Adjuvant chemotherapy omission after pancreatic cancer resection: a French nationwide study.

BACKGROUND: Adjuvant chemotherapy (AC) improves the prognosis after pancreatic ductal adenocarcinoma (PDAC) resection. However, previous studies have shown that a large proportion of patients do not receive or complete AC. This national study examined the risk factors for the omission or interruption of AC. METHODS: Data of all patients who underwent pancreatic surgery for PDAC in France between January 2012 and December 2017 were extracted from the French National Administrative Database. We considered "omission of adjuvant chemotherapy" (OAC) all patients who failed to receive any course of gemcitabine within 12 postoperative weeks and "interruption of AC" (IAC) was defined as less than 18 courses of AC. RESULTS: A total of 11 599 patients were included in this study. Pancreaticoduodenectomy was the most common procedure (76.3%), and 31% of the patients experienced major postoperative complications. OACs and IACs affected 42% and 68% of the patients, respectively. Ultimately, only 18.6% of the cohort completed AC. Patients who underwent surgery in a high-volume centers were less affected by postoperative complications, with no impact on the likelihood of receiving AC. Multivariate analysis showed that age ≥ 80 years, Charlson comorbidity index (CCI) ≥ 4, and major complications were associated with OAC (OR = 2.19; CI95%[1.79-2.68]; OR = 1.75; CI95%[1.41-2.18] and OR = 2.37; CI95%[2.15-2.62] respectively). Moreover, age ≥ 80 years and CCI 2-3 or ≥ 4 were also independent risk factors for IAC (OR = 1.54, CI95%[1.1-2.15]; OR = 1.43, CI95%[1.21-1.68]; OR = 1.47, CI95%[1.02-2.12], respectively). CONCLUSION: Sequence surgery followed by chemotherapy is associated with a high dropout rate, especially in octogenarian and comorbid patients.

Studying the stability of polymer nanoparticles by size exclusion chromatography of radioactive polymers.

The properties of nanomedicines will influence how they can deliver drugs to patients reproducibly and effectively. For conventional pharmaceutical products, Chemistry, Manufacturing and Control (CMC) documents require monitoring stability and storage conditions. For nanomedicines, studying these important considerations is hindered by a lack of appropriate methods. In this paper, we show how combining radiolabelling with size exclusion chromatography, using a method called SERP (for Size Exclusion of Radioactive Polymers), can inform on the in vitro degradation of polymer nanoparticles. Using nanoparticles composed of biodegradable poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA), we show that SERP is more sensitive than dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) to detect degradation. We also demonstrate that the properties of the polymer composition and the nature of the aqueous buffer affect nanoparticle degradation. Importantly, we show that minute changes in stability that cannot be detected by DLS and NTA impact the pharmacokinetic of nanoparticles injected in vivo. We believe that SERP might prove a valuable method to document and understand the pharmaceutical quality of polymer nanoparticles.

Optimization of a lipid nanoparticle-based protocol for RNA transfection into primary mononuclear phagocytes.

The effective delivery of synthetic RNA into mononuclear phagocytes is a prerequisite for experimental research and therapeutic development. However, traditional methods are highly ineffective and toxic for these cells. Here, we aimed to optimize a transfection protocol for primary bone marrow-derived phagocytes, specifically dendritic cells and macrophages, using lipid nanoparticles generated by microfluidics. Our results show that a lipid mixture similar to that used in Moderna's COVID-19 messenger RNA vaccine outperforms the others tested. Improved messenger RNA transfection can be achieved by replacing uridine with methylpseudouridine but not methoxyuridine, which interferes with transfection. The addition of diphenyleneiodonium or apocynin can enhance transfection in a cell type-dependent manner without adverse effects, while apolipoprotein E provides no added value. These optimized transfection conditions can also be used for microRNA agonists and antagonists. In sum, this study offers a straightforward, highly efficient, reproducible, and nontoxic protocol to deliver RNA into different primary mononuclear phagocytes in culture.

Encapsulation of conjugated linoleic acid and ruminant trans fatty acids to study the prevention of metabolic syndrome-a review.

Studies have reported the potential benefits of consuming conjugated linoleic acid (CLA) and ruminant trans fatty acids (R-TFAs) in reducing the risk factors of metabolic syndrome (MetS). In addition, encapsulation of CLA and R-TFAs may improve their oral delivery and further decrease the risk factors of MetS. The objectives of this review were (1) to discuss the advantages of encapsulation; (2) to compare the materials and techniques used for encapsulating CLA and R-TFAs; and (3) to review the effects of encapsulated vs non-encapsulated CLA and R-TFAs on MetS risk factors. Examination of papers citing micro- and nano-encapsulation methods used in food sciences, as well as the effects of encapsulated vs non-encapsulated CLA and R-TFAs, was conducted using the PubMed database. A total of 84 papers were examined; of these, 18 studies were selected that contained information on the effects of encapsulated CLA and R-TFAs. The 18 studies that described encapsulation of CLA or R-TFAs indicated that micro- or nano-encapsulation processes stabilized CLA and prevented oxidation. CLA was mainly encapsulated using carbohydrates or proteins. So far, oil-in-water emulsification followed by spray-drying were the frequently used techniques for encapsulation of CLA. Further, 4 studies investigated the effects of encapsulated CLA on MetS risk factors compared with non-encapsulated CLA. A limited number of studies investigated the encapsulation of R-TFAs. The effects of encapsulated CLA or R-TFAs on the risk factors for MetS remain understudied; thus, additional studies comparing the effects of encapsulated and non-encapsulated CLA or R-TFAs are needed.

Conventional cytotoxic chemotherapy for gastrointestinal cancer in patients with cirrhosis: A multicentre case-control study.

BACKGROUND & AIMS: Progresses in management make a higher proportion of cirrhotic patients with gastrointestinal (GI) cancer candidates to chemotherapy. Data are needed on the safety and liver-related events associated with the use of chemotherapy in these patients. METHODS: Forty-nine patients with cirrhosis receiving chemotherapy against GI cancer from 2013 to 2018 were identified in the French Health Insurance Database using ICD-10 codes K70-K74, and matched 1:2 to non-cirrhotic controls (n = 98) on age, tumour type and type of treatment. Adverse events (AE), dose tapering, discontinuation rate, liver-related events and survival rate were compared. RESULTS: Patients with cirrhosis (Child-Pugh A 91%) more often received lower doses (38.8% vs 7.1%, p < .001), without significant differences in terms of grade 3/4 AE or dose tapering rates (29.6% vs. 36.7%; 22.3% vs 24.4%, respectively). Treatment discontinuation rate was higher in patients with cirrhosis (23.3% vs. 11.3%, p = .005). Child-Pugh (p = .007) and MELD (p = .025) scores increased under chemotherapy. Five patients with cirrhosis (10.2%) had liver decompensation within 12 months, and 17.2% of deaths in the cirrhosis group were liver-related versus 0% in matched controls. WHO-PS stage > 1 (HR 3.74, CI95%: 2.13-6.57, p < .001), TNM-stage M1 (HR 3.61, CI 95%: 1.82-7.16, p < .001), non-colorectal cancer (HR 1.73, CI 95%: 1.05-2.86, p = .032) and bilirubin higher than 5 mg/dL (HR 2.26, CI 95%: 1.39-3.70, p < .001) were independent prognostic factors of 2-year mortality, whereas cirrhosis was not. CONCLUSIONS: Chemotherapy should be proposed only in patients with compensated cirrhosis with close monitoring of liver function. Dose management remains challenging. Multidisciplinary management is warranted to improve these patients' outcomes.

Animal Models in Eye Research: Focus on Corneal Pathologies.

The eye is a complex sensory organ that enables visual perception of the world. The dysfunction of any of these tissues can impair vision. Conduction studies on laboratory animals are essential to ensure the safety of therapeutic products directly applied or injected into the eye to treat ocular diseases before eventually proceeding to clinical trials. Among these tissues, the cornea has unique homeostatic and regenerative mechanisms for maintaining transparency and refraction of external light, which are essential for vision. However, being the outermost tissue of the eye and directly exposed to the external environment, the cornea is particularly susceptible to injury and diseases. This review highlights the evidence for selecting appropriate animals to better understand and treat corneal diseases, which rank as the fifth leading cause of blindness worldwide. The development of reliable and human-relevant animal models is, therefore, a valuable research tool for understanding and translating fundamental mechanistic findings, as well as for assessing therapeutic potential in humans. First, this review emphasizes the unique characteristics of animal models used in ocular research. Subsequently, it discusses current animal models associated with human corneal pathologies, their utility in understanding ocular disease mechanisms, and their role as translational models for patients.

Enhancing collaboration between geriatricians, oncologists, and pharmacists to optimize medication therapy in older adults with cancer: A position paper from SOFOG-SFPO.

Optimizing anticancer treatment and medication therapy in older patients with cancer requires a multidisciplinary approach, with a strong collaboration between geriatricians, oncologists and pharmacists. While all patients can benefit, some clinical situations seem to be high-priority. Careful attention should be given to patients with cardiovascular comorbidities and/or diabetes, which are prone to decompensate during anticancer treatment and often involve multiple medications. Another great concern is the risk of falls, closely related to polypharmacy, hence the need for a comprehensive medication review. Managing the pharmacological treatment of depression is also challenging and require shared expertise. Finally, pharmacists can prove valuable in situations of adherence difficulties or use of complementary medicines. Collaborative practice should begin at initiation of anticancer treatment and continue throughout the care pathway, as continuous reassessment is essential. Although the integration of pharmacists in multidisciplinary teams is often challenged by funding, collaborative should still be strongly encouraged.

Design of experiment and machine learning inform on the 3D printing of hydrogels for biomedical applications.

In the biomedical field, 3D printing has the potential to deliver on some of the promises of personalized therapy, notably by enabling point-of-care fabrication of medical devices, dosage forms and bioimplants. To achieve this full potential, a better understanding of the 3D printing processes is necessary, and non-destructive characterization methods must be developed. This study proposes methodologies to optimize the 3D printing parameters for soft material extrusion. We hypothesize that combining image processing with design of experiment (DoE) analyses and machine learning could help obtaining useful information from a quality-by-design perspective. Herein, we investigated the impact of three critical process parameters (printing speed, printing pressure and infill percentage) on three critical quality attributes (gel weight, total surface area and heterogeneity) monitored with a non-destructive methodology. DoE and machine learning were combined to obtain information on the process. This work paves the way for a rational approach to optimize 3D printing parameters in the biomedical field.

Glioblastoma-targeted, local and sustained drug delivery system based on an unconventional lipid nanocapsule hydrogel.

The objective of this work was to develop an implantable therapeutic hydrogel that will ensure continuity in treatment between surgery and radiochemotherapy for patients with glioblastoma (GBM). A hydrogel of self-associated gemcitabine-loaded lipid nanocapsules (LNC) has shown therapeutic efficacy in vivo in murine GBM resection models. To improve the targeting of GBM cells, the NFL-TBS.40-63 peptide (NFL), was associated with LNC. The LNC-based hydrogels were formulated with the NFL. The peptide was totally and instantaneously adsorbed at the LNC surface, without modifying the hydrogel mechanical properties, and remained adsorbed to the LNC surface after the hydrogel dissolution. In vitro studies on GBM cell lines showed a faster internalization of the LNC and enhanced cytotoxicity, in the presence of NFL. Finally, in vivo studies in the murine GBM resection model proved that the gemcitabine-loaded LNC with adsorbed NFL could target the non-resected GBM cells and significantly delay or even inhibit the apparition of recurrences.

Stability of Opened Durvalumab (IMFINZI) Vials. The Beginning of the End of Costly Product Wastage?

Durvalumab is a monoclonal antibody approved for the treatment of lung, urothelial and biliary tract cancers. Durvalumab is supplied in vials as a solution containing no preservatives. Monographs recommend single use of durvalumab vials, and that any leftovers be discarded within 24 h. Thus, significant portions of unused product from opened vials are wasted on a daily basis, generating considerable financial losses. The objective of the present study was to assess the physicochemical and microbiological stability of durvalumab vials kept at 4 °C or room temperature, at 7 and 14 days after opening. Following pH and osmolality measurements, turbidity and submicronic aggregation of durvalumab solution were evaluated by spectrophotometry and dynamic light scattering, respectively. Moreover, steric exclusion high performance liquid chromatography (SE-HPLC), ion exchange HPLC (IEX-HPLC) and peptide mapping HPLC were used to respectively assess aggregation/fragmentation, charge distribution and primary structure of durvalumab. Microbiological stability of durvalumab was evaluated by incubation of vial leftovers on blood agar. All experiments showed physicochemical and microbiological stability of durvalumab vial leftovers for at least 14 days when aseptically handled and kept at either 4 °C or at room temperature. These results suggest the possible extension of utilization of durvalumab vial leftovers well beyond 24 h.

Industrial and Ruminant Trans-Fatty Acids-Enriched Diets Differentially Modulate the Microbiome and Fecal Metabolites in C57BL/6 Mice.

Industrially originated trans-fatty acids (I-tFAs), such as elaidic acid (EA), and ruminant trans-fatty acids (R-tFAs), such as trans-palmitoleic acid (TPA), may have opposite effects on metabolic health. The objective was to compare the effects of consuming 2-3% I-tFA or R-tFA on the gut microbiome and fecal metabolite profile in mice after 7 and 28 days. Forty C57BL/6 mice were assigned to one of the four prepared formulations: lecithin nanovesicles, lecithin nanovesicles with EA or TPA, or water. Fecal samples and animals' weights were collected on days 0, 7, and 28. Fecal samples were used to determine gut microbiome profiles by 16S rRNA sequencing and metabolite concentrations by GC/MS. At 28 days, TPA intake decreased the abundance of Staphylococcus sp55 but increased Staphylococcus sp119. EA intake also increased the abundance of Staphylococcus sp119 but decreased Ruminococcaceae UCG-014, Lachnospiraceae, and Clostridium sensu stricto 1 at 28 days. Fecal short-chain fatty acids were increased after TPA while decreased after EA after 7 and 28 days. This study shows that TPA and EA modify the abundance of specific microbial taxa and fecal metabolite profiles in distinct ways.

Dual-Labelled Nanoparticles Inform on the Stability of Fluorescent Labels In Vivo.

Fluorescent labelling is commonly used to monitor the biodistribution of nanomedicines. However, meaningful interpretation of the results requires that the fluorescent label remains attached to the nanomedicine. In this work, we explore the stability of three fluorophores (BODIPY650, Cyanine 5 and AZ647) attached to polymeric hydrophobic biodegradable anchors. Using dual-labelled poly(ethylene glycol)-b-poly(lactic acid) (PEG-PLA) nanoparticles that are both radioactive and fluorescent, we investigated how the properties of the fluorophores impact the stability of the labelling in vitro and in vivo. Results suggest that the more hydrophilic dye (AZ647) is released faster from nanoparticles, and that this instability results in misinterpretation of in vivo data. While hydrophobic dyes are likely more suitable to track nanoparticles in biological environments, quenching of the fluorescence inside the nanoparticles can also introduce artefacts. Altogether, this work raises awareness about the importance of stable labelling methods when investigating the biological fate of nanomedicines.

C57bl/6 Mice Show Equivalent Taste Preferences toward Ruminant and Industrial Trans Fatty Acids.

Two distinct types of trans fatty acids (TFA) are found in the diet. Industrial TFA such as elaidic acid (EA) have deleterious effects on metabolic risk factors, and oppositely ruminant TFA including trans-palmitoleic acid (TPA) may have beneficial effects. The objective is to evaluate the taste preference between EA, TPA, lecithin or water. In this study, 24 female C57BL/6 mice were microchipped and placed in two separate IntelliCages®. Nano encapsulated TFA or lecithin were added to drinking water in different corners of the cage with normal diet. The study was carried out over 5 weeks, during which mice were exposed to water only (weeks 1 and 3), TFA or lecithin (week 2), and EA or TPA (weeks 4 and 5). Mice weights, corner visits, nose pokes (NP), and lick number were measured each week. The results demonstrated that mice consume more TFA, either EA or TPA, compared with lecithin. In addition, the mice licked more EA compared with TPA in one cage; conversely, in the other cage they licked more TPA compared with EA. However, when TFA positions were swapped, mice had equal licks for EA and TPA. In sum, mice preferred TFA, in equal matter compared with controls; therefore, the results demonstrate the potential for TFA-type substitution in diet.

Preserving bone in cancers of the elderly: A necessity.

The occurrence of bone fractures is frequent in the elderly population, and in cancer patients, especially with bone metastases. The growing incidence of cancer associated with an aging population implies important health challenges, including bone health. Decisions on cancer care in older adults have to take into account older adults' specificities. Screening tools as G8 or VES 13 and evaluating tools as comprehensive geriatric assessment (CGA) do not include bone-related items. Bone risk assessment is indicated according to identification of geriatric syndromes such as falls, history, and the oncology treatment plan. Some cancer treatments disrupt bone turnover and decrease bone mineral density. This is mainly caused by hypogonadism, induced by hormonal treatments and some chemotherapies. Treatments can also cause direct (i.e., chemotherapy, radiotherapy or glucocorticoids) or indirect toxicity through electrolyte disorders (i.e., some chemotherapies or tyrosine kinase inhibitors) on bone turnover. Bone risk prevention is multidisciplinary. Certain interventions proposed in the CGA aim to improve bone health and reduce the risk of falling. It is also based on the drug management of osteoporosis, and the prevention of complications from bone metastases. Management of fractures, related or not to bone metastases relates to the concept of orthogeriatrics. It is also based on the benefit-risk ratio of the operation, access to minimally invasive techniques, prehabilitation or rehabilitation, but also the prognosis related to cancer and geriatric syndromes. Bone health is essential in older cancer patient's care. Bone risk assessment should be part of CGA in routine use and specific decision-making tools should be developed. Bone event management must be integrated throughout the patient's care pathway and oncogeriatrics multidisciplinarity should include rheumatological expertise.

Projecting overall survival in health-economic models: uncertainty and maturity of data.

OBJECTIVE: As lifetime horizons are considered for economic evaluations, the Kaplan-Meier (KM) estimate is used to extrapolate survival in cases of immature overall survival (OS) data. This study estimated the error induced by the choice of distribution when extrapolating different levels of OS maturity. METHODS: Fifteen phase 3 trials reporting KM estimates of OS where at least 70% maturity (i.e. 70% of the population had died during follow-up) were included and compared to artificially created truncated data (30 and 50% maturity). Individual patient-data were reproduced using the Guyot algorithm based on digitized KM curves. Parametric survival distributions were fit for each arm in each study, for each maturity level, using the same time horizon (equal to the maximum follow-up). For each KM curve, the best distribution was chosen based on visual inspection, Akaike/Bayesian information criteria, and external validity. Outcomes were measured as life expectancy in months (LM) and life months gained (LMG). RESULTS: The Weibull (33%), log-logistic (32%) and log-normal (27%) were most often selected as the best fitting distribution. Compared to LM at full maturity, LM was overestimated in 23 and 40% of cases, at 30 and 50% maturity, respectively. Mean absolute error was 2.12months at 30% maturity, and decreased to 0.88months at 50% maturity. When comparing to mature data, the mean percentage of error in LMG was 126.4 and 62.4% at 30 and 50% maturity, respectively. CONCLUSION: The extent of OS maturity increases the risk of error when projecting long-term life expectancy for economic models. Even marginal gains in OS maturity result in more accurate estimations and should be considered when developing models.

The mechanisms of anti-PEG immune response are different in the spleen and the lymph nodes.

Polyethylene glycol (PEG) is a common ingredient in nanomedicines and pharmaceuticals. Recent studies show that approximately 20-70% of humans have anti-PEG antibodies that can recognize the polymer. Because these anti-PEG antibodies can reduce the effectiveness of certain PEGylated therapeutics, understanding how these immunoglobulins are produced is important. In this work, we investigate the mechanisms of the anti-PEG immune response, following the injection of polymeric nanoparticles by different routes of administration. We observed that the extent of systemic absorption and splenic deposition cannot predict the production of anti-PEG IgM - possibly because redundant biological pathways can be involved. Data obtained by surgically removing the spleen or depleting the complement activity suggest that the mechanisms behind the anti-PEG immune response differ between intravenous and subcutaneous injections. While B cells from the spleen appear to necessitate complement proteins to interact with nanoparticles, internalization by follicular B cells from the lymph nodes is unaffected by depletion of the cascade. This study confirms that the biological mechanisms involved in the immune recognition of nanomedicines varies based on the administration route. This knowledge can be utilized to use nanomedicines to engage the immune system in differentiated ways.

Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study.

PURPOSE: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. METHOD: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93). CONCLUSION: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study.

Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.

[Rethinking the management of elderly cancer patients : Proposals from the Age Cancer Priorities French Group]. / Repenser la prise en charge des sujets âgés atteints d'un cancer : propositions du groupe Priorités Âge Cancer.

The growing incidence of cancer associated with an aging population implies important health challenges that require questioning on the care management of older adults with cancer. There is a need to rethink the care management of older cancer patients with patient-centered decisions and an adjustment of the care pathway for this population. The Priorities Age Cancer (PAC) French group, made up of physicians, pharmacists and researchers in geriatric oncology, set up proposals to answer this need. First, the heterogeneity and the specificities of older adults as well as their preferences regarding cancer treatment goals, care management decisions must be patient-centered. The frailty screening tools should be generalized in clinical practice to provide geriatric assessment-guided recommendations and help for treatment decisions, and patients' involvement and shared decision should be developed. Second, older adults with cancer confront a complex health care system that demands a high level of health literacy. The caregivers, playing an essential role, may not be prepared for all these challenges. Thus, there is a need to promote health literacy by patient education, and patient-experts should be involved in health pathway. Third, there is a need to deal with dedicated partners and adjust the care pathway. New pathway careers as case-management nurses and specialized pharmacists should be involved in patient care and may play a central role together with other careers. Community-Hospital coordination should also be reinforced.