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Objectives: Insight into the aggressiveness of potential breast cancers found in screening may optimize recall decisions. Specific growth rate (SGR), measured on mammograms, may provide valuable prognostic information. This study addresses the association of SGR with prognostic factors and overall survival in patients with invasive carcinoma of no special type (NST) from a screened population. Methods: In this historic cohort study, 293 women with NST were identified from all participants in the Nijmegen screening program (2003–2007). Information on clinicopathological factors was retrieved from patient files and follow-up on vital status through municipalities. On consecutive mammograms, tumor volumes were estimated. After comparing five growth functions, SGR was calculated using the best-fitting function. Regression and multivariable survival analyses described associations between SGR and prognostic factors as well as overall survival. Results: Each one standard deviation increase in SGR was associated with an increase in the Nottingham prognostic index by 0.34 [95% confidence interval (CI): 0.21–0.46]. Each one standard deviation increase in SGR increased the odds of a tumor with an unfavorable subtype (based on histologic grade and hormone receptors; odds ratio 2.14 [95% CI: 1.45–3.15]) and increased the odds of diagnosis as an interval cancer (versus screen-detected; odds ratio 1.57 [95% CI: 1.20–2.06]). After a median of 12.4 years of follow-up, 78 deaths occurred. SGR was not associated with overall survival (hazard ratio 1.12 [95% CI: 0.87–1.43]). Conclusions: SGR may indicate prognostically relevant differences in tumor aggressiveness if serial mammograms are available. A potential association with cause-specific survival could not be determined and is of interest for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: For patients diagnosed with metastatic colorectal cancer, having colorectal liver metastases along with metastases in other organs may be deemed a contraindication for local treatment with curative intent. This observational study investigates whether administering local treatment to all metastatic sites could enhance overall survival rates. A total of 941 patients were included, among whom were 60 patients with metastases in both the liver and other organ(s). Our findings reveal that although patients with both liver and extrahepatic metastases exhibited lower survival rates compared to those with solely liver metastases, a survival plateau emerged after approximately 6.2 years. This implies that comprehensive local treatment of all metastatic sites might confer benefits for long-term survival. These insights could impact decision making regarding the scope of local treatment for patients with colorectal cancer that have metastases in multiple organs. Background: The simultaneous presence of colorectal liver metastases (CRLMs) and extrahepatic metastases in patients with colorectal cancer (CRC) can be considered a relative contraindication for local treatment with curative intent. This study aims to assess the survival outcomes of patients with CRLMs and extrahepatic metastases after comprehensive local treatment of all metastatic sites. Methods: Patients with CRLMs who received local treatment of all metastatic sites were extracted from the prospective AmCORE registry database and subdivided into two groups: CRLM only vs. CRLM and extrahepatic metastasis. To address potential confounders, multivariate analysis was performed. The primary endpoint was overall survival (OS). Results: In total, 881 patients with CRLM only and 60 with CRLM and extrahepatic disease were included, and the median OS was 55.7 months vs. 42.7 months, respectively. Though OS was significantly lower in patients with concomitant extrahepatic metastases (HR 1.477; 95% CI 1.029–2.121; p = 0.033), the survival curve plateaued after 6.2 years. Extrahepatic manifestations were pulmonary (43.3%), peritoneal (16.7%) and non-regional lymph node metastases (10.0%). In patients with pulmonary and non-regional lymph node metastases, OS did not significantly differ from patients with CRLM-only disease; concomitant peritoneal metastases showed an inferior OS (HR 1.976; 95% CI 1.017–3.841, p = 0.041). Conclusions: In this comparative series, OS was inferior for patients with multi-organ metastatic CRC versus patients with CRLMs alone. Nonetheless, the long-term survival curve plateau seemed to justify local treatment in a subset of patients with multi-organ metastatic CRC, especially for patients with CRLMs and pulmonary or lymph node metastases. [ABSTRACT FROM AUTHOR]

Adults aged ≥80 years (the oldest‐old) comprise the fastest growing age group in Western populations. Yet little is known about their cancer burden. In this nationwide study, we assessed their trends in incidence, treatment and survival over a 30‐year period, and predicted their future cancer incidence. All 2 468 695 incident cancer cases during 1990 to 2019 were selected from the Netherlands Cancer Registry, of whom 386 611 were diagnosed in the oldest‐old (16%). The incidence of the oldest‐old was predicted until 2032. Net and overall survival (OS) were calculated. Patients were divided into four age groups (<80, 80‐84, 85‐89 and ≥90 years). The incidence of the oldest‐old doubled between 1990 and 2019 and is expected to grow annually with 5% up to 2032. In virtually all cancers the share of oldest‐old patients grew, but declined for prostate cancer (25% in 1990‐1994 vs 13% in 2015‐2019). The proportion of undetermined disease stage increased with age in most cancers. The application of systemic therapy increased, albeit less pronounced in the oldest‐old than their younger counterparts (1990 vs 2019: 12%‐34%, 3%‐15%, 2%‐7% and 1%‐3% in <80, 80‐84, 85‐89 and ≥90 years old). Five‐year OS of the oldest‐old patients increased by 7 percentage points (to 26%) between 1990 to 1994 and 2015 to 2019 compared to 19 percentage points (to 63%) in <80 years old. The oldest‐old cancer patients are a rapidly growing group who benefitted less from improvements in cancer treatment than younger patients, reflecting the multiple challenges faced in the care of the oldest‐old. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma (UM) is the most common eye tumor in adults. It is associated with dismal survival once metastasized. The treatment landscape has changed over the last years for the primary tumor, and new therapeutic options are being investigated for metastatic UM. However, it remains unclear if patients diagnosed in recent decades have a better survival compared to patients diagnosed in earlier decades. In this study, we use national data from patients diagnosed in the Netherlands between 1989 and 2019. We show that survival improvement was not related to the period of diagnosis but related to the treatment of the eye tumor with radiotherapy (for overall survival and cancer-specific survival) and female gender (for overall survival). Background: Uveal melanoma (UM) is a rare intraocular tumor with a dismal prognosis once metastasized. This study provides a nationwide overview and time trends of patients diagnosed with primary UM in the Netherlands between 1989 and 2019. Methods: A retrospective population-based cohort study based on patients with primary UM from the database of the Netherlands Cancer Registry (NCR), linked with the national population registry Statistics Netherlands on inhabitants' cause of death. Two time periods (1989–2004, 2005–2019) were compared with descriptive statistics. Kaplan–Meier and (multivariate) Cox proportional hazard models were used to assess changes over time for overall survival (OS) and cancer-specific survival (CSS). Results: In total, 5036 patients were analyzed with a median age of 64.0 years at the time of diagnosis. The number of patients increased over time. In the first (1989–2004) and second (2005–2019) period, 32% versus 54% of the patients received radiotherapy (p < 0.001). The median FU time was 13.4 years. The median OS of the first and second periods was 9.5 (95% CI 8.7–10.3) versus 11.3 years (95% CI 10.3–12.3; p < 0.001). The median CSS was 30.0 years (95% CI NA) in the first period and not reached in the second period (p = 0.008). In multivariate analysis (MVA), female gender (HR 0.85; 95% CI 0.79–0.92, p < 0.001) and radiotherapy treatment (HR 0.73; 95% CI 0.64–0.83, p < 0.001) were associated with better OS. Radiotherapy treatment (HR 0.74; 95% CI 0.61–0.90, p = 0.002) was also associated with better CSS. The period of diagnosis was not associated with OS or CSS. Conclusions: In this study of patients with primary UM, there was a shift to the diagnosis of smaller tumors, possibly due to stage migration. There was also an increase in eye-preserving treatments over time. OS and CSS were modestly improved in the second time period; however, the time period was not associated with OS or CSS in multivariate analyses. [ABSTRACT FROM AUTHOR]

Simple Summary: There has been a growing interest in the interplay between the immune system and the prognosis of epithelial ovarian cancer (EOC). It has become clear that EOC has the ability to escape destruction by the immune system by creating a highly immunosuppressive microenvironment in the abdominal cavity. The first case of an advanced-stage EOC patient who experienced the complete disappearance of her cancer following sepsis without undergoing cancer treatment was reported in 2018. Sepsis has the ability to both activate and suppress the immune system, presenting potential beneficial as well as detrimental effects. It is still unclear what impact sepsis has on the prognosis of advanced-stage EOC. This study's aim was to assess the impact of sepsis on the oncologic outcomes of advanced-stage EOC patients. Of 215 OC patients, a total of 18 advanced-stage EOC patients experienced sepsis. Their survival outcomes were compared with 3988 unmatched and 54 matched patients from the Netherlands Cancer Registry (NCR). The overall and progression-free survival was similar between the sepsis and (un)matched patients from the NCR. Our study suggests that sepsis and its subsequent immune response, overall, does not substantially influence the prognosis of EOC patients. Objective: The sepsis-induced inflammatory response may potentially affect malignant cells. Recently, a case of spontaneous regression of a histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC) following sepsis was reported. The aim of our study was to assess the impact of sepsis on the oncologic outcomes of advanced-stage EOC patients. Methods: Gynecologic oncologic patients admitted to the Intensive Care Unit of three oncologic centers between 2006 and 2019 were identified and patients who experienced sepsis following advanced-stage EOC diagnosis were selected. Survival outcomes were compared with advanced-stage EOC patients from the Netherlands Cancer Registry (NCR). To correct for case-mix differences, propensity score matching using 1:3 nearest neighbor matching was conducted after which survival analyses were repeated. Results: A total of 18 of 215 patients with advanced-stage EOC experienced sepsis. Sepsis patients had similar distributions of patient, tumor, and treatment characteristics to 3988 patients from the NCR cohort. A total of 3 of 18 patients died from the complications of sepsis. While the remaining patients initially responded to treatment, 14/15 patients relapsed. The median (IQR) overall survival was 31 (24–44) and 35 (20–60) months for the sepsis and unmatched NCR cohort (p = 0.56), respectively. The median (IQR) progression-free survival was 16 (11–21) and 16 (11–27) months (p = 0.90), respectively. Survival outcomes did not differ following propensity matching (overall survival of 31 (24–44) vs. 36 (20–56) months, p = 0.40; progression-free survival of 16 (11–21) and 16 (12–21) months, p = 0.72). Conclusion: In this observational study, the occurrence of sepsis did not affect the oncologic and survival outcomes of advanced-stage EOC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: CAR T-cell therapy has emerged as the new standard of care for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), but real-world outcomes differ across countries. Additionally, real-world data on health-related quality of life (HR-QoL) are scarce but important, as they reflect the direct experience of patients. In the Netherlands, patients can be referred to the CAR-T tumorboard, a national CAR-T expert panel, who decide whether CAR-T is a feasible treatment option. This multicenter study reports on the favorable outcomes, including the HR-QoL, of axicabtagene ciloleucel (axi-cel) for patients with R/R LBCL after ≥2 lines of systemic therapy in the Netherlands. On the other hand, we show that a substantial proportion of patients are still in need of alternative treatments, including improved CAR-T strategies, as they are unfit for or do not respond to axi-cel. Comparing real-world outcomes between cohorts could help to select best practices and further optimize CAR-T treatment. The real-world results of chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) substantially differ across countries. In the Netherlands, the CAR-T tumorboard facilitates a unique nationwide infrastructure for referral, eligibility assessment and data collection. The aim of this study was to evaluate real-world outcomes of axicabtagene ciloleucel (axi-cel) in the Dutch population, including the thus-far underreported effects on health-related quality of life (HR-QoL). All patients with R/R LBCL after ≥2 lines of systemic therapy referred for axi-cel treatment between May 2020–May 2022 were included (N = 250). Of the 160 apheresed patients, 145 patients received an axi-cel infusion. The main reason for ineligibility was rapidly progressive disease. The outcomes are better or at least comparable to other studies (best overall response rate: 84% (complete response: 66%); 12-month progression-free-survival rate and overall survival rate: 48% and 62%, respectively). The 12-month NRM was 5%, mainly caused by infections. Clinically meaningful improvement in several HR-QoL domains was observed from Month 9 onwards. Expert-directed patient selection can support effective and sustainable application of CAR-T treatment. Matched comparisons between cohorts will help to understand the differences in outcomes across countries and select best practices. Despite the favorable results, for a considerable proportion of patients with R/R LBCL there still is an unmet medical need. [ABSTRACT FROM AUTHOR]

Simple Summary: Up to 50% of patients diagnosed with advanced melanoma develop brain metastases during the course of their disease. The prognosis of melanoma patients is heavily affected by the presence of brain metastases. Unfortunately, there is a lack of data on prognostic factors for these patients. Many of these patients are treated with immune checkpoint inhibitors. Therefore, the aim of our study was to identify prognostic factors in melanoma patients with brain metastases treated with immune checkpoint inhibitors. In a population of 1278 advanced melanoma patients, we found that serum lactate dehydrogenase levels were the strongest clinical parameter associated with survival. This information is useful for both doctors and patients to provide more insight into patients' prognoses. The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab–nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients' survival based on their baseline and disease characteristics. [ABSTRACT FROM AUTHOR]

When analysing patient survival, one is often interested in cause of death. Little is known about the presence of population mortality in advanced melanoma patients. The aim of this study was to assess population mortality after different response states in advanced melanoma patients in the Netherlands, and analyse the contribution of disease and population mortality for different age groups. We selected patients diagnosed between 2013 and 2019 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. A multi-state model with response states integrating population mortality was fitted. One-year landmark analyses were performed to assess outcomes after each response state. Overall, 5119 patients were selected. Five-year probabilities of melanoma-related mortality in patients alive in complete response at one year after diagnosis increased with age, and was 17.2% (95% confidence interval: 13.0–21.4) for patients aged <65 years and 28.7% (95% confidence interval: 24.3–33.1) in patients aged ≥80 years. Population mortality only played a large role for older patients (75 years and above) alive at 1 year after diagnosis with a partial or complete response. Even though survival outcomes of advanced melanoma patients have improved over the last decade, the vast majority of patients still die due to melanoma-related mortality. • Melanoma-related mortality after tumour responses has not been studied so far. • Using multi-state models, the prognostic impact of response states was assessed. • Melanoma-related mortality dominates population mortality in advanced melanoma. • Population mortality plays a role in patients ≥75 years who respond to therapy. [ABSTRACT FROM AUTHOR]

Background. FOLFIRINOX chemotherapy is the current Dutch standard of care for locally advanced (LAPC) and metastatic pancreatic cancer (PDAC) patients with good performance status. The objective of this study was to evaluate real-world response rates and survival in advanced PDAC and to assess conditional survival after FOLFIRINOX. Methods. A multicenter, retrospective cohort study was conducted in four hospitals in the Netherlands. Consecutive patients with LAPC or metastatic PDAC, treated with FOLFIRINOX, were included. Results. Between 2012 and 2018, 284 patients were included: n = 136 with LAPC and n = 148 with metastatic PDAC. Objective response rates were similar in both the groups: 14.0% in LAPC and 18.2% in metastatic patients. The disease control rate was higher in LAPC patients (77.2%) compared to metastatic PDAC (51.4%, P < 0.001). Median overall survival (OS) in LAPC patients was 12.7 months (95% CI 11.4–14.1 months). Their 2-year survival probability increased from 14% to 26% one year after the completion of FOLFIRINOX. Median OS in metastatic PDAC patients was 8.1 months (95% CI 6.5–9.6 months); 2-year survival probability increased from 10% to 29% after one year. Discussion. Our study provides real-world estimates of response rates, survival, and conditional survival in patients with advanced PDAC treated with FOLFIRINOX. These results are useful for patient counseling and clinical decision making. [ABSTRACT FROM AUTHOR]

Simple Summary: The introduction of a revised staging system (FIGO 2018 staging system) for cervical cancer has led to a significant change in stage allocation for patients with early stage disease. It remains unclear how this change should be translated into treatment options, including less extensive surgery. With this Dutch national study we evaluated whether the revised staging system resulted in a more accurate prediction of overall and recurrence free survival compared to the previous FIGO 2009 staging system. In addition, we assessed other factors which may help the paradigm of treatment. We concluded that the revised FIGO 2018 staging system gives a more precise indication of survival outcomes of women with early stage cervical cancer. In addition, we believe that aside from stage, tumor characteristics, such as LVSI, and depth of invasion should be considered when offering patients less radical or less extensive treatment. The FIGO 2018 staging system was introduced to allow better prognostic differentiation in cervical cancer, causing considerable stage migration and affecting treatment options. We evaluated the accuracy of the FIGO 2018 staging in predicting recurrence free (RFS) and overall survival (OS) compared to FIGO 2009 staging in clinically early stage cervical cancer. We conducted a nationwide retrospective cohort study, including 2264 patients with preoperative FIGO (2009) IA1, IA2 and IB1 cervical cancer between 2007–2017. Kaplan–Meier analyses were used to assess survival outcomes. Logistic regression was used to assess risk factors for lymph node metastasis and parametrial invasion. Stage migration occurred in 48% (22% down-staged, 26% up-staged). Survival data of patients down-staged from IB to IA1/2 disease were comparable with FIGO 2009 IA1/2 and better than patients remaining stage IB1. LVSI, invasion depth and parametrial invasion were risk factors for lymph node metastases. LVSI, grade and age were associated with parametrial invasion. In conclusion, the FIGO 2018 staging system accurately reflects prognosis in early stage cervical cancer and is therefore more suitable than the FIGO 2009 staging. However subdivision in IA1 or IA2 based on presence or absence of LVSI instead of depth of invasion would have improved accuracy. For patients down-staged to IA1/2, less radical surgery seems appropriate, although LVSI and histology should be considered when determining the treatment plan. [ABSTRACT FROM AUTHOR]

Sex and gender are modulators of health and disease and may have impact on treatment allocation and survival in patients with cancer. In this study, we analyzed the impact of sex and gender on treatment allocation and overall survival in patients with stage I-III pancreatic cancer. Patients with stage I-III pancreatic cancer diagnosed between 2015 and 2020 were selected from the nationwide Netherlands Cancer Registry. Associations between sex and gender and the probability of receiving surgical and/or systemic treatment were examined with multivariable logistic regression analyses. Overall survival was assessed with log rank test and multivariable Cox proportional hazard analysis. Among 6855 patients, 51.2 % were female. Multivariable logistic regression analyses with adjustment for known confounders (age, performance status, comorbidities, tumor location, tumor stage and previous malignancies) showed that females less often received systemic chemotherapy compared to males (OR 0.799, 95 %CI 0.703–0.909, p <.001). No difference was found in the probability for undergoing surgical resection. Furthermore, females had worse overall survival compared to males (median OS 8.5 and 9.2 months respectively, 95 %CI 8.669–9.731). This nationwide study found that female patients with stage I-III pancreatic cancer significantly less often received systemic treatment and had worse overall survival as compared to males. Disparities in pancreatic cancer care can be decreased by recognizing and resolving potential obstacles or biases in treatment decision-making. • Impact of sex and gender was investigated in patients with stage I-III pancreatic cancer • Females less frequently received systemic treatment compared to males • Sex and potentially gender may impact treatment and survival in stage I-III pancreatic cancer [ABSTRACT FROM AUTHOR]

Small intestinal adenocarcinomas (SIAs) are rare. Hence, randomized controlled trials are lacking and understanding of the disease features is limited. This nationwide cohort investigates incidence, treatment and prognosis of SIA patients, to improve disease outcome. Data of 2697 SIA patients diagnosed from January 1999 through December 2019 were retrieved from the Netherlands Cancer Registry and Pathology Archive. Incidence was calculated using the revised European Standardized Rate. The influence of patient and tumor characteristics on overall survival (OS) was studied using survival analyses. The age-standardized incidence rate almost doubled from 0.58 to 1.06 per 100,000 person-years, exclusively caused by an increase in duodenal adenocarcinomas. OS did not improve over time. Independent factors for a better OS were a younger age, jejunal tumors, Lynch syndrome and systemic therapy. Only 13.8% of resected patients was treated with adjuvant chemotherapy, which improved OS compared to surgery alone in stage III disease (HR 0.47 (0.35–0.61)), but not in the limited group of deficient mismatch repair (MMR) patients (n = 53, HR 0.93 (0.25–3.47)). In the first-line setting, CAPOX was associated with improved OS compared to FOLFOX (HR 0.51 (0.36–0.72)). For oligometastatic patients, a metastasectomy significantly improved OS (HR 0.54 (0.36–0.80)). The incidence of SIAs almost doubled in the past 20 years, with no improvement in OS. This retrospective non-randomized study suggests the use of adjuvant chemotherapy for stage III disease and first-line CAPOX for metastatic patients. For selected oligometastatic patients, a metastasectomy may be considered. MMR-status testing could aid in clinical decision-making. • A large nationwide cohort study of 2697 small intestinal adenocarcinomas (SIAs). • The incidence of duodenal adenocarcinomas almost doubled with no improvement in OS. • Despite adjuvant chemotherapy prolonging OS, only 13.8% of eligible patients were treated. • In the first-line setting CAPOX prolonged OS compared to FOLFOX and capecitabine. • A metastasectomy in patients with one distant metastasis was associated with OS. [ABSTRACT FROM AUTHOR]