39 patients (55%) with no differences among strategies. After CR, 26 patients underwent an allogenic transplant, with a significant overall survival benefit compared to non-transplanted patients (p = 0.012). After a median observation of 8 months from CNS relapse, 23 patients (32%) were alive. In multivariate analysis, the time to CNS relapse was the strongest predictor of a lower 2-year post-relapse survival (p<0.001). In conclusion, in adult ALL the outcome after a CNS relapse remains very poor. Effective CNS prophylaxis remains the best approach and allogenic transplant should be pursued when possible.

Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study

Objective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up. Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse. Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787). Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.

Could (should) we abandon total body irradiation for conditioning in children with leukemia.

Total body irradiation (TBI) is used since the introduction of hematopoietic cell transplantation (HCT) decades ago to eradicate patients normal and malignant hematopoiesis prior to its replacement with stem cells from an HLA-matched or mismatched donor. Over the many years of its use, long-term side effects became obvious especially in younger pediatric patients who received an allogeneic transplantation for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). These long-term known side effects of TBI including the occurrence of second malignancies can significantly impair the quality of life of the patients either still during childhood and/or when they reach adulthood. Although the benefit of a TBI-based conditioning regimen has been shown recently in a large randomized study, concerns remain whether TBI should be from now on the standard conditioning regimen for all children with ALL. The introduction of sensitive methods for detection of minimal residual disease (MRD) and new immunotherapies using bispecific antibodies or chimeric antibody receptor (CAR) T-cells in combination with non-TBI-based conditioning regimens have shown already promising results comparable with the outcome after TBI-based standard transplants or even better. In this review, various approaches are discussed which have been and should further be investigated in prospective trials with the aim to avoid TBI and its long-term side effects in pediatric patients with ALL.

Longitudinal Preclinical Imaging Characterizes Extracellular Drug Accumulation After Radiation Therapy in the Healthy and Leukemic Bone Marrow Vascular Microenvironment.

PURPOSE: Recent initial findings suggest that radiation therapy improves blood perfusion and cellular chemotherapy uptake in mice with leukemia. However, the ability of radiation therapy to influence drug accumulation in the extracellular bone marrow tissue is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton microscopy (L-QMPM) to characterize the bone marrow vasculature (BMV) and drug accumulation in the extracellular bone marrow tissue before and after radiation therapy in mice bearing leukemia. METHODS AND MATERIALS: We developed a longitudinal window implant for L-QMPM imaging of the calvarium BMV before, 2 days after, and 5 days after total body irradiation (TBI). Live time-lapsed images of a fluorescent drug surrogate were used to obtain measurements, including tissue wash-in slope (WIStissue) to measure extracellular drug accumulation. We performed L-QMPM imaging on healthy C57BL/6 (WT) mice, as well as mice bearing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). RESULTS: Implants had no effects on calvarium dose, and parameters for wild-type untreated mice were stable during imaging. We observed decreased vessel diameter, vessel blood flow, and WIStissue with the onset of AML and ALL. Two to 10 Gy TBI increased WIStissue and vessel diameter 2 days after radiation therapy in all 3 groups of mice and increased single-vessel blood flow in mice bearing ALL and AML. Increased WIStissue was observed 5 days after 10 Gy TBI or 4 Gy split-dose TBI (2 treatments of 2 Gy spaced 3 days apart). CONCLUSIONS: L-QMPM provides stable functional assessments of the BMV. Nonmyeloablative and myeloablative TBI increases extracellular drug accumulation in the leukemic bone marrow 2 to 5 days posttreatment, likely through improved blood perfusion and drug exchange from the BMV to the extravascular tissue. Our data show that neo-adjuvant TBI at doses from 2 Gy to 10 Gy conditions the BMV to improve drug transport to the bone marrow.

THYROID DISEASE IN THE LATE OBSERVATION PERIOD UPON CHEMO AND RADIOTHERAPY IN CHILDREN/SURVIVORS OF ACUTE LYMPHOBLASTIC LEUKEMIA. / KhVOROBY ShchYTOPODIBNOÏ ZALOZY PISLIa KhIMIO TA PROMENEVOÏ TERAPIÏ U DITEI, IaKI PERENESLY GOSTRU LIMFOBLASTNU LEIKEMIIu, U VIDDALENOMU PERIODI SPOSTEREZhENNIa.

OBJECTIVE: to assess the thyroid disease in the late observation period in children who had received chemo- andradiotherapy for the acute lymphoblastic leukemia (ALL) taking into account gender, age period and disease sub-type. MATERIALS AND METHODS: The incidence and nature of thyroid disease (hypothyroidism, thyroiditis, and thyroid can-cer) were studied in children-survivors of acute lymphoblastic leukemia (ALL) being in remission from 6 to 25 years.The distribution of patients by leukemia subtypes was as follows: «common¼ - 67.4 %, pre-B - 23.9 %, pro-B andT-cell - 4.3 %. Children had been receiving chemo- and radiotherapy according to the protocol. Regarding the ageof patients at the time of ALL diagnosis the prepubertal, pubertal and postpubertal periods were taken into account.The endocrine diseases in family history, body weight at birth, serum content of free thyroxine, pituitary thyroid-stimulating hormone, cortisol, iron, ferritin and thyroperoxidase antibodies were evaluated and assayed. RESULTS: Thyroid disease in children was emerging in the first 2-3 years after the ALL treatment with an incidenceof 22.8 % (hypothyroidism - 14.1 %, autoimmune thyroiditis - 7.6 %, papillary cancer - 1.1 %). Seven children inthis group had received radiotherapy (12-18 Gy doses) on the central nervous system (CNS). No correlation wasfound between the radiation exposure event itself, radiation dose to the CNS and thyroid disease in the long-termfollow-up period. Thyroid cancer had developed in a child 11 years upon chemo- and radiotherapy. Hypothyroidismwas more often diagnosed in the patients of prepubertal age (rs = 0.49). There were endocrine diseases in thefamily history in about a half of children, being significantly higher than in the general sample (р < 0.05). The bodyweight at birth of a child who had later developed hypothyroidism was less than in children having got thyroiditis(rs = 0.57). CONCLUSIONS: Disorders in endocrine regulation and of thyroid in particular can affect the prognosis of blood can-cer course in the long-term follow-up in children, especially in prepubertal age, which requires systematic supervi-sion by hematologist and endocrinologist.

Complete reversal of bilateral optic nerve infiltration from lymphoblastic leukemia using chemotherapy without adjuvant radiotherapy.

BACKGROUND: Leukemic involvement of the eyes is rare, therefore, treatment relies on previous case reports. The treatment of ocular complications poses additional difficulties, because the eye is considered as a pharmacological "sanctuary" for patients with acute lymphoblastic leukemia (ALL). Therefore, radiotherapy is the main therapeutic choice; however, it might lead to many important side effects. To the best of our knowledge, this is the first case report of a bilateral leukemic optic nerve infiltration that remitted with chemotherapy without adjuvant radiotherapy. CASE PRESENTATION: A 30-year-old female patient with previous history of remitted ALL presented with a one-week history of floaters in her right eye. Her ophthalmological exam showed remarkable optic disc swelling, in both eyes. She was diagnosed with ALL relapse presenting as a bilateral optic nerve leukemic infiltration. Local radiotherapy was planned for both eyes, however, due to efficient recovery with chemotherapy, it was cancelled. Allogenic bone marrow transplantation was subsequently performed. The patient is being followed up and ALL remitted. CONCLUSION: Leukemia relapse on central nervous system, despite rare, is a sign of poor prognosis and requires prompt treatment. Its occurrence on ocular tissues is even rarer. It is hypothesized that the blood-brain barrier limits the delivery of chemotherapeutic drugs to the eye and infiltration of the optic nerve by leukemic cells might prejudice the flow of cerebrospinal fluid between the cranial space and the optic disc.

Are radiation-induced cavernomas clinically relevant findings? Results from long-term follow-up with brain magnetic resonance imaging of childhood cancer survivors.

INTRODUCTION: Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations. PATIENTS AND METHODS: We analyzed retrospectively long-term follow-up data of 36 childhood cancer survivors after initial diagnosis with acute leukemia (n = 18) or brain tumor (n = 18), all treated with cranial radiotherapy. Detected RIC in long-term follow-up brain MRI (1.5 or 3 Tesla) were classified following the Zabramski MRI classification and were categorized into "high" (Zabramski type I, II or V) or "low" (type III or IV) risk of hemorrhage. RESULTS: 18 patients (50%) showed RIC with a significant relation to the original tumor entity (p = 0.023) and the cumulative radiation dose to the brain (p = 0.016): all 9 childhood cancer survivors diagnosed with medulloblastoma developed RIC. We classified RIC in only 3/36 childhood cancer survivors (8%) (1 patient with acute lymphoblastic leukemia [Zabramski type II] and 2 patients with medulloblastoma [type I and type II]) as high risk for hemorrhage, the remaining RIC were classified as Zabramski type IV with low risk for hemorrhage. None of the childhood cancer survivors with RIC showed symptomatic hemorrhages. CONCLUSIONS: RIC are common late effects in childhood cancer survivors treated with cranial radiotherapy affecting half of these patients. However, only a few RIC (occurring in 8% of all reviewed childhood cancer survivors) were classified as high risk for hemorrhage and none of the childhood cancer survivors with RIC developed symptomatic hemorrhages. Thus, we conclude that RIC are low-risk findings in brain MRI and the course is mainly benign.

[Role of radiotherapy in haematology]. / Place de la radiothérapie en hématologie.

The management of myeloid and lymphoid disease is essentially based on chemotherapy and targeted therapies. Since radiotherapy could be responsible for severe late toxicities, essentially due to conventional bidimensional irradiation techniques, many trials have attempted to omit radiotherapy or to scale down the dose in their therapeutic strategy. Nevertheless, radiotherapy still plays a role for curative or symptomatic purposes.

Late isolated central nervous system relapse in childhood B-cell acute lymphoblastic leukemia treated with intensified systemic therapy and delayed reduced dose cranial radiation: A report from the Children's Oncology Group study AALL02P2.

BACKGROUND: Patients with late, ≥18 months postdiagnosis, isolated central nervous relapse (iCNS-R) of B-acute lymphoblastic leukemia (ALL) have excellent outcomes with chemotherapy plus cranial radiotherapy, with 5-year overall survival (OS) approaching 80% in POG 9412. Subsequent relapse and radiation-related morbidity remain the causes of treatment failure and long-term sequelae. COG AALL02P2 aimed to maintain outcomes in patients with late iCNS-R using intensified chemotherapy and a decrease in cranial irradiation from 1800 to 1200 cGy. PROCEDURES: COG AALL02P2 enrolled 118 eligible patients with B-cell ALL (B-ALL) and late iCNS-R who received intensified systemic therapy, triple intrathecal chemotherapy, and 1200 cGy cranial irradiation delivered at 12 months, with maintenance chemotherapy continuing until 104 weeks postdiagnosis. RESULTS: The 3-year event-free survival (EFS) and OS were 64.3% ± 4.5% and 79.6% ± 3.8%, with 46.1% (18/39) of second relapses including the CNS. Of the 112 patients who completed therapy, 78 received protocol-specified radiation. Study enrollment was closed after interim monitoring analysis showed inferior EFS compared to POG 9412. Patients with initial NCI standard-risk classification fared better than high-risk patients. CONCLUSIONS: COG AALL02P2 showed inferior EFS but similar OS compared to POG 9412. Limitations included a small sample size, more intensive prior therapies, and a significant number of patients (34/118, 29%) who did not receive protocol-directed radiation due to early relapse prior to 1 year or did not otherwise follow the treatment plan. New approaches are needed to improve outcome for these patients and determine the optimal timing and dose of cranial radiation in the treatment of iCNS-R.

Biophysical Characterization of the Leukemic Bone Marrow Vasculature Reveals Benefits of Neoadjuvant Low-Dose Radiation Therapy.

PURPOSE: Although vascular alterations in solid tumor malignancies are known to decrease therapeutic delivery, the effects of leukemia-induced bone marrow vasculature (BMV) alterations on therapeutic delivery are not well known. Additionally, functional quantitative measurements of the leukemic BMV during chemotherapy and radiation therapy are limited, largely due to a lack of high-resolution imaging techniques available preclinically. This study develops a murine model using compartmental modeling for quantitative multiphoton microscopy (QMPM) to characterize the malignant BMV before and during treatment. METHODS AND MATERIALS: Using QMPM, live time-lapsed images of dextran leakage from the local BMV to the surrounding bone marrow of mice bearing acute lymphoblastic leukemia (ALL) were taken and fit to a 2-compartment model to measure the transfer rate (Ktrans), fractional extracellular extravascular space (νec), and vascular permeability parameters, as well as functional single-vessel characteristics. In response to leukemia-induced BMV alterations, the effects of 2 to 4 Gy low-dose radiation therapy (LDRT) on the BMV, drug delivery, and mouse survival were assessed post-treatment to determine whether neoadjuvant LDRT before chemotherapy improves treatment outcome. RESULTS: Mice bearing ALL had significantly altered Ktrans, increased νec, and increased permeability compared with healthy mice. Angiogenesis, decreased single-vessel perfusion, and decreased vessel diameter were observed. BMV alterations resulted in disease-dependent reductions in cellular uptake of Hoechst dye. LDRT to mice bearing ALL dilated BMV, increased single-vessel perfusion, and increased daunorubicin uptake by ALL cells. Consequently, LDRT administered to mice before receiving nilotinib significantly increased survival compared with mice receiving LDRT after nilotinib, demonstrating the importance of LDRT conditioning before therapeutic administration. CONCLUSION: The developed QMPM enables single-platform assessments of the pharmacokinetics of fluorescent agents and characterization of the BMV. Initial results suggest BMV alterations after neoadjuvant LDRT may contribute to enhanced drug delivery and increased treatment efficacy for ALL. The developed QMPM enables observations of the BMV for use in ALL treatment optimization.

Genetic variation in the body mass index of adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

BACKGROUND: Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL. METHODS: Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2-stage genome-wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi-square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors. RESULTS: In a meta-analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL (LINC00856 rs575792008 and EMR1 rs62123082; PMeta < 5E-8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci (P < 7.0E-5) were further identified. At 2 CRT-interacting loci, DNA methylation patterns may have differed by age. CONCLUSIONS: Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors.

Prediction of Cranial Radiotherapy Treatment in Pediatric Acute Lymphoblastic Leukemia Patients Using Machine Learning: A Case Study at MAHAK Hospital.

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is the most common blood disease in children and is responsible for the most deaths amongst children. Due to major improvements in the treatment protocols in the 50-years period, the survivability of this disease has witnessed dramatic rise until this date which is about 90 percent. There are many investigations tending to indicate the efficiency of cranial radiotherapy found out that without that, outcome of the patients did not change and even it improved at some cases. METHODS: the main aim of this study is predicting cranial radiotherapy treatment in pediatric acute lymphoblastic leukemia patients using machine learning. Scope of this paper is intertwined with predicting the necessity of one of the treatment modalities that has been used for many years for this group of patients named Cranial Radiotherapy (CRT). For this purpose, a case study is considered at Mahak charity hospital. In this paper, our focus is on ALL patients aged 0 to 17 treated at Mahak hospital, one of the best centers for treatment of childhood malignancies in Iran. Dataset analyzed in this study is gathered by the research team from patient's paper-based files. Our dataset consists of 241 observations on patients with 31 attributes after the data cleaning process. Our designed machine learning model for predicting cranial radiotherapy treatment in pediatric acute lymphoblastic leukemia patients is a stacked ensemble classifier of independently strong models with a meta-learner to tune the weights and parameters of the base classifiers. RESULTS: The stacked ensemble classifier show highly reasonable performance with AUC of 87.52%. Moreover, the attributes are ranked based on their predictive power and the most important variable for CRT necessity prediction is the disease relapse. CONCLUSION: In order to conclude, derived from previous studies regarding CRT it is not only cost-effective but also more healthy to eradicate the use of CRT for the treatment of childhood ALL. Furthermore, it is valuable to increase the clinical databases by creating more synthetic health databases not only for research purposes but also for physicians to keep track of their patient's status.   
.

Technical note: factors affecting dose distribution in the overlap region of two-segment total body irradiation by helical tomotherapy.

OBJECTIVE: To assess the effects of various treatment planning parameters to identify the optimal gap distance for precise two-segment total body irradiation (TBI) using helical tomotherapy (HT) with fixed jaw mode. METHODS AND MATERIALS: Data of a treatment plan for 8 acute leukemia patients (height range: 109-130 cm) were analyzed. All patients underwent total-body computed tomography (CT) with 5-mm slice thickness. A lead wire, placed at 10 cm above the patella, was used to mark the boundary between the two segments. Target volumes and organs at risk were delineated using a Varian Eclipse 10.0 physician's workstation. Different distances between the lead wire and the boundary of the two targets were used. CT images were transferred to the HT workstation to design the treatment plans, by adjusting parameters, including the field width (FW; 2.5 cm, and 5 cm), pitch (0.287 and 0.430), modulation factor (1.8). The plans were superimposed to analyze the dose distributions in the overlap region when varying target gap distances, FWs, pitches to determine the optimal combinations. RESULTS: The pitch did not affect the dose distribution in the overlap region. The dose distribution in the overlap region was mostly homogeneous when the target gap distance was equal to the FW. Increased FW diminished the effect of the target gap distance on the heterogeneous index of the overlap region. CONCLUSIONS: In two-segment TBI treatments by HT with Helix mode, a gap distance equal to the FW may achieve optimal dose distribution in the overlap region.

Habilidades funcionais e qualidade de vida em crianças com Leucemia Linfoblástica Aguda / Functional abilities and quality of life in children withacute lymphoblastic leukemia

Objetivo: Comparar as capacidades funcionais e a qualidade de vida entre crianças com leucemia linfoblástica aguda em tratamento com quimioterapia e/ou radioterapia e crianças sem o tratamento, de 4 a 7 anos de idade. Método: Participaram do estudo 50 crianças, sendo 25 em tratamento (grupo experimental) e 25 que já terminaram o tratamento (grupo controle), avaliados por meio do Inventário de Avaliação Pediátrica de Incapacidade (PEDI) e da Escala de Qualidade de Vida da Criança (AUQEI). Resultados: Não houve diferença entre os grupos nos escores brutos do PEDI e na pontuação do AUQEI. Os escores normativos do PEDI apresentaram-se predominantemente abaixo do esperado para a idade em ambos os grupos. A pontuação do AUQEI demonstrou uma qualidade de vida prejudicada no grupo experimental e no controle. Conclusão: Sugere-se que a leucemia linfoblástica aguda e seus tratamentos (quimio e radioterápicos) geram prejuízos funcionais e psicossociais, tanto no momento do tratamento oncológico como após sua conclusão e remissão da doença. É relevante que haja promoção de um acompanhamento longitudinal e multiprofissional da criança com câncer, a fim de minimizar os danos e reinseri-la na comunidade efetivamente.