Search

While hypofractionated stereotactic body radiotherapy (SBRT) has been largely adopted in the adult setting, its use remains limited in pediatric patients. This is due, among other factors, to fear of potential toxicities of hypofractionated regimens at a young age. In this context, we report the preliminary acute (<3 months from SBRT) and middle-term (3–24 months) toxicity results of a national prospective study investigating SBRT in pediatric patients. Between 2013 and 2019, 61 patients were included. The first 40 patients (median age: 12 y, range: 3–20) who completed a 2-year-follow-up were included in the present analysis. SBRT was used for treating lung, brain or (para)spinal lesions, either as first irradiation (35%) or in the reirradiation setting (65%). Acute and middle-term grade ≥2 toxicities occurred in 12.5 and 7.5% of the patients, respectively. No grade ≥4 toxicities occurred. Almost all toxicities occurred in the reirradiation setting. SBRT showed a favorable safety profile in young patients treated for lung, brain, and (para)spinal lesions. SBRT appeared to be safe in pediatric patients treated for multiple oncology indications. These results support further evaluation of SBRT, which may have a role to play in this patient population in the future. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aimed to analyze the treatment and outcomes of older glioblastoma patients. Forty-four patients older than 70 years of age were referred to the Paul Strauss Center for chemotherapy and radiotherapy. The median age was 75.5 years old (range: 70-84), and the patients included 18 females and 26 males. The median Karnofsky index (KI) was 70%. The Charlson indices varied from 4 to 6. All of the patients underwent surgery. O6-methylguanine-DNA methyltransferase (MGMT) methylation status was determined in 25 patients. All of the patients received radiation therapy. Thirty-eight patients adhered to a hypofractionated radiation therapy schedule and six patients to a normofractionated schedule. Neoadjuvant, concomitant and adjuvant chemotherapy regimens were administered to 12, 35 and 20 patients, respectively. At the time of this analysis, 41 patients had died. The median time to relapse was 6.7 months. Twenty-nine patients relapsed, and 10 patients received chemotherapy upon relapse. The median overall survival (OS) was 7.2 months and the one- and two-year OS rates were 32% and 12%, respectively. In a multivariate analysis, only the Karnofsky index was a prognostic factor. Hypofractionated radiotherapy and chemotherapy with temozolomide are feasible and acceptably tolerated in older patients. However, relevant prognostic factors are needed to optimize treatment proposals. [ABSTRACT FROM AUTHOR]

Background: Intensity modulated radiotherapy is an efficient radiotherapy technique to increase dose in target volumes and decrease irradiation dose in organs at risk. This last objective is mainly relevant in children. However, previous results suggested that IMRT could increase low dose, factor of risk for secondary radiation induced cancer. This study was performed to compare dose distributions with 3D-radiotherapy (3D-RT) and IMRT with tomotherapy (HT) in children with neuroblastoma. Seven children with neuroblastoma were irradiated. Treatment plans were calculated for 3D-RT, and for HT. For the volume of interest, the PTV-V95% and conformity index were calculated. Dose constraints of all the organs at risk and integral dose were compared. Results: The conformity index was statistically better for HT than for 3D-RT. PTV-V95% constraint was reached in 6 cases with HT compared to 2 cases with 3D-RT. For the ipsilateral kidney of the tumor, the V12 Gy constraint was reached for 3 patients with both methods. The values were lower with HT than with 3D-RT in two cases and higher in one case. The threshold was not reached for one patient with either technique, but the value was lower with HT than with 3D-RT. For the contralateral kidney of the tumors, the V12 Gy constraint was reached for all patients with both methods. The values were lower with HT than with 3D-RT in 5 of 7 children, equal in one patient and higher in one patient. The organ-at-risk volumes receiving low doses were significantly lower with 3D-RT but larger for the highest doses, compared to those irradiated with HT. The integral doses were not different. Conclusions: IMRT with HT allows a better conformity treatment, a more frequently acceptable PTV-V95% than 3D-RT and, concomitantly, a better shielding of the kidneys. The integral doses are comparable between both techniques but consideration of differences in dose distribution between the two techniques, for the organs at risk, has to be taken in account when validating treatment [ABSTRACT FROM AUTHOR]

Simple Summary: What is the influence of a one-on-one procedure announcement delivered by a radiation therapist before radiation therapy? In this trial randomizing 126 patients, no significant differences in mean trait or state anxiety scores measured before CT scan simulation, during the first and second sessions, or at the completion of radiotherapy were noted. Patients who benefited from the procedure announcement were significantly better informed of the treatment positioning and in vivo dosimetry. For patients, this specific procedure was not able to decrease their level of anxiety. Background: Anxiety impacts patient outcomes and quality of life in response to cancer diagnosis. A prospective phase 3 trial randomizing 126 patients was conducted to determine whether a specific one-on-one procedure announcement provided by a radiation therapist before CT scan simulation decreases anxiety for patients with breast cancer requiring radiotherapy. Material and Methods: Anxiety was measured using the STAI form, and the QLQ-C30 and BR-23 questionnaires were used to evaluate quality of life. Results: Mean trait or state anxiety scores before CT scan simulation, before the first and second sessions, and at the end of radiation treatment were not significantly different. We observed a decrease in the level of anxiety with time; however, no significant difference in mean state anxiety scores at any of the time intervals was detected. Factors, such as anxiety trait score, professional and marital status, age, and use of alternative therapy, did not significantly influence the evolution of anxiety status over time or the mean value. Anxiety was significantly influenced by the level of fatigue. Patients who benefited from the radiation therapists' advice felt significantly better informed. Conclusions: The one-on-one program announcement occurring before CT scan simulation led to patients being more informed and greater satisfaction but did not decrease anxiety. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the characteristics of early second breast cancer (SBC) among survivors of childhood and young adult malignancy treated with irradiation. We conducted a multicenter retrospective study of women who presented with breast cancer aged 50 years or younger in nine French centers. 121 patients and 141 SBC were analyzed (invasive = 130; non-invasive = 11). The mean age at first cancer diagnosis was 15 years and at initial SBC diagnosis was 38 years. Bilateral disease before the age of 51 years was diagnosed in 16% of the females. The majority of SBC were invasive carcinomas (92%). Among the invasive carcinomas, 39% had a histoprognostic score of III, 3.1% overexpressed HER2 and 29% were triple negative. The proportion of triple negative phenotype SBC was higher in patients older at first cancer diagnosis [RR = 1.2, 95% CI (1.1–1.3)]. 94% of triple negative SBCs developed in breast tissue which had received >20 Gy. We found a high proportion of aggressive SBC following thoracic radiotherapy in childhood or early adulthood. SBC screening is recommended by scientific societies for these child/young–adulthood cancer survivors in the same way as the one for high risk women because of constitutional mutations. Our results support these recommendations, not only because of a similar cumulative risk, but also because of the aggressive histological characteristics. [ABSTRACT FROM AUTHOR]

Purpose: Medulloblastoma has recently been characterized as a heterogeneous disease with 4 distinct molecular subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4, with a new definition of risk stratification. We report progression-free survival, overall survival, and long-term cognitive effects in children with standard-risk medulloblastoma exclusively treated with hyperfractionated radiation therapy (HFRT), reduced boost volume, and online quality control, and we explore the prognostic value of biological characteristics in this chemotherapy-naïve population., Methods and Materials: Patients with standard-risk medulloblastoma were enrolled in 2 successive prospective multicentric studies, MSFOP 98 and MSFOP 2007, and received exclusive HFRT (36 Gy, 1 Gy/fraction twice daily) to the craniospinal axis followed by a boost at 68 Gy restricted to the tumor bed (1.5 cm margin), with online quality assurance before treatment. Patients with MYC or MYCN amplification were not excluded at the time of the study. We report progression-free survival and overall survival in the global population, and according to molecular subgroups as per World Health Organization 2016 molecular classification, and we present cognitive evaluations based on the Wechsler scale., Results: Data from 114 patients included in the MSFOP 98 trial from December 1998 to October 2001 (n = 48) and in the MSFOP 2007 from October 2008 to July 2013 (n = 66) were analyzed. With a median follow-up of 16.2 (range, 6.4-19.6) years for the MSFOP 98 cohort and 6.5 (1.6-9.6) years for the MSFOP 2007 cohort, 5-year overall survival and progression-free survival in the global population were 84% (74%-89%) and 74% (65%-81%), respectively. Molecular classification was determined for 91 patients (WNT [n = 19], SHH [n = 12], and non-WNT/non-SHH [n = 60]-including group 3 [n = 9], group 4 [n = 29], and not specified [n = 22]). Our results showed more favorable outcome for the WNT-activated subgroup and a worse prognosis for SHH-activated patients. Three patients had isolated extra-central nervous system relapse. The slope of neurocognitive decline in the global population was shallower than that observed in patients with a normofractionated regimen combined with chemotherapy., Conclusions: HFRT led to a 5-year survival rate similar to other treatments combined with chemotherapy, with a reduced treatment duration of only 6 weeks. We confirm the MSFOP 98 results and the prognostic value of molecular status in patients with medulloblastoma, even in the absence of chemotherapy. Intelligence quotient was more preserved in children with medulloblastoma who received exclusive HFRT and reduced local boost, and intelligence quotient decline was delayed compared with patients receiving standard regimen. HFRT may be appropriate for patients who do not consent to or are not eligible for prospective clinical trials; for patients from developing countries for whom aplasia or ileus may be difficult to manage in a context of high cost/effectiveness constraints; and for whom shortened duration of RT may be easier to implement., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Survival of childhood, adolescent and young adult (CAYA) cancers has increased with progress in the management of the treatments and has reached more than 80% at 5 years. Nevertheless, these survivors are at great risk of second cancers and non-malignant co-morbidities in later life. DeNaCaPST is a non-interventional study whose aim is to organize a national screening for thyroid cancer and breast cancer in survivors of CAYA cancers. It will study the compliance with international recommendations, with the aim, regarding a breast screening programme, of offering for every woman living in France, at equal risk, an equal screening., Method: DeNaCaPST trial is coordinated by the INSERM 1018 unit in cooperation with the LEA (French Childhood Cancer Survivor Study for Leukaemia) study's coordinators, the long term follow up committee and the paediatric radiation committee of the SFCE (French Society of Childhood Cancers). A total of 35 centres spread across metropolitan France and la Reunion will participate. FCCSS (French Childhood Cancer Survivor Study), LEA and central registry will be interrogated to identify eligible patients. To participate, centers agreed to perform a complete "long-term follow-up consultations" according to good clinical practice and the guidelines of the SFCE (French Society of Children Cancers)., Discussion: As survival has greatly improved in childhood cancers, detection of therapy-related malignancies has become a priority even if new radiation techniques will lead to better protection for organs at risk. International guidelines have been put in place because of the evidence for increased lifetime risk of breast and thyroid cancer. DeNaCaPST is based on these international recommendations but it is important to recognize that they are based on expert consensus opinion and are supported by neither nonrandomized observational studies nor prospective randomized trials in this specific population. Over-diagnosis is a phenomenon inherent in any screening program and therefore such programs must be evaluated.

French medical laboratories must be accredited before November 2016 according to NF/EN/ISO 15189 standard. However, technical accreditation guidelines cannot be applied literally for the determination of specific IgE for several reasons: more than 600 allergen tests, lack of international gold standard, limited external quality controls. Furthermore, the technique for determination of specific IgE is CE DM-IVD marked, common to all specificities, automatised, standardized according to a single calibration curve. Thus, we propose an efficient but reasonable solution conform to the idea of the accreditation by validating the process. We recommend: a flexible extend type A; choice of only one representative allergen (Dermatophagoides pteronyssinus) for repeatability and precision (20 tests, 2 levels 0.5-1 and 8-12 kUA/L) performed on patients sera, reproducibility (30 consecutive determinations using an Internal Quality Control/IQC), accuracy (IQC and rare External Quality Controls) compared with peers. Sensitivity, specificity, dynamic range, detection threshold are determinated by the provider. Linearity may be checked if the laboratory practices sample dilution for values higher than the upper limit guaranteed by the provider. In the absence of international gold standard, the uncertainty is not measurable. In case of change of instrument, the results obtained by the systems must be compared through 35 tests of different specificities distributed across the range of calibration and including 5 values close to the detection limit. This methodology allows a scientifically effective verification, technically and financially reasonable, to ensure the excellence of the performance of the laboratory with regard to peers and users (allergologists and patients).

Roscovitine, a specific inhibitor of MPF kinase activity, has been shown to block efficiently and reversibly the meiotic resumption of oocytes from different species, including cattle. In view to verify that oocytes maintain germinal vesicle like molecular activities under roscovitine treatment, we compared in the present study the M-phase Promoting Factor (MPF) and Mitogen Activated Protein (MAP) kinase activities; protein synthesis and phosphorylation patterns in oocytes and cumulus cells; and CDK1 and Cyclin B messengers storage under control culture and under roscovitine inhibition. We observed that roscovitine induced a full and reversible inhibition of MPF kinase activity and of the activating phosphorylation of both ERK1/2 MAPK. During in vivo maturation, there was a highly significant increase in the relative mRNA level of both cyclin B1 and CDK1 whereas during in vitro culture, the relative amount of CDK1 messenger was reduced. These messengers may be used as markers for the optimization of in vitro maturation treatment. Roscovitine reversibly prevented this drop in relative quantities of CDK1 messenger. Oocytes cultured in the presence of roscovitine maintained a GV like profile of protein synthesis except that two proteins of 48 and 64 kDa specific of matured oocytes also appeared under roscovitine treatment. However, roscovitine did not prevent most of the modifications of protein phosphorylation pattern observed during maturation. In conclusion, results of this study revealed that the use of roscovitine did not prevent all the events related to maturation of bovine oocytes., (Copyright 2004 Wiley-Liss, Inc.)

The main limit of in vitro production of domestic mammal embryos comes from the low capacity of in vitro matured oocytes to develop after fertilization. As soon as they are separated from follicular environment, oocytes spontaneously resume meiosis without completion of their terminal differentiation. Roscovitine (ROS), an inhibitor of M-phase promoting factor (MPF) kinase activity reversibly blocks the meiotic resumption in vitro. However, in cattle maturing oocytes several cellular events such as protein synthesis and phosphorylation, chromatin condensation and nuclear envelope folding escape ROS inhibition suggesting the alternative pathways in oocyte maturation. We compared the level of synthesis and phosphorylation of several protein kinases during bovine cumulus oocyte complex (COC) maturation in vitro in the presence or not of epidermal growth factor (EGF) and ROS. We showed that during the EGF-stimulated maturation, ROS neither affected the decrease of EGF receptor (EGFR) nor did inhibit totally its phosphorylation in cumulus cells and also did not totally eliminate tyrosine phosphorylation in oocytes. However, ROS did inhibit the Phosphoinositide 3-kinase (PI3) activity when oocytes mature without EGF. Accumulation of Akt/PKB (protein kinase B), JNK1/2 (jun N-terminal kinases) and Aurora-A in oocytes during maturation was not affected by ROS. However, the phosphorylation of Akt but not JNKs was diminished in ROS-treated oocytes. Thus, PI3 kinase/Akt, JNK1/2 and Aurora-A are likely to be involved in the regulation of bovine oocyte maturation and some of these pathways seem to be independent to MPF activity and meiotic resumption. This complex regulation may explain the partial meiotic arrest of ROS-treated oocytes and the accelerated maturation observed after such treatment., (Copyright 2004 Wiley-Liss, Inc.)