Trends in incidence of infrequent and frequent synchronous metastases from colorectal cancer.

BACKGROUND: Population-based data on the incidence of frequent colorectal metastases are fairly scarce, while that on rare metastatic sites are lacking. AIMS: The aim of this study was to provide epidemiological indicators of metastatic sites frequency in patients with colorectal cancer. METHODS: Incidence was modelled using Poisson and Joinpoint regressions in a population-based cancer registry study including metastatic colorectal cancers diagnosed between 1991 and 2020 (N = 5,199). Tumor molecular markers were collected for the [2016-2020] period. RESULTS: Liver, peritoneum, lung and bone were the most frequent metastatic sites. Among frequent sites, incidence of liver and lung sites decreased in men respectively since 1999 and 2010, whereas in women incidence of liver and peritoneum sites increased steadily throughout the whole period. Each of the other sites concerned less than 3% of metastatic colorectal cancer cases and presented standardized incidence rates between 0.19 and 1.39 per 1,000,000. Among rare sites, incidence of adrenal glands, supraclavicular lymph node, mediastinum and ascites had doubled in [2016-2020] as compared to the 25 previous years. BRAFV600E variant was more frequent in presence of carcinomatosis, and absence of liver and lung metastasis while KRAS variant was more frequent in presence of lung metastasis. CONCLUSION: This study provides unprecedented incidence indicators for rare synchronous metastases of colorectal cancer.

Estimating cure and risk of death from other causes of cancer patients: EUROCARE-6 data on head & neck, colorectal, and breast cancers.

BACKGROUND: To estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population. METHODS: A new modelling approach, that corrects for patients' extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40-79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries. FINDINGS: Young male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4. INTERPRETATION: Not considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients' quality of life.

Molecular relapse after first-line intensive therapy in patients with CBF or NPM1-mutated acute myeloid leukemia - a FILO study.

Patients with Core-Binding Factor (CBF) and NPM1-mutated acute myeloid leukemia (AML) can be monitored by quantitative PCR after having achieved first complete remission (CR) to detect morphologic relapse and drive preemptive therapy. How to best manage these patients is unknown. We retrospectively analyzed 303 patients with CBF and NPM1-mutated AML, aged 18-60 years, without allogeneic hematopoietic cell transplantation (HCT) in first CR, with molecular monitoring after first-line intensive therapy. Among these patients, 153 (51%) never relapsed, 95 (31%) had molecular relapse (53 received preemptive therapy and 42 progressed to morphologic relapse at salvage therapy), and 55 (18%) had upfront morphologic relapse. Patients who received preemptive therapy had higher OS than those who received salvage therapy after having progressed from molecular to morphologic relapse and those with upfront morphologic relapse (three-year OS: 78% vs. 51% vs. 51%, respectively, P = 0.01). Preemptive therapy included upfront allogeneic HCT (n = 19), intensive chemotherapy (n = 21), and non-intensive therapy (n = 13; three-year OS: 92% vs. 79% vs. 58%, respectively, P = 0.09). Although not definitive due to the non-randomized allocation of patients to different treatment strategies at relapse, our study suggests that molecular monitoring should be considered during follow-up to start preemptive therapy before overt morphologic relapse.

Differences in survival and recurrence of colorectal cancer by stage across population-based European registries.

Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age-standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5-year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5-year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five-year cumulative rate of recurrence among resected patients with stage I-III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population-based collection of cancer recurrence information is crucial to enhance efforts for evidence-based management of colorectal cancer follow up.

Impact of socio-economic environment on incidence of primary liver cancer in France between 2006 and 2016.

BACKGROUND AND AIMS: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). METHOD: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation. RESULTS: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9-10.66] per 100 000 person-years, Q2 11.43 [10.48-12.47] (p < .0001), Q3 11.81 [10.82-12.89] (p < .0001), Q4 12.26 [11.25-13.37] (p < .001) and Q5 11.53 [10.57-12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407). CONCLUSION: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies.

Net survival in colon and rectal cancer by stage according to neoadjuvant treatment. A French population-based study.

AIM: Real-life estimations of survival by stage in colorectal cancer are scanty. We estimated population-based net survival by pathological stage and location, and for rectal cancer by patterns of evolution according to clinical and pathological stage with regard to neoadjuvant therapy. METHOD: Age-standardized net survival was estimated on 19,630 colorectal cancers diagnosed between 2009 and 2015. RESULTS: Five-year net survival was 64 % for colon and 62 % for rectal cancer. The highest absolute difference between colon and rectum was 12 % for stage II women aged 75 (91% vs. 79 %). Among patients with clinical stage III rectal cancer, 67 % no longer had pathological node involvement after neoadjuvant treatment. Survival was similar in clinical stage I, II or III and pathological stage III after neoadjuvant treatment and in pathological stage III without neoadjuvant treatment (between 67 % and 72 %). It ranged between 80 and 82 % in pathological stage II, without neoadjuvant treatment or with clinical stage I, II or III before neoadjuvant treatment. Survival ranged between 93 % and 95 % in pathological stage I, treated with surgery only or with clinical stage II or III before neoadjuvant treatment. CONCLUSION: Prognosis is associated with stage determined on surgical specimens rather than stage at the initial workup.

Survival variability across hospitals after resection for pancreatic adenocarcinoma: A multilevel survival analysis on a high-resolution population-based study.

INTRODUCTION: Resection is the cornerstone of curative management for pancreatic ductal adenocarcinoma (PDAC). Hospital surgical volume influence post-operative mortality. Few is known about impact on survival. METHODS: Population included 763 patients resected for PDAC within the 4 French digestive tumor registries between 2000 and 2014. Spline method was used to determine annual surgical volume thresholds influencing survival. A multilevel survival regression model was used to study center effect. RESULTS: Population was divided into three groups: low-volume (LVC) (<41 hepatobiliary/pancreatic procedures/year), medium-volume (MVC) (41-233) and high-volume centers (HVC) (>233). Patients in LVC were older (p = 0.02), had a lower rate of disease-free margins (76.7% vs. 77.2% and 69.5%, p = 0.028) and a higher post-operative mortality than in MVC and HVC (12.5% and 7.5% vs. 2.2%; p = 0.004). Median survival was higher in HVC than in other centers (25 vs. 15.2 months, p < 0.0001). Survival variance attributable to center effect accounted for 3.7% of total variance. In multilevel survival analysis, surgical volume explained the inter-hospital survival heterogeneity (non-significant variance after adding the volume to the model p = 0.3). Patients resected in HVC had a better survival than in LVC (HR 0.64 [0.50-0.82], p < 0.0001). There was no difference between MVC and HVC. CONCLUSION: Regarding center effect, individual characteristics had little impact on survival variability across hospitals. Hospital volume was a major contributor to the center effect. Given the difficulty of centralizing pancreatic surgery, it would be wise to determine which factors would indicate management in a HVC.

Relationship between comorbidities, mutational profile, and outcome after intensive chemotherapy in patients older than 60 years with acute myeloid leukemia: Assessment of different risk scores.

The aim of this study was to evaluate how comorbidities and molecular landscape relate to outcome in patients with acute myeloid leukemia (AML) aged 60 years or older who received intensive induction therapy. In 91 patients, 323 mutations were identified in 77 genes by next-generation sequencing, with a median of four mutations per patient, with NPM1, FLT3, TET2, and DNMT3A being the most frequently mutated genes. A multistate model identified FLT3, IDH2, RUNX1, and TET2 mutations as associated with a higher likelihood of achieving complete remission while STAG2 mutations were associated with primary refractory disease, and DNMT3A, FLT3, IDH2, and TP53 mutations with mortality after relapse. Ferrara unfitness criteria and performance status were the best predictors of short-term outcome (area under the curve = 82 for 2-month survival for both parameters), whereas genomic classifications better predicted long-term outcome, with the Patel risk stratification performing the best over the 5-year follow-up period (C-index = 0.63 for event-free and overall survival). We show that most genomic prognostic classifications, mainly used in younger patients, are useful for classifying older patients, but to a lesser extent, because of different mutational profiles. Specific prognostic classifications, incorporating performance status, comorbidities, and cytogenetic/molecular data, should be specifically designed for patients over 60 years.

Biliary tract cancers have distinct epidemiological patterns and clinical characteristics according to tumour site.

BACKGROUND: Little is known about the epidemiology of biliary tract cancers over the last decade. We investigated trends in incidence, treatment and prognosis of biliary tract cancers according to anatomic site. METHODS: 714 biliary tract cancers recorded between 2012 and 2019 in the French population-based cancer registry of Burgundy were included. Trends in world age-standardized incidence were depicted using Poisson regression. RESULTS: Intrahepatic cholangiocarcinoma accounted for 40% of biliary tract cancer. Half of the patients were older than 75 years at diagnosis. Incidence of biliary tract cancer did not vary over time, except a slight increase in intrahepatic cholangiocarcinoma in men and a decrease in the ampulla in both sexes. Among non-metastatic patients, the proportion who underwent R0 resection ranged from 15% for intrahepatic cholangiocarcinoma to 58% for ampulla cancer (p < 0.001). Age, performance status and hospital type were associated with resection. Among unresected patients, 45% received chemotherapy. Older age, jaundice, increasing performance status and comorbidities index negatively affected chemotherapy administration. Net survival was higher for ampulla than for other sites, regardless of patient and treatment characteristics. CONCLUSION: Biliary tract cancers present different patterns in incidence. The ampulla site should be considered separately in clinical trials due to its better outcomes.

Predictors of Survival in Elderly Patients with Metastatic Colon Cancer: A Population-Based Cohort Study.

Oncological strategies in the elderly population are debated. The objective of this study was to determine the predictive factors of survival in patients aged 80 years and older with metastatic colon cancer. Data from four digestive tumour registry databases were used in this analysis. This population-based retrospective study included 1115 patients aged 80 years and older with stage IV colon adenocarcinoma diagnosed between 2007 and 2016. Cox regression was used to assess the impact of different prognostic factors. Age was significantly correlated with the surgical treatment (p < 0.001) but not with overall survival. Patients with a low comorbidity burden had better survival than patients with higher comorbidities scores (9.4 (0−123) versus 7.9 (0−115) months) (p = 0.03). Surgery was more common for proximal colon cancer (p < 0.001), but the location of the primary lesion was not correlated with improved survival (p = 0.07). Patients with lung metastases had a better prognosis than those with liver metastases (HR 0.56 95% CI 0.40, 0.77 p < 0.001); multiple organ involvement had the worst survival (HR 1.32 95% CI 1.15, 1.51 p < 0.001). Chemotherapy was associated with improved survival for both operated (HR 0.45 95% CI 0.35, 0.58 p < 0.001) and non-operated patients (HR 0.41 95% CI 0.34, 0.50 p < 0.001). The majority of patients receiving adjuvant treatment had a low comorbidity burden. In our study, the location of metastases but not the primary tumor location had an impact on overall survival. Low comorbidity burden, curative surgery, and chemotherapy had a significant advantage for elderly patients with metastatic colon cancer.

Incidence and Survival in Synchronous and Metachronous Liver Metastases From Colorectal Cancer.

Importance: Although treatment and prognosis of synchronous liver metastases from colorectal cancer are relatively well known, a comparative description of the incidence, epidemiological features, and outcomes of synchronous and metachronous liver metastases is lacking. The difference in prognosis between patients with synchronous and metachronous liver metastases is controversial. Objective: To investigate temporal patterns in the incidence and outcomes of synchronous vs metachronous liver metastases from colorectal cancer. Design, Setting, and Participants: This population-based cohort study used information from a French regional digestive cancer registry accounting for 1 082 000 inhabitants. A total of 26 813 patients with a diagnosis of incident colorectal adenocarcinoma diagnosed between January 1, 1976, and December 31, 2018, were included. Data were analyzed from February 7 to May 20, 2022. Main Outcomes and Measures: Age-standardized incidence was calculated. Univariate and multivariate net survival analyses were performed. Results: Of 26 813 patients with colorectal cancer (15 032 men [56.1%]; median [IQR] age, 73 [64-81] years), 4546 (17.0%) presented with synchronous liver metastases. The incidence rate of synchronous liver metastases was 6.9 per 100 000 inhabitants in men and 3.4 per 100 000 inhabitants in women, with no significant variation since 2000. The 5-year cumulative incidence of metachronous liver metastases decreased from 18.6% (95% CI, 14.9%-22.2%) during the 1976 to 1980 period to 10.0% (95% CI, 8.8%-11.2%) during the 2006 to 2011 period. Cancer stage at diagnosis was the strongest risk factor for liver metastases; compared with patients diagnosed with stage II cancer, patients with stage III cancer had a 2-fold increase in risk (subdistribution hazard ratio, 2.42; 95% CI, 2.08-2.82) for up to 5 years. Net survival at 1 year was 41.8% for synchronous liver metastases and 49.9% for metachronous metastases, and net survival at 5 years was 6.2% for synchronous liver metastases and 13.2% for metachronous metastases. Between the first (1976-1980) and last (2011-2016) periods, the adjusted ratio of death after synchronous and metachronous metastases was divided by 2.5 for patients with synchronous status and 3.7 for patients with metachronous status. Conclusions and Relevance: In this study, the incidence of colorectal cancer with synchronous liver metastases changed little over time, whereas there was a 2-fold decrease in the probability of developing metachronous liver metastases. Survival improved substantially for patients with metachronous liver metastases, whereas improvement was more modest for those with synchronous metastases. The differences observed in the epidemiological features of synchronous and metachronous liver metastases from colorectal cancer may be useful for the design of future clinical trials.

Health status of prevalent cancer cases as measured by mortality dynamics (cancer vs. noncancer): Application to five major cancers sites.

BACKGROUND: Cancer prevalence is heterogeneous because it includes individuals who are undergoing initial treatment and those who are in remission, experiencing relapse, or cured. The proposed statistical approach describes the health status of this group by estimating the probabilities of death among prevalent cases. The application concerns colorectal, lung, breast, and prostate cancers and melanoma in France in 2017. METHODS: Excess mortality was used to estimate the probabilities of death from cancer and other causes. RESULTS: For the studied cancers, most deaths from cancer occurred during the first 5 years after diagnosis. The probability of death from cancer decreased with increasing time since diagnosis except for breast cancer, for which it remained relatively stable. The time beyond which the probability of death from cancer became lower than that from other causes depended on age and cancer site: for colorectal cancer, it was 6 years after diagnosis for women (7 years for men) aged 75-84 and 20 years for women (18 years for men) aged 45-54 years, whereas cancer was the major cause of death for women younger than 75 years whatever the time since diagnosis for breast and for all patients younger than 75 years for lung cancer. In contrast, deaths from other causes were more frequent in all the patients older than 75 years. Apart from breast cancer in women younger than 55 years and lung cancer in women older than 55 years and men older than 65 years, the probability of death from cancer among prevalent cases fell below 1%, with varying times since diagnosis. CONCLUSIONS: The authors' approach can be used to better describe the burden of cancer by estimating outcomes in prevalent cases.

First estimates of diffuse gastric cancer risks for carriers of CTNNA1 germline pathogenic variants.

BACKGROUND: Pathogenic variants (PV) of CTNNA1 are found in families fulfilling criteria for hereditary diffuse gastric cancer (HDGC) but no risk estimates were available until now. The aim of this study is to evaluate diffuse gastric cancer (DGC) risks for carriers of germline CTNNA1 PV. METHODS: Data from published CTNNA1 families were updated and new families were identified through international collaborations. The cumulative risk of DGC by age for PV carriers was estimated with the genotype restricted likelihood (GRL) method, taking into account non-genotyped individuals and conditioning on all observed phenotypes and genotypes of the index case to obtain unbiased estimates. A non-parametric (NP) and the Weibull functions were used to model the shape of penetrance function with the GRL. Kaplan-Meier incidence curve and standardised incidence ratios were also computed. A 'leave-one-out' strategy was used to evaluate estimate uncertainty. RESULTS: Thirteen families with 46 carriers of PV were included. The cumulative risks of DGC at 80 years for carriers of CTNNA1 PV are 49% and 57%, respectively with the Weibull GRL and NP GRL methods. Risk ratios to population incidence reach particularly high values at early ages and decrease with age. At 40 years, they are equal to 65 and 833, respectively with the Weibull GRL and NP GRL. CONCLUSION: This is the largest series of CTNNA1 families that provides the first risk estimates of GC. These data will help to improve management and surveillance for these patients and support inclusion of CTNNA1 in germline testing panels.

Combination of CDX2 H-score quantitative analysis with CD3 AI-guided analysis identifies patients with a good prognosis only in stage III colon cancer.

AIM: Stratification of colon cancer (CC) of patients with stage II and III for risk of relapse is still needed especially to drive adjuvant therapy administration. Our study evaluates the prognostic performance of two known biomarkers, CDX2 and CD3, standalone or their combined information in stage II and III CC. PATIENTS AND METHODS: CDX2 and CD3 expression was evaluated in Prodige-13 study gathering 443 stage II and 398 stage III primary CC on whole slide colectomy. We developed for this study an H-score to quantify CDX2 expression and used our artificial intelligence (AI)-guided tissue analysis ColoClass to detect CD3 in tumour core and invasive margin. Association between biomarkers and relapse-free survival was investigated. RESULTS: Univariate analysis showed that the combined variable CD3-TC and CD3-IM was associated with prognosis in both stage II and stage III. CDX2, on the contrary, was associated with prognosis only in stage III. We subsequently associated CDX2 and combined immune parameters only in stage III. This multivariate analysis allowed us to distinguish a proportion of stage III CC harbouring a high CDX2 expression and a high immune infiltration with a particularly good prognosis compared to their counterpart. CONCLUSION: This study validated the prognostic role of CDX2 and CD3 evaluated with immunohistochemistry procedures in stage III but not in stage II. This association would be conceivable in a routine pathology laboratory and could help oncologist to consider chemotherapy de-escalation for a part of stage III patients.

Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries. Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method. Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country. Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians. Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.

Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.

BACKGROUND: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. METHODS: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. FINDINGS: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. INTERPRETATION: The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. FUNDING: Deutsche Krebshilfe.

Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study.

DDX41 germline mutations (DDX41MutGL) are the most common genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia (AML). Recent reports suggest that DDX41MutGL myeloid malignancies could be considered as a distinct entity, even if their specific presentation and outcome remain to be defined. We describe here the clinical and biological features of 191 patients with DDX41MutGL AML. Baseline characteristics and outcome of 86 of these patients, treated with intensive chemotherapy in 5 prospective Acute Leukemia French Association/French Innovative Leukemia Organization trials, were compared with those of 1604 patients with DDX41 wild-type (DDX41WT) AML, representing a prevalence of 5%. Patients with DDX41MutGL AML were mostly male (75%), in their seventh decade, and with low leukocyte count (median, 2 × 109/L), low bone marrow blast infiltration (median, 33%), normal cytogenetics (75%), and few additional somatic mutations (median, 2). A second somatic DDX41 mutation (DDX41MutSom) was found in 82% of patients, and clonal architecture inference suggested that it could be the main driver for AML progression. DDX41MutGL patients displayed higher complete remission rates (94% vs 69%; P < .0001) and longer restricted mean overall survival censored at hematopoietic stem cell transplantation (HSCT) than 2017 European LeukemiaNet intermediate/adverse (Int/Adv) DDX41WT patients (5-year difference in restricted mean survival times, 13.6 months; P < .001). Relapse rates censored at HSCT were lower at 1 year in DDX41MutGL patients (15% vs 44%) but later increased to be similar to Int/Adv DDX41WT patients at 3 years (82% vs 75%). HSCT in first complete remission was associated with prolonged relapse-free survival (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88; P = .02) but not with longer overall survival (hazard ratio, 0.77; 95% confidence interval, 0.35-1.68; P = .5).

Management and Outcomes of Pancreatic Cancer in French Real-World Clinical Practice.

Background: Our objective was to describe real-world patterns of care and outcomes in pancreatic cancer. Methods: 912 patients diagnosed with pancreatic cancer from 2014 to 2017 were registered by the population-based cancer registry of Burgundy (France). Progression-free and net survival were estimated. Results: at diagnosis, 52% of tumors were associated with metastases. Among the 20% of patients fulfilling resectability criteria, half of those aged 75−84 years and none of those ≥85 years actually underwent resection. Age was not associated with 3-year observed survival in patients who underwent resection. Overall, 77% of patients aged <75 years, 55% of those aged 75−84 years and 8% of those ≥85 years received chemotherapy. Among patients who were offered chemotherapy, 73% of those aged ≥85 years refused. Chemotherapy toxicity was higher with Gemcitabine_Oxaliplatin/Gemcitabine_Abraxane and FOLFIRINOX than with Gemcitabine alone. Patients resected after induction FOLFIRINOX and those treated with adjuvant Gemcitabine presented the lowest risk of progression. Three-year net survival was 35% in patients with non-metastatic resectable tumors and under 10% for other patients. Conclusions: Only half of patients aged 75−84 years with a resectable tumor actually underwent resection. Two thirds of patients aged ≥85 years refused chemotherapy, thus underlining the need to expand geriatric assessments.