Search

Scarce data investigate the impact of radiotherapy (RT) on biology markers. An analysis of ancillary study of RIT (Radiation Impact on Thromboembolic events) prospective trial was carried out. All patients with non-metastatic solid tumors and treated with radiotherapy and/or brachytherapy in curative and consenting to have blood samples were included. A significant decrease in white blood count, (i.e. lymphocytes, monocytes, neutrophils and basophils) and platelet counts was observed after RT and maintained at 6 months. Whereas, eosinophils, D-dimers and hemoglobin levels were affected respectively 3 months and 6 months after RT initiation. Conversely, red cells count and CRP level were not affected by RT. This study is an advocacy to develop an understanding of basic immune system in relation with RT.

We report the results from a multicentre retrospective study of 220 adult patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) for therapy-related acute myeloid leukemia (t-AML). Median age at t-AML diagnosis was 56 years, with a prior history of haematological (45%) or gynaecological neoplasia (37%). Median time from cytotoxic exposure to t-AML diagnosis was 54.7 months. At transplant, around 20% of patients had measurable residual disease and 3% of patients were not in complete remission. The median follow-up was 21.4 months (Q1-Q3, 5.9–52.8). At 12 months, overall survival (OS), event-free survival (EFS), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS) were 60.7% (95% CI 54.6–67.5), 52.8% (95% CI 46.5–68.4), and 44.1% (95% CI 37.6–51.8), respectively. At 5 years, OS, EFS, and GRFS were 44.1% (95% CI 37.4–52.1), 40.4% (95% CI 33.9–48.1), and 35.3% (95% CI 28.8–43.3), respectively. At last follow-up, 44% of patients were in complete remission (n = 96) and transplant-related mortality accounted for 39% of all deaths (n = 119). Multivariable analysis revealed that uncontrolled t-AML at transplant was associated with lower EFS (HR 1.94, 95% CI 1.0-3.7, p = 0.041). In conclusion, alloHSCT for t-AML shows encouraging results and offers additional opportunity with the emergence of novel pre-graft therapies.

International audience; Cardiotoxicity is a common side effect induced by cancer therapies, which increases the risk of long-term morbidity and mortality in cancer survivors. To date, the mechanism leading to this toxicity is still unclear, thus complicating cardiac safety assessment and predictive factor identification. The advances in technology, particularly regarding radiation therapy and constant development of novel antineoplastic agents, require urgent development of efficient preclinical models to detect drug cardiotoxicity. A myriad of empirical preclinical models have been used to investigate cardiotoxicity, though with limited success. Recently, multicellular spheroid models have gained attention by mimicking the in vivo microenvironment. The aim of this review is to focus on the most relevant preclinical models used to assess antineoplastic drug- and radiotherapy-related cardiotoxicities, with an overview on their current use. It also aims to discuss the possible directions of translational research in the cardio-oncology field.

Resume La telemedecine est en plein essor, se declinant en differents sous-domaines, dont la teleconsultation. La chronicite des pathologies ainsi que le recours accru aux services de sante sont deux caracteristiques qui placent la teleconsultation comme une solution numerique adaptee aux besoins du patient et des professionnels de sante. La crise sanitaire a rapidement propulse l’implementation de ce dispositif en vie reelle, y compris dans les services d’oncologie medicale, de radiotherapie et d’hematologie. A ce jour, les moyens mis en œuvre pour accelerer le virage numerique sont nombreux pour installer durablement la telemedecine en pratique courante. Nous detaillons, dans cette revue de la litterature, le deploiement historique et juridique de la telemedecine, avec un focus specifique sur la teleconsultation et la teleoncologie.

Resume Objectifs de l’etude La consultation annuelle de suivi apres la radiotherapie d’un cancer de la prostate se resume en un entretien oral avec un oncologue radiotherapeute. L’objectif de ce travail etait de sonder la population cible sur ses connaissances et perceptions de la teleconsultation. Materiel et methodes Une etude prospective a ete menee a l’Institut de cancerologie Lucien Neuwirth chez les patients en cours de traitement ou de suivi au cours du printemps 2019 (n = 158). Un autoquestionnaire a ete elabore pour les besoins de l’etude. La satisfaction et l’enthousiasme du patient ont ete evalues a l’aide d’une echelle visuelle analogique (de 0/10 a 10/10). Resultats Cent cinquante-huit patients ont accepte de repondre a l’enquete. La quasi-totalite de la population utilisait le telephone comme moyen de communication et 56 % des patients disposaient d’une connexion internet. Environ 56 % des patients affirmaient avoir des notions sur la teleconsultation, sans n’avoir jamais eu recours a ce dispositif. Si 60,8 % des patients ne seraient pas opposes a une proposition de teleconsultation avec un enthousiasme d’EVA (Echelle visuelle analogique) mediane de 6/10, les avis etaient partages concernant le mode surveillance : 48,7 % souhaitaient conserver une surveillance classique et 48,7 % envisageaient d’alterner entre consultation presentielle et teleconsultation. Conclusion Cette enquete de faisabilite menee sur une population de seniors montre que la teleconsultation est une option envisageable pour le suivi apres la radiotherapie du cancer de la prostate, meme si un travail d’information et d’education therapeutique sera necessaire pour encadrer cette nouvelle pratique.

Coronavirus disease outbreak has affected all aspect of clinical care including cancer clinical trials. To minimize exposure of frail cancer patients, an implementation of telemedicine was retained. The impact of this implementation on primary and secondary endpoints criteria of ongoing clinical trials was analyzed. Out of 128 oncology clinical trials, 25 (19%) had an implementation of teleconsultation. Poor data reporting induced mainly a bias on qualitative and descriptive primary endpoints than those assessing efficacy (80% vs 20%; p < 0.001). The integration of telemedicine and E-technologies in the medical practices and clinical trials must be designed and validated.

Invasive fungal infections incidence in patients with hematological malignancies is increasing. Air treatment remains an essential preventive measure. Guidelines state that high-risk patients should be housed in units equipped with High-Efficiency Particulate Air filtration. Mobile air-treatment devices may be considered as alternatives or as a complement to the ventilation system. We assessed the decontamination performances of a new mobile air-treatment device in a conventional hematology room. This device connected or not to a plenum combining Ultra-Low Particulate Air filtration and non-thermal catalysis process has been evaluated with or without healthcare activities (one sampling at-rest and triplicate samplings in activity). Environmental particulate, airborne and surface fungal and total mesophilic flora (TMF) samplings were performed with a total of 1800 min of particles counting, 144 air and 240 surface samplings. At-rest, both devices achieved a 2-log decrease of airborne particles, ISO 4 being the maximal particle class reached under the plenum. Whatever the healthcare activities and the location in the room, ISO 7 was the maximal particle class reached. TMF and fungal air contamination were lower during healthcare activities when the air portable cleaners were running. The bed was the area the least contaminated in the room. No differences were observed for surface contamination. This work provides arguments of the efficacy of a new mobile air-treatment device to decrease particle counts and airborne bioburden in real-life conditions. Studies have yet to be conducted to document the impact of these devices on the risk of invasive aspergillosis in immunocompromised patients.

Resume Introduction Peu de donnees existent quant aux patients âges traites pour un cancer de la prostate resistant a la castration metastatique (CPRCM). L’objectif etait d’analyser la prise en charge des patients d’au moins 80 ans traites par docetaxel pour un CPRCM. Materiel et methodes Les donnees des octogenaires traites par docetaxel pour un CPRCM etaient recueillies de facon retrospective de 2009 a 2019 dans trois centres francais. La survie, les caracteristiques cliniques et pathologiques etaient recueillies ainsi que les traitements recus avant et apres docetaxel. Resultats Les donnees de 89 patients ont ete analysees. Au total, 20,2 % avaient recu le regime standard et 79,8 % ont une dose adaptee. Les patients du groupe adapte etaient significativement plus âges que les patients du groupe standard. Les autres caracteristiques cliniques et les scores geriatriques etaient similaires. Les reductions de dose pour toxicite etaient plus frequentes dans le groupe standard que dans le groupe adapte (p = 0,04). La survie globale mediane de la population totale etait de 13,3 mois. Elle etait plus longue dans le groupe standard que dans le groupe adapte (26,1 mois vs. 12,4 mois = 0,009). En analyse multivariee, le docetaxel employe a dose standard etait un facteur pronostic independant. Conclusion Cette etude suggere un reel benefice d’une prise en charge standard, meme chez les patients les plus âges. L’evaluation geriatrique doit permettre, parmi les patients definis comme fragiles par un score de depistage ou par l’oncologue, de depister les patients finalement eligibles au traitement standard.

Stereotactic body radiotherapy (SBRT) is a young technology that can deliver a high dose of radiation to the target, utilizing either a single dose or a small number of fractions with a high degree of precision within the body. Various technical solutions co-exist nowadays, with particular features, possibilities and limitations. Health care authorities have currently validated SBRT in a very limited number of locations, but many indications are still under investigation. It is therefore challenging to accurately appreciate the SBRT therapeutic index, its place and its role within the anticancer therapeutic arsenal. The aim of the present review is to provide SBRT definitions, current indications, and summarize the future ways of research. There are three validated indications for SBRT: un-resecable T1-T2 non small cell lung cancer

The management of patients undergoing immunosuppressive agents is really challenging. Based on precaution principle, it seems mandatory to stop immunosuppressive (or immunomodulating) agents during radiation. Yet, it is impossible in grafted patients. It is possible in patients with autoimmune disease, but in this case, the autoimmune disease might modify patient's radio-sensitivity. We provide a short review about the safety of radiotherapy in grafted/auto-immune patients. The literature is limited with data coming from outdated case-report or case-control studies. It seems that radiotherapy is feasible in grafted patients, but special dose-constraints limitations must probably be considered for the transplant and the other organs at risk. There is very little data about the safety of radiotherapy, when associated with immunomodulating agents. The most studied drug is the methotrexate but only its prescription as a chemotherapy (high doses for a short period of time) was reported. When used as an immunomodulator, it should probably be stopped 4 months before and after radiation. Apart from rheumatoid arthritis, it seems that collagen vascular diseases and especially systemic scleroderma and systemic lupus erythematous feature increased radio-sensitivity with increased severe late toxicities. Transplanted patients and collagen vascular disease patients should be informed that there is very little data about safety of radiation in their case.

Guidelines for tyrosine kinase inhibitor (TKI)-treated chronic phase-chronic myeloid leukemia (CML) management are essentially based on data from clinical research trials; however, real-world data should be valuable for optimizing such recommendations. Here, we analyzed the data collected in the French CML Observatory database, a multicenter real-world cohort (n = 646), using a first-line "intention-to-treat" analysis strategy. This cohort included patients treated with first-line imatinib (n = 484), nilotinib (n = 103), dasatinib (n = 17), imatinib and interferon (n = 9), or second-generation (2G)-TKIs and interferon (n = 29). The cumulative incidence of major molecular response (MMR), MR4, MR4.5 and MR5 confirmed the faster response kinetics with 2G-TKIs. Multivariate analysis identified being a woman and residual disease at month 6 as the main predictive factors of deep molecular response (DMR). Moreover, 30% of patients met the criteria for treatment discontinuation (5 years of treatment and ≥ 2 years of DMR), but only 38% of them stopped treatment. Among the 92 patients who actually discontinued treatment due to optimal response, 31.5% relapsed (48% of them after 6 months of TKI discontinuation). Multivariate analysis identified age and TKI duration as factors positively correlated with treatment-free remission maintenance. Late ( 6 months) relapses were more frequent in patients with the e14a2 BCR::ABL transcript. Relapse rate was higher in patients who stopped TKI before than after 5 years of treatment (52.6% vs 26%; p = 0.040). These results advocate caution concerning early treatment withdrawal, including in patients receiving 2G-TKIs. This still recruiting database is a valuable source of information for the real-world follow-up of patients with CML.

Infections are common with significant mortality and morbidity in patients with graft-versus-host disease (GvHD). Extracorporeal photopheresis (ECP) is an advantageous treatment option for patients with GvHD because it is not immunosuppressive. The objective of this study was to assess the rate of infections and to determine risk factors in patients with GvHD.In a single-center cohort, we retrospectively collected data on infectious episodes by evaluating the clinical records of patients with GvHD treated by ECP since 2011.A total of 47 patients were included in this study. At ECP initiation, there were 10 patients with acute GvHD and 37 with chronic GvHD. At the final follow-up, 200 infectious episodes were diagnosed in 91.5% of patients with an average follow-up of 25.9 months (ie, 1.97 infections per patient per year). Most episodes had positive outcomes as there was no death related to infections, and only six infections required long-term treatment. Higher dose of corticosteroids at the initiation of ECP was significantly associated with a shorter onset of the first infection (hazard ratio [HR] = 2.05; 95% confidence interval [CI] [1.17, 3.57]; P = .013). Unrelated donor transplants were significantly associated with a lower rate of infection (HR = 0.61; 95% CI [0.39, 0.95]; P = .028).The results of our study suggest that ECP is associated with a low infection rate and an optimal clinical efficacy. Thus, ECP is still a suitable treatment for GvHD. Yet, a future study with a larger cohort will be necessary to deepen the identification of risk factors for infection.

Thromboembolic events frequently complicate the course of malignancy and represent a major cause of morbidity and mortality in cancer patients. In contrast to chemotherapy and other systemic therapies, little is known about the impact of ionizing radiations on the incidence of venous thromboembolism (VTE) in cancer patients.In the present prospective study, we aimed to investigate the incidence, management, and outcome of VTE in newly diagnosed cancer patients who received curative radiotherapy.VTE was found in 8 patients, out of 401 patients at a median time of 80 days after radiotherapy initiation. The incidence rate of VTE at 6 months post-treatment was 2% (95% CI, 0.9-3.7), with 50% of cases occurring during the radiotherapy course and 50% of cases in patients who received or were receiving chemotherapy. As none of the patients harbored a personal history of VTE, no prophylactic measure was initiated during cancer therapy. Most patients received monotherapy with low-molecular-weight heparin and were still on surveillance at the end of the study. No specific clinical risk factor was identified that might systematically indicate the need of thromboprophylaxis in the context of curative radiotherapy.Although this pan-cancer descriptive study did not relate an increased risk of short-term thrombosis following ionizing radiation, it provides important insight as a basis for future studies with subcategories of cancer, in order to in fine guide further recommendations in frail patients.NCT02696447.

Acute myeloid leukemias (AMLs) are a group of hematologic malignancies that are heterogeneous in their molecular and immunophenotypic profiles. Identification of the immunophenotypic differences between AML blasts and normal myeloid hematopoietic precursors (myHPCs) is a prerequisite to achieving better performance in AML measurable residual disease follow-ups. In the present study, we applied high-dimensional analysis algorithms provided by the Infinicyt 2.0 and Cytobank software to evaluate the efficacy of antibody combinations of the EuroFlow AML/myelodysplastic syndrome panel to distinguish AML blasts with recurrent genetic abnormalities (n = 39 AML samples) from normal CD45low CD117+ myHPCs (n = 23 normal bone marrow samples). Two types of scores were established to evaluate the abilities of the various methods to identify the most useful parameters/markers for distinguishing between AML blasts and normal myHPCs, as well as to distinguish between different AML groups. The Infinicyt Compass database-guided analysis was found to be a more user-friendly tool than other analysis methods implemented in the Cytobank software. According to the developed scoring systems, the principal component analysis based algorithms resulted in better discrimination between AML blasts and myHPCs, as well as between blasts from different AML groups. The most informative markers for the discrimination between myHPCs and AML blasts were CD34, CD36, human leukocyte antigen-DR (HLA-DR), CD13, CD105, CD71, and SSC, which were highly rated by all evaluated analysis algorithms. The HLA-DR, CD34, CD13, CD64, CD33, CD117, CD71, CD36, CD11b, SSC, and FSC were found to be useful for the distinction between blasts from different AML groups associated with recurrent genetic abnormalities. This study identified both benefits and the drawbacks of integrating multiple high-dimensional algorithms to gain complementary insights into the flow-cytometry data.

International audience; BackgroundGenome analysis could provide tools to assess predictive molecular biomarkers of radioresistance.MethodsHead and neck squamous cell carcinoma patients included in ProfiLER study and who underwent a curative radiotherapy were screened. Univariate and Cox multivariate analyses were performed to explore the relationships between molecular abnormalities, infield relapse and complete tumor response after radiation.ResultsOne hundred and forty-three patients were analyzed. PIK3CA mutation and genomic instability of MAP kinases pathway were found to be prognostic factors of loco-regional relapse in multivariate analysis with respectively HR 0.33, 95% CI 0.13–0.83, p = 0.005 and HR 0.61, 95% CI 0.38–0.96, p = 0.025. Instability of apoptosis pathway was found to be a prognostic factor of complete response after radiotherapy with HR 0.24, 95% CI 0.07–0.88, p = 0.04.ConclusionThis sub analysis suggests that PIK3CA mutation, variation of copy number of MAP kinases and apoptosis pathways play a significant role in the radioresistance phenomenon

Complementary and alternative medicines (CAMs) play more and more a significant role both in France and all over the world. Yet, their definition and their role in cancer treatments legitimately raise concerns. This article aims at establishing a picture of the CAMs admitted by the French Medical Board as well as those which are new or in common medical practices in France. We start with a brief reminder of their origin, their status and how they are used. Then, we review the literature about some of the best clinical trials using CAMs in cancer patients. To finish, we try to understand what makes CAMs so thrilling, but also why they create controversy and which common points they may have with conventional medicine.

Endocrine treatment represents the cornerstone of endocrine-sensitive pre-menopausal early breast cancer. The estrogen blockade plays a leading role in the therapeutic management with surgery, radiotherapy and selective antiestrogen treatment. For several years, selective estrogen receptor modulators, such as tamoxifen, have revolutionized medical care of hormone receptors-positive breast cancer and have conquered the therapeutic arsenal while becoming the gold standard of treatment. Other combinations associating the ovarian function suppression using LHRH agonists with tamoxifen or aromatase inhibitors have been recently investigated, leading to mitigated opinions regarding the clinical benefit of these associations. We propose here a comprehensive overview on existing data and their actualization concerning LHRH analogues, whilst emphasizing benefit-risk balance for this targeted population.

Purpose: It is usual for cancer patients to use complementary and alternative medicines (CAMs) and yet the literature evaluating their efficacy in cancer patients is very limited. The objective of the present study was to report on the nature, frequency of use, and patient-reported outcome of CAMs in a single-center study. Methods: All the consecutive patients treated between November 2017 and June 2018 at the Lucien Neuwirth Cancer Institute (France) were screened. Their reasons for using CAMs and their usage habits were collected. Patients evaluated their benefit. Results: Of the 209 patients screened, 200 patients were included. CAMs ranged from osteopathy, homeopathy, acupuncture, healing touch, magnetism, naturopathy, suction cups, Chinese medicine, reflexology, to hypnosis. CAMs were widely used (n = 166, 83%), the first being osteopathy (n = 99, 49.5%), the second homeopathy (n = 78, 39.0%), and finally acupuncture (n = 76, 38.0%). Whatever the CAM, high satisfaction rates were reported (median satisfaction: 61–81%). CAMs were mainly used to prevent/treat side effects of anticancer treatments (81.2% for healing touch), increase well-being (55.4% for naturopathy), improve the immune system (16.9% for homeopathy), and treat cancer (n = 3, 5.1% for homeopathy). Patients could easily consider using CAMs, as up to 50.8% would have accepted a consultation. Conclusions: The reasons for using CAMs differed among patients. They praised CAMs and kept asking for more information although there is limited evidence about their efficacy in the literature. Thus, prospective randomized controlled trials exploring the safety and efficacy of CAMs in cancer patients are needed.

Innovation in radiotherapy should meet multiple challenges, both technically, biologically, clinically and socially. Scientific, technological and biological advances have resulted in major changes in the implementation, indications, and therapeutic index of radiotherapy over the last century. Based on technical innovations (conformal radiotherapy, intensity modulation, CBCT, stereotactic body radiotherapy and MRI embedded system) and knowledge in cancer biology ("oxygen effect", "checkpoints", targeted therapies, molecular profiles and immunotherapy) highlighted in recent decades, the news in radiotherapy is rich and varied. The 2018 news are particularly focused in the role of hypofractionation in prostate cancer, the use of stereotactic body radiotherapy in oligometastatic patients, the possibility of de-intensify treatment in HPV-related oropharynx cancer, and the combination of short-term androgen deprivation to prostate bed salvage radiotherapy. The present manuscript reviews the 2018 latest advances.

Limited data are available about non-anticancer treatment (NACTs)/radiation combinations. MORSE 02-17 was the first study to report on the interaction resulting from such combinations in a heterogeneous population. Therefore, the aim of this study was to describe acute and late toxicities in a homogenous cohort of cancer patients receiving NACTs and undergoing radiation therapy.An analysis of the RIT (Radiation Impact on Thromboembolic events) prospective trial was carried-out. Patients with non-metastatic solid tumors and treated with radiotherapy and/or brachytherapy in a curative intent between 2016 and 2019 were included. Data about NACTs and toxicities were then collected.Out of 382 patients, 293 were prescribed NACTs (76.7%) with a median number of 3.6 (range: 1-14) NACTs per patient. Among1006 NACTs, the most prescribed drugs were anti-hypertensive, in 153 patients (52.2%). In accordance with MORSE 02-17 data, four of the main side effects of radiotherapy were analysed: genitourinary, gastrointestinal, dermatitis/mucositis and fatigue. Regarding acute and late toxicities -whatever the grade- no statistical difference was found between NACTs classes and these toxicities.When we compared the rates of toxicities with literature data, NACTs did not seem to have a worsening effect. One could conclude that NACTs concomitantly given with RT do not influence toxicity outcome. We then advocate a development of new platform for toxicity profile investigation of drugs-RT combination.

Purpose/Objective(s) Late adverse events following radiotherapy (RT) are tissue complications present in 5 to 10% of RT patients. Deficiencies in DSB (double strand break) repair are associated with a large number of diseases including immunodeficiency and susceptibility to radiation-induced adverse effects. To quantify the patients DSB repair capacities can predict individual radiosensitivity and discriminate patients at high risk of developing radiotoxicity in order to improve their therapeutic management. Materials/Methods A functional fluorescent multiplexed DSB repair assay, NEXT-SPOT, was used to profile simultaneously four DSB repair pathways (HR, NHEJ, SSA and alt-EJ), in peripheral blood mononuclear cells (PBMC) lysates, from a cohort of patients undergoing RT. Patients with either non-metastatic prostate or breast cancers were enrolled and patients’ characteristics (sex, age, BMI), lifestyle habits (smoking and drinking), and concomitant treatments were collected. Radiation-induced adverse events were recorded for at least 6 months after the beginning of RT. The balance between the DSB repair mechanisms in the patients’ PBMC collected before and early during the treatment course was assessed. Impact of different parameters (radiation dose, received treatments, life style) on the DSB repair capacities was evaluated, and the ability of the test to predict radiation-induced adverse effects was determined using Random Forest and Boruta algorithms. Results The DSB repair profile was established before and after few fractions of RT for 149 and 50 patients with breast and prostate cancer, respectively. Radiation-induced cutaneous and gastro-intestinal/genitourinary adverse events were considered, in breast and prostate cancer patients, respectively. The DSB repair activities were compared between patients with and without grade ≥3 adverse events, occurring > 6 months after the beginning of RT. Significant differences were detected on the blood sample taken before the beginning of the treatment. HR and NHEJ were significantly upregulated in patients who developed late grade ≥3 adverse events (P = 0.0005 and 0.0054 respectively). Conversely, the relative contributions of SSA and alt-EJ were down-regulated in these patients (P = 0.0022 and 0.0034, respectively). The best biomarker combination defined with the Random Forest and Boruta algorithms predicted the appearance of severe late adverse events with 100% sensibility and 77% specificity using the blood sample taken before RT. Conclusion With this clinical proof-of-concept we identified blood radiotoxicity biomarkers based on the comprehensive analysis of DSB repair activities. This assay enabled to detect simultaneously defects in all DSB repair pathways and identified patients with an increased risk of late severe radiotoxicity following radiotherapy. These promising results require confirmation on a larger cohort.

Telemedicine is booming with different sub-domains, including telehealth consultation. Pathology chronicity as well as the increased use of health services are two characteristics that underline the importance of telehealth consultation for patient's needs and health professionals. The actual viral pandemic has inadvertently aided the adoption of telehealth, including in medical oncology, radiotherapy and hematology departments. To date, numerous tools are available to accelerate the digital transformation in clinical practice. In this review of the literature, we detail the historical and legal set up of telemedicine, focusing especially on teleconsultation and teleoncology.

Highlights • CDK 4/6 inhibitors - palbociclib, ribociclib and abomaciclib - were approved by EMA. • They are currently prescribed in combination with hormone therapy to treat hormone receptor positive, HER2 negative metastatic or locally advanced breast cancer. • Most pre-clinical studies refer to the synergistic effect of CDK4/6i-radiotherapy combination. • The issue of their safe combined use with palliative or curative radiotherapy has only been explored through limited retrospective data., Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) namely palbociclib, ribociclib and abemaciclib were granted approval by the European Medicines Agency (EMA) between 2017 and 2018. They are currently prescribed in combination with hormone therapy to treat hormone receptor positive, HER2 negative metastatic or locally advanced breast cancer. Their combination with radiotherapy raises safety concerns as preclinical data enlightened their possible synergistic effect. Moreover, data about toxicity when combining CDK4/6i with radiotherapy are scarce. This review of literature focused on the use of CDK4/6i combined with radiotherapy. It aimed at listing every published data about such combination so as to understand its possible resulting toxicity in metastatic breast cancer.

Summary Introduction Radiation therapy is a core modality for cancer treatment. Around 40% of cancer cures include the use of radiotherapy, either as a single strategy or combined with other treatments. In the past decade, substantial technical advances and novel insights into radiobiological properties have considerably improved patients’ outcomes. This study overviewed the landscape of clinical research at our radiotherapy department. Methods We surveyed our institutional database of clinical trials to collect information for completed or ongoing radiation therapy clinical trials, from 2005 to December 2017 at the Lucien Neuwirth cancer institute. Results A total of 31 clinical trials were undertaken during the study period, of which 4 studies (12.9%) were industry-sponsored and 3 studies (9.7%) were launched by our radiotherapy unit. The vast majority of clinical trials (83.9%) were dedicated to unique organ localization, especially urological cancer (prostate or bladder) (42%). We also observed a shift towards more phase II trials during the study period as well as a special focus on elderly population. Over the last decade, the number of included patients increased by a 5.3 fold input, with 135 inclusions before 2011 and 720 inclusions after 2011. Discussion This study provided an observational and comprehensive analysis of radiotherapy research. From a monocentric point-of-view, these results reflected the on-going progress of worldwide radiotherapy research. Based on a 13-years’ experience, this study aimed at highlighting essential cues to ensure efficient and perennial research.

Emerging evidence indicates that in myelodysplastic syndromes (MDS), the bone marrow (BM) microenvironment may also contribute to the ineffective, malignant haematopoiesis in addition to the intrinsic abnormalities of haematopoietic stem precursor cells (HSPCs). The BM microenvironment influences malignant haematopoiesis through indirect mechanisms, but the processes by which the BM microenvironment directly contributes to MDS initiation and progression have not yet been elucidated. Our previous data showed that BM-derived stromal cells (BMSCs) from MDS patients have an abnormal expression of focal adhesion kinase (FAK). In this study, we characterise the morpho-phenotypic features and the functional alterations of BMSCs from MDS patients and in FAK knock-downed HS-5 cells. The decreased expression of FAK or its phosphorylated form in BMSCs from low-risk (LR) MDS directly correlates with BMSCs&rsquo, functional deficiency and is associated with a reduced level of haemoglobin. The downregulation of FAK in HS-5 cells alters their morphology, proliferation, and differentiation capabilities and impairs the expression of several adhesion molecules. In addition, we examine the CD34+ healthy donor (HD)-derived HSPCs&rsquo, properties when co-cultured with FAK-deficient BMSCs. Both abnormal proliferation and the impaired erythroid differentiation capacity of HD-HSPCs were observed. Together, these results demonstrate that stromal adhesion mechanisms mediated by FAK are crucial for regulating HSPCs&rsquo, homeostasis.

Concerns have been raised about potential toxic interactions when colony-stimulating factors (CSFs) and chemoradiation are concurrently performed. In 2006, the ASCO guidelines advised against their concomitant use. Nevertheless, with the development of modern radiotherapy techniques and supportive care, the therapeutic index of combined chemotherapy, radiotherapy, and CSFs is worth reassessing. Recent clinical trials testing chemoradiation in lung cancer let investigators free to decide the use of concomitant CSFs or not. No abnormal infield event was reported after the use of modern radiotherapy techniques and concomitant chemotherapy regimens. These elements call for further investigation to set new recommendations in favour of the association of chemoradiation and CSFs. Moreover, radiotherapy could induce anticancer systemic effects mediated by the immune system in vitro and in vivo. With combined CSFs, this effect was reinforced in preclinical and clinical trials introducing innovative radioimmunotherapy models. So far, the association of radiation with CSFs has not been combined with immunotherapy. However, it might play a major role in triggering an immune response against cancer cells, leading to abscopal effects. The present article reassesses the therapeutic index of the combination CSFs-chemoradiation through an updated review on its safety and efficacy. It also provides a special focus on radioimmunotherapy.

Myeloid sarcoma (MS) are extramedullary tumors of myeloid precursors, generally occurring in a setting of acute myeloid leukemia (AML), chronic myeloid leukemia (CML), myelodysplastic syndromes (MD...

Introduction: About 50% of patients with solid tumors receive radiotherapy (RT) which induces cancer cells death through radiation-induced DNA damage. Five to 10% of these patients experience severe toxicity that can heavily impact their quality of life. The identification of predictive biomarkers to discriminate patients at high risk of developing radiotoxicity is needed to move towards a personalized treatment and to improve the management of these patients. Purpose: The aim of this clinical proof-of-concept was to identify blood radiotoxicity biomarkers based on a comprehensive analysis of several DNA repair activities. We relied on the hypothesis that DNA damage, DNA repair and inflammation are functionally associated and mutually supportive, and related to the appearance of side effects. Methods: 200 patients with either prostate or breast cancer who underwent RT were enrolled at the Lucien Neuwirth Cancer institute. Late radio-induced adverse events were recorded 6 months after the beginning of the treatment. Three blood samples per patient were collected before and early during the treatment course to monitor the ability of enzymes contained in lymphocytes to repair series of DNA lesions immobilized on biochip (Glyco-SPOT assay). We analyzed the association between the Base Excision Repair (BER), the primary pathway responsible for DNA repair during inflammation, and the appearance of severe late radiation-induced effects (3 in the female and 4 in the male cohort). Results: Late severe (Grade ≥3) and late moderate (Grade ≥2) radiation-induced events were recorded. Cutaneous, and gastro-intestinal and genitourinary adverse events, were considered respectively in breast cancer and prostate cancer patients. We observed some significantly lower BER activities in breast cancer patients who developed severe late events compared to those who did not. By contrast, it was the opposite in prostate cancer patients. In both cohort we defined a combination of biomarkers that predicted the appearance of severe late adverse events with 100% sensitivity and 100% negative predictive value using the blood sample taken after the first dose of RT. Conclusion: The risk of late radiotoxicity could be accurately predicted on the basis of combination of BER-related biomarkers. Interestingly, the biomarkers differed in breast and prostate cancer patients suggesting that beyond inflammation, hormone pathway regulation impacted the BER response to ionizing radiation, and the relationship with long-term severe side effects. These results require confirmation on a larger cohort. Citation Format: Giovanna Muggiolu, Libert Libert, Elisabeth Daguenet, Thierry Maillet, Claire Rodriguez-Lafrasse, Sylvie Sauvaigo, Nicolas Magné. A DNA repair biomarker signature to predict radiotherapy side-effects in breast and prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 680.

Introduction: Radiotherapy (RT) can induce with short-term (acute) and long term toxicity. Although acute toxicity is generally well tolerated, long term toxicity might be irreversible and progressive over time. RT induces damage in healthy tissue, triggers inflammation and bystander effects in non-irradiated cells. The toxicity is dependent on many variables and precise knowledge on the responsible mechanisms is still lacking. Purpose: DNA damage, DNA repair and inflammation are known to interplay. Because of the specific involvement of Base Excision Repair (BER) in Reactive Oxygen and Nitrogen species (RONs)-induced lesions and inflammation, we monitored BER activities in patients receiving radiotherapy to investigate glycosylase/AP endonucleases activities as potential biomarkers of radiotoxicity. First, impact of gender, age, concomitant treatment, body mass index (BMI), smoking and alcohol consumption, on basal repair levels, and radiation-induced repair activities were evaluated. Methods: About 220 patients suffering from non-metastatic breast or prostate cancer and treated by radiotherapy (RT) were enrolled by Institut de Cancérologie Lucien Neuwirth. 8 mL of blood was collected prior to RT, 24h after the first radiation dose and before the 6th radiation dose. We then used the Glyco-SPOT assay to quantify BER activities, and nucleases level in lysates prepared from the patients' lymphocytes. Patients were followed-up for at least 6 months. Clinical and toxicity data were collected. All adverse events (AE; acute, sub-acute and late) were scored according to Common Terminology Criteria for Adverse Events. Results: Due to differences in the BER profile between prostate and breast cancer patients, the two groups were analyzed separately. We provide a descriptive overview of recorded AE for each group, according to time period. Some significant specific changes in BER activities where associated with smoking, alcohol consumption, BMI, treatment type and age. Conclusion: Known risk factors significantly affected some BER activities. Males and females should be considered independently for radiotoxicity biomarkers identification using glycosylase/AP endonuclease/nucleases related biomarkers. The identification of possible confounding factors is a prerequisite to any selection of radiotoxicity biomarkers. Citation Format: Sylvie Sauvaigo, Giovanna Muggiolu, Sarah Libert, Elisabeth Daguenet, Claire Rodriguez-Lafrasse, Thierry Maillet, Nicolas Magné. Prospective study for the identification of DNA repair radiotoxicity biomarkers in breast and prostate cancer patients: Cohort description and descriptive statistics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 681.

Background: High dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (ASCT) is widely used in multiple myeloma (MM) patients as upfront and salvage therapy. However, the safety and efficacy of ASCT in patients with renal insufficiency (RI) is controversial, which have led to an inconsistent arbitrary cut-off for creatinine clearance (CrCl) for performing ASCT. Here we analyzed prospectively the outcomes of MM patients with severe RI who underwent ASCT. Methods: We enrolled prospectively 50 newly diagnosed MM patients who had a serum CrCl of Results: The patients characteristics at enrollment are given in Table 1. We focused on 44 patients who were beyond 3 months post-ASCT. Light chain MM was frequent (12%), 10% had high risk cytogenetics, 36% increased serum LDH and 10% extramedullary disease. Induction chemotherapies included bortezomib plus IMiDs in 25/44 patients with ≥2 lines of chemotherapy in 12/44. The pre-transplant disease status was sCR in =5%, CR in =15%, VGPR in =39%, and PR in =41% of patients. The number of days of cytapheresis was 2 or less in 95% of cases and the median number of CD34+ cells collected was 3.3 x 106 (1.3-9.5). The median time from diagnosis to ASCT was 175 days (103-307). HDM was 140 mg/m2 in 42/44 patients and 200 mg/m2 in 2/44. All, except two, received consolidation post ASCT (34% missing) and 52% had maintenance therapy (all lenalidomide except two receiving bortezomib) and 7% had no maintenance (41% pending). Toxicity: We observed one death during the first 100 days post-ASCT, secondary to a septic shock on day 42. The median time to neutrophil engraftment was 12 days (9-68) and to platelet engraftment 13 days (10-70). Among patients receiving RBC transfusions (75%) and platelet transfusions (84%), the median number of RBC transfusions was 3 (1-6) and that of platelet transfusions was 3 (1-10). Response: Nine patients (70%) achieved dialysis independence from the time of diagnosis: 13 patients were on dialysis at diagnosis, 5 at the time of ASCT and 4 three months post-ASCT. Renal function improved post-ASCT in 34% of patients, 14% moving from a CrCl of Conclusions: In this preliminary analysis, HDM with ASCT proved to be safe and effective in MM patients with RI at transplant. We observed one death among 44 patients within the first 3 months post-ASCT. A more detailed report of the toxicity will be presented during the meeting along with the survival. Disclosures Vincent: takeda: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; janssen: Membership on an entity's Board of Directors or advisory committees, Other: Congress support. Mohty:Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Karlin:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Personal fees; Sanofi: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees. Morel:Janssen: Honoraria. Rubio:Medac: Consultancy; Gilead: Honoraria; MSD: Honoraria; Novartis: Honoraria; Neovii: Research Funding.

Introduction: Cancer and anti-cancer therapies are often associated with pain, loss of self-worth, anxiety, and depression. Alternative therapies such as art therapy are available to improve patients’ quality of life, by reducing asthenia, depression, anxiety and pain. Objective: The aim of this study was to assess the effectiveness of art therapy, namely theatre and plastic art workshops, on well-being and quality of life of participants in the Lucien Neuwirth Cancer Institute. Methods: A prospective study was conducted at the Lucien Neuwirth Cancer Institute (France), between April 2018 and July 2018. Cancer patients followed at the Institute have been asked to participate in 10 2-h sessions, once a week, based on theatre and plastic art workshops. Self-report questionnaires were used to evaluate both psychological and quality of life domains, but also satisfaction and well-being, before (pre-test) and after the last session (early post-test), as well as 1-month post-experimentation (late post-test). Results: Among the 14 patients who were enroled, the QLQ-C30 questionnaire revealed a pre-test median score of 50.0, an early post-test score of 51.5, and the late post-test revealed a score of 48.0. The anxiety test revealed median scores of 8.0 (pre-test), 6.0 (early post-test) and 6.0 (late post-test), respectively. The depression test reported median scores of 4.0 (pre-test), 5.0 (early post-test) and 6.0 (late post-test), respectively. The median well-being score difference observed between the beginning and the end of sessions is +2.13. The minimum satisfaction score observed is 3.50 out of 10, and the maximum is 10 out of 10. The median is between 7.00 and 10.00. Conclusions: Art therapy sessions had an impact on patients’ welfare. We also reported a trend towards amelioration of quality of life that could probably be confirmed in a larger population, and potentially with a different methodology.

There is very few data about the management of elderly patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to analyze the management of patients aged 80 and over treated with docetaxel for a mCRPC.Clinical and pathological characteristics of octogerians treated with docetaxel were collected retrospectively from 3 French centers from 2009 to 2019. Patient's outcome, treatments administered before and/or after docetaxel were also analyzed.Data of 89 patients could be analyzed. A total of 20.2 % of patients received the standard regimen and 79.8 % received an adapted one. Patients in the adapted group were significantly older than in standard one. Other patient's characteristics - including the geriatric scales - were similar. Dose reductions for toxicity were more frequent in the standard group (P=0.04). The median overall survival of the total population was 13.3 months. It was longer in the standard group than in the adapted group (26.1 months vs 12.4 months=0.01). In multivariate analysis, the type of docetaxel regimen (standard versus adapted) was an independent predictor of survival.This study suggests the benefit of the standard management even in oldest patients. A geriatric evaluation should certainly be processed in patients with poor oncogeriatric scale in order to select the sub-population able to receive the full dose standard docetaxel regimen.

The management of patients undergoing immunosuppressive agents is really challenging. Based on precaution principle, it seems mandatory to stop immunosuppressive (or immunomodulating) agents during radiation. Yet, it is impossible in grafted patients. It is possible in patients with autoimmune disease, but in this case, the autoimmune disease might modify patient's radio-sensitivity. We provide a short review about the safety of radiotherapy in grafted/auto-immune patients. The literature is limited with data coming from outdated case-report or case-control studies. It seems that radiotherapy is feasible in grafted patients, but special dose-constraints limitations must probably be considered for the transplant and the other organs at risk. There is very little data about the safety of radiotherapy, when associated with immunomodulating agents. The most studied drug is the methotrexate but only its prescription as a chemotherapy (high doses for a short period of time) was reported. When used as an immunomodulator, it should probably be stopped 4 months before and after radiation. Apart from rheumatoid arthritis, it seems that collagen vascular diseases and especially systemic scleroderma and systemic lupus erythematous feature increased radio-sensitivity with increased severe late toxicities. Transplanted patients and collagen vascular disease patients should be informed that there is very little data about safety of radiation in their case.

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.

Stereotactic body radiotherapy (SBRT) is a young technology that can deliver a high dose of radiation to the target, utilizing either a single dose or a small number of fractions with a high degree of precision within the body. Various technical solutions co-exist nowadays, with particular features, possibilities and limitations. Health care authorities have currently validated SBRT in a very limited number of locations, but many indications are still under investigation. It is therefore challenging to accurately appreciate the SBRT therapeutic index, its place and its role within the anticancer therapeutic arsenal. The aim of the present review is to provide SBRT definitions, current indications, and summarize the future ways of research. There are three validated indications for SBRT: un-resecable T1-T2 non small cell lung cancer,3 slow-growing pulmonary metastases secondary to a stabilized primary, and the tumours located close to the medulla. In other situations, the benefit of SBRT is still to be demonstrated. One of the most promising way of research is the ablative treatment of oligo metastatic cancers, with recent studies suggesting a survival benefit. Furthermore, the most recent data suggest that SBRT is safe. Finally, the SBRT combined with immune therapies is promising, since it could theoretically trigger the adaptative anticancer response.

Introduction. Allogeneic stem cell transplantation (SCT) can be curative for those with high-risk or recurrent hematologic cancers including T-cell non-Hodgkin's lymphoma (TCL). For patients lacking an HLA-matched related donor, donor sources such as haplo-identical (Haplo) relatives or cord blood (UCB) represent reasonable alternatives. There is currently little data on the outcome of TCL patients undergoing alternative donor transplantation. The Société Francophone de Greffe de Moelle et de Transplantation Cellulaire (SFGM-TC) conducted this study to evaluate the outcome of recipients of alternate donor allo-SCT for TCL. Methods. 95 patients with non epidermotropic TCL, transplanted between 2003 and 2017, reported to ProMISE (Project Manager Internet Server), an internet-based system shared by 36 Francophone transplantation centers, were reviewed. Comparisons of outcome after transplants from different donors (Haplo, n=41 vs UCB, n=54) were performed with regard to overall survival (OS), non-relapse mortality (NRM), relapse and acute/chronic graft-versus-host disease (aGVHD/cGVHD) incidence. Results. Patients' characteristics are detailed in Table 1. Median age at HSCT was 42.5 (range, 3.6 - 68) years, with an older cohort for the Haplo group (50.7 vs 33.6 for UCB, p< .001). Except for the median year of transplantation (median year 2017 for Haplo vs 2010 for UCB,) and the myeloablative regimen (22% for Haplo vs 48% for UCB, p .009), both Haplo and UCB groups were comparable concerning interval from diagnosis to HSCT, donor/recipient CMV status, sex and ABO mismatch. Patients received a median of 2 (range, 1-5 for Haplo; 1-6 for UCB) therapeutic lines. Twenty-eight (10 in Haplo vs 18 in UCB, p NS) underwent auto- or allo-SCT prior to Haplo or UCB-HSCT. Median time to engraftment was shorter (19 vs 25 days, p .025) in Haplo recipients. According to donor type, no differences were found in univariate analysis for the CI of grade II-IV aGVHD (35% vs 35%, p .88) and cGVHD (30% vs 28%, p .49). Median follow-up was 24 months and 47 months for Haplo and UCB recipients, respectively (p .004). At 12 months, OS was 71% and 50% (p .033), progression-free survival (PFS) 63% and 44% (p .045) and NMR 7% and 26% (p .014) in HSCT from Haplo and UCB, respectively. Relapse incidence was similar following HSCT from Haplo and UCB (32% vs 31%). Conclusion. Based on these first results, our study suggests that Haplo-HSCT is a strategy achieving prolonged survival as compared to UCB donors, due to less toxicity and similar incidence of relapse. An analysis of influencing factors will be further detailed. Figure Disclosures Blaise: Jazz Pharmaceuticals: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria; Sanofi: Honoraria. Socie:Alexion: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Robin:Novartis Neovii: Research Funding.

International audience; How radiotherapy counters immune evasion In conventional radiotherapy (RT), the relative biologic effectiveness of radiation is influenced by radiobiological determinants, the so-called ‘5Rs’: Repair, Repopulation, Redistribution, Reoxygenation, and Radiosensitivity.1 A linear-quadratic model prevails to describe the radiation response of the tumor, in which the α/β ratio is used to characterize the sensitivity of a particular tissue type to fractionation. Fractionation serves to decrease acute, and especially late, toxicity to surrounding normal tissue exposed to RT. Commonly, curative RT is delivered in daily doses of 1.8–2.2 Gy for 5–8 weeks, whereas hypofractionation is defined as a delivery of greater than 2.2 Gy per fraction. With sophisticated advances in RT technologies, delivering higher doses of RT per fraction [i.e. increased biologically effective dose (BED)] in a shorter timeframe appears a safe option. Indeed, increased BED could be achieved with larger fraction sizes relative to conventionally fractionated RT. While early radiobiological studies had found that the major mechanisms of action of radiation were related to DNA damage and subsequent cell death of dividing cells, novel insights on radiation effects have uncovered the immunomodulatory properties of ionizing radiation.2

Complementary and alternative medicines (CAMs) play more and more a significant role both in France and all over the world. Yet, their definition and their role in cancer treatments legitimately raise concerns. This article aims at establishing a picture of the CAMs admitted by the French Medical Board as well as those which are new or in common medical practices in France. We start with a brief reminder of their origin, their status and how they are used. Then, we review the literature about some of the best clinical trials using CAMs in cancer patients. To finish, we try to understand what makes CAMs so thrilling, but also why they create controversy and which common points they may have with conventional medicine.