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Objective: Phase I clinical trials usually include patients with advanced disease who have failed standard therapies and should benefit from early palliative care. We try to assess whether PALLIA 10, a score developed in France to help identify patients who might benefit from a palliative care referral, could be used in a phase I department trial., Methods: We assessed PALLIA 10 score and other prognostic factors in patients enrolled in phase I trials at Gustave Roussy Cancer Center prospectively during two periods of time (cohort 1 (C1) and 2 (C2)). A double-blind assessment of the PALLIA 10 score was done in C2 by a palliative care specialist and a nurse., Results: From 1 July 2018 to 1 November 2018 (C1) and from 1 December 2020 to 16 April 2021 (C2), 86 patients were assessed in C1 and 302 in C2. Median PALLIA 10 was very low in both cohorts (median 1, range 1-5 in C1 and 1-8 in C2). On C1 and C2, 12% and 5% of patients had a dedicated palliative consultation. In C2, assessment of PALLIA 10 score was significantly different between palliative care physician (median 5, range 3-8), phase I physician (median 1, range 1-6) and phase I nurse (median 3, range 1-8) (p<0.001)., Conclusion: Median PALLIA 10 score was low when assessed by the phase I physician, which suggests the need for a better tool and appropriate clinician's education to implement early palliative care in clinical practice and trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Aging is an important risk factor for cancers and is associated with poor prognosis. Weakness of the immune system, also called immunosenescence may occur with older age. The impact of aging on efficacy and safety of immune checkpoint blockers, such as anti-programmed death (ligand) PD-(L)1, remains undetermined. This study aims to evaluate the incidence of immune-related adverse events (irAEs) in patients aged 70 years or older than their younger counterparts., Methods: Patients with advanced solid tumors treated at Gustave Roussy with an anti-PD-(L)1 monotherapy between June 2014 and October 2017 were prospectively included within the dedicated irAEs pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie). The incidence of irAEs of grade ≥II was compared between patients aged ≥70 (old patients, OP) versus patients aged < 70 years (young patients, YP) using a chi-squared test. Survivals were estimated using the Kaplan-Meier method., Results: Among the 603 patients treated by anti-PD(L)1, 191 were ≥70 y.o (OP) and 424 < 70 y.o (YP). The median (range) age of OP and YP were respectively 77 (70-93) and 59 years old (17-69). A total of 165 irAEs occurred in these patients (103 grade II and 58 grade III-IV). The overall incidence of grade ≥II irAEs was higher in OP than in YP (33% versus 25%, p = 0.03). In addition, OP were more prone of having multiples irAEs compared with YP (p = 0.037). Skin toxicities were more frequent in OP than in YP (p = 0.007) but endocrine toxicities were less frequent in OP than in YP (p = 0.044). This higher level of irAEs seems to be responsible for a higher rate of treatment discontinuation in OP (p = 0.2). There was no statistical difference in median time to toxicity, exposure to steroids or survival between the two groups., Conclusion: Although anti-PD-(L)1 immunotherapies remain an acceptable treatment option for older patients, prescribers should be aware that irAEs are more frequent in the elderly. Further translational studies are warranted to better understand the relationship between aging and irAEs., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy., Methods: We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively., Findings: Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1., Interpretation: Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

Background: In the United States, the Agency for Healthcare Research and Quality (AHRQ) has developed 20 Patient Safety Indicators (PSIs) to measure the occurrence of hospital adverse events from medico-administrative data coded according to the ninth revision of the international classification of disease (ICD-9-CM). The adaptation of these PSIs to the WHO version of ICD-10 was carried out by an international consortium., Methods: Two independent teams transcoded ICD-9-CM diagnosis codes proposed by the AHRQ into ICD-10-WHO. Using a Delphi process, experts from six countries evaluated each code independently, stating whether it was "included", "excluded" or "uncertain". During a two-day meeting, the experts then discussed the codes that had not obtained a consensus, and the additional codes proposed., Results: Fifteen PSIs were adapted. Among the 2569 proposed diagnosis codes, 1775 were unanimously adopted straightaway. The 794 remaining codes and 2541 additional codes were discussed. Three documents were prepared: (1) a list of ICD-10-WHO codes for the 15 adapted PSIs; (2) recommendations to the AHRQ for the improvement of the nosological frame and the coding of PSI with ICD-9-CM; (3) recommendations to the WHO to improve ICD-10., Conclusions: This work allows international comparisons of PSIs among the countries using ICD-10. Nevertheless, these PSIs must still be evaluated further before being broadly used., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Allocation of organs is organized on a regional basis in France. We assessed regional differences in access to organ transplant., Material and Methods: We used the recipient database and the waiting list database from the year 1994 onward. We estimated median waiting time by region and organ. The probability of receiving a transplant was estimated using the Kaplan-Meier method. Between-region comparisons used the log-rank test, with adjustment for blood type and disease category., Results: At the end of a 4-month follow-up period, 49% of 3,553 patients had received transplants: 64% of 797 benefited from liver transplants, 52% of 549 from heart transplants, and 22% of 2,207 from kidney transplants. Death rates on the waiting lists were 10%, 14%, and 1% for patients selected for liver, heart, and kidney transplant, respectively. Transplantation percentage (all organs) decreased from 63% in the West to 43% in the Paris region and mortality increased from 2% in the West to 7% in the Southeast. All tests of inter-regional differences were statistically significant., Conclusion: Factors explaining geographic differences related to the background of transplant teams, activity of organ procurement, and severity of patients on the list.

Despite progress realised in transplantation and organ procurement, there is an increasing gap between the number of patients on the national waiting list and the number of harvested organs. As a result, the appropriate organs must be matched with the appropriate patient, with two constraints: equity and efficacy. In a context of lack of organs, another public health problematic is to conciliate both the interests of a given patient and the interests of those on the waiting lists. In 1996, the French secretary of state for health instituted a public consultation committee chaired by the vice-president of the Comité consultatif national d'éthique, Counsellor Jean Michaud, to study organ allocation rules and to plan recommendations for the future. Using, as a starting point, the allocation rules initiated in the past by France Transplant and transiently applied by l'Etablissement français des Greffes, the committee conducted a large audition of health care professionals concerned with transplantation, individuals qualified in ethics, laws, sociology or ethnology, politicians and a sample representation of the population. A new corpus of allocation rules and procedures was then defined according to the committee recommendations and the advice of all medico-surgical transplantation teams, and published as a ministerial order in the Journal officiel de la République française in november 1996. It specifies shared principles and organ by organ specific allocation rules.

Using the complete, multicentric Registry of organ transplantation in France, from 1970 to 1992, including 26,485 transplantations (kidney, heart, heart-lungs, lungs, liver), we studied four statistical parametres: 1. movement on the waiting list; 2. mean waiting time; 3. actuarial survival of the graft for the kidney, heart and liver; 4. number of recipients surviving with a functioning graft as of 31 December 1992. Patients awaiting a kidney transplant comprise a group that differs epidemiologically from the others on the basis of the length of the waiting list, entering and existing flux, and for the mortality rate of patients waiting for a graft. Similarly, the actuarial survival profile is different for the first year in kidney transplant recipients compared to the others.