Nuclear PRMT5 is a biomarker of sensitivity to tamoxifen in ERα+ breast cancer.

Endocrine therapies targeting estrogen signaling, such as tamoxifen, have significantly improved management of estrogen receptor alpha (ERα)-positive breast cancers. However, their efficacy is limited by intrinsic and acquired resistance to treatment, and there is currently no predictive marker of response to these anti-estrogens to guide treatment decision. Here, using two independent cohorts of breast cancer patients, we identified nuclear PRMT5 expression as an independent predictive marker of sensitivity to tamoxifen. Mechanistically, we discovered that tamoxifen stimulates ERα methylation by PRMT5, a key event for its binding to corepressors such as SMRT and HDAC1, participating in the inhibition of the transcriptional activity of ERα. Although PRMT5 is mainly localized in the cytoplasm of tumor cells, our analyses show that tamoxifen triggers its nuclear translocation in tamoxifen-sensitive tumors but not in resistant ones. Hence, we unveil a biomarker of sensitivity to tamoxifen in ERα-positive breast tumors that could be used to enhance the response of breast cancer patients to endocrine therapy, by fostering its nuclear expression.

A Digital Solution for an Advanced Breast Tumor Board: Pilot Application Cocreation and Implementation Study.

BACKGROUND: Cancer treatment is constantly evolving toward a more personalized approach based on clinical features, imaging, and genomic pathology information. To ensure the best care for patients, multidisciplinary teams (MDTs) meet regularly to review cases. Notwithstanding, the conduction of MDT meetings is challenged by medical time restrictions, the unavailability of critical MDT members, and the additional administrative work required. These issues may result in members missing information during MDT meetings and postponed treatment. To explore and facilitate improved approaches for MDT meetings in France, using advanced breast cancers (ABCs) as a model, Centre Léon Bérard (CLB) and ROCHE Diagnostics cocreated an MDT application prototype based on structured data. OBJECTIVE: In this paper, we want to describe how an application prototype was implemented for ABC MDT meetings at CLB to support clinical decisions. METHODS: Prior to the initiation of cocreation activities, an organizational audit of ABC MDT meetings identified the following four key phases for the MDT: the instigation, preparation, execution, and follow-up phases. For each phase, challenges and opportunities were identified that informed the new cocreation activities. The MDT application prototype became software that integrated structured data from medical files for the visualization of the neoplastic history of a patient. The digital solution was assessed via a before-and-after audit and a survey questionnaire that was administered to health care professionals involved in the MDT. RESULTS: The ABC MDT meeting audit was carried out during 3 MDT meetings, including 70 discussions of clinical cases before and 58 such discussions after the implementation of the MDT application prototype. We identified 33 pain points related to the preparation, execution, and follow-up phases. No issues were identified related to the instigation phase. Difficulties were grouped as follows: process challenges (n=18), technological limitations (n=9), and the lack of available resources (n=6). The preparation of MDT meetings was the phase in which the most issues (n=16) were seen. A repeat audit, which was undertaken after the implementation of the MDT application, demonstrated that (1) the discussion times per case remained comparable (2 min and 22 s vs 2 min and 14 s), (2) the capture of MDT decisions improved (all cases included a therapeutic proposal), (3) there was no postponement of treatment decisions, and (4) the mean confidence of medical oncologists in decision-making increased. CONCLUSIONS: The introduction of the MDT application prototype at CLB to support the ABC MDT seemed to improve the quality of and confidence in clinical decisions. The integration of an MDT application with the local electronic medical record and the utilization of structured data conforming to international terminologies could enable a national network of MDTs to support sustained improvements to patient care.

Pembrolizumab in Lymphopenic Metastatic Breast Cancer Patients Treated with Metronomic Cyclophosphamide: A Clinical and Translational Prospective Study.

Purpose: Metastatic endocrine-resistant breast cancer (MBC) is a disease with poor prognosis and few treatment options. Low lymphocyte count is associated with limited overall survival. In a prospective cohort of lymphopenic patients with HER-2 negative MBC, we assessed the clinical and biological impact of pembrolizumab combined with metronomic cyclophosphamide. Experimental Design: This multicenter Phase II study evaluated the safety and clinical activity of pembrolizumab (intravenous (IV), 200mg, every 3 weeks) combined with metronomic cyclophosphamide (50mg/day, per os) in lymphopenic adult patients with HER2-negative MBC previously treated by at least one line of chemotherapy in this setting according to a Simon's minimax two-stage design. Blood and tumor samples were collected to assess the impact of the combined treatment on circulating immune cells and the tumor immune microenvironment through multiparametric flow cytometry and multiplex immunofluorescence analyses. Primary endpoint was the clinical benefit rate at 6 months of treatment (CBR-6M). Secondary endpoints were objective response rate (ORR), duration of response, progression free survival (PFS), and overall survival (OS). Results: Two out of the twenty treated patients presented clinical benefit (one Tumor Mutational Burden (TMB)-high patient with complete response (CR) and one patient with objective response (OR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) associated with a strong increase of cytokine-producing and proliferating CD4+ T cells and higher CD8+ T cells to macrophage ratios in the tumor. This impact on CD4+ and CD8+ T cell polyfunctionality was still observed more than one year for the patient with CR. A decreased in their absolute number of CD4+ and CD8+ memory T cells was observed in other patients. Conclusion: Pembrolizumab combined with metronomic cyclophosphamide was well tolerated, and displayed limited anti-tumoral activity in lymphopenic MBC. Correlative translational data of our trial advocates for additional studies with other chemotherapy combinations.

Cardiovascular Diseases Following Breast Cancer: Towards a Case-by-Case Assessment Through a Prediction Risk Score Model in 943 Patients.

OBJECTIVES: To identify patients at high risk of developing cardiovascular disease through the identification of risk factors among a large population of breast cancer women and to assess the performance of Abdel-Qadir risk prediction model score. MATERIALS AND METHODS: The medical records and baseline characteristics of all patients/tumors diagnosed with breast cancer from 2010 to 2011 in a French comprehensive cancer center were collected. Cardiovascular events were defined as arterial and cardiac events, atrial fibrillation and venous thromboembolism occurring during the 5-year follow-up. Abdel-Qadir multivariable prediction model for major adverse cardiovascular events were used with the concordance index (c-index) score to assess calibration by comparing predicted risks to observed probabilities. RESULTS: Among the 943 breast cancer patients included, 83 patients (8.8%) presented with at least one cardiovascular event, leading to a cumulative incidence of 0.07 at 5 years (95% confidence interval [CI], 0.055-0.088). The cumulative incidence of atrial fibrillation at 5 years was 0.01 (95% CI, 0.005-0.018). Factors associated with the occurrence of cardiovascular events were pre-existing cardiovascular diseases including high blood pressure (hazard ratio [HR]=1.78, 95% CI=1.07-2.97, P=0.028), acute coronary syndrome (HR=5.28, 95% CI: 2.16-12.88, P<0.05) and grade 3 Scarff-Blool-Richardson (HR=1.95, 95% CI: 1.21-3.15, P=0.006). With a c-index inferior to 0.7, the Abdel-Qadir score was not fully validated in our population. CONCLUSION: These findings call for the assessment of the performance of risk prediction models such as Abdel-Qadir score coupled with other factors such as Scarff Bloom and Richardson grading in order to identify patients at high risk of experiencing cardiotoxicity.

Breast cancer treatment-related cardiovascular disturbances: advocacy for a watchful attitude in this never-ending story.

INTRODUCTION: Thanks to the emergence of new therapeutics, prognosis and outcome of breast cancer patients (any subtype) have improved significantly. This raises the issue of the interactions and side effects related to the use of multiple drugs. Thus, to decide on a treatment, the optimal benefit risk-ratio should be carefully watched as toxicities such as cardiac ones effect on long-term survival. Indeed, nowadays in France, cardiovascular diseases rank first as causes of death in women. AREAS COVERED: This non-exhaustive review aims to report the currently available data on cardiac side effects caused by the use of emerging drugs in breast cancer, in localized or metastatic diseases alike. We will focus on HER2-inhibitors, cyclin-dependent-kinase 4/6 and PARP inhibitors, chemotherapy and immunotherapy, before discussing the means of prevention. EXPERT OPINION: Although this issue has largely been studied, the recent emergence of new drugs emphasizes the necessity for oncologists to adapt their practice to a multidisciplinary model that includes cardio-oncology.

Nouvelles stratégies thérapeutiques dans les cancers du sein HER2-surexprimé: New therapeutic strategies in HER2-positive breast cancer.

Breast cancer with HER2-amplification accounts for 20 % of breast cancers. The management of patients has dramatically changed with the advent of anti-HER2 treatment, especially the monoclonal antibodies since 2000 in the metastatic and (neo)-adjuvant setting, leading to an improvement of patient outcomes. If therapeutic arsenal has been gradually enhanced with the targeting of HER receptors family, resistances to these treatments are observed, hence the development of new therapeutic strategies. This review provides an updated look of novel therapeutic strategies in HER2-positive breast cancer, as well as future perspectives, both in the adjuvant and metastatic setting.

Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls?

The AKT protein kinase plays a central role in several interconnected molecular pathways involved in growth, apoptosis, angiogenesis, and cell metabolism. It thereby represents a therapeutic target, especially in hormone receptor-positive (HR) breast cancers, where the PI3K/AKT signaling pathway is largely hyperactivated. Moreover, resistance to therapeutic classes, including endocrine therapy, is associated with the constitutive activation of the PI3K/AKT pathway. Improved knowledge on the molecular mechanisms underlying resistance to endocrine therapy has led to the diversification of the therapeutic arsenal, notably with the development of PI3K and mTOR inhibitors, which are currently approved for the treatment of advanced HR-positive breast cancer patients. AKT itself constitutes a novel pharmacological target for which AKT inhibitors have been developed and tested in clinical trials. However, despite its pivotal role in cell survival and anti-apoptotic mechanisms, as well as in endocrine therapy resistance, few drugs have been developed and are available for clinical practice. The scope of the present review is to focus on the pivotal role of AKT in metastatic breast cancer through the analysis of its molecular features and to discuss clinical implications and remaining challenges in the treatment of HR-positive metastatic breast cancer.

Cardio-Oncology Preclinical Models: A Comprehensive Review.

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.

A Review of the Role of Hypoxia in Radioresistance in Cancer Therapy.

Hypoxia involves neoplastic cells. Unlike normal tissue, solid tumors are composed of aberrant vasculature, leading to a hypoxic microenvironment. Hypoxia is also known to be involved in both metastasis initiation and therapy resistance. Radiotherapy is the appropriate treatment in about half of all cancers, but loco-regional control failure and a disease recurrence often occur due to clinical radioresistance. Hypoxia induces radioresistance through a number of molecular pathways, and numerous strategies have been developed to overcome this. Nevertheless, these strategies have resulted in disappointing results, including adverse effects and limited efficacy. Additional clinical studies are needed to achieve a better understanding of the complex hypoxia pathways. This review presents an update on the mechanisms of hypoxia in radioresistance in solid tumors and the potential therapeutic solutions.

Radioresistance and genomic alterations in head and neck squamous cell cancer: Sub-analysis of the ProfiLER protocol.

BACKGROUND: Genome analysis could provide tools to assess predictive molecular biomarkers of radioresistance. METHODS: Head 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. RESULTS: One 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. CONCLUSION: This sub analysis suggests that PIK3CA mutation, variation of copy number of MAP kinases and apoptosis pathways play a significant role in the radioresistance phenomenon.

TP53 Mutation as a Prognostic and Predictive Marker in Sarcoma: Pooled Analysis of MOSCATO and ProfiLER Precision Medicine Trials.

(1) Background: locally resected high-grade sarcomas relapse in 40% of cases. There is no prognostic or predictive genomic marker for response to peri-operative chemotherapy. (2) Methods: MOSCATO and ProfiLER are pan-tumor prospective precision medicine trials for advanced tumors. Molecular analysis in both trials comprised targeted next-generation sequencing and comparative genomic hybridization array. We investigated if molecular alterations identified in these trials in sarcomas were associated with disease-free survival (DFS) and response to anthracyclines. (3) Results: this analysis included 215 sarcomas, amongst which 53 leiomyosarcomas, 27 rhabdomyosarcomas, 20 undifferentiated pleomorphic sarcomas, and 17 liposarcomas. The most frequently altered gene was TP53 (46 mutations and eight deletions). There were 149 surgically resected localized sarcomas. Median DFS in TP53 wild type (WT), deleted, and mutated sarcomas was 16, 10, and 10 months, respectively (p = 0.028; deletions: HR = 1.55; 95% CI = 0.75-3.19; mutations: HR = 1.70; 95%CI = 1.13-2.64). In multivariate analysis, TP53 mutations remained associated with shorter DFS (p = 0.027; HR = 2.30; 95%CI = 1.10-4.82). There were 161 localized and advanced sarcomas evaluable for response to anthracyclines. Objective response rates were 35% and 55% in TP53 WT and mutated sarcomas, respectively (OR = 2.24; 95%CI = 1.01-5.03; p = 0.05). In multivariate analysis, TP53 mutations remained associated with increased response (OR = 3.24; 95%CI = 1.30-8.45; p = 0.01). (4) Conclusions: TP53 mutations are associated with shorter DFS and increased response to anthracyclines. Post-validation, these findings could assist in decision-making for peri-operative treatments.

[New therapeutic strategies in HER2-positive breast cancer]. / Nouvelles stratégies thérapeutiques dans les cancers du sein HER2-surexprimé.

Breast cancer with HER2-amplification accounts for 20% of breast cancers. The management of patients has dramatically changed with the advent of anti-HER2 treatment, especially the monoclonal antibodies since 2000 in the metastatic and (neo)-adjuvant setting, leading to an improvement of patient outcomes. If therapeutic arsenal has been gradually enhanced with the targeting of HER receptors family, resistances to these treatments are observed, hence the development of new therapeutic strategies. This review provides an updated look of novel therapeutic strategies in HER2-positive breast cancer, as well as future perspectives, both in the adjuvant and metastatic setting.

Cutting Edge: mTORC1 Inhibition in Metastatic Breast Cancer Patients Negatively Affects Peripheral NK Cell Maturation and Number.

NK cells are cytotoxic lymphocytes displaying strong antimetastatic activity. Mouse models and in vitro studies suggest a prominent role of the mechanistic target of rapamycin (mTOR) kinase in the control of NK cell homeostasis and antitumor functions. However, mTOR inhibitors are used as chemotherapies in several cancer settings. The impact of such treatments on patients' NK cells is unknown. We thus performed immunophenotyping of circulating NK cells from metastatic breast cancer patients treated with the mTOR inhibitor everolimus over a three-month period. Everolimus treatment resulted in inhibition of mTORC1 activity in peripheral NK cells, whereas mTORC2 activity was preserved. NK cell homeostasis was profoundly altered with a contraction of the NK cell pool and an overall decrease in their maturation. Phenotype and function of the remaining NK cell population was less affected. This is, to our knowledge, the first in vivo characterization of the role of mTOR in human NK cells.

Effectiveness of a nurse-led telephone follow-up in the therapeutic management of patients receiving oral antineoplastic agents: a randomized, multicenter controlled trial (ETICCO study).

PURPOSE: The use of oral cancer drugs (OAD) has increased over the last two decades. The objective of this study was to measure the impact of a nurse-led telephone follow-up in the therapeutic management of patients treated with an OAD regarding toxicity, medication adherence and quality of life. METHODS: A randomized, multicenter, controlled trial was conducted. All consecutive over 18-year-old patients, treated in medical oncology, radiotherapy, or hematology departments, receiving OAD for any cancer were invited to participate to the study. A total of 183 patients treated for solid or hematological cancers with an OAD were randomly assigned to receive a nurse-led telephone follow-up or standard care for 24 weeks. Data were collected between 2015 and 2018. RESULTS: Nurse telephone follow-up did not improve the global score toxicity in the intervention group. However, telephone calls directed by trained nurses induced a significant decrease in number of patients with grade 3 adverse events throughout the follow-up [OR 0.45 (IC à 95%) (0.23, 0.9)](P = 0.03). There was no significant difference in quality of life and medication adherence between groups at any follow-up time point. CONCLUSIONS: In this first French real-life study, the advice provided by qualified nurses via phone calls improved the management of grade 3 toxicities but failed to demonstrate an improvement of all grades of toxicities. More prospective studies are needed to confirm the impact of telephone calls on the toxicities related to OAD. TRIAL REGISTRATION: Clinical trial registration is NCT02459483. Protection committee SUD-ESTI registration is 2015-A00527-42 on 13 April 2015. National Agency for the Safety of Medicines and Health Products registration is 150619-B on the 27 may 2015.

Body surface area capping may not improve cytotoxic drugs tolerance.

Capping body surface area (BSA) at 2 m2 is a routine clinical practice. It aims at reducing toxicities in over 2 m2 BSA patients. 455,502 computerized chemotherapy prescriptions made between 2011 and 2017 were taken from BPC software. Chemotherapy computerized order entry is created by a senior physician prescribers before patient consultation. Only prescriptions with dose calculation involving BSA were selected. 51,179 chemotherapy prescriptions were analyzed; corresponding to 7206 patients who received intravenous chemotherapy. The number of chemotherapy prescriptions in over 2 m2 BSA patients was nearly the same in the hematology as in the oncology departments. But, 79.1% of prescriptions were capped at 2 m2 in the oncology department contrary to 21.9% in the hematology department. Practices analysis showed more dose limitation in palliative situations in both departments. Unexpectedly, 6.53% of capped prescriptions were performed in patients with normal BMI. The patients who received capped doses of chemotherapy had neither fewer dose reductions due to toxicity nor deterioration of their general condition. Capping did not induce fewer dose reductions in patients with BSA greater than 2 m2. Prospective studies in this population are needed to standardize chemotherapy administration in population with BSA > 2 m2.

Predictive resistance factors in lung cancer patients treated with Nivolumab. Retrospective study.

OBJECTIVES: Immunotherapy is the current treatment in non-small cell lung cancer (NSCLC). 20% of patients treated with immunotherapy have a prolonged response. What about the remaining 80%? How can we explain that some patients get no benefit from immunotherapy? MATERIEL AND METHODS: We retrospectively analyzed predictive factors of primary or secondary resistance to immunotherapy in NSCLC patients from 2 French hospitals between 2015 and 2018. Moreover, we evaluated whether PD1 inhibitor had an impact on the antitumor effects of salvage chemotherapy administered after immunotherapy. We chose to focus on taxanes. RESULTS: Ninety-six patients were included in this cohort, 65(68%) patients were considered as having primary resistance and 31(32%) secondary resistance. Resistant populations did not differ. At immunotherapy initiation, median survival was 4.6 months for primary resistant patients (95%CI-4.6-6.8) and 15.6 months (95%CI-9.8-NA) for secondary resistant patients. The disease control rates with taxane were 15% in pre immunotherapy conditions vs 50% in post immunotherapy. Response rates improved regardless of the status of resistance. CONCLUSION: This study enriches data about immunotherapy in real-life in NSCLC. Prognostic resistance factors still seem complicated to identify. The high rate of taxane responders in post immunotherapy in this retrospective cohort support the use of taxane in therapeutic escape.

Targeted and immune therapies among patients with metastatic renal carcinoma undergoing hemodialysis: A systemic review.

BACKGROUND: Patients with severe renal impairment or undergoing hemodialysis are usually excluded from clinical trials. Available data regarding safety and activity of systemic therapies (ST) in hemodialyzed patients are scarce. METHODS: Clinical data were searched through PubMed database until April 2020 according to PRISMA criteria. Efficacy, safety and pharmacokinetic (PK) assessment of ST were reported. RESULTS: Among 270 references, 56 reports were evaluated in full text: 41 were included for efficacy and 42 for safety analysis (sunitinib n = 68, bevacizumab n = 6, everolimus n = 28, temsirolimus n = 17, sorafenib n = 55, axitinib n = 13, pazopanib n = 13, nivolumab n = 18, cabozantinib n = 0, lenvatinib n = 0, and ipilimumab n = 0). Twelve of the reports included PK assessment among dialyzed patients. Hemodialysis did not seem to modify the expected efficacy and safety of each compound among patients undergoing hemodialysis. PK assessments were not modified in comparison with a population not undergoing dialysis. CONCLUSION: Targeted and Immune therapies seem to be effective and can be used among patients undergoing hemodialysis. Due to frailty and comorbidities associated to chronic hemodialysis enhanced vigilance for these therapies within this specific population is recommended. Dedicated prospective clinical trials would definitely help to obtain data with a higher level of evidence.

Cardiovascular disease events within 5 years after a diagnosis of breast cancer.

BACKGROUND: Concern for cardiovascular disease (particularly atrial fibrillation-AF) among women with breast cancer is becoming a major issue. We aimed at determining the incidence of cardiovascular disease events (AF, arterial and cardiac events, venous-thromboembolism-VTE) in patients diagnosed with breast cancer, and assessing potential risk factors. METHODS: We reviewed medical records of all patients diagnosed with breast cancer from 2010 to 2011 in our cancer center. Baseline characteristics of patients and tumors were collected. The main outcome was the occurrence of cardiovascular disease events (AF, VTE, arterial and cardiac events) during the 5-years follow-up. RESULTS: Among the 682 breast cancer patients, 22 (3.2%) patients had a history of atrial fibrillation. Thirty-four patients (5%) presented at least one cardiovascular disease event, leading to a cumulative incidence of 5.8% events at 5-years ([3.8-7.7] CI 95%), with most of them occurring in the first 2 years. AF cumulative incidence was 1.1% ([0.1-2.1] CI 95%). Factors associated with the occurrence of cardiovascular disease events (including AF) were an overexpression of HER-2 (HR 2.6 [1.21-5.56] p < 0.011), UICC-stage III tumors or more (HR 5.47 [2.78-10.76] p < 0.001) and pre-existing cardiovascular risk factors (HR 2.91 [1.36-6.23] p < 0.004). CONCLUSION: The incidence of cardiovascular disease events was 5.8% ([3.8-7.7] CI 95%), with HER-2 over-expression, UICC-stage III tumors or more and pre-existing cardiovascular diseases being associated with them. These findings call for the development of preventive strategies in patients diagnosed with breast cancer.

[Docetaxel for octogerian metastatic castration-resistant prostate cancer patient: A multicentric ten years' experience]. / Docétaxel dans le cancer de prostate métastatique résistant à la castration chez l'octogénaire : analyse multicentrique de dix ans de pratique.

INTRODUCTION: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSION: 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.

Chemoradiation and granulocyte-colony or granulocyte macrophage-colony stimulating factors (G-CSF or GM-CSF): time to think out of the box?

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.