다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21590

Cancer statistics, 2020.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21654

Cancer Statistics, 2021.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population‐based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized‐stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized‐stage diagnoses (from 17% in 2004 to 28% in 2018) and 3‐year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.3322/caac.21708

Cancer statistics, 2022

BackgroundWe assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non–small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. MethodsWe assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. ResultsCommon side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1501824

Pembrolizumab for the treatment of non-small cell lung cancer

Ponction pleurale : un guidage par échographie permet-il de diminuer les complications ?

Biologic staging of non-small-cell lung cancer: prospect or proposal?

Introduction La vinorelbine orale est un traitement valide dans la prise en charge du cancer bronchique non a petite cellule metastatique (CBNPC) et une option dans le mesotheliome pleural malin (MPM). L’utilisation d’un schema metronomique, base sur une modelisation mathematique permettant de selectionner un schema therapeutique optimal au regard de l’efficacite et de la tolerance, a ete validee [1] . Nous rapportons ici les resultats de la phase Ib d’expansion basee sur la vinorelbine orale selon un schema metronomique, dans le traitement des CBNPC et des MPM avances, refractaires. Methodes Les patients presentant un CBNPC metastatique ou un MPM ayant progresse apres un traitement standard etaient eligibles. La vinorelbine orale etait administree selon le schema metronomique de 60 mg a j1, 30 mg a j2 et 60 mg a j4, de facon hebdomadaire, jusqu’a progression ou toxicite inacceptable. La tolerance etait evaluee par les CTC 4.0 et la reponse radiologique par les RECIST 1.1 ou modifies (MPM). Resultats Vingt-trois patients ont ete evalues, et 20 patients ont ete traites (75 % d’hommes, âge median : 67,5 ans), comprenant 14 CBNPC. Tous les patients ont recu au moins une semaine de traitement (3 doses). Au moment de l’analyse, la mediane de suivi etait de 13,8 semaines (1–24) et la mediane de duree de traitement de 11 semaines (1–24). Asthenie, diarrhee et nausees de grade 1 etaient les effets indesirables les plus frequemment retrouves (60 %, 35 % et 20 %). Onze patients ont presente une anemie de grade 2 (65 %) et 5 patients ont presente une neutropenie de grade 4 (25 %). La meilleure reponse observee etait une reponse partielle chez 2 patients (10 %) et une maladie stable chez 13 patients (65 %), soit un taux de controle de la maladie de 75 %. Conclusion Le schema de vinorelbine metronomique 60/30/60 mg est bien tolere et permet un controle de la maladie chez une proportion non negligeable de patients, dans cette population lourdement pretraitee. L’analyse PK/PD et l’integration de ces donnees dans le modele mathematique pourraient permettre une adaptation du schema actuel d’administration. Les resultats seront mis a jour lors du congres.

Modélisation mathématique dans un essai clinique de phase 1 : application dans le traitement des cancers bronchiques non à petites cellules et des mésothéliomes avancés, par vinorelbine orale, selon un schéma métronomique

103 Background: Accumulating evidence pointed to the impact of the intestinal microbiota on ICI outcomes across various cancers. Although specific gut microbial species have been associated with beneficial responses ( i.e. Akkermansia muciniphila (Akk)), no consensus exists on a gut fingerprint predicting immunoresistance to clinical routine use. Methods: NCT04567446 provided whole genome sequencing (WGS) of longitudinal fecal samples from patients (pts) with advanced non-small cell lung cancer (NSCLC) during ICI (alone or with chemotherapy) in France and Canada. Topological Pearson networks clustered into species interacting groups (SIG) correlating with overall survival (OS; OS<12=NR; OS>12=R). Forty harmful (SIG1) and thirty-four beneficial (SIG2) WGS species were associated with NR and R to ICI. A monodimensional score (TOPOSCORE) based on SIG1/SIG2 ratio combined with Akk relative abundance was calculated and compared to machine-learning (ML) algorithms. Multivariate Cox analysis (MVA) adjusted for established risk factors (ATB, gender, age, ECOG, PD-L1, LIPI score). Intraindividual dynamics of the TOPOSCORE was evaluated in pts with at least two fecal samples. Three independent cohorts of NSCLC and genitourinary (GU) cancers pts validated the data. Results: In n=245 and n=148 NSCLC pts, we could classify pts into dysbiotic (SIG1+,33%) and eubiotic (SIG2+, 67%), using the TOPOSCORE. Pts falling within the SIG2+ exhibited a significantly prolonged OS than pts falling into SIG1+ (HR: (95% CI), 0.50 (0.36-0.71), p<0.0001). TOPOSCORE also predicted OS in 277 ICI-treated NSCLC and GU pts and compared to the state-of-the-art ML algorithms, held the highest percentage of correct predictions (63%). At MVA, TOPOSCORE was independently associated with OS (HR: 0.56 (0.39-0.81), p=0.002). Analyzing the intraindividual dynamics of the TOPOSCORE (n=67), we found that 74% of SIG2+ and 68% of SIG1+ individuals remained in their initial classification during ICI treatment. We finally scaled the calculation of the TOPOSCORE down to 24WGS (instead 75WGS) and set up a qPCR-based friendly-user test capable of accurately identifying the fecal presence of the bacteria of interest within 48 hrs. We confirmed (n=323) that OS was superior in those pts harboring a 24-bacteria-qPCR-based TOPOSCORE falling within the SIG2+ category (HR: 0.65 (0.48 to 0.87), p=0.0005). Conclusions: TOPOSCORE represents a robust biomarker predicting and following the dynamic of the immunoresistance to ICI across cancers on an individual basis. By converting the WGS TOPOSCORE to a qPCR-based test with a rapid turnaround time, it will be possible to adopt this score in routine clinical practice to improve pts stratification and ICI success rates guiding the selection of dysbiotic pts amenable to microbiota-centered interventions and eubiotic fecal microbiota transplantation donors. Clinical trial information: NCT04567446 .

Friendly-user score assessing gut dysbiosis and resistance to immune checkpoint inhibitors (ICI).

Management of NSCLC patients is more and more individualized especially on the base of bioguided treatments. In order to guarantee an access for all the patients too this type of strategy, the French NCI supports since 2006 a nationwide network of 28 regional genetics center. The financial support is based on public funds. The French NCI recommends today the assessment of seven biomarkers for all stage IV non squamous NSCLC patients. Due to financial and technical reasons, this recommendation must be followed. However, the molecular profiling of lung cancer patients would ideally be extended across all stages and all histological types of the disease in order to improve our knowledge in this field and provides the patient with an opportunity to access a bioguided treatment as frequently as possible.

Fabrice Barlesi

Papers

Ponction pleurale : un guidage par échographie permet-il de diminuer les complications ?

Biologic staging of non-small-cell lung cancer: prospect or proposal?

Modélisation mathématique dans un essai clinique de phase 1 : application dans le traitement des cancers bronchiques non à petites cellules et des mésothéliomes avancés, par vinorelbine orale, selon un schéma métronomique

Friendly-user score assessing gut dysbiosis and resistance to immune checkpoint inhibitors (ICI).

Plateformes de biologie moléculaire en oncologie thoracique : quelles recherches, pour qui ?