Paris Cancer Institute CARPEM has a strong activity in Geriatric Oncology and the Geriatric Cancer Program involved 4 departments of APHP.Centre (Geriatric, Biology Physiology and genomic medicine, Oncology and radiotherapy and Psychiatry) working together. It is one of the most important centers dedicated to geriatric oncology in the Great Paris area and at the national level. 4 physicians are dedicated to geriatric cancer patients care. They are associated with physicians of other specialties in this program including surgeons and biologists and altogether 15 beds are dedicated to geriatric oncology. The APHP.Centre take care of 3347 cancer patients older than 75 years old in 2018. The geriatric oncology program involves 3 sites European Georges-Pompidou (HEGP) Cochin (CCH) and Corentin-Celton (CCL), with different complementary orientations. On HEGP and CCH sites, there are both medical and surgery strengths. The CCL site is dedicated to rehabilitation care of older people with cancer and it is planned to triple its number of beds (from 10 to 30 beds) in the coming year with a focus on peri-operative care.
All these activities are structured around 2 weekly cancer multidisciplinary team meetings, on each site (Monday and Wednesday) including members of the geriatric oncology programs. These meetings follow the INCA national guidelines, and ESMO.
Clinical research in Geriatric oncology program is performed with open ongoing clinical trials (EGESOR ; IMPROVED ; NUTRIAGE CANCER ; PALOMAGE (see annex 2), a hospital database called “ELCAPA” (ie Elderly Cancer Patients), an international development of treatment decision support tools (G8-modified, G-CODE,..) and an experimental program of integrated medicine called ARIANE on one-day hospital. All these clinical researches are dedicated to the development of tools and therapeutics for improving treatment of elderly patients with cancer.
Incidence and mortality of cancer according to ageRed curves incidence; Blue curves mortalitySquare men; Triangle women
In western countries, two thirds of newly diagnosed cancers and three quarters of cancer-related deaths occur in patients aged 65 or over. Moreover, standardized cancer treatments are difficult to implement in older patients, due to (i) their under representation in cancer trial populations and (ii) their heterogeneity in terms of social environment, comorbidities, dependency and mobility, nutritional status, mood, and cognitive status. The International Society of Geriatric Oncology (SIOG) recommends to perform a comprehensive geriatric assessment (CGA) before the cancer treatment decision is taken for older patients; the CGA assesses the above-mentioned heterogeneity and detects vulnerabilities likely to lead to poor outcomes and treatment complications.
The ELCAPA cohort (lead by Pr E. Paillaud) is one of the most important prospective cohort survey of consecutive patients age 70 years or older who had newly diagnosed cancer and were referred to one of geriatric oncologic clinics in one of 19 hospitals in the great Paris area, before cancer treatment decisions. Up to September 30th, 2019, 5005 patients were included. From the ELCAPA cohort, we demonstrated that nearly 21% of patients had changes made to their initial cancer treatment plan on the basis of CGA results. This study, ELCAPA-01, was published in the Journal of Clinical Oncology (1). Since there, twelve other international publications have been conducted, investigating clinical relevance of CGA to detect health problems (2), the prognosis value of CGA for predicting chemotherapy toxicity and mortality (3), relevance of frailty screening tools (4) and classifications (5) in predicting mortality and unscheduled admissions.
More recently, a research program in ethics sciences on ELCAPA cohort has been developed. In addition, since 2017, a collection of biological samples from the ELCAPA cohort (ELCAPA-BIO) has been started collecting plasma and serum in order to isolate circulating tumor DNA and constitutional DNA for inclusion in translational research projects. Under the supervision of Pr E. Paillaud and the French Society of Geriatric Oncology, the Unicancer cooperative group GERICO dedicated to clinical research in geriatric oncology and with the collaboration of International Society of Geriatric Oncology, an international development of cancer treatmentdecision for elderly people support tools has been done (G-CODE & Modified G8) (6,7)
The experimental program of integrated medicine called ARIANE was developed with one-day evaluation combined consultations of cardiologist, social worker, diabetologist, anesthetist, pharmacist, pain specialist, dietician, psychologist and geriatricians. This program developed at CCH aims at approaching the complexity of older patient (8), choosing the most adapted treatment (8,9) and at reducing complications during the course of cancer treatment.
Translational research involves 3 Inserm research teams located to the PARCC and the Cordeliers Research Center. These research teams are led by E. Tartour, MF. Mamzer, and P. Laurent-Puig.
The main translational research field is about the biologic and immunologic factors in order to find predictive markers of toxicity and therapeutic responses (C. Granier, E. Tartour, E. Paillaud, PN. Bories, P. Boudou-Rouquette, MA. Loriot, M. Gisselbrecht, A Chahwakilian).
The advent of immunotherapy via inhibitors of the PD-1 / PD-L1 axis or the interaction of CTLA-4 / CD80-CD86 constitutes a real therapeutic progress in oncology. However, very few efficacy and tolerability data for older patients have been published to date. The physiological remodeling of the immune system called “immunosenescence” is a result of qualitative and quantitative defects affecting both innate and adaptive immunity and may be the cause of lower efficacy or poor tolerance of PD-1 / PD-1 inhibitors. How immunosenescence influences the response and the toxicity to anti-PD-1/PD-L1 in the geriatric population has not been studied. Our previous work concerns the role of specific subgroups of T cell populations in their tumor immune surveillance and effect (11-12).
We are planning to study immunosenescence pattern in the older population treated by immunotherapies targeting PD-1 and to highlight the impact of some immunosenescence parameters on response and toxicity to these therapies.
Older patients are expected to have a potentially different pharmacokinetics of chemotherapy because of the reduced liver and renal metabolism with age, lower lean body mass. Moreover, older patients frequently have polymedication and are susceptible to experience drug-drug interactions. Our previous work found that reduced lean body mass may be associated with the overexposure and toxicity of Erlotinib in older patients (TKI)(13). We are planning to study the role of the lean body mass and of pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of tyrosine kinase inhibitors in older patients.
One other major translational research concerns the social sciences and medical ethics (P Caillet, E Paillaud, C Denis, MF Mamzer). Our first works were dedicated to preferences about information and decision-making among older patients (14). The main objective of this integrated research program is to favor the implementation of a real “health democracy policy” in the “real life” context of the Paris Cancer Institute: CARPEM (15-16). To allow that at both individual (empowerment) and collective (governance participation) levels, special attention has to be paid to health literacy, and numeric health literacy, particularly for older patients. Using research action methods, we will build both adapted communication tools with older patients to facilitate their empowerment and an empowerment scale.
We also developed one translational research on supporting care with a focus on depressive symptom profiles (17), nutritional alterations (18,19) and rehabilitation in older cancer patients (C Lemogne, P Caillet, M Gisselbrecht, A Boudou-Rouquette, C Le Bris, Miss Peliconi, Miss Cavalieri, Miss Cuesca, E Paillaud).
We start a translational research between surgeons and geriatricians on peri-operative involvement of geriatricians during head and neck (20) and abdominal surgeries (P Caillet, M Gisselbrecht, R Douard, AS Bats, F Audenet, Miss C Le Bris, Miss M Peliconi et Miss M Cavalieri, Miss E Cuesca, E Paillaud ).
The Geriatric Oncology Program integrates 12 interns each year and 3 fellows.
Monthly dedicated internal seminars are organized. Medical teams are widely involved in the university teaching of geriatric oncology in University of Paris and in several national teaching degrees/master’s degrees in the field of Geriatric Oncology (DIU in Geriatric Oncology at Paris Descartes and Sorbonne Universities coordinated by E Paillaud, DIU Digestive cancer at Paris Descartes and Sorbonne Universities by P Caillet, Capacité of geriatric medicine at University of Paris by M Gisselbrecht/P Caillet, Optionnel of cancer in older patients at University of Paris coordinated by M Gisselbrecht, DES of geriatrician at Sorbonne Universities by E Paillaud) and biomedical (Master-BioMedical Engineering by C Granier ; Parcours initiation à la recherche -Immunologie by C Granier).
Dedicated external seminars on geriatric oncology for oncology clinics or nursing home or rehabilitation wards in Ile de France are organized every year (scientific day Paris Descartes – Korian, training at “Clinique de la Porte Verte” …).
Medical and surgery teams are involved in teaching programs of international and French medical societies, regional cancer programs (International Society of Geriatric Oncology; French Society of Geriatric Oncology, Canceropôle Ile-de-France, Gerontôpole Ile-de-France, Francilian Oncogeriatric Group, Réseau régional de cancérologie Ile-de-France).
In the next years we want to evaluate a program based on perioperative geriatric intervention named IMPROVE. A growing proportion of older cancer patients are presenting for surgery because of the aging of the population. Selecting the older patients for abdominal, gynecological and urological surgeries is challenging due to diminish overall health, patient multimorbidity, functional decline, and limited data to guide decisions. Despite improvement in surgical techniques and recovery after surgery, the rate of mortality and postoperative complications are much higher in older patients than in the younger ones.
We strongly think that Pperi-operative involvement of geriatricians may improve care management older patients with cancer, particularly frail older patients. Identifying comorbid conditions and aging-related physiologic changes that increase the risk of peri-operative morbi-mortality may allow surgeons, anesthetists and oncologists to develop peri-operative customized treatment adjustments and to implement interventions designed to decrease the risk of poorer outcomes. The objective of the IMPROVE program will be to assess the impact of a perioperative geriatric intervention during abdominal cancers in terms of patient’s outcomes (morbi-mortality, autonomy, quality of life) and care organization.
The selected following publications highlight the strength of clinical and translational research developed in the geriatric program:
1- Caillet P, Canoui-Poitrine F, Vouriot J, Berle M, Reinald N, Krypciak S, Bastuji-Garin S, Culine S, Paillaud E. Comprehensive geriatric assessment in the decision-making process in elderly patients with cancer: ELCAPA study. J Clin Oncol. 2011;29(27):3636-42.
2- Paillaud E, Liuu E, Laurent M, Le Thuaut A, Vincent H, Raynaud-Simon A, Bastuji-Garin S, Tournigand C, Caillet P, Canoui-Poitrine F; ELCAPA Study Group. Geriatric syndromes increased the nutritional risk in elderly cancer patients independently from tumour site and metastatic status. The ELCAPA-05 cohort study. Clin Nutr. 2014 Apr;33(2):330-5.
3- Ferrat E, Paillaud E, Laurent M, Le Thuaut A, Caillet P, Tournigand C, Lagrange JL, Canouï-Poitrine F, Bastuji-Garin S; ELPACA Study Group. Predictors of 1-Year Mortality in a Prospective Cohort of Elderly Patients With Cancer. J Gerontol A Biol Sci Med Sci. 2015 Sep;70(9):1148-55.
4- Pamoukdjian F, Liuu E, Caillet P, Herbaud S, Gisselbrecht M, Poisson J, Boudou-Rouquette P, Zelek L, Paillaud E. How to Optimize Cancer Treatment in Older Patients: An Overview of Available Geriatric Tools. Am J Clin Oncol. 2019 Feb;42(2):109-116
5- Ferrat E, Paillaud E, Caillet P, Laurent M, Tournigand C, Lagrange JL, Droz JP, Balducci L, Audureau E, Canouï-Poitrine F, Bastuji-Garin S, on behalf of the ELCAPA Study Group. Performance of Four Frailty Classifications in Older Patients with Cancer: Prospective ELCAPA Cohort Study. J Clin Oncol 2017 Mar;35(7):766-777
6-Martinez-Tapia C, Paillaud E, Liuu E, Tournigand C, Ibrahim R, Fossey-Diaz V, Culine S, Canoui-Poitrine F, Audureau E; ELCAPA Study Group. Prognostic value of the G8 and modified-G8 screening tools for multidimensional health problems in older patients with cancer. Eur J Cancer. 2017 Sep;83:211-219.
7-Paillaud E, Soubeyran P, Caillet P, Cudennec T, Brain E, Terret C, Etchepare F, Mourey L, Aparicio T, Pamoukdjian F, Audisio RA, Rostoft S, Hurria A, Bellera C, Mathoulin-Pélissier S; G-CODE collaborators. Eur J Cancer. 2018 Nov;103:61-68
8- Pascaline Boudou-Rouquette, Olivier Huillard, Audrey Thomas-Schoemann, Anne Chahwakilian, Galdric Orvoen, Antoine Tesniere, Laure Cabanes, Julie Giroux, Anatole Cessot, Jean Stephanazzi, Helen Mosnier-Pudar, Jean-Philippe Durand, Vincent Montheil, Jerome Alexandre, Francois Goldwasser Multidisciplinary risk assessment to reveal cancer treatments in unfit cancer patients. Journal of Clinical Oncology 32, no. 15_suppl (May 20, 2014) 9551
9–Beinse G, Emile G, Cessot A, Boudou-Rouquette P, Huillard O, Saidu NE, Borghese B, Goldwasser F, Pujade Lauraine E, Alexandre J. A Real-Life Experience of Bevacizumab in Elderly Women With Advanced Ovarian Carcinoma. Int J Gynecol Cancer.2016 Sep;26(7):1196-200.
10- Bonnet C, Boudou-Rouquette P, Azoulay-Rutman E, Huillard O, Golmard JL, Carton E, Noé G Vidal M, Orvoen G, Chah Wakilian A, Villeminey C, Blanchet B, Alexandre J, Goldwasser F, Thomas-Schoemann A. Potential drug-drug interactions with abiraterone in metastatic castration-resistant prostate cancer patients: a prevalence study in France. Cancer Chemother Pharmacol.2017 May;79(5):1051-1055.
11– Mami-Chouaib F, Blanc C, Corgnac S, Hans S, Malenica I, Granier C, Tihy I, Tartour E. Resident memory T cells, critical components in tumor immunology. J Immunother Cancer. 2018 Sep 4;6(1):87.
12- Granier C, Gey A, Dariane C, Mejean A, Timsit MO, Blanc C, Verkarre V, Radulescu C, Fabre E, Vano Y, Oudard S, Badoual C, Tartour E.[Tim-3: a novel biomarker and therapeutic target in oncology]. Med Sci (Paris). 2018 Mar;34(3):231-237.
13- Bigot F, Boudou-Rouquette P, Arrondeau J, Thomas-Schoemann A, Tlemsani C, Chapron J, Huillard O, Cessot A, Vidal M, Alexandre J, Blanchet B, Goldwasser F. Erlotinib pharmacokinetics: a critical parameter influencing acute toxicity in elderly patients over 75 years-old. Invest New Drugs. 2017 Apr;35(2):242-246.
14- Paillaud E, Canoui-Poitrine F, Varnier G, Anfasi-Ebadi N, Guery E, Saint Jean O, Gisselbrecht M, Aparicio T, Bastuji-Garin S, Laurent M, Caillet P and ELCAPA Study Group. Preferences about Information and Decision-Making among Older Patients with and without Cancer. Age Ageing 2017 Jul 1;46(4):665-6716.
15- Mamzer MF, Duchange N, Darquy S, Marvanne P, Rambaud C, Marsico G, Cerisey C, Scotté F, Burgun A, Badoual C, Laurent-Puig P, Hervé C. Partnering with patients in translational oncology research: ethical approach. J Transl Med. 2017 Apr8;15(1):74.
16- Mamzer MF, Dubois S, Saout C; participants of Round Table «Topical Subject» of Giens XXXIII, Albin N, Béhier JM, Buisson A, Diebolt V, Delaitre O, Duguet C, Fagon JY, Gaillard S, Le Jeunne C, Mazars R, Micallef J, Nabarette H, Piazza L, Raynaud C, Varoqueaux N. How to strengthen the presence of patients in health technology assessments conducted by the health authorities. Therapie. 2018 Feb;73(1):95-105.
17-Gouraud C, Paillaud E, Martinez-Tapia C, Segaux L, Reinald N, Laurent M, Corsin L, Hoertel N, Gisselbrecht M, Mercadier E, Boudou-Rouquette P, Chahwakilian A, Bastuji-Garin S, Limosin F, Lemogne C, Canouï-Poitrine F; ELCAPA Study Group. Depressive Symptom Profiles and Survival in Older Patients with Cancer: Latent Class Analysis of the ELCAPA Cohort Study. Oncologist. 2018 Dec 31.
18- Pamoukdjian F, Aparicio T, Canoui-Poitrine F, Duchemann B, Lévy V, Wind P, Ganne N, Sebbane G, Zelek L, Paillaud E. Obesity survival paradox in cancer patients: Results from the Physical Frailty in older adult cancer patients (PF-EC) study. Clin Nutr. 2018 Dec 13.
19- Caillet P, Liuu E, Raynaud Simon A, Bonnefoy M, Guerin O, Berrut G, Lesourd B, Jeandel C, Ferry M, Rolland Y, Paillaud E. Association between cachexia, chemotherapy and outcomes in older cancer patients: A systematic review.Clin Nutr. 2017 Dec;36(6):1473-1482
20- Brugel L, Laurent M, Caillet P, Radenne A, Durand-Zaleski I, Martin M, Baron M, de Kermadec H, Bastuji-Garin S, Canouï-Poitrine F, Paillaud E. Impact of comprehensive geriatric assessment on survival, function, and nutritional status in elderly patients with head and neck cancer: protocol for a multicentre randomised controlled trial (EGeSOR). BMC Cancer. 2014 Jun 13;14:427.
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Carina Binet : Secrétaire Général du CARPEM
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Aurore Hattabi, PhD : Coordinatrice Scientifique du CARPEM
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