Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma

Calidad de vida; Sarcoma de tejido blando localmente avanzado; RadioterapiaQualitat de vida; Sarcoma de teixit tou localment avançat; RadioteràpiaQuality of life; Locally advanced soft-tissue sarcoma; Radiation therapyPurpose Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. Methods and Materials Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. Results During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. Conclusions NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit–risk ratio of NBTXR3 plus RT

Rituximab in addition to LMB-based chemotherapy regimen in children and adolescents with primary mediastinal large B-cell lymphoma: results of the French LMB2001 prospective study

Primary mediastinal large B-cell lymphoma (PMLBL) is a rare entity predominantly affecting adolescents and young adults. Recently, an international phase II trial in pediatric patients using dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) failed to reproduce excellent survival reported in some adult studies. The optimal therapy regimen needs to be determined in this disease. The French prospective LMB2001 trial included all patients ≤18 years with mature B-cell lymphoma treated in French centers. For patients with PMLBL, treatment included four to eight courses of Lymphomes Malins B (LMB)-based chemotherapy without radiotherapy. From 2008, rituximab was added before each chemotherapy course. From 09/2001 to 03/2012, 42 patients with PMLBL were registered. The median age was 15 years (range, 8-18). Twenty-one patients were treated with chemotherapy plus rituximab. The median follow-up was 7.1 years (interquartile range, 5.8-11.1). Five-year event-free and overall survival were 88.1% (95% confidence interval (CI): 75.0-94.8) and 95.2% (95% CI: 84.0-98.7) for the whole population. The 5-year EFS was 81.0% (95% CI: 60.0-92.3) and 95.2% (95% CI: 77.3-99.2) (hazard ratio =0.24; 95% CI: 0.03- 2.2) and 5-year overall survival was 90.5% (95% CI: 71.1-97.3) and 100% for patients treated without and with rituximab, respectively. Only one of 21 patients treated with rituximab and LMB-based chemotherapy had local early treatment failure but achieved prolonged complete remission with second-line chemotherapy and radiotherapy. Intensive LMBbased chemotherapy with rituximab achieved excellent survival in children/adolescents with PMLBL. Further international prospective studies are required to confirm these results in this population

Helical tomotherapy craniospinal irradiation in primary brain tumours: Toxicities and outcomes in a peadiatric and adult population

Objective: As craniospinal irradiation (CSI) is delivered more frequently by helical tomotherapy (HT) with few reports about late effects, we analysed all patients treated in our centre over an 11-year period. Methods and materials: Our study included all patients that underwent CSI by HT, between September 2009 and January 2020, in the Department of Radiation Oncology of the Toulouse Cancer Institute. Acute radiotherapy toxicities were reported and medium- to long-term outcomes analysed. Results: Among the 79 patients included, 70.9 % were younger than 18 years at diagnosis, the median age was 13 (range: 1–52) at the time of radiation therapy, 67.1 % of patients had medulloblastoma. Half of them (49.4 %) had a metastatic disease at diagnosis. The median dose of CSI was 36 Gy (range, 18–36). Seventy-seven patients received a radiation boost to the original location of the primary tumour (97.5 %), 32 patients also received a boost to their metastatic sites (40.5 %). Median follow-up was 55.5 months (95 %CI = [41.2; 71.8]). The 3-year event-free survival rate was 66.3 % (95 %CI = [54.2; 75.9]). Most patients presented with acute haematological toxicities during CSI (85.9 %), predominantly severe thrombocytopenia (39.7 %). Among the 64 patients assessed for medium- and long-term outcomes, 52 survived and 47 were alive and disease-free at the latest follow-up visit on record. There were 3.8 % secondary tumours: two meningiomas and one diffuse intrinsic pontine glioma. Adult and paediatric patients respectively presented with secondary cataract (4.3 % vs 22.0 %), persistent hearing disorders (26.1 % vs 29.3 %), pulmonary or cardiac late effects (4.3 % vs 2.4 %), hormonal pituitary gland deficiencies (30.0 % vs 56.8 %) and psycho-cognitive disorders (56.5 % vs 53.7 %). Conclusion: CSI dispensed by HT, did not result in any additional acute or late toxicities when compared to 3D-CSI. There was no increase in the secondary tumour rate compared to that reported in the literature

Apport des forages profonds aux reconstitutions paléoenvironnementales et paléoclimatiques des bassins carbonifères à permiens du nord-est du Massif Central

National audienc

Palaeoenvironmental reconstitutions of the late Carboniferous to Permian intracontinental basins of the north-eastern Massif Central (France)

International audienc

Ponatinib in childhood Philadelphia chromosome–positive leukaemias: an international registry of childhood chronic myeloid leukaemia study

International audienceBackground: Ponatinib is effective in adults with Philadelphia chromosome-positive (Ph+) leukaemias, but scant data are available regarding the use of this tyrosine kinase inhibitor in children.Aims: The aim of this study isto describe the tolerance and efficacy of compassionate use of ponatinib in a paediatric cohort of patients with Ph+ leukaemias.Methods: Data from 11 children with chronic myeloid leukaemia (CML) registered to the international registry of childhood chronic myeloid leukaemia and from 3 children with Ph+ acute lymphoblastic leukaemia (Ph+ ALL) treated with ponatinib were collected retrospectively.Results: In 11 girls and 3 boys (median age 14 years), ponatinib was used as a second- to eighth-line treatment. Ponatinib was administered as single therapy (9 patients) or in combination with chemotherapy (8 patients). The status of the disease when ponatinib was started was as follows: CML in advanced phases (n = 8), CML in chronic phase without achievement of molecular response (n = 2) or presence of T315I mutation (n = 1) and Ph + ALL in molecular (n = 1) or marrow (n = 2) relapses. The median dose administered was 21.4 mg/m2 and median duration of ponatinib was 2.5 months. Ponatinib alone or in combination with chemotherapy administered on 16 occasions led to achievement of major molecular response in 50% of cases. Ponatinib was used as a bridge to transplant in 4 cases. Among the 9 patients treated with ponatinib alone, toxicity grade III-IV (2 patients) was exclusively haematologic. No vascular events related to ponatinib were observed.Conclusion: Ponatinib may be a reasonable additional treatment option for children with Ph+ leukaemias who have failed several lines of therapy

Brachytherapy for uterine cervix-limited acute myeloid leukemia relapse

Acute myeloid leukemia (AML) may extend to extra-medullary sites at diagnosis or at relapse, either isolated or associated with bone marrow disease. Granulocytic sarcoma of uterine cervix is rare, and there is no established treatment for this disease. Two cases of uterine cervix-limited AML relapse showed that brachytherapy may be an effective therapeutic option in this setting along with chemotherapy, with good tolerance

Radiother Oncol

To evaluate efficacy and feasibility of high-dose intensity-modulated radiotherapy (RT) with pre-operative helical tomotherapy, delivering 54 Gy/30 fractions in patients with retroperitoneal liposarcomas (RPLS). Patients with operable, biopsy-proven, RPLS were included in this phase II multicenter study (ClinicalTrials.gov: NCT01841047). The primary objectives were to analyze loco-regional relapse free survival (LRFS), overall survival (OS) and toxicities, graded according to CTCAE V3.0. From April 2009 to September 2013, 48 patients were included. Histological types were: 20 well differentiated and 28 dedifferentiated liposarcomas. Median clinical target volume (CTV) was 2570 cc (range, 230-8734 cc). The radio-surgical schedule was completed as planned in all patients apart from one. A monobloc wide excision was achieved for all patients. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1, 2%).With a median follow-up of 5.5 years, 3-year LRFS rate was 74.2% (95%CI: [59.1%; 84.5%]). At 5 years, cumulative incidence of loco-regional relapse for well differentiated and dedifferentiated RPLS was 10% and 18%, respectively. The 5-year OS was 73.9% [95%CI: 58.7-84.3%]. During RT, the most common grade 3-4 adverse events were hematological (N = 20; 41.6%). After surgery and during follow-up, 17 patients (35.4%) presented a grade 3-4 toxicity. Two patients (4.1%) died due to a duodenal toxicity. Nine second cancers were observed. From this phase II trial of preoperative RT in RPLS patients, the dose level proposed cannot be considered safe, leading to non-negligible toxicity and second cancers rates. Our results, combined with STRASS-1 study, suggest that the ideal indication of RT for patients with RPLS still remains to be determined

Long-term side effects of radiotherapy for pediatric localized neuroblastoma

International audienceIntroduction - Neuroblastoma (NB) is the most frequent indication for extracranial pediatric radiotherapy. As long-term survival of high-risk localized NB has greatly improved, we reviewed treatment-related late toxicities in pediatric patients who received postoperative radiotherapy (RT) for localized NB within two French prospective clinical trials: NB90 and NB94. Patients and methods - From 1990-2000, 610 children were enrolled. Among these, 35 were treated with induction chemotherapy, surgery, and RT. The recommended RT dose was 24 Gy at ≤ 2 years, 34 Gy at > 2 years, ± a 5 Gy boost in both age groups. Results - The 22 patients still alive after 5 years were analyzed. The median follow-up time was 14 years (range 5-21 years). Late effects after therapy occurred in 73 % of patients (16/22), within the RT field for 50 % (11/22). The most frequent in-field effects were musculoskeletal abnormalities (n = 7) that occurred only with doses > 31 Gy/1.5 Gy fraction (p = 0.037). Other effects were endocrine in 3 patients and second malignancies in 2 patients. Four patients presented with multiple in-field late effects only with doses > 31 Gy. Conclusion - After a median follow-up of 14 years, late effects with multimodality treatment were frequent. The most frequent effects were musculoskeletal abnormalities and the threshold for their occurrence was 31 Gy

Metabolic activity determines survival depending on the level of lymph node involvement in cervical cancer

Abstract Background To assess the impact of PET/CT functional parameters on survival, locoregional, and distant failure according to the most distant level of lymph node [18F]FDG uptake in patients with locally advanced cervical cancer (LACC). Methods Retrospective study including 148 patients with LACC treated with concurrent chemoradiotherapy after PET/CT and para-aortic lymph node (PALN) surgical staging. Two senior nuclear medicine physicians reviewed all PET/CT exams and retrieved tumor and lymph node metabolic parameters: SUVmax, MTV, TLG. Oncological outcomes according to metabolic parameters and level of lymph node spread on PET/CT were assessed. Results In patients without lymph node uptake on PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 5.14 95%CI = [2.15–12.31]), OS (HR = 6.10 95%CI = [1.89–19.70]), and time to distant (HR = 4.73 95%CI = [1.55–14.44]) and locoregional recurrence (HR = 5.18 95%CI = [1.72–15.60]). In patients with pelvic lymph node (PLN) uptake but without PALN uptake on [18F]FDG-PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 3.17 95%CI = [1.02–9.83]) and OS (HR = 3.46 95%CI = [0.96–12.50]), and the number of PLN fixations was associated with DFS (HR = 1.30 95%CI = [1.10–1.53]), OS (HR = 1.35 95%CI = [1.11–1.64]), and time to distant (HR = 1.35 95%CI = [1.08–1.67]) and locoregional recurrence (HR = 1.31 95%CI = [1.08–1.59]). There was no significant association between cervical tumor metabolic or lymph node metrics and survival outcome in patients with PALN uptake. Conclusions Cervical MTV is more accurate than SUVmax to predict survival outcome in patients with locoregional disease confined to the pelvis and should be implemented in routine clinical practice. Prognostic value of metabolic metrics disappears with PALN uptake, which is associated with distant failure in nearly half of patients. Graphical Abstrac