Hospital-based palliative care referrals: determinants in older adults with cancer.

OBJECTIVES: Early palliative care improves the quality of life of older patients with cancer. This work aimed to analyse the effect of sociodemographic, geriatric, and tumour-related determinants on hospital-based palliative care (HPC) referral in older patients with cancer, taking into account competing risk of death. METHODS: Older adults with diagnosed cancer from 2014 to 2018 according to the general cancer registry of Gironde (French department) were identified in three population-based cohorts on ageing (PAQUID, 3C - Three City, AMI). Cause-specific Cox models focused on 10 usual determinants in geriatric oncology and palliative care: age, gender, living alone, place of residency, tumour prognosis, activities of daily living (ADL) and instrumental-ADL (IADL) limitations, cognitive impairment, depressive disorders, and polypharmacy. RESULTS: 131 patients with incident cancer (mean age: 86.2 years, men: 62.6%, poor cancer prognosis: 32.8%) were included, HPC occurring for 26 of them. Unfavourable cancer prognosis was a key determinant for HPC referral (HR 7.02, 95% CI 2.86 to 17.23). An altered IADL score was associated with precocious (first year) referral (HR 3.21, 95% CI 1.20 to 8.64, respectively). Women had a higher rate immediately (first week) after diagnosis (HR 8.64, 95% CI 1.27 to 87.27). CONCLUSIONS: Cancer prognosis, functional decline and gender are independent factors of HPC referral in older patients with cancer. These findings may help for a better anticipation of the healthcare pathway.

Assessing patient-reported outcomes (PROs) and patient-related outcomes in randomized cancer clinical trials for older adults: Results of DATECAN-ELDERLY initiative.

As older adults with cancer are underrepresented in randomized clinical trials (RCT), there is limited evidence on which to rely for treatment decisions for this population. Commonly used RCT endpoints for the assessment of treatment efficacy are more often tumor-centered (e.g., progression-free survival). These endpoints may not be as relevant for the older patients who present more often with comorbidities, non-cancer-related deaths, and treatment toxicity. Moreover, their expectation and preferences are likely to differ from younger adults. The DATECAN-ELDERLY initiative combines a broad expertise, in geriatric oncology and clinical research, with interest in cancer RCT that include older patients with cancer. In order to guide researchers and clinicians coordinating cancer RCT involving older patients with cancer, the experts reviewed the literature on relevant domains to assess using patient-reported outcomes (PRO) and patient-related outcomes, as well as available tools related to these domains. Domains considered relevant by the panel of experts when assessing treatment efficacy in RCT for older patients with cancer included functional autonomy, cognition, depression and nutrition. These were based on published guidelines from international societies and from regulatory authorities as well as minimum datasets recommended to collect in RCT including older adults with cancer. In addition, health-related quality of life, patients' symptoms, and satisfaction were also considered by the panel. With regards to tools for the assessment of these domains, we highlighted that each tool has its own strengths and limitations, and very few had been validated in older adults with cancer. Further studies are thus needed to validate these tools in this specific population and define the minimum clinically important difference to use when developing RCTs in this population. The selection of the most relevant tool should thus be guided by the RCT research question, together with the specific properties of the tool.

Evaluating video-based consultations in routine clinical practice at a comprehensive cancer center.

INTRODUCTION: Integrating telemedicine into cancer care remains a major challenge. There are little clinical evidence for teleconsultation efficacy and safety in daily oncology practice. This study as a pioneering experience, aimed to analyze patient and physician opinions regarding the implementation of telemedicine consultations, and to identify major limitations of telehealth spread in an oncology institute. MATERIAL AND METHODS: During COVID-19 lockdown, patients and physicians who took part to at least one video-based teleconsultation between March and May 2020, were enrolled in this observational study. All eligible patients received an anonymous online questionnaire. On the other hand, all physicians eligible to participate were asked through email to complete a questionnaire. RESULTS: In this study, 31 physicians and 304 patients consented to participate in this study by answering the questionnaire and were included. Regarding telemedicine satisfaction, 65.8% of patients were satisfied. The lack of clinical examination was the major limitation reported by 77% of patients. Patients belonging to a high socio-professional category were statistically more dissatisfied with the relationship with their doctor (OR = 2.31 and 95% CI [1.12; 4.74]). CONCLUSION: This study showed promising results of incorporating video-based teleconsultations into cancer patient management. Randomized clinical trials are needed in order to accelerate the digital implementation in clinical practice.

Evolution of Patterns of Care and Outcomes in the Real-Life Setting for Patients with Metastatic GIST Treated in Three French Expert Centers over Three Decades.

Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors characterized by KIT or PDGFRA mutations. Over three decades, significant changes in drug discovery and loco-regional (LR) procedures have impacted treatment strategies. We assessed the evolution of treatment strategies for metastatic GIST patients treated in the three national coordinating centers of NetSarc, the French network of sarcoma referral centers endorsed by the National Institute of Cancers, from 1990 to 2018. The primary objective was to describe the clinical and biological profiles as well as the treatment modalities of patients with metastatic GIST in a real-life setting, including access to clinical trials and LR procedures in the metastatic setting. Secondary objectives were to assess (1) patients' outcome in terms of time to next treatment (TNT) for each line of systemic treatment, (2) patients' overall survival (OS), (3) evolution of patients' treatment modalities and OS according to treatment access: <2002 (pre-imatinib approval), 2002-2006 (pre-sunitinib approval), 2006-2014 (pre-regorafenib approval), post 2014, and (4) the impact of clinical trials and LR procedures on TNT and OS in the metastatic setting. 1038 patients with a diagnosis of GIST made in one of the three participating centers between 1990 and 2018 were included in the national prospective database. Among them, 492 patients presented metastasis, either synchronous or metachronous. The median number of therapy lines in the metastatic setting was 3 (range 0-15). More than half of the patients (55%) participated in a clinical trial during the course of their metastatic disease and half (51%) underwent additional LR procedures on metastatic sites. The median OS in the metastatic setting was 83.4 months (95%CI [72.7; 97.9]). The median TNT was 26.7 months (95%CI [23.4; 32.3]) in first-line, 10.2 months (95%CI [8.6; 11.8]) in second line, 6.7 months (95%CI [5.3; 8.5]) in third line, and 5.5 months (95%CI [4.3; 6.7]) in fourth line, respectively. There was no statistical difference in OS in the metastatic setting between the four therapeutic periods (log rank, p = 0.18). In multivariate analysis, age, AFIP Miettinen classification, mutational status, surgery of the primary tumor, participation in a clinical trial in the first line and LR procedure to metastatic sites were associated with longer TNT in the first line, whereas age, mitotic index, mutational status, surgery of the primary tumor and LR procedure to metastatic sites were associated with longer OS. This real-life study advocates for early reference of metastatic GIST patients to expert centers to orchestrate the best access to future innovative clinical trials together with LR strategies and further improve GIST patients' survival.

Impact of the coronavirus disease 2019 pandemic on sarcoma management in France: a 2019 and 2020 comparison.

Background: The coronavirus disease 2019 (COVID-19) pandemic was an unprecedented shock to the healthcare systems, and its consequences on managing rare cancers are unknown. We investigated COVID-19's impact on the activity of sarcoma-labeled networks by comparing key indicators in 2019-2020 (before and during the pandemic, respectively). Methods: We compared the incidence of limb and trunk soft tissue sarcomas, surgery rate, surgery center, surgery quality, and surgery delays nationally and in various regions, focusing on the three most severely affected regions. Findings: In this study, sarcoma incidence did not decrease, and the tumor and patient characteristics were similar in both years. The number of patients who underwent surgery in the labeled centers increased significantly (63% versus 57%, p = 0.015), the rate of R0 resection increased (55% versus 47%, p = 0.004), and the rate of re-excision decreased (12% versus 21%, p < 0.0001). In the univariate analysis, the time to surgery was similar in both years. Cox regression analysis revealed that the factors associated with a longer time to surgery were age > 70 years (p = 0.003), retroperitoneal location (p > 0.001), tumor size (p < 0.001), deep tumors (p < 0.001), and regions (p < 0.001). However, we have observed an increase in the time before surgery in the regions most stroked by the COVID-19 pandemic. Interpretation: The model of the labeled center network for managing rare tumors was resilient. Paradoxically, the quality indicators improved during the pandemic due to the direct referral of patients with sarcomas to the labeled centers. Summary: This study shows that a nationwide network organization has made it possible to maintain care for these rare tumors during the pandemic.

Survival outcomes of patients with metastatic non-small cell lung cancer receiving chemotherapy or immunotherapy as first-line in a real-life setting.

Treatment of metastatic non-small cell lung cancer (mNSCLC) has been modified due to the development of immunotherapy. We assessed survival outcomes (overall [OS] and progression-free [rwPFS] survivals, time-to-next-treatment [TNT]) in mNSCLC patients after first-line immunotherapy and chemotherapy in real-life settings. Association between rwPFS and TNT, two candidate surrogate endpoints (SE), with OS was assessed. This retrospective multi-center study uses data from patients included in the Epidemio-Strategy Medico-Economic program with mNSCLC over 2015-2019. The impact of treatment on rwPFS/OS was evaluated with Cox models. Individual-level associations between SE and OS were estimated with an iterative multiple imputation approach and joint survival models. The population included 5294 patients (63 years median age). Median OS in immunotherapy group was 16.4 months (95%CI [14.1-NR]) and was higher than in chemotherapy group (11.6 months; 95%CI [11.0-12.2]). Improved OS was observed for the immunotherapy group after 3 months for subjects with performance status 0-1 (HR = 0.59; 95%CI [0.42-0.83], p < 0.01). The associations between rwPFS and TNT with OS were close ([Formula: see text]=0.57). Results emphasized a survival improvement with immunotherapy for patients in good health condition. There was moderate evidence of individual-level association between candidate SE and OS.

One-Year Follow-Up of Seroprevalence of SARS-CoV-2 Infection and Anxiety among Health Workers of a French Cancer Center: The PRO-SERO-COV Study.

Infection of SARS-CoV-2 among health workers (HWs) in contact with cancer patients has been a major issue since the beginning of the pandemic. We aimed to assess the serological immune status of SARS-CoV-2 infection among these HWs. A prospective cohort study was initiated in the comprehensive cancer center of the Nouvelle-Aquitaine region (NA, France). Volunteer HWs working on March 2020 without active infection or symptoms of COVID-19 completed a self-questionnaire and had a blood test at inclusion, at 3 and 12 months. Positive serological status of SARS-CoV-2 infection was defined by anti-nucleocapsid antibodies and/or IgG anti-spike antibodies, except at 12 months due to vaccine. Half of the HWs were included (N = 517) and 89% were followed for three months (N = 500) and one year (N = 462). Seroprevalence of SARS-CoV-2 infection was 3.5% (95% CI: 1.9-5.1), 6.2% (95% CI: 4.1-8.3), and 10% (95% CI: 7.2-12.7) on June-September 2020, September 2020-January 2021, and June-October 2021, respectively. At 12 months, 93.3% had detectable antibodies with 80% vaccinated in the first three months of vaccine availability. The COVID-19-free policy of the institution, respect for barrier gestures, high and early vaccination of HWs, and low prevalence of SARS-CoV-2 in NA may explain the low rate of seropositivity among the HWs of the Institut Bergonié.

Association between pre-diagnosis geriatric syndromes and overall survival in older adults with cancer (the INCAPAC study).

INTRODUCTION: Several population-based studies have reported disparities in overall survival (OS) among older patients with cancer. However, geriatric syndromes, known to be associated with OS in the geriatric population, were rarely studied. Thus, our aim was to identify the determinants of OS among French older adults with cancer, including geriatric syndromes before cancer diagnosis. MATERIALS AND METHODS: Using cancer registries, we identified older subjects (≥65 years) with cancer in three French prospective cohort studies on aging from the Gironde department. Survival time was calculated from the date of diagnosis to the date of all-cause death or to the date of last follow-up, whichever came first. Demographic and socioeconomic characteristics, smoking status, self-rated health, cancer-related factors (stage at diagnosis, treatment), as well as geriatric syndromes (polypharmacy, activity limitation, depressive symptomatology, and cognitive impairment or dementia) were studied. Analyses were performed using Cox proportional hazard models for the whole population, then by age group (65-84 and 85+). RESULTS: Among the 607 subjects included in the study, the median age at cancer diagnosis was 84 years. Smoking habits, activity limitations, cognitive impairment or dementia, advanced cancer stage and absence of treatment were significantly associated with lower OS in the analysis including the whole population. Women presented higher OS. Factors associated with OS differed by age group. Polypharmacy was inversely associated with OS in older adults aged 65-84 and 85 + . DISCUSSION: Our findings support that geriatric assessment is needed to identify patients at higher risk of death and that an evaluation of activity limitation in older adults is essential. Improving early detection could enable interventions to address factors (activity limitations, cognitive impairment) associated with OS, potentially reducing disparities and lead to earlier palliative care.

Prediction of survival after a lung transplant at 1 year (SALTO cohort) using information available at different key time points.

OBJECTIVES: A lung transplant is the final treatment option for end-stage lung disease. We evaluated the individual risk of 1-year mortality at each stage of the lung transplant process. METHODS: This study was a retrospective analysis of patients undergoing bilateral lung transplants between January 2014 and December 2019 in 3 French academic centres. Patients were randomly divided into development and validation cohorts. Three multivariable logistic regression models of 1-year mortality were applied (i) at recipient registration, (ii) the graft allocation and (iii) after the operation. The 1-year mortality was predicted for individual patients assigned to 3 risk groups at time points A to C. RESULTS: The study population consisted of 478 patients with a mean (standard deviation) age of 49.0 (14.3) years. The 1-year mortality rate was 23.0%. There were no significant differences in patient characteristics between the development (n = 319) and validation (n = 159) cohorts. The models analysed recipient, donor and intraoperative variables. The discriminatory power (area under the receiver operating characteristic curve) was 0.67 (0.62-0.73), 0.70 (0.63-0.77) and 0.82 (0.77-0.88), respectively, in the development cohort and 0.74 (0.64-0.85), 0.76 (0.66-0.86) and 0.87 (0.79 - 0.95), respectively, in the validation cohort. Survival rates were significantly different among the low- (< 15%), intermediate- (15%-45%) and high-risk (> 45%) groups in both cohorts. CONCLUSIONS: Risk prediction models allow estimation of the 1-year mortality risk of individual patients during the lung transplant process. These models may help caregivers identify high-risk patients at times A to C and reduce the risk at subsequent time points.

Survival after breast cancer according to participation in organised or opportunistic screening and deprivation.

BACKGROUND: Many studies have investigated the survival of women by comparing those who participated in organised screening with those who did not. However, among those who do not participate in organised screening, some women undergo opportunistic screening, but these women remain difficult to identify, particularly in France. Therefore, the aim of this study was to identify opportunistic screening, and then to study survival after breast cancer separately according to participation in organised, opportunistic or no screening, and taking into account sociodemographic inequalities. METHODS: The study population was identified from 3 French cancer registries, whose data was crossed with the screening coordination centers and the National Health Data System to identify the different type of screening. The European Deprivation Index was used to define the level of deprivation. We estimated net survival using the Pohar-Perme method. RESULTS: The 5-year net survival probabilities were higher for women who attended organised screening (97.0 %) than for women with opportunistic screening (94.1 %) or non-attenders (78.1 %). According to the level of deprivation, a significant difference was observed between the groups of women screened by organised and opportunistic screening, compared to the non-attenders. CONCLUSION: The identification of opportunistic screening is an important element in identifying women who do not screening. It enables to us to see that women who do not attend any screening have a much higher loss-of-opportunity in terms of survival than those who participate in organised or opportunistic screening, and even more so in the most deprived areas.

Neoadjuvant chemotherapy and radiotherapy for locally advanced breast cancer: Safety and efficacy of reverse sequence compared to standard technique?

BACKGROUND: The reverse sequence of neoadjuvant chemotherapy, preoperative radiotherapy, mastectomy then immediate breast reconstruction is currently proposed for selected patients with locally advanced breast cancer. Few studies have compared it to the standard sequence of neoadjuvant chemotherapy, mastectomy and radiotherapy with or without differed reconstruction. Our study compares overall (OS) and recurrence-free (RFS) survivals of breast cancer patients treated with reverse sequence compared to the standard technique. METHODS: In this retrospective, single center study at a Comprehensive Cancer Center in France, patients were included if: female, age <65y, had received neoadjuvant chemotherapy, mastectomy and radiotherapy, and were M0. Outcomes for patients treated by reverse sequence (RS) are compared to those for patients treated by standard sequence (ST). Data was collected from medical records. RESULTS: From January 2009 to April 2018, 222 eligible patients were treated, 46 by RS and 176 by ST. Mean follow-up was 61.7 months. Five-year OS and RFS did not differ between groups. 5-yr OS: 88.4% 95%CI [74.1-95.0] for RS and 81.5% 95%CI [74.0-87.0] for ST (P = 0.4412); 5-yr RFS: 78.3% 95%CI [61.9-88.3] for RS and 70.1% 95%CI [62.2-76.7] for ST (P = 0.3003). Overall treatment time was significantly shorter in the RS group, and the rate of severe surgical complications did not differ between groups. CONCLUSIONS: For locally advanced breast cancer patients with an indication for radiation therapy the reverse sequence offers similar safety and efficacy results as the standard treatment while allowing immediate breast reconstruction. However, careful patient selection is necessary, particularly with regard to preoperative lymph node invasion.

Geriatric impairments were directly and indirectly associated with mortality in older patients with cancer: a structural equation analysis.

OBJECTIVES: We assessed the direct and indirect effects between six geriatric domains and 6- and 12-month mortality in older cancer patients. STUDY DESIGN AND SETTING: We included cancer patients aged ≥70 years from the Elderly Cancer Patients cohort, referred for geriatric assessment between 2007 and 2016. We used structural equation modelling to examine the interrelationships between six geriatric domains (function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support) and the direct and indirect relationships between these domains, the cancer stage, site, and treatment on the one hand and mortality on the other. RESULTS: The analysis included 1,434 patients (mean age: 80 ± 5.6 years; women: 48%; main cancer sites: digestive tract [36.2%], urinary tract and prostate [26.6%], and breast [16.5%]; metastatic cancer: 48%). Direct relationships to 6- and 12-month mortality were identified for functional impairment (standardized coefficient [SC]: 0.37 [P < 0.001] and 0.32 [P < 0.001], respectively), poor nutritional status (SC: 0.11 [P = 0.005] and 0.14 [P = 0.001]), poor social support (SC = 0.07 [P = 0.08] and 0.09 [P = 0.02]), cancer site, stage, and treatment. The effects of comorbidities, cognitive impairment, and depression on mortality were mediated by functional and nutritional status. CONCLUSION: In older cancer patients, functional and nutritional impairments were the strongest direct prognostic geriatric factors for mortality.

Overall and net survival of patients with sarcoma between 2005 and 2010: Results from the French Network of Cancer Registries (FRANCIM).

BACKGROUND: Sarcomas are rare, heterogeneous, ubiquitously localized malignancies with many histologic subtypes and genomic patterns. The survival of patients with sarcoma has rarely been described based on this heterogeneity; therefore, the authors' objective was to estimate survival outcomes in patients who had sarcomas using the 2020 version of the World Health Organization classification of soft tissue and bone tumors. METHODS: Patients older than 15 years who had incident sarcoma diagnosed between 2005 and 2010 were extracted from 14 French population-based cancer registries covering 18% of the French metropolitan population. Vital status for each patient was actively followed up to June 30, 2013. Net survival (NS) was estimated using the unbiased Pohar-Perme method. RESULTS: Overall, 4202 patients were included. NS declined with increasing age at diagnosis. According to topographic groups, large 5-year NS disparities were observed, ranging from 47% among women with gynecologic sarcomas to 89% among patients with skin sarcomas. Patients with soft tissue, bone, and gastrointestinal sarcomas had 5-year NS rates of 53%, 61%, and 70%, respectively. Similar heterogeneity was observed according to histologic subtypes, with 5-year NS ranging from 19% for patients with angiosarcomas to 96% for patients with dermatofibrosarcomas. Patients with sarcoma who displayed missense mutations had a better 5-year NS (74%); those with MDM2-amplified sarcomas had the worst NS (45%). CONCLUSIONS: NS rates in patients with sarcoma are presented here for the first time based on the 2020 World Health Organization classification applied to population-based registry data. Large prognostic heterogeneity was observed based on age, topographic and histologic groups, and genomic alteration profiles, constituting a benchmark for future studies and clinical trials.

Targeted Therapy for Older Patients with Non-Small Cell Lung Cancer: Systematic Review and Guidelines from the French Society of Geriatric Oncology (SoFOG) and the French-Language Society of Pulmonology (SPLF)/French-Language Oncology Group (GOLF).

Systematic molecular profiling and targeted therapy (TKI) have changed the face of Non-Small Cell Lung Cancer (NSCLC) treatment. However, there are no specific recommendations to address the prescription of TKI for older patients. A multidisciplinary task force from the French Society of Geriatric Oncology (SoFOG) and the French Society of Pulmonology/Oncology Group (SPLF/GOLF) conducted a systematic review from May 2010 to May 2021. Protocol registered in Prospero under number CRD42021224103. Three key questions were selected for older patients with NSCLC: (1) to whom TKI can be proposed, (2) for whom monotherapy should be favored, and (3) to whom a combination of TKI can be proposed. Among the 534 references isolated, 52 were included for the guidelines. The expert panel analysis concluded: (1) osimertinib 80 mg/day is recommended as a first-line treatment for older patients with the EGFR mutation; (2) full-dose first generation TKI, such as erlotinib or gefitinib, is feasible; (3) ALK and ROS1 rearrangement studies including older patients were too scarce to conclude on any definitive recommendations; and (4) given the actual data, TKI should be prescribed as monotherapy. Malnutrition, functional decline, and the number of comorbidities should be assessed primarily before TKI initiation.

Trabectedin plus Durvalumab in Patients with Advanced Pretreated Soft Tissue Sarcoma and Ovarian Carcinoma (TRAMUNE): An Open-Label, Multicenter Phase Ib Study.

PURPOSE: Trabectedin has shown preclinical synergy with immune checkpoint inhibitors in preclinical models. PATIENTS AND METHODS: TRAMUNE is a phase Ib study investigating the combination of trabectedin with durvalumab through a dose escalation phase and two expansion cohorts, soft tissue sarcoma (STS) and ovarian carcinoma. Trabectedin was given at three dose levels (1 mg/m2, 1.2 mg/m2, and 1.5 mg/m2) on day 1, in combination with durvalumab, 1,120 mg on day 2, every 3 weeks. The primary endpoints were the recommended phase II dose (RP2D) of trabectedin combined with durvalumab and the objective response rate (ORR) as per RECIST 1.1. The secondary endpoints included safety, 6-month progression-free rate (PFR), progression-free survival (PFS), overall survival, and biomarker analyses. RESULTS: A total of 40 patients were included (dose escalation, n = 9; STS cohort, n = 16; ovarian carcinoma cohort, n = 15, 80% platinum resistant/refractory). The most frequent toxicities were grade 1-2 fatigue, nausea, neutropenia, and alanine/aspartate aminotransferase increase. One patient experienced a dose-limiting toxicity at dose level 2. Trabectedin at 1.2 mg/m2 was selected as the RP2D. In the STS cohort, 43% of patients experienced tumor shrinkage, the ORR was 7% [95% confidence interval (CI), 0.2-33.9], and the 6-month PFR was 28.6% (95% CI, 8.4-58.1). In the ovarian carcinoma cohort, 43% of patients experienced tumor shrinkage, the ORR was 21.4% (95% CI, 4.7-50.8), and the 6-month PFR was 42.9% (95% CI, 17.7-71.1). Baseline levels of programmed death-ligand 1 expression and CD8-positive T-cell infiltrates were associated with PFS in patients with ovarian carcinoma. CONCLUSIONS: Combining trabectedin and durvalumab is manageable. Promising activity is observed in patients with platinum-refractory ovarian carcinoma. See related commentary by Digklia et al., p. 1745.

Impact of the COVID-19 lockdown in France on the diagnosis and staging of breast cancers in a tertiary cancer centre.

OBJECTIVES: Due to COVID-19, a lockdown took place between March 17 and May 1, 2020, in France. This study evaluates the impact of the lockdown on the diagnosis and staging of breast cancers in a tertiary cancer centre. METHODS: Our database was searched for all consecutive invasive breast cancers diagnosed in our institution during the lockdown (36 working days), during equivalent periods of 36 working days before and after lockdown and a reference period in 2019. The number and staging of breast cancers diagnosed during and after lockdown were compared to the pre-lockdown and reference periods. Tumour maximum diameters were compared using the Mann-Whitney test. Proportions of tumour size categories (T), ipsilateral axillary lymph node invasion (N) and presence of distant metastasis (M) were compared using Fisher's exact test. RESULTS: Compared to the reference period (n = 40 in average), the number of breast cancers diagnosed during lockdown (n = 32) decreased by 20% but increased by 48% after the lockdown (n = 59). After the lockdown, comparatively to the reference period, breast cancers were more often symptomatic (86% vs 57%; p = 0.001) and demonstrated bigger tumour sizes (p = 0.0008), the rates of small tumours (T1) were reduced by 38%, locally advanced cancers (T3, T4) increased by 80% and lymph node invasion increased by 64%. CONCLUSION: The COVID-19 lockdown was associated with a 20% decrease in the number of diagnosed breast cancers. Because of delayed diagnosis, breast cancers detected after the lockdown had poorer prognosis with bigger tumour sizes and higher rates of node invasion. KEY POINTS: • The number of breast cancer diagnosed in a large tertiary cancer centre in France decreased by 20% during the first COVID-19 lockdown. • Because of delayed diagnosis, breast cancers demonstrated bigger tumour size and more frequent axillary lymph node invasion after the lockdown. • In case of a new lockdown, breast screening programme and follow-up examinations should not be suspended and patients with clinical symptoms should be encouraged to seek attention promptly.

Prognostic Value of Routinely Measured Inflammatory Biomarkers in Older Cancer Patients: Pooled Analysis of Three Cohorts.

BACKGROUND: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers. METHODS: A pooled analysis of prospective multicenter cohorts of cancer patients aged ≥70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP ≤ 10 mg/L, albumin ≥ 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI). RESULTS: Overall, 1800 patients were analyzed (mean age: 79 ± 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03-9.89] for GPS1, 11.64 [4.54-29.81] for GPS2, and 7.15 [3.22-15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79-3.34] for GPS1, 3.97 [2.93-5.37] for GPS2, and 2.81 [2.17-3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80-0.83]) was increased by adding GPS (C = 0.84 [0.82-0.85]; NRI events (NRI+) = 10% [2-16]) and CRP/albumin ratio (C = 0.83 [0.82-0.85]; NRI+ = 14% [2-17]). CONCLUSIONS: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients.

Molecular profiling of advanced soft-tissue sarcomas: the MULTISARC randomized trial.

BACKGROUND: Soft-tissue sarcomas (STS) represent a heterogeneous group of rare tumors including more than 70 different histological subtypes. High throughput molecular analysis (next generation sequencing exome [NGS]) is a unique opportunity to identify driver mutations that can change the usual one-size-fits-all treatment paradigm to a patient-driven therapeutic strategy. The primary objective of the MULTISARC trial is to assess whether NGS can be conducted for a large proportion of metastatic STS participants within a reasonable time, and, secondarily to determine whether a NGS-guided therapeutic strategy improves participant's outcome. METHODS: This is a randomized, multicentre, phase II/III trial inspired by the design of umbrella and biomarker-driven trials. The setting plans up to 17 investigational centres across France and the recruitment of 960 participants. Participants aged at least 18 years, with unresectable locally advanced and/or metastatic STS confirmed by the French sarcoma pathological reference network, are randomized according to 1:1 allocation ratio between the experimental arm "NGS" and the standard "No NGS". NGS will be considered feasible if (i) NGS results are available and interpretable, and (ii) a report of exome sequencing including a clinical recommendation from a multidisciplinary tumor board is provided to investigators within 7 weeks from reception of the samples on the biopathological platform. A feasibility rate of more than 70% is expected (null hypothesis: 70% versus alternative hypothesis: 80%). In terms of care, participants randomized in "No NGS" arm and who fail treatment will be able to switch to the NGS arm at the request of the investigator. DISCUSSION: The MULTISARC trial is a prospective study designed to provide high-level evidence to support the implementation of NGS in routine clinical practice for advanced STS participants, on a large scale. TRIAL REGISTRATION: clinicaltrial.gov NCT03784014 .

Determinants of the access to remote specialised services provided by national sarcoma reference centres.

BACKGROUND: Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients. METHODS: Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery. RESULTS: Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities. CONCLUSIONS: In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks' organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis.

Palliative care referral in cancer patients with regard to initial cancer prognosis: a population-based study.

OBJECTIVES: More than half of cancer patients require palliative care; however, inequality in access and late referral in the illness trajectory are major issues. This study assessed the cumulative incidence of first hospital-based palliative care (HPC) referral, as well as the influence of patient-, tumor-, and care-related factors. STUDY DESIGN: This is a retrospective population-based study. METHODS: The study included patients from the 2014 population-based cancer registry of Gironde, France. International Classification of Diseases, Tenth Revision, coding for palliative care identified HPC referrals from 2014 to 2018. The study included 8424 patients. Analyses considered the competing risk of death and were stratified by initial cancer prognosis (favorable vs unfavorable [if metastatic or progressive cancer]). RESULTS: The 4-year incidence of HPC was 16.7% (95% confidence interval, 16.6-16.8). Lung cancer led to more referrals, whereas breast, colorectal, and prostatic locations were associated to less frequent HPC compared with other solid tumors. Favorable prognosis central nervous system tumors and unfavorable prognosis hematological malignancies also showed less HPC. The incidence of HPC was higher in tertiary centers, particularly for older patients. In the favorable prognosis subgroup, older and non-deprived patients received more HPC. In the unfavorable prognosis subgroup, the incidence of HPC was lower in patients who lived in rural areas than those who lived in urban areas. CONCLUSIONS: One-sixth of cancer patients require HPC. Some factors influencing referral depend on the initial cancer prognosis. Our findings support actions to improve accessibility, especially for deprived patients, people living in rural areas, those with hematological malignancies, and those treated outside tertiary centers. In addition, consideration of age as factor of HPC may allow for improved design of the referral system.