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.

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.

Estimating complete cancer prevalence in Europe: validity of alternative vs standard completeness indexes.

Introduction: Comparable indicators on complete cancer prevalence are increasingly needed in Europe to support survivorship care planning. Direct measures can be biased by limited registration time and estimates are needed to recover long term survivors. The completeness index method, based on incidence and survival modelling, is the standard most validated approach. Methods: Within this framework, we consider two alternative approaches that do not require any direct modelling activity: i) empirical indices derived from long established European registries; ii) pre-calculated indices derived from US-SEER cancer registries. Relying on the EUROCARE-6 study dataset we compare standard vs alternative complete prevalence estimates using data from 62 registries in 27 countries by sex, cancer type and registration time. Results: For tumours mostly diagnosed in the elderly the empirical estimates differ little from standard estimates (on average less than 5% after 10-15 years of registration), especially for low prognosis cancers. For early-onset cancers (bone, brain, cervix uteri, testis, Hodgkin disease, soft tissues) the empirical method may produce substantial underestimations of complete prevalence (up to 20%) even when based on 35-year observations. SEER estimates are comparable to the standard ones for most cancers, including many early-onset tumours, even when derived from short time series (10-15 years). Longer observations are however needed when cancer-specific incidence and prognosis differ remarkably between US and European populations (endometrium, thyroid or stomach). Discussion: These results may facilitate the dissemination of complete prevalence estimates across Europe and help bridge the current information gaps.

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.

A new cure model that corrects for increased risk of non-cancer death: analysis of reliability and robustness, and application to real-life data.

BACKGROUND: Non-cancer mortality in cancer patients may be higher than overall mortality in the general population due to a combination of factors, such as long-term adverse effects of treatments, and genetic, environmental or lifestyle-related factors. If so, conventional indicators may underestimate net survival and cure fraction. Our aim was to propose and evaluate a mixture cure survival model that takes into account the increased risk of non-cancer death for cancer patients. METHODS: We assessed the performance of a corrected mixture cure survival model derived from a conventional mixture cure model to estimate the cure fraction, the survival of uncured patients, and the increased risk of non-cancer death in two settings of net survival estimation, grouped life-table data and individual patients' data. We measured the model's performance in terms of bias, standard deviation of the estimates and coverage rate, using an extensive simulation study. This study included reliability assessments through violation of some of the model's assumptions. We also applied the models to colon cancer data from the FRANCIM network. RESULTS: When the assumptions were satisfied, the corrected cure model provided unbiased estimates of parameters expressing the increased risk of non-cancer death, the cure fraction, and net survival in uncured patients. No major difference was found when the model was applied to individual or grouped data. The absolute bias was < 1% for all parameters, while coverage ranged from 89 to 97%. When some of the assumptions were violated, parameter estimates appeared more robust when obtained from grouped than from individual data. As expected, the uncorrected cure model performed poorly and underestimated net survival and cure fractions in the simulation study. When applied to colon cancer real-life data, cure fractions estimated using the proposed model were higher than those in the conventional model, e.g. 5% higher in males at age 60 (57% vs. 52%). CONCLUSIONS: The present analysis supports the use of the corrected mixture cure model, with the inclusion of increased risk of non-cancer death for cancer patients to provide better estimates of indicators based on cancer survival. These are important to public health decision-making; they improve patients' awareness and facilitate their return to normal life.

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.

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.

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.

Influence of non-clinical factors on restorative rectal cancer surgery: An analysis of four specialized population-based digestive cancer registries in France.

BACKGROUND: This study aims to measure the association between deprivation, health care accessibility and health care system with the likelihood of receiving non-restorative rectal cancer surgery (NRRCS). METHODS: All adult patients who had rectal resection for invasive adenocarcinoma diagnosed between 2007 and 2016 in four French specialised cancer registries were included. A multilevel logistic regression with random effect was used to assess the link between patient and health care structure characteristics on the probability of NRRCS. RESULTS: 2997 patients underwent rectal cancer resection in 68 health care structures: 708 (23.63%) had NRRCS. The likelihood of receiving NRCCS was associated with patients' characteristics (97%): age, sub peritoneal rectal tumors, neoadjuvant therapy, residual tumour and stage III . There was no impact of European Deprivation Index or remoteness on NRRCS. Inter-health care structure variability was modest (3%), of which 50% was explained by the high group volume of colorectal procedures and the type of health care structure which were associated with less NRRCS (p<0.01). CONCLUSION: There is an influence of operating volume and type of structure on the probability of NRRCS, but it has truly little importance in explaining differences in performances. The probability of NRRCS is mainly affected by clinical determinant.

Surgical treatment of digestive cancer in a well-defined elderly population.

INTRODUCTION: Digestive cancer is of concern because of its frequency and severity with an increasing older median age of onset. The purpose of this study was to describe in a well-defined population presenting with non-metastatic digestive cancer the frequency of surgical resection and outcomes according to age. PATIENTS AND METHODS: We analyzed 7760 patients with a non-metastatic digestive cancer, recorded in the Burgundy population-based digestive cancer registry between 2009 and 2017. There were 3506 non-colorectal cancers and 4254 colorectal cancers with 3292 colon and 962 rectal cancers. The frequency of surgical resection was analyzed according to age (classified into four categories <70, [70-80[, [80-85[, and ≥85), sex, comorbidities and obesity. Postoperative mortality at 30 and 90 days was determined according to age, sex, comorbidity, obesity, location, surgery R0 or not. The 5-year survival study included 2952 patients with colorectal cancer, non-metastatic and who benefited from an R0 resection. RESULTS: Overall, 64% of the patients with M0 digestive cancer underwent a surgical resection, varying from 31% for Non colorectal Digestive cancers to 94% for colon site. The percentage of patients operated on for a resectable disease decreases from 71% before age 70 to 43% from age 85. Age and comorbidities were the main criteria influencing the probability of resection. At 30 days, postoperative mortality was 3%, all localizations and ages combined. At 90 days, this rate was 5%. In patients over 85 years old it gradually increases from 7% at 30 days and to 10% at 90 days. A man under 70 years of age has a net survival of 0.88 at 5 years, and 0.91 for a woman. For a man between 70 and 80 years old, it decreases to 0.81 and to 0.66 from 80 years old. In women, net survival is 0.87 between 70 and 80 years of age at 5 years, then drops to 0.75 from age 80. CONCLUSION: Our study shows a drop in access to surgery at different pivotal ages depending on the tumor location. This sudden drop in the resection rate is not justified by the increase in mortality with age, which is linear. In addition, the expected benefits of surgery are significant, with a net survival, mainly after the 1st year, of the same order as for younger patients. Age by itself should not be the only criterion in the medical decision. The challenge is to detect and treat the comorbidities that worsen the operative risk and the prognosis. There are few data on the management of digestive cancers specifically in the elderly. Our study shows that access to surgery is strongly linked to age and this in a non-linear way, whereas the expected benefits of surgery are significant, of the same order as for younger patients. Age itself should not be the only criterion in the medical decision.

Integrative Clinical and DNA Methylation Analyses in a Population-Based Cohort Identifies CDH17 and LRP2 as Risk Recurrence Factors in Stage II Colon Cancer.

Stage II colon cancer (CC), although diagnosed early, accounts for 16% of CC deaths. Predictors of recurrence risk could mitigate this but are currently lacking. By using a DNA methylation-based clinical screening in real-world (n = 383) and in TCGA-derived cohorts of stage II CC (n = 134), we have devised a novel 40 CpG site-based classifier that can segregate stage II CC into four previously undescribed disease sub-classes that are characterised by distinct molecular features, including activation of MYC/E2F-dependant proliferation signatures. By multivariate analyses, hypermethylation of 2 CpG sites at genes CDH17 and LRP2, respectively, was found to independently confer either significantly increased (CDH17; p-value, 0.0203) or reduced (LRP2; p-value, 0.0047) risk of CC recurrence. Functional enrichment and immune cell infiltration analyses, on RNAseq data from the TCGA cohort, revealed cases with hypermethylation at CDH17 to be enriched for KRAS, epithelial-mesenchymal transition and inflammatory functions (via IL2/STAT5), associated with infiltration by 'exhausted' T cells. By contrast, LRP2 hypermethylated cases showed enrichment for mTORC1, DNA repair pathways and activated B cell signatures. These findings will be of value for improving personalised care paths and treatment in stage II CC patients.

Socioeconomic Environment and Survival in Patients with Digestive Cancers: A French Population-Based Study.

Social inequalities are an important prognostic factor in cancer survival, but little is known regarding digestive cancers specifically. We aimed to provide in-depth analysis of the contextual social disparities in net survival of patients with digestive cancer in France, using population-based data and relevant modeling. Digestive cancers (n = 54,507) diagnosed between 2006-2009, collected through the French network of cancer registries, were included (end of follow-up 30 June 2013). Social environment was assessed by the European Deprivation Index. Multidimensional penalized splines were used to model excess mortality hazard. We found that net survival was significantly worse for individuals living in a more deprived environment as compared to those living in a less deprived one for esophageal, liver, pancreatic, colon and rectal cancers, and for stomach and bile duct cancers among females. Excess mortality hazard was up to 57% higher among females living in the most deprived areas (vs. least deprived) at 1 year of follow-up for bile duct cancer, and up to 21% higher among males living in the most deprived areas (vs. least deprived) regarding colon cancer. To conclude, we provide a better understanding of how the (contextual) social gradient in survival is constructed, offering new perspectives for tackling social inequalities in digestive cancer survival.

Outcomes of anus squamous cell carcinoma. Management of anus squamous cell carcinoma and recurrences.

BACKGROUND: Little is known about the management of squamous cell carcinoma of the anal canal and its recurrence at a population level. The aim of this study was to draw a picture of management, recurrence and survival in squamous cell carcinoma of the anal canal. MATERIAL AND METHODS: The 5-year probability of recurrences was estimated using the cumulative incidence function to consider competing risks of death. Net survival was estimated and a multivariate survival analysis was performed. The study was conducted using data of the Burgundy Digestive Cancer Registry. Overall, 273 squamous cell carcinomas of the anal canal registered between 1998 and 2014 were considered. RESULTS: Overall, 80% of patients were treated with curative intent. Of these, 61% received chemoradiotherapy, 35% received radiotherapy and 4% received abdominoperineal resection alone. After these treatments, for cure the 5-year cumulative recurrence rate was 27% overall; it was 20% after chemoradiotherapy and 38% after radiotherapy. Five-year net survival was 71% overall; it was 81% after chemoradiotherapy and 55% after radiotherapy. CONCLUSIONS AND RELEVANCE: Chemoradiotherapy was highly effective in routine practice. We confirm that it is difficult to distinguish between persistent active disease and local inflammation due to radiotherapy. Squamous cell carcinoma of the anal canal recurrences remains a substantial problem, highlighting the interest of prolonged surveillance. Aggressive management of recurrences may be beneficial.

Flexible Modeling of Net Survival and Cure by AML Subtype and Age: A French Population-Based Study from FRANCIM.

With improvements in acute myeloid leukemia (AML) diagnosis and treatment, more patients are surviving for longer periods. A French population of 9453 AML patients aged ≥15 years diagnosed from 1995 to 2015 was studied to quantify the proportion cured (P), time to cure (TTC) and median survival of patients who are not cured (MedS). Net survival (NS) was estimated using a flexible model adjusted for age and sex in sixteen AML subtypes. When cure assumption was acceptable, the flexible cure model was used to estimate P, TTC and MedS for the uncured patients. The 5-year NS varied from 68% to 9% in men and from 77% to 11% in women in acute promyelocytic leukemia (AML-APL) and in therapy-related AML (t-AML), respectively. Major age-differenced survival was observed for patients with a diagnosis of AML with recurrent cytogenetic abnormalities. A poorer survival in younger patients was found in t-AML and AML with minimal differentiation. An atypical survival profile was found for acute myelomonocytic leukemia and AML without maturation in both sexes and for AML not otherwise specified (only for men) according to age, with a better prognosis for middle-aged compared to younger patients. Sex disparity regarding survival was observed in younger patients with t-AML diagnosed at 25 years of age (+28% at 5 years in men compared to women) and in AML with minimal differentiation (+23% at 5 years in women compared to men). All AML subtypes included an age group for which the assumption of cure was acceptable, although P varied from 90% in younger women with AML-APL to 3% in older men with acute monoblastic and monocytic leukemia. Increased P was associated with shorter TTC. A sizeable proportion of AML patients do not achieve cure, and MedS for these did not exceed 23 months. We identify AML subsets where cure assumption is negative, thus pointing to priority areas for future research efforts.

Chemotherapy of metastatic colon cancer in France: A population-based study.

AIMS: to describe, using data from a cancer registry in a well-defined French population, the therapeutic strategies and survival of patients with metastatic colon cancer (mCC). METHODS: all patients with synchronous mCC diagnosed within the 2005-2014 period recorded in the digestive cancers registry of Burgundy were included. RESULTS: 1286 mCC patients were included (57% male), of which 34.5% did not receive any antitumor treatment. Both, advanced age (≥75 years) and the Charlson comorbidity score ≥2 were significantly associated with the absence of antitumor treatment. Among the patients treated with chemotherapy, 59 and 33% received at least two and three lines, respectively. Most patients treated with chemotherapy (68%) did not receive first-line targeted therapy. Of patients aged ≥75 years, 57% received no chemotherapy and 56% of treated patients had first-line treatment only. CONCLUSION: this population-based study shows that more than one-third of patients with mCC receive no chemotherapy and that only 59% of treated patients receive treatment beyond the first line. This study also highlights the fact that more than half of patients ≥75 years do not get any antitumor treatment. In patients <75 years, the proportion of patients receiving chemotherapy and/or undergoing curative intent surgery tended to increase over time.

Differences in the management and survival of metastatic colorectal cancer in Europe. A population-based study.

BACKGROUND: The management regarding metastatic colorectal cancer throughout Europe is not well known. AIMS: To draw a European comparison of the management and prognosis of metastatic colorectal cancers. METHODS: Factors associated with chemotherapy administration were identified through logistic regressions. Net survival was estimated and crude probabilities of death related to cancer and other causes using a flexible cumulative hazard model. RESULTS: Among the 13 227 patients with colorectal cancer diagnosed between 2010 and 2013 in cancer registries from 10 European countries, 3140 were metastatic. 62% of metastatic patients received chemotherapy. Compared to Spain, the related adjusted odds ratios ranged from 0.7 to 4.0 (P<0.001) according to country. The 3-year net survival by country ranged between 16% and 37%. The survival gap between countries diminished from 21% to 10% when adjusting for chemotherapy, age and sex. Geographical differences in the crude probability of death related to cancer were large for patients <70 or ≥80 years at diagnosis. CONCLUSION: Heterogeneity in the application of European guidelines partly explain these differences. General health between populations, accessibility to a reference centre, or provision of health care could also be involved. Further population-based studies are warranted to disentangle between these possible explanations.