Waisse Waissi

Very long-term survival has seldom been reported in primary central nervous system lymphoma (PCNSL) We report the updated outcome of patients treated in the C5R protocol from 1982 to 2001 in the Centre Leon Berard with a median follow-up of 35 years. This retrospective analysis included the 43 patients treated within the C5R protocol combining HDMTX ARA-C and alkylating agents, with a consolidation with 20 Gys whole brain radiotherapy (WBRT) and a 30Gys boost. The first cohort includes the 25 patients of the initial C5R publication; the second cohort includes all subsequent 18 patients treated with C5R until 2001 in trials. Thirty-nine deaths are documented. Median OS and PFS are 7.0 years (95%CI:1.9–12.1) and 4.7 years (95%CI: 0.33-9.01) respectively. Three patients are alive disease-free at 27, 28, and 44 years after treatment, 2 retired, 1 professionally active. While no prospective neurocognitive assessment was conducted, 14 patients presented neurocognitive deterioration for a projected incidence of 60% at 20 years. Second primary cancers were reported in 6 patients for a projected incidence of 38% at 20 years. The causes of death were PCNSL, neurotoxicity, and second cancers in 24 (55.8%), 5 (11.6%) and 5 (11.6%) of patients respectively, with 4 (9,3%) deaths during treatment and 1 (2.3%) of unknown cause. Very long-term survivors are observed in PCNSL treated 25 to 44 years ago. Late relapses, late neurocognitive decline and second cancers are common and important causes of deaths.

L’incidence de l’adénocarcinome pancréatique (PDAC) est en nette augmentation en France durant ces dernières années. Son pronostic reste très péjoratif avec une survie globale à 5 ans inférieure à 9%. Environ 30% des patients se présentent avec un cancer localement avancé pouvant bénéficier d’une chimioradiothérapie.Ce travail de thèse a évalué le potentiel de l’inhibition de la PARP par l’olaparib associé à la chimioradiothérapie à base de gemcitabine dans les PDAC. Après avoir montré la radiosensibilisation in vitro sur 4 lignées cellulaires BRCA1/2 sauvage, nous avons validé cette radiosensibilisation in vivo et plus particulièrement avec la protonthérapie. L’analyse des données transcriptomiques après traitement a montré une dérégulation des gènes impliquées dans la régulation des microvésicules, des ARN longs non codants et a identifié une signature associée au traitement par la gemcitabine. Enfin, en évaluant le talazoparib, nous avons montré que la radiosensibilisation est augmenté comparativement à l’olaparib.

Introduction: Soft tissue sarcomas of the extremities (ESTSs) pose significant challenges in treatment and management due to their diverse nature and potential complications. This study aimed to assess complications associated with multimodal treatments involving surgery and radiotherapy (RT) and to identify potential risk factors. Methods: We retrospectively analyzed nonmetastatic ESTS patients treated with surgery and pre- or post-operative RT between 2007 and 2020 in Strasbourg, France. Complications, including wound complications (WCs), lymphedema, acute and chronic RT-related complications, and fractures, were meticulously evaluated. Results: A total of 169 patients diagnosed with localized ESTSs were included, with a median age of 64 years (range 21–94 years). ESTSs primarily occurred proximally (74.6%) and in the lower limbs (71%). The median follow-up was 5.5 years. WCs occurred in 22.5% of patients, with proximal and lower extremity tumors being significant risk factors. Acute RT-related complications included radiodermatitis, with grade ≥ 2 occurring in 43.1% of patients, which was associated with superficial tumors. Three patients had an edema grade ≥ 2. Chronic complications included telangiectasias (21.7%) and fibrosis (38.7%), with higher rates associated with larger PTVs and higher RT doses, respectively. Fractures occurred in 5 patients, mainly in the tibia (40%). Conclusions: Multimodal treatment of ESTSs demonstrated excellent tolerance, with manageable side effects. Numerous risk factors have been highlighted, providing insights for optimizing treatment strategies and enhancing patient care in this rare disease.

Introduction: The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and heterogeneous studies. Methods: We retrospectively analyzed nonmetastatic ESTS patients treated with RT between 2007 and 2020 in Strasbourg, France. We assessed local control (LC), distant control (DC), overall survival (OS), and complications. Results: A total of 169 patients diagnosed with localized ESTS were included. The median age was 64 years (range 21–94 years). ESTS primarily occurred proximally (74.6%) and in the lower limbs (71%). Most tumors were grade 2–3 (71.1%), deep-seated (86.4%), and had R0 margins (63.9%). Most patients were treated with helical tomotherapy (79.3%). The median biologically effective dose (BED) prescribed was 75 BEDGy₄ (range 45.0–109.9). The median follow-up was 5.5 years. The 5- and 10-year LC, DC, and OS rates were 91.7%, 76.8%, and 83.8% and 84.2%, 74.1%, and 77.6%, respectively. According to the univariate analysis, LC was worse for patients who received less than 75 BEDGy₄ (p = 0.015). Deep tumors were associated with worse OS (p < 0.05), and grade 2–3 and undifferentiated pleomorphic sarcoma (UPS) were linked to both shorter DC and shorter OS (p < 0.05). IMRT was associated with longer LC than 3DRT (p = 0.018). Multivariate analysis revealed that patients with liposarcoma had better OS (p < 0.05) and that patients with distant relapse had shorter OS (p < 0.0001). Conclusion: RT associated with surgical resection was well tolerated and was associated with excellent long-term rates of LC, DC, and OS. Compared with 3DRT, IMRT improved local control. Liposarcoma was a favorable prognostic factor for OS. Intermediate- and high-grade tumors and deep tumors were associated with lower DC and OS.

Soft tissue sarcomas of the extremities are rare tumors with various prognostic factors. Their management is debatable due to their inconsistent results within the literature and the lack of large prospective studies. The objective of this systematic review is to analyze the available scientific data on prognostic factors concerning the characteristics of the patients, the disease and the treatments performed, as well as their potential complications, on studies with a median follow-up of 5 years at minimum. A search of articles following the “PRISMA method” and using the PubMed search engine was conducted to select the most relevant studies. Twenty-five articles were selected, according to preestablished criteria. This review provides a better understanding of the prognosis and disease outcome of these tumors. Many factors were described comparing the frequency of occurrence according to the studies, which remain heterogeneous between them. Significant factors that could orient patients to radiotherapy were highlighted. These positive prognostic factors provide valuable insight to optimize radiotherapy treatments for patients treated for soft tissue sarcoma of the extremities.

The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR). From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT. Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04). In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.

Sarcomas gather a heterogeneous group of mesenchymal malignant tumors including more than 150 different subtypes. Most of them represent aggressive tumors with poor prognosis at the advanced stage, despite the better molecular characterization of these tumors and the development of molecular-driven therapeutic strategies. During the last decade, immunotherapy has been developed to treat advanced cancers, mainly thanks to immune checkpoint inhibitors (ICI) such as anti-PD1/PDL1 and later to adoptive immune cell therapies. In this review, we aim to summarize the state of the art of immunotherapy in soft tissue sarcomas (STS). Overall, the clinical trials of ICI that included a wide diversity of STS subtypes reported limited efficacy with some outlying responders. Both emerging biomarkers are of interest in selecting good candidates and in the development of combination therapies. Finally, the recent breakthroughs of innovative adoptive therapies in STS seem highly promising.

Definitive external beam radiotherapy (EBRT) is an unusual treatment of unresectable soft-tissue sarcomas (STS). Recent technical innovations and physical advantages of particle therapies may impro...

Pancreatic ductal adenocarcinoma is a devastating disease with a 5-year overall survival of 9% for all stages. Gemcitabine-based chemoradiotherapy for locally advanced pancreatic cancer is highly toxic. We conducted an in vitro study to determine whether poly(ADP-ribose) polymerase-1 inhibition radiosensitized gemcitabine-based chemotherapy. Human pancreatic cancer cell lines, MIA PaCa-2, AsPC-1, BxPC-3 and PANC-1 were treated with gemcitabine (10 nM) and/or olaparib (1 µM). Low-LET gamma single dose of 2, 5 and 10 Gy radiations were carried out. Clonogenic assay, PAR immunoblotting, cell cycle distribution, γH2Ax, necrotic and autophagic cell death quantifications were performed. Treatment with olaparib alone was not cytotoxic, but highly radiosensitized cell lines, particularly at high dose per fraction A non-cytotoxic concentration of gemcitabine radiosensitized cells, but less than olaparib. Interestingly, olaparib significantly enhanced gemcitabine-based radiosensitization in PDAC cell lines with synergistic effect in BxPC-3 cell line. All cell lines were radiosensitized by the combination of gemcitabine and olaparib, through an increase of unrepaired double-strand, a G2 phase block and cell death. Radiosensitization was increased with high dose of radiation. The combination of olaparib with gemcitabine-based chemoradiotherapy could lead to an enhancement of local control in vivo and an improvement in disease-free survival.