Thiotepa‐based versus total body irradiation‐based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long‐established ones. This retrospective matched‐pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa‐based (n = 121) or a cyclophosphamide/total body irradiation‐based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA‐matched sibling or an unrelated donor. With a median follow‐up of 44 months, the outcome was similar in both groups. Acute graft‐versus‐host disease grade II‐IV was observed in 25% after thiotepa‐containing regimen versus 35% after TBI (P = 0.06). The 2‐yr cumulative incidence of chronic graft‐versus‐host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non‐relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia‐free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.     

A single-gradient junction technique to replace multiple-junction shifts for craniospinal irradiation treatment

Craniospinal irradiation (CSI) requires abutting fields at the cervical spine. Junction shifts are conventionally used to prevent setup error–induced overdosage/underdosage from occurring at the same location. This study compared the dosimetric differences at the cranial-spinal junction between a single-gradient junction technique and conventional multiple-junction shifts and evaluated the effect of setup errors on the dose distributions between both techniques for a treatment course and single fraction. Conventionally, 2 lateral brain fields and a posterior spine field(s) are used for CSI with weekly 1-cm junction shifts. We retrospectively replanned 4 CSI patients using a single-gradient junction between the lateral brain fields and the posterior spine field. The fields were extended to allow a minimum 3-cm field overlap. The dose gradient at the junction was achieved using dose painting and intensity-modulated radiation therapy planning. The effect of positioning setup errors on the dose distributions for both techniques was simulated by applying shifts of ± 3 and 5 mm. The resulting cervical spine doses across the field junction for both techniques were calculated and compared. Dose profiles were obtained for both a single fraction and entire treatment course to include the effects of the conventional weekly junction shifts. Compared with the conventional technique, the gradient-dose technique resulted in higher dose uniformity and conformity to the target volumes, lower organ at risk (OAR) mean and maximum doses, and diminished hot spots from systematic positioning errors over the course of treatment. Single-fraction hot and cold spots were improved for the gradient-dose technique. The single-gradient junction technique provides improved conformity, dose uniformity, diminished hot spots, lower OAR mean and maximum dose, and one plan for the entire treatment course, which reduces the potential human error associated with conventional 4-shifted plans.     

Long-term outcomes of APBI via multicatheter interstitial HDR brachytherapy: Results of a prospective single-institutional registry

PurposeLong-term outcome reports of accelerated partial-breast irradiation (APBI) are limited. Here, we report the 10-year outcomes of APBI delivered using multicatheter interstitial implant (ISI) brachytherapy.Methods and materialsPatients with early-stage breast cancer treated with APBI via ISI brachytherapy were enrolled in a prospective registry. Selection criteria included age ≥40 years, ductal carcinoma in situ or invasive tumor ≤3 cm, negative margins (≥2 mm), and negative axillary nodes. 34 Gy in 10 twice-daily fractions was administered to 2 cm of breast tissue surrounding the surgical bed. Toxicity and cosmetic outcomes were collected prospectively.ResultsA total of 175 patients were included. The median followup time was 10.0 years. Ten-year ipsilateral breast tumor control, regional control, freedom from distant metastasis, breast cancer–specific survival, and overall survival were 92.1%, 96.9%, 97.4%, 97.1%, and 81.2%, respectively. High-grade disease was correlated with increase in the rate of ipsilateral breast tumor recurrence. Grade 1 or 2 skin toxicity was present in 44 patients, and Grade 3 skin toxicity was present in only 1 patient. There were no Grade 4 or higher toxicities observed. Thirty-seven patients developed fat necrosis. Dose Homogeneity Index of ≤0.85 and integrated reference air-kerma of >3400 cGycm²/h correlated with higher rates of fat necrosis. There were 115 (66%), 51 (29%), 8 (5%), and 0 (0%) patients having excellent, good, fair, and poor cosmetic outcomes, respectively.ConclusionsAPBI using ISI brachytherapy offers excellent clinical outcomes in appropriately selected patients with excellent cosmetic outcomes and low rates of toxicities such as symptomatic fat necrosis.     

Radiothérapie stéréotaxique extracrânienne et oligométastases

In stage IV cancers, locoregional management of primitive tumours as surgery and/or radiotherapy improved both progression-free survival and overall survival. Among metastatic cancer patients, some of them are considered as oligometastatic stage as they present few metastatic sites associated with low tumor aggressiveness. For those patients, metastatic local control, and therefore prolonged time to progression should be reached through local treatments as surgery and/or radiofrequency ablation and/or stereotactic radiotherapy. Here we propose a review of oligometastatic stage and results from extracranial stereotactic radiotherapy in terms of efficacy and tolerance.     

Effects of ultrasound irradiation on enzymatic hydrolysis of protein and application for the determination of tetracyclines in complex matrices

The widespread use of tetracyclines (TCs) in food animals has led to concerns regarding unsafe residue levels in feed, food and manure. The determination of TCs in such matrices suffers from interference by the interactions between proteins and TCs. Three deproteination methods were compared in this study. In contrast with acid deproteination, which caused a large loss of TCs due to the strong adsorption of TCs on protein precipitates, a normal enzymatic hydrolysis was confirmed to have a merit of effectively releasing TCs from protein matrices, but required treatment time as long as 16 h. The adoption of ultrasound irradiation was proposed to shorten the enzymatic hydrolysis time. After investigating the effects of ultrasound power and irradiation time, the conditions of the ultrasound‐enhanced enzymatic hydrolysis were optimized as ultrasound power of 100 W and irradiation time of 6 min. The ultrasound‐enhanced enzymatic hydrolysis treatment of 6 min yielded recovery of TCs (from protein‐containing matrices) as high as that obtained by the normal enzymatic hydrolysis treatment of 16 h. The acceleration effect of ultrasound irradiation was attributed to ultrasound‐induced cavitation, which increased exposure of both the functional groups of trypsin and the C‐terminal amino acid in the protein that was a cleavage site for trypsin attack. When the ultrasound‐enhanced enzymatic hydrolysis method was used to determine TCs in complex matrices, it was found that this new method achieved recoveries of 89.5, 117.7, 110.4 and 100.0% for oxytetracycline, tetracycline, chlortetracycline and doxycycline, being much higher than those (29.6–39.4%) obtained using the common acid deproteination process. Copyright © 2017 John Wiley & Sons, Ltd.     

TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice

Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation.     

Accelerated partial breast irradiation with interstitial multicatheter brachytherapy after breast-conserving surgery for low-risk early breast cancer

Patients with low-risk invasive ductal carcinoma treated with breast-conserving surgery (BCS) were included in a multicatheter brachytherapy APBI protocol. The primary endpoint was ipsilateral breast recurrence. Between December 2008–December 2017, 186 low-risk breast cancer patients were treated with APBI using interstitial multicatheter brachytherapy and followed prospectively. At 5-years of follow-up, cumulative local recurrence (LR) and cause-specific survival was 1.1% (95% CI 0.3–1.9) and 98.3% (95% CI 97.3–99.3%) respectively. No grade 3 adverse effects were observed. Postoperative APBI using multicatheter brachytherapy after BCS in early breast cancer patients have excellent rates of local control and survival, without significant toxicity.     

Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer Patients: Secondary Findings From the Prospective Randomized Phase 3 CONVERT Trial

Introduction

The impact of the dose and fractionation of thoracic radiotherapy on the risk of developing brain metastasis (BM) has not been evaluated prospectively in limited stage SCLC patients receiving prophylactic cerebral irradiation (PCI).