The contribution of second primary cancers to the mortality of patients with a first primary breast cancer.

PURPOSE: Second primary cancers (SPCs) are estimated to affect nearly 5% of patients with breast cancer within 10 years of their diagnosis. This study aimed to estimate the contribution of SPCs to the mortality of patients with a breast first primary cancer (FPC). METHODS: A population-based cohort of 17,210 patients with a breast FPC diagnosed between 2000 and 2010 was followed for SPCs (31/12/2015) and vital status (30/06/2021). Patients diagnosed with an SPC (265 synchronous and 897 metachronous, ≤ 1 and > 1 year after the FPC, respectively) were matched (1:3, by five-year age group and year of breast FPC diagnosis) to those without an SPC and alive when the corresponding SPC was diagnosed. RESULTS: Significantly higher hazards of death were found among patients with an SPC [hazard ratio of 1.56, 95% confidence interval (CI) 1.29-1.89 for synchronous SPCs; and 2.85, 95%CI 2.56-3.17 for metachronous SPCs] compared to patients with a breast FPC only. Estimates were higher for synchronous lung, stomach, non-Hodgkin lymphoma and breast SPCs, and metachronous liver, stomach, ovary, lung, rectum, corpus uteri, colon, breast, and non-Hodgkin lymphoma SPCs. The 15-year cumulative mortality was 59.5% for synchronous SPCs and 68.7% for metachronous SPCs, which was higher than in patients with a breast FPC only (43.6% and 44.8%, respectively). CONCLUSIONS: In Northern Portugal, patients with an SPC following a breast FPC have a higher mortality compared with patients with a breast FPC only.

Second primary cancers among females with a first primary breast cancer: a population-based study in Northern Portugal.

PURPOSE: To estimate the incidence rate of second primary cancers (SPCs) and the cumulative incidence of metachronous [diagnosed > 2 months after a first primary cancer (FPC)] SPCs in patients with a breast FPC, and to compare the incidence of SPC [overall, synchronous (≤ 2 months of the FPC) and metachronous] with that expected in the general female population. METHODS: A cohort of patients with a breast FPC from the North Region Cancer Registry of Portugal, diagnosed in 2000-2010 (n = 15,981), was followed to 31 December 2015 for synchronous and metachronous SPCs. Cumulative incidence of metachronous SPCs considering death as a competing event, and incidence rates and standardized incidence ratios of SPCs were estimated. RESULTS: The diagnosis of an SPC occurred in 1229 (7.7%) of patients with a breast FPC. SPCs occurred mainly in the breast, followed by digestive organs, lung, thyroid, and female genital organs. Globally, patients with a breast FPC had a higher incidence for all types of cancer compared to the general female population, and in particular for cancers of the breast, stomach, colon, lung, lymphoma, uterus, and ovary. The 10-year cumulative incidence of metachronous SPCs following a breast FPC was 6.6% and the corresponding 10-year cumulative mortality was 26.2%. CONCLUSION: In Portugal, patients with a breast FPC have a higher incidence of cancer compared to the general female population, highlighting important aspects of care, surveillance, and counselling among this growing number of patients.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

The impact of the COVID-19 pandemic on the short-term survival of patients with cancer in Northern Portugal.

The COVID-19 pandemic led to potential delays in diagnosis and treatment of cancer patients, which may negatively affect the prognosis of these patients. Our study aimed to quantify the impact of COVID-19 on the short-term survival of cancer patients by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. All cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, and prostate, from the Portuguese Oncology Institute of Porto (IPO-Porto) and diagnosed between 2 March and 1 July of 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Information regarding sociodemographic, clinical and treatment characteristics were collected from the cancer registry database and clinical files. Vital status was assessed to 31 October of the respective years. Cox proportional hazards regression was used to estimate crude and propensity score-adjusted hazards ratio (HR) and 95% confidence intervals (95% CIs) of death. During follow-up to 31 October, there were 154 (11.8%) deaths observed before COVID-19 and 131 (17.2%) after COVID-19, corresponding to crude and adjusted HRs (95% CI) of 1.51 (1.20-1.91) and 1.10 (0.86-1.40), respectively. Significantly higher adjusted hazards of death were observed for patients with Stage III cancer (HR = 2.37; 95% CI: 1.14-4.94) and those undergoing surgical treatment (HR = 3.97; 95% CI: 1.14-13.77) or receiving radiotherapy (HR = 1.96; 95% CI: 1.96-3.74), while patients who did not receive any treatment had a lower mortality hazards (HR = 0.62; 95% CI: 0.46-0.83). The higher overall short-term mortality observed during the COVID-19 pandemic largely reflects the effects of the epidemic on the case-mix of patients being diagnosed with cancer.

Small cell lung cancer treatment and survival in Portugal: A retrospective analysis from the I-O Optimise initiative.

OBJECTIVE: We aim to describe treatment patterns and overall survival (OS) among a Portuguese cohort of patients with small cell lung cancer (SCLC). METHODS: This study utilised a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with SCLC at IPO-Porto between January 2012 and June 2017, with follow-up to December 2017, were included. Patients were stratified into subgroups with limited disease (LD) or extensive disease (ED). Treatment analyses were performed from 2015 onwards. RESULTS: Overall, 227 patients diagnosed with SCLC (37 LD; 190 ED) were analysed. Median OS (interquartile range [IQR]) was 15.0 months (3.8-39.3) for LD-SCLC and 5.0 months (1.7-10.3) for ED-SCLC. Among 19 patients diagnosed with LD-SCLC from 2015 onwards, 12 (63.2%) received initial treatment with systemic anticancer therapy (SACT) ± radiotherapy; 6 (31.6%) received best supportive care (BSC). Among 89 patients with ED-SCLC, 57 (68.5%) received SACT ± palliative radiotherapy; 28 (31.5%) received BSC. For patients receiving platinum doublet chemotherapy (±radiotherapy), median OS (IQR) was not reached for LD-SCLC and 5.4 months (2.3-10.9) for ED-SCLC. CONCLUSION: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for patients diagnosed with SCLC, particularly those with ED, and highlights a need for more effective therapies.

Real-world treatment patterns and survival outcomes for advanced non-small cell lung cancer in the pre-immunotherapy era in Portugal: a retrospective analysis from the I-O Optimise initiative.

BACKGROUND: As part of the multinational I-O Optimise research initiative, this retrospective cohort study of patients with advanced non-small cell lung cancer (NSCLC) evaluated real-world treatment patterns and survival prior to immunotherapy reimbursement in Portugal. METHODS: This study utilized a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with stage IIIB or IV NSCLC from January 2012 to December 2016 at IPO-Porto, with follow-up to June 2017, were included. Treatment analyses were performed from 2015 onwards. Kaplan-Meier methods were used for overall survival (OS). Factors associated with OS and systemic anti-cancer therapy (SACT) treatment were assessed using multivariate statistical models. RESULTS: Of 1524 patients diagnosed with NSCLC at IPO-Porto, 1008 patients had advanced disease (stage IIIB: 10.1%, 154/1524, stage IV: 56.0%, 854/1524). For those with advanced disease, median age was 65 years (range: 21-92) and 75.6% (762/1008) were male. Median OS (interquartile range [IQR]) was 11.4 (5.2-26.9) months for stage IIIB and 6.3 (2.4-15.0) months for stage IV. Factors associated with decreased risk of death included female sex and epidermal growth factor receptor gene (EGFR)/anaplastic lymphoma kinase gene (ALK) mutations/rearrangements; factors associated with increased risk of death included older age and stage IV disease. Among patients diagnosed in 2015 or 2016, 75.8% (297/392) received ≥1 line of SACT. Platinum-based chemotherapy was the most common first-line therapy (non-squamous cell carcinoma [NSQ]: 72.9%; squamous cell carcinoma [SQ] 87.3%, 55/63; patients with EGFR/ALK mutations/rearrangements primarily received tyrosine kinase inhibitors). The likelihood of receiving SACT was lower in older patients and those diagnosed with stage IV disease. Patients not receiving SACT had poor survival outcomes (median OS [IQR]: NSQ, 1.8 [1.1-3.1] months; SQ, 2.3 (1.3-3.4) months), while median OS (IQR) in SACT-treated patients was 12.6 (6.1-24.5) months for NSQ and 10.3 (5.7-15.9) months for SQ. CONCLUSIONS: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for advanced NSCLC in the pre-immunotherapy era, with nearly one-quarter of patients not receiving SACT. Even in patients receiving SACT, median survival was only about 1 year.

Real-world treatment patterns, resource use and cost burden of multiple myeloma in Portugal.

OBJECTIVE: We provide a real-world overview of multiple myeloma (MM) treatment patterns, outcomes and healthcare resource use (HRU) in Portugal. METHODS: Data were collected retrospectively from consecutive patients diagnosed/treated at the Portuguese Oncology Institute of Porto (IPO-Porto) between 2012 and 2015. Primary objectives were progression-free survival (PFS) and overall survival (OS), with treatment patterns and HRU secondary. Analysis was by line of therapy (LOT), and post hoc by age (<65/≥65 years). RESULTS: 165, 73 and 32 patients received first, second and third LOTs respectively (N = 187). OS probabilities were 91.5%, 83.2% (<65 years) and 86.6%, 65.3% (≥65 years) at 12, 24 months respectively. PFS decreased from the start of each LOT for both age groups and was less for patients ≥65 years. Younger patients received more combination treatment (immunomodulatory drugs + proteasome inhibitors) and stem cell transplants, and had higher mean costs than older patients (€81,213 vs. €36,864 where three LOTs were received). Cost drivers were medications, transplantations and hospitalisations. CONCLUSION: Our results suggest divergence between younger and older MM patients. Older patients had lower OS and PFS probabilities, HRU costs and fewer stem cell transplantations. The treatment patterns in each LOT may differ from other countries' findings, suggesting treatment heterogeneity.

MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors.

BACKGROUND: Contemporary challenges of prostate cancer (PCa) include overdiagnosis and overtreatment, entailing the need for novel clinical tools to improve risk stratification and therapy selection. PCa diagnosis and prognostication might be perfected using epigenetic biomarkers, among which aberrant DNA methylation of microRNA promoters has not been systematically explored. Herein, we identified aberrantly methylated microRNAs promoters in PCa and assessed its diagnostic and prognostic biomarker potential. METHODS: Using HumanMethylation450 BeadChip-based analysis differentially methylated CpGs in microRNA promoters were identified. Promoter methylation of six microRNAs (miR-34b/c, miR-129-2, miR-152, miR-193b, miR-663a and miR-1258) was analyzed by qMSP in three sets (180 prostatectomies, 95 urine sediments and 74 prostate biopsies). Biomarkers' diagnostic (validity estimates) and prognostic [disease-free (DFS) and disease-specific survival (DSS)] performance was assessed. RESULTS: Significantly higher promoter methylation levels in PCa were confirmed for six candidate microRNAs. Except for miR-152, all displayed AUC values higher than 0.90, with miR-1258 and miR-193b disclosing the best performance (AUC = 0.99 and AUC = 0.96, respectively). In urine samples, miR-193b showed the best performance (91.6% sensitivity, 95.7% specificity, AUC = 0.96). Moreover, higher miR-129-2 independently predicted for shorter DSS and miR-34b/c methylation levels independently predicted for shorter DFS and DSS. CONCLUSIONS: Quantitative miR-193b, miR-129-2 and miR-34b/c promoter methylation might be clinically useful PCa biomarkers for non-invasive detection/diagnosis and prognostication, both in tissue and urine samples.

No inequalities in survival from colorectal cancer by education and socioeconomic deprivation - a population-based study in the North Region of Portugal, 2000-2002.

BACKGROUND: Association between cancer survival and socioeconomic status has been reported in various countries but it has never been studied in Portugal. We aimed here to study the role of education and socioeconomic deprivation level on survival from colorectal cancer in the North Region of Portugal using a population-based cancer registry dataset. METHODS: We analysed a cohort of patients aged 15-84 years, diagnosed with a colorectal cancer in the North Region of Portugal between 2000 and 2002. Education and socioeconomic deprivation level was assigned to each patient based on their area of residence. We measured socioeconomic deprivation using the recently developed European Deprivation Index. Net survival was estimated using Pohar-Perme estimator and age-adjusted excess hazard ratios were estimated using parametric flexible models. Since no deprivation-specific life tables were available, we performed a sensitivity analysis to test the robustness of the results to life tables adjusted for education and socioeconomic deprivation level. RESULTS: A total of 4,105 cases were included in the analysis. In male patients (56.3 %), a pattern of worse 5- and 10-year net survival in the less educated (survival gap between extreme education groups: -7 % and -10 % at 5 and 10 years, respectively) and more deprived groups (survival gap between extreme EDI groups: -5 % both at 5 and 10 years) was observed when using general life tables. No such clear pattern was found among female patients. In both sexes, when likely differences in background mortality by education or deprivation were accounted for in the sensitivity analysis, any differences in net survival between education or deprivation groups vanished. CONCLUSIONS: Our study shows that observed differences in survival by education and EDI level are most likely attributable to inequalities in background survival. Also, it confirms the importance of using the relevant life tables and of performing sensitivity analysis when evaluating socioeconomic inequalities in cancer survival. Comparison studies of different healthcare systems organization should be performed to better understand its influence on cancer survival inequalities.

Real­world retrospective study of early­stage prostate cancer at a Portuguese Comprehensive Cancer Centre: The PEarlC study.

Despite the high prevalence of localised prostate cancer (LPC) and locally advanced prostate cancer (LAPC), evidence on the characteristics of patients, treatments and clinical outcomes stratified by disease risk is limited. The PEarlC study was conducted to characterise a cohort of patients with early-stage prostate cancer that included real-world clinical outcomes. Retrospective data from a cohort of patients diagnosed with LPC/LAPC between 2015 and 2017 and followed up until December 2020 at a Portuguese comprehensive cancer centre (IPO Porto) was analysed. Patients were classified as LPC (high- or non-high-risk) or LAPC according to European Association of Urology guidelines, were eligible if diagnosed at stage I-III and followed up in Urology, Medical Oncology or Radiation Oncology outpatient clinics of IPO Porto. Data was collected from the medical/administrative records database. Clinical outcomes included prostate-specific antigen (PSA) progression-free survival, metastasis-free survival, disease-free survival, progression-free survival, overall survival (OS), PSA response (palliative) and no evidence of residual tumour (prostatectomy). Time-to-event outcomes were compared between subgroups using the log-rank test. A total of 790 patients were included (54.8% non-high-risk LPC, 30.9% high-risk LPC, 14.3% LAPC) and the median follow-up was 46.7 months. Patients had a median age of 68.0 years. The majority of patients were stage II (52.9%) and Eastern Cooperative Oncology Group 0-1 (99.9%) and received treatment with curative intent (85.4%). The median was only achieved in progression-free survival (29.9 months; 95% CI, 26.5-41.0 months), as evaluated in palliative patients. At year 5, 82.9% were free of PSA progression (curative), 87.5% were metastasis-free, 83.7% were disease-free, all patients in palliative treatment progressed and the 5-year OS rate was 92.9% (CI 95%, 90.2-95.7%). Among patients with LPC, OS was worse in high-risk vs. non-high-risk patients (5-year OS rate, 88.8% vs. 96.8%; hazard ratio=3.34, CI 95%, 1.64-7.05; P=0.001). PSA response rate was 81.4% in the palliative setting. There was no evidence of residual tumour in 61.6% of patients who underwent prostatectomy. Although most patients with early-stage prostate cancer treated at IPO Porto showed positive 5-year real-world outcomes, patients with high-risk LPC showed worse OS compared with patients with non-high-risk LPC and therefore a poorer prognosis. The present large-sample real-world study is an important contribution to reducing the evidence gap on prostate cancer.

Factors Associated With Long Survival in Patients With Cancer Admitted to Palliative Care: An Exploratory Study.

Objective: Some patients with cancer admitted to palliative care have relatively long survivals of 1 year or more. The objective of this study was to find out factors associated with prolonged survival. Methods: Retrospective case-control study comparing the available data of patients with cancer who survived more than 1 year after admission in a palliative care service with patients with cancer who survived 6 months or less. The intended proportion was 4 controls for each case. Patients were identified through electronic records from 2012 until 2018. Results: And 1721 patients were identified. Of those patients, 111 (6.4%) survived for at least 1 year, and 363 (21.1%) were included as controls according to the established criteria. The intended proportion could not be reached; the proportion was only 3.3:1. The median survival of cases was 581 days (range: 371-2763), and the median survival of controls was 57 days (range: 1-182). In the multivariable analysis, patients with a hemoglobin ≥ 10.6 g/dL and a creatinine level >95 µmol/L had a higher probability of living more than 1 year. In contrast, patients with abnormal cognition, pain, anorexia, liver metastases, an Eastern Cooperative Oncology Group performance status >1, and a neutrophil/lymphocyte ratio ≥ 3.43 had a low probability of living more than 1 year. Conclusion: Several factors were statistically associated positively or negatively with prolonged survival. However, the data of this study should be confirmed in other studies.

The crosstalk between Stroke and Cancer: Incidence of cancer after a first-ever cerebrovascular event in a population-based study.

OBJECTIVES: To determine the cancer incidence after the first-ever cerebrovascular event (CVE) and compare it to the cancer incidence in the population from the same region. METHODS: We evaluated 1069 patients with a first-ever CVE (Ischaemic or haemorrhagic stroke and Transient Ischaemic Attack) from a prospective population registry of stroke and transient focal neurological attacks, diagnosed between 2009 and 2011. We conducted a structured search to identify cancer-related variables and case-fatality for a period of 8 years following CVE. Cancer incidence in CVE patients was compared to the North Region Cancer Registry (RORENO). RESULTS: We found that 90/1069 (8.4%) CVE patients developed cancer after a first-ever CVE. Overall cancer annual incidence rate was higher after a CVE (820/100,000, 95%CI: 619-1020) than in general population (513/100,000, 95%CI: 508-518). In the 45-54 age group cancer incidence post-CVE was 3.2-fold (RR, 95%CI: 1.6-6.4) higher compared to the general population, decreasing gradually in older age-groups. Median time between CVE and cancer was 3.2 years (IQR = 1.4-5.2). Lower respiratory tract and colorectal were the most frequent cancer types. In univariable models, male sex (sHR = 1.78, 95%CI: 1.17-2.72, p = 0.007), tobacco use (sHR = 2.04, 95%CI: 1.31-3.18, p = 0.002) and peripheral artery disease (sHR = 2.37, 95%CI: 1.10-5.13, p = 0.028) were associated to higher cancer risk after CVE. After adjustment, tobacco use (sHR = 1.84, 95%CI: 1.08-3.14, p = 0.026) remained associated to a higher risk of cancer. CONCLUSIONS: At the population level, patients presenting a first-ever CVE have higher cancer incidence, that is particularly prominent in younger age-groups. Higher cancer incidence, delayed cancer diagnosis and increased mortality post-CVE warrants further research on long-term cancer surveillance in first-ever CVE survivors.

Cancer incidence and survival (1997-2006) among adolescents and young adults in the north of Portugal.

Cancer is the first cause of natural death among young subjects. Population-based statistics are important to evaluate the burden of disease and the effectiveness of healthcare provision. We aimed to describe cancer incidence and survival among adolescents (15-19 years) and young adults (20-24 years) in the north of Portugal. Data on the cancers diagnosed between 1997 and 2006 were obtained from the Portuguese North Region Cancer Registry, and incidence rates were computed. Vital status was determined until December 2010. Survival was estimated using the Kaplan-Meier survival function. Trends on cancer incidence were assessed using the Joinpoint regression analysis. A total of 1223 cases were diagnosed: 441 among adolescents and 782 among young adults. Overall incidence rate was 198.3 per million adolescents [95% confidence interval (95% CI): 135.7-260.9] and 306.2 per million young adults (95% CI: 262.3-350.0). The most frequent tumors were Hodgkin lymphoma (adolescents: 21.0%; young adults: 14.8%), thyroid carcinoma (adolescents: 11.5%; young adults: 16.2%), and germ cell tumors (adolescents: 11.1%; young adults: 16.3%). Cancer incidence significantly increased among young adults [annual average percent change: 3.6%, (95% CI: 1.7-5.4)], while appears to vary randomly among adolescents. Overall five-year observed survival was 77.2% (95% CI: 72.9%-80.8%) among adolescents and 81.3% (95% CI: 78.4%-83.9%) among young adults, lower in males. In conclusion, cancer incidence among adolescents and young adults is higher in the north of Portugal than in other European countries, especially of thyroid tumors. Between 1997 and 2006, the incidence increased significantly in young adults.

The impact of the coronavirus disease 2019 pandemic on the diagnosis and treatment of cancer in Northern Portugal.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has affected the availability of healthcare resources, and adjustments to cancer care have been necessary considering the risk of morbidity by COVID-19 and of cancer progression. This study aims to quantify the impact of the COVID-19 pandemic on the care of patients with cancer by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. METHODS: Cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, prostate, non-Hodgkin lymphoma, and leukemia from the Portuguese Oncology Institute of Porto, and diagnosed between 2 March and 1 July 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Those with the first treatment outside the Portuguese Oncology Institute of Porto were excluded. Sociodemographic, clinical and treatment characteristics were obtained from the cancer registry database and clinical files. RESULTS: The absolute number of new cancer cases decreased nearly 40% after the COVID-19 pandemic (from 1430 to 866). The largest decreases were observed for cervical (-74.3%) and prostate (-71.7%) cancers. Cases were more often diagnosed at more advanced stages in 2020 (P = 0.001), and the proportion of patients not starting any treatment until 1 July was just under 20% in 2019 and nearly 40% in 2020. The median times from symptoms onset, first medical exam and first appointment to diagnosis, and from diagnosis to first appointment, multidisciplinary tumor board meeting and first treatment were shorter after COVID-19. CONCLUSIONS: There was a notable overall decrease in cancer diagnoses after COVID-19, with changes in the characteristics of incident cases.

Risk and Survival of Third Primary Cancers in a Population-Based Cohort of Breast Cancer Patients.

Introduction: The growing number of women diagnosed with breast cancer (BCa) together with high survival has resulted in an increasing population of survivors at risk of subsequent primary cancers. This study aimed to estimate the long-term risk and survival of third primary cancers (TPCs) among females with a first primary BCa. Methods: Breast first primary cancers (FPCs) from the Portuguese North Region Cancer Registry, diagnosed between 2000 and 2010 (n = 15,981), were followed for a TPC (December 31, 2015) and death from any cause (June 30, 2021). The cumulative incidence of and mortality among TPCs were estimated. To compare survival, female patients with a TPC were matched (1:1, by age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC + SPC patients without a TPC. Results: Overall, 67 (0.4% of FPCs and 5.4% of SPCs) TPCs were diagnosed. The most common TPC sites were digestive, breast, and female genital organs. Among all FPCs, the 15-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.69% (0.47-0.90%) and among SPCs, 7.21% (4.99-9.43%). The 15-year cumulative mortality of TPCs and matched patients was 70.0% and 51.5%, respectively. For TPCs, compared to matched SPC only patients, the age-adjusted hazard ratio (95% CI) for death was 2.86 (1.61-5.07). Discussion/Conclusion: The most common TPC sites were digestive, breast, and female genital organs, with a 15-year cumulative incidence of 0.69% among FPCs. TPCs had a worse long-term survival compared to patients with an SPC only.

Costs, effectiveness, and safety associated with Chimeric Antigen Receptor (CAR) T-cell therapy: Results from a comprehensive cancer center.

Real world effectiveness, toxicity and costs analyses from chimeric antigen receptor (CAR)-T cell therapy are of utmost relevance to determine whether and how to offer patients highly personalized immunotherapy. In this study, we aimed at describing CAR T-cells effectiveness, safety and costs in a Portuguese Comprehensive Cancer Center. We performed a retrospective descriptive study of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma and transformed follicular lymphoma referred to CAR T-cell therapy, between May 2019 and February 2021. Rates of treatment response, toxicity and survival (Kaplan-Meier method) were analyzed by intention-to-treat. Direct medical costs stratified by inpatient-care, outpatient-care, and diagnostic-therapeutic procedures (DTP) were derived based on resources used and their respective unit costs. In twenty patients (median age 49.5y; 55%male; 70%DLBCL; 50% with primary refractory disease), best overall and complete response rates were 65.0% and 45.0%, respectively. Median overall (OS) and progression-free survivals were 9.2 and 7.3 months; 12-month OS rate was 42.6% (95%CI:23.2-78.3). Grade≥3 cytokine release syndrome and neurotoxicity occurred in 5.6% and 11.1% of patients, respectively. CAR T-cell therapy expenditure, including adverse events costs, was 7 176 196€, or 286 238€ when excluding drug cost. Median cost for treated patient was 355 165€ with CAR T-cell drug cost accounting for 97.0% of the overall expense. Excluding CAR T-cell acquisition cost, inpatient-care and DTP accounted for 57% and 38% of total cost/patient, respectively. Our findings highlight the heavy economic burden of CAR T-cell therapy driven by drug acquisition costs.

Pancreatic neuroendocrine neoplasms: survival trend analysis of a comprehensive center.

Objectives: Therapeutic options for pancreatic neuroendocrine neoplasia (Pan-NEN) have increased over the last decade. We aim to understand the evolution of the prognosis of patients with diagnosis of Pan-NEN within a 12-year period, considering the implementation of new treatments. Methods: This study is a retrospective cohort study of patients diagnosed with Pan-NENs between 2006 and 2017. Survival outcome estimates were calculated by Kaplan-Meier method. The impact of baseline clinicopathological characteristics on survival was explored with the use of Cox proportional hazard model. Results: Of the 97 patients, 77 (79.9%) had well-differentiated neuroendocrine tumor (NET) according to WHO 2010 classification, and 52 (53.6%) had localized or locoregional disease. There were no differences between clinicopathological characteristics and survival outcomes when comparing patients diagnosed between 2006-2011 and 2012-2017. Neuroendocrine carcinoma - HR 2.76, 95% CI 1.17-6.55 - and stages III and IV at diagnosis were independent poor prognostic factors - HR 6.02, 95% CI 2.22-16.33 and HR 6.93, 95% CI 2.94-16.32, respectively. Conclusions: The new therapeutic approaches did not induce better survival outcomes on Pan-NEN in recent years. This is possibly due to the indolent nature of NET grades 1 and 2, even metastatic, allowing patients to be submitted to new target therapies along their disease course.

Colorectal Screening Program in Northern Portugal: First Findings.

INTRODUCTION: In Portugal, a colorectal cancer screening program based on faecal immunochemical test followed by colonoscopy was shown to be cost-effective for individuals between 50 and 74 years old. We report the first findings of the implementation of a population-based program In Northern Portugal. MATERIAL AND METHODS: In the pilot phase, eligible subjects were allocated either to a direct mailing invitation or to primary care centers. In the first year of program implementation, we assessed the uptake rate, the faecal immunochemical test -positivity rate, the diagnostic yield of advanced neoplasia, and the quality parameters for post-faecal immunochemical test + colonoscopy. RESULTS: We invited 100 501 eligible subjects (49% male with a median age of 55 years). Of these, 5228 participated in the pilot phase and 95 273 participated in the first year of the program. In the first year of the program, the adherence was 29%, with a positivity rate of 5% and a 60% compliance to colonoscopy. The faecal immunochemical test-detection rate of advanced neoplasia was 0.35/1000 subjects, and the positive predictive value at post- faecal immunochemical test + colonoscopy was 44% and 2% for advanced adenoma and invasive cancer, respectively. No major adverse events were reported after colonoscopy. DISCUSSION: The suboptimal adherence to faecal immunochemical test and post-faecal immunochemical test + colonoscopy remains the most urgent step to be addressed. CONCLUSION: A centralized invitation system based on direct mailing was feasible and both colonoscopy quality and diagnostic yield were adequate antecipating the success of the programme.

Introdução: Em Portugal, foi demonstrado que o rastreio do cancro colo-rectal, baseado no teste imunoquímico fecal seguido de colonoscopia, seria custo-efetivo para indivíduos entre os 50 e 74 anos. Neste artigo reportamos os primeiros resultados da implementação do programa de base populacional na região Norte de Portugal. Material e Métodos: Na fase piloto, os sujeitos elegíveis foram alocados a dois métodos, por convite através do correio ou por meio de entrega direta nos centros de saúde. No primeiro ano de implementação do programa avaliámos a taxa de adesão, a taxa de positividade de teste imunoquímico fecal, o rendimento diagnóstico de neoplasia avançada e os parâmetros de qualidade da colonoscopia pós- teste imunoquímico fecal positivo. Resultados: Foram convidados 100 501 indivíduos elegíveis (49% do sexo masculino com idade mediana de 55 anos). Destes, 5228 participaram na fase piloto e 95 273 participaram no primeiro ano do programa. No primeiro ano do programa, a adesão foi de 29%, com taxa de positividade de 5% e adesão de 60% às colonoscopias. A taxa de deteção de teste imunoquímico fecal de neoplasia avançada foi de 0,35/1000 indivíduos, e o valor preditivo positivo na colonoscopia pós-teste imunoquímico fecal positivo foi de 44% e 2% para adenoma avançado e cancro invasivo, respetivamente. Não foi relatado nenhum evento adverso após colonoscopia. Discussão: A adesão subótima a teste imunoquímico fecal e colonoscopia pós-teste imunoquímico fecal continua a ser a etapa mais problemática. Conclusão: Um sistema de convite centralizado foi viável, a qualidade das colonoscopias realizadas e o rendimento diagnóstico adequados antecipando o sucesso do programa.

Association of Sentinel Node Biopsy and Pathological Report Completeness with Survival Benefit for Cutaneous Melanoma and Factors Influencing Their Different Uses in European Populations.

Objectives: Standard care for cutaneous melanoma includes an accurate pathology report (PR) and sentinel lymph node biopsy (SLNB) for staging clinically node-negative >1 mm melanomas. We aimed to investigate the frequency of these indicators across European countries, also assessing consequences for survival. Methods: We analyzed 4245 melanoma cases diagnosed in six European countries in 2009−2013. Multivariable logistic regression was used to estimate the Odds Ratio (OR) of receiving complete PR with eight items or SLNB and model-based survival to estimate the five-year relative excess risks of death (RER). Results: Overall, 12% patients received a complete PR (range 2.3%, Estonia­20.1%, Italy); SLNB was performed for 68.8% of those with cN0cM0 stage (range 54.4%, Spain­81.7%, Portugal). The adjusted OR of receiving a complete PR was lower than the mean in Estonia (OR 0.11 (0.06−0.18)) and higher in Italy (OR 6.39 (4.90−8.34)) and Portugal (OR 1.39 (1.02−1.89)); it was higher for patients operated on in specialized than general hospitals (OR 1.42 (1.08−1.42)). In the multivariate models adjusted for age, sex, country and clinical-pathological characteristics, the RER resulted in being higher than the reference for patients not receiving a complete PR with eight items (RER 1.72 (1.08−2.72)), or for those not undergoing SLNB (RER 1.76 (1.26−2.47)) Patients with non-metastatic node-negative thickness >1 mm melanoma who did not undergo SLNB had a higher risk of death (RER (RER 1.69 (1.02−2.80)) than those who did. Conclusions: Accurate pathology profiling and SLNB carried survival benefit. Narrowing down between-countries differences in adhesion to guidelines might achieve better outcomes.

Dealing with missing information on covariates for excess mortality hazard regression models - Making the imputation model compatible with the substantive model.

Missing data is a common issue in epidemiological databases. Among the different ways of dealing with missing data, multiple imputation has become more available in common statistical software packages. However, the incompatibility between the imputation and substantive model, which can arise when the associations between variables in the substantive model are not taken into account in the imputation models or when the substantive model is itself nonlinear, can lead to invalid inference. Aiming at analysing population-based cancer survival data, we extended the multiple imputation substantive model compatible-fully conditional specification (SMC-FCS) approach, proposed by Bartlett et al. in 2015 to accommodate excess hazard regression models. The proposed approach was compared with the standard fully conditional specification multiple imputation procedure and with the complete-case analysis using a simulation study. The SMC-FCS approach produced unbiased estimates in both scenarios tested, while the fully conditional specification produced biased estimates and poor empirical coverages probabilities. The SMC-FCS algorithm was then used for handling missing data in the evaluation of socioeconomic inequalities in survival from colorectal cancer patients diagnosed in the North Region of Portugal. The analysis using SMC-FCS showed a clearer trend in higher excess hazards for patients coming from more deprived areas. The proposed algorithm was implemented in R software and is presented as Supplementary Material.