Impact of time-to-treatment on survival for advanced non-small cell lung cancer patients in the Netherlands: a nationwide observational cohort study.

BACKGROUND: The assumption that more rapid treatment improves survival of advanced non-small cell lung cancer (NSCLC) has not yet been proven. We studied the relation between time-to-treatment and survival in advanced stage NSCLC patients in a large multicentric nationwide retrospective cohort. Additionally, we identified factors associated with delay. METHOD: We selected 10 306 patients, diagnosed and treated between 2014 and 2019 for clinical stage III and IV NSCLC, from the Netherlands Cancer Registry that includes nationwide data from 109 Dutch hospitals. Associations between survival and time-to-treatment were tested with Cox proportional hazard regression analyses. Time-to-treatment was adjusted for multiple covariates including diagnostic procedures and type of therapy. Factors associated with delay were identified by multilevel logistic regression. RESULTS: Risk of death significantly decreased with longer time-to-treatment for stage III patients receiving only radiotherapy (adjusted HR, aHR >21 days: 0.59 (95% CI 0.48 to 0.73)) or any type of systemic therapy (aHR >49 days: 0.72 (95% CI 0.56 to 0.91)) and stage IV patients receiving chemotherapy and/or immunotherapy (aHR >21 days: 0.81 (95% CI 0.73 to 0.88)). No significant association was found for stage III patients treated with chemoradiotherapy and stage IV patients treated with targeted therapy. More complex diagnostic procedures often delay treatment. CONCLUSION: Although in general it is important to start treatment as early as possible, our study finds no evidence that a more rapid start of treatment improves outcomes in advanced stage NSCLC patients. The benefit of urgent treatment is probably confounded by unmeasured patient and tumour characteristics and, clinical urgency dictating timelines of treatment. Time-to-treatment and its impact should be continuously evaluated as therapeutic strategies continue to evolve and improve.

Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study.

INTRODUCTION: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure. This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993. MATERIALS AND METHODS: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry. Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR). Treatment pattern and Kaplan-Meier overall survival analyses were performed. RESULTS: In total, 12 168 patients were included in the study. For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01). Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01). From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%). Overall, 62.2% of patients received no antitumour treatment. The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%). The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001). CONCLUSION: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups. The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time. The majority of patients do not receive treatment though and prognosis is still poor.

Non-Small-Cell Lung Cancer Patients with a High Predicted Risk of Irradical Resection: Can Chemoradiotherapy Offer Similar Survival?

PURPOSE: Irradical resection of non-small-cell lung cancer (NSCLC) is a detrimental prognostic factor. Recently, Rasing et al. presented an internationally validated risk score for pre-treatment prediction of irradical resection. We hypothesized that chemoradiation therapy (CRT) could serve as an alternative approach in patients with a high risk score and compared overall survival (OS) outcomes between surgery and CRT. METHODS: Patients from a population-based cohort with stage IIB-III NSCLC between 2015 and 2018 in The Netherlands were selected. Patients with a 'Rasing score' > 4 who underwent surgery were matched with patients who underwent CRT using 1:1 nearest-neighbor propensity score matching. The primary endpoint of OS was compared using a Kaplan-Meier analysis. RESULTS: In total, 2582 CRT and 638 surgery patients were eligible. After matching, 523 well-balanced pairs remained. Median OS in the CRT group was 27.5 months, compared with 45.6 months in the surgery group (HR 1.44, 95% CI 1.23-1.70, p < 0.001). The 114 surgical patients who underwent an R1-2 resection (21.8%) had a worse median OS than the CRT group (20.2 versus 27.5 months, HR 0.77, 95% CI 0.61-0.99, p = 0.039). CONCLUSION: In NSCLC patients at high predicted risk of irradical resection, CRT appears to yield inferior survival compared with surgery. Therefore, choosing CRT instead of surgery cannot solely be based on the Rasing score. Since patients receiving an R1-2 resection do have detrimental outcomes compared with primary CRT, the treatment decision should be based on additional information, such as imaging features, comorbidities, patient preference, and the surgeon's confidence in achieving an R0 resection.

Trends in mediastinal nodal staging and its impact on unforeseen N2 and survival in lung cancer.

INTRODUCTION: Guidelines for invasive mediastinal nodal staging in resectable nonsmall cell lung cancer (NSCLC) have changed over the years. The aims of this study were to describe trends in invasive staging and unforeseen N2 (uN2) and to assess a potential effect on overall survival. METHODS: A nationwide Dutch cohort study included all clinical stage IA-IIIB NSCLC patients primarily treated by surgical resection between 2005 and 2017 (n=22 555). We assessed trends in invasive nodal staging (mediastinoscopy 2005-2017; endosonography 2011-2017), uN2 and overall survival and compared outcomes in the entire group and in clinical nodal stage (cN)1-3 patients with or without invasive staging. RESULTS: An overall increase in invasive nodal staging from 26% in 2005 to 40% in 2017 was found (p<0.01). Endosonography increased from 19% in 2011 to 32% in 2017 (p<0.01), while mediastinoscopy decreased from 24% in 2011 to 21% in 2017 (p=0.08). Despite these changes, uN2 was stable over the years at 8.7%. 5-year overall survival rate was 41% for pN1 compared to 37% in single node uN2 (p=0.18) and 26% with more than one node uN2 (p<0.01). 5-year overall survival rate of patients with cN1-3 with invasive staging was 44% versus 39% in patients without invasive staging (p=0.12). CONCLUSION: A significant increase in invasive mediastinal nodal staging in patients with resectable NSCLC was found between 2011 and 2017 in the Netherlands. Increasing use of less invasive endosonography prior to (or as a substitute for) surgical staging did not lead to more cases of uN2. Performance of invasive staging indicated a possible overall survival benefit in patients with cN1-3 disease.

The psychosocial impact of living with mesothelioma: Experiences and needs of patients and their carers regarding supportive care.

OBJECTIVE: Mesothelioma is a rare cancer with a poor prognosis caused by exposure to asbestos. Psychosocial support and care for mesothelioma patients and their carers is limited and not tailored to their specific needs. The aim of this study was to explore patients' and carers' needs and experiences regarding psychosocial support and their coping mechanisms dealing with psychosocial problems. METHODS: A qualitative study was performed using semi-structured interviews with both mesothelioma patients and their carers. Participants were recruited through two specialised hospitals and two patient organisations. All interviews were transcribed verbatim and thematically analysed. RESULTS: Ten patients (70% male, mean age 67.7) and five carers (20% male, mean age 65) participated in the study. The main themes identified for patients were active coping, limited needs and limited knowledge and awareness about psychosocial support. The main themes for carers were passive coping and 'it's all about the patient'. CONCLUSION: Mesothelioma patients do not seem to have high needs for psychosocial support, whereas carers do. However, knowledge about and awareness of psychosocial support is low among mesothelioma patients. The findings from this study should be used to adjust guidelines for psychosocial support in mesothelioma patients and their carers.

Health-Related Quality of Life, Satisfaction with Care, and Cosmetic Results in Relation to Treatment among Patients with Keratinocyte Cancer in the Head and Neck Area: Results from the PROFILES Registry.

BACKGROUND: Little is known about the impact of keratinocyte cancer (KC) and its treatment on health-related quality of life (HRQoL). OBJECTIVES: The objectives of the present study were (1) to evaluate HRQoL among patients with KC in a population-based setting and compare this with an age- end sex-matched normative population and (2) to compare HRQoL, satisfaction with care, and cosmetic results among patients who underwent conventional excision, Mohs' micrographic surgery, or radiotherapy. METHOD: A random sample of 347 patients diagnosed with cutaneous basal cell or squamous cell carcinoma in the head and neck area between January 1, 2010, and December 31, 2014, were selected from the Netherlands Cancer Registry (NCR) and were invited to complete a questionnaire on HRQoL, satisfaction with care, and cosmetic results. Data were collected within Patient-Reported Outcomes Following Initial Treatment and Long-term Evaluation of Survivorship (PROFILES). Outcomes were compared to an age- and sex-matched normative population. RESULTS: Two hundred fifteen patients with KC returned a completed questionnaire (62% response). Patients with KC reported better global quality of life (79.6 vs. 73.3, p < 0.01) and less pain (p < 0.01) compared to the normative population. No statistically significant differences in HRQoL, satisfaction with care, and cosmetic results were found between patients with KC who underwent conventional excision, Mohs' micrographic surgery, or radiotherapy. CONCLUSIONS: The impact of KC and its treatment seems relatively low and more positive than negative as patients reported better HRQoL compared to an age- and sex-matched normative population, probably due to adaptation. No statistically significant differences between treatment types were found concerning HRQoL, patient satisfaction, and cosmetic results. This information could be used by healthcare professionals involved in KC care to improve patients' knowledge about different aspects of the disease as patient's preference is an important factor for treatment choice.

Video-assisted thoracic lobectomy versus stereotactic body radiotherapy for stage I nonsmall cell lung cancer in elderly patients: a propensity matched comparative analysis.

Comparative studies of the overall survival (OS) in elderly patients with nonsmall cell lung cancer (NSCLC) after surgery or stereotactic body radiotherapy (SBRT) have been limited by mixed extents of resection and different surgical approaches.792 patients aged ≥65 years with clinical stage I NSCLC underwent video-assisted thoracic surgery (VATS) lobectomy or SBRT between 2010 and 2015. The propensity score-matched primary analysis included data from the full cohort; the secondary analysis included data from a subgroup of patients with data on pulmonary function.Median OS for unmatched patients was 77 months for patients undergoing VATS lobectomy and 38 months for SBRT. The 1-, 3- and 5-year OS rates after VATS lobectomy were 92%, 76% and 65%, and after SBRT were 90%, 52% and 29% (p<0.001). Median OS for matched patients in the primary analysis was 77 months for patients undergoing VATS lobectomy and 33 months for SBRT. The 1-, 3- and 5-year OS rates after VATS lobectomy were 91%, 68% and 58%, and after SBRT were 87%, 46% and 29% (p<0.001). The survival advantage with VATS lobectomy persisted in the secondary analysis after adjusting for non-matched variables (p=0.034).We suggest that elderly patients with stage I NSCLC undergoing VATS lobectomy have a better rate of OS than patients undergoing SBRT, irrespective of matching. This could be clinically important in decision-making for elderly patients who can tolerate surgery.

An actualised population-based study on the use of radiotherapy in breast cancer patients in the Netherlands.

The utilization rate of RT increased from 64.4% in 2011 to 70.3% in 2015. After BCS and mastectomy, 97.3% and 26.1% of the patients received RT, respectively. For patients undergoing BCS and mastectomy, lower age and ER + tumours were associated with higher RT utilisation rates. After mastectomy, also larger tumour sizes, lymph node involvement, grade-2 and 3 tumours and diagnosis in more recent years were associated with higher RT use.

Immortal time bias in pharmacoepidemiological studies on cancer patient survival: empirical illustration for beta-blocker use in four cancers with different prognosis.

Immortal time bias (ITB) is still seen frequently in medical literature. However, not much is known about this bias in the field of cancer (pharmaco-)epidemiology. In context of a hypothetical beneficial beta-blocker use among cancer patients, we aimed to demonstrate the magnitude of ITB among 9876 prostate, colorectal, lung and pancreatic cancer patients diagnosed between 1998 and 2011, which were selected from a database linkage of the Netherlands Cancer Registry and the PHARMO Database Network. Hazard ratios (HR) and 95% confidence intervals from three ITB scenarios, defining exposure at a defined point after diagnosis (model 1), at any point after diagnosis (model 2) and as multiple exposures after diagnosis (model 3), were calculated to investigate the association between beta-blockers and cancer prognosis using Cox proportional hazards regression. Results were compared to unbiased estimates derived from the Mantel-Byar model. Ignoring ITB led to substantial smaller HRs for beta-blocker use proposing a significant protective association in all cancer types [e.g. HR 0.18 (0.07-0.43) for pancreatic cancer in model 1], whereas estimates derived from the Mantel-Byar model were mainly suggesting no association [e.g. HR 1.10 (0.84-1.44)]. The magnitude of bias was consistently larger among cancer types with worse prognosis [overall median HR differences between all scenarios in model 1 and Mantel-Byar model of 0.56 (prostate), 0.72 (colorectal), 0.77 (lung) and 0.85 (pancreas)]. In conclusion, ITB led to spurious beneficial associations of beta-blocker use among cancer patients. The magnitude of ITB depends on the duration of excluded immortal time and the prognosis of each cancer.

Improvement in population-based survival of stage IV NSCLC due to increased use of chemotherapy.

This study aimed to investigate which factors were associated with the administration of chemotherapy for patients with stage IV non-small cell lung cancer (NSCLC), and their relation to survival at a population-based level. All patients with NSCLC stage IV from 2001 to 2012 were identified in the Netherlands Cancer Registry in the Eindhoven area (n = 5,428). Chemotherapy use and survival were evaluated by logistic and Cox regression analyses, respectively. The proportion of patients receiving chemotherapy increased from 30% in 2001 to 48% in 2012. Higher rates were found among younger patients [multivariable odds ratio (OR(≤ 64_vs._≥ 75_years)): 1.8 (95%CI 1.6-2.1)], high socioeconomic status [OR(high_vs._low): 1.8 (95%CI 1.6-2.2)], no comorbidity [OR0_vs._≥ 2 : 1.5 (95%CI 1.3-1.8)], diagnosed in recent years [OR(2010-2012_vs._2001-2003): 2.0 (95%CI 1.6-2.3)] and adenocarcinoma [ORsquamous_vs._adenocarcinoma : 0.8 (95%CI 0.6-0.9)]. Having liver metastasis was associated with reduced odds (OR(liver_ vs._brain): 0.8 (95%CI 0.7-1.0). The variation between hospitals was large, up to OR 2.0 (95%CI 1.5-2.6). Median survival increased from 18 weeks in 2001-2003 to 21 weeks in 2010-2012 (log-rank p = 0.007), and was 35 weeks in patients with and 10 weeks without chemotherapy. The multivariable hazard of death reduced significantly over time [HR(2001-2003_vs._2010-2012): 1.1 (95%CI 1.0-1.2), HR(2004-2005_vs._2010-2012): 1.2 (95%CI 1.1-1.3)] and only remained significant for 2004-2006 after additional adjustment for chemotherapy [final multivariable model, HR(2004-2006_vs._2010-2012): 1.1 (95%CI 1.0-1.2)]. Besides, prognostic factors were having chemotherapy [final multivariable model: HR 0.4 (95%CI 0.4-0.4)], female sex [HRmale_vs._female : 1.1 (95%CI 1.0-1.1)], socioeconomic status [HR(intermediate_and_high_vs._low) both 0.9 (95%CI 0.9-1.0)], comorbidity [HR(unknown_vs._≥ 2): 1.3 (95%CI 1.2-1.5)], histology [HRother_vs._adenocarcinoma : 1.1 (95%CI 1.1-1.2)], and location of metastasis [range: 1.2 (HR(lymph_nodes_vs._brain)) - 1.6 (HR(liver_vs._brain))]. In conclusion, population-based survival increased due to increasing administration rates of chemotherapy. The administration of chemotherapy was affected by hospital of diagnosis and both patient and tumour characteristics. Identifying patients who benefit from chemotherapy should become a key issue.

Does adjuvant chemoradiotherapy improve the prognosis of gastric cancer after an r1 resection? Results from a dutch cohort study.

OBJECTIVE: The aim of this study was to investigate the impact of adjuvant chemoradiotherapy (CRT) on survival of non-metastatic gastric cancer patients who had undergone an R1 resection. METHODS: We compared the survival of patients after an R1 gastric cancer resection from the population-based Netherlands Cancer Registry who did not receive adjuvant CRT (no-CRT group) with the survival of resected patients who had been treated with adjuvant CRT (CRT group) at our institute. Patients who had a resection between 2002 and 2011 were included. CRT consisted of radiotherapy (45 Gy) combined with concurrent cisplatin- or 5-fluorouracil-based chemotherapy. The impact of CRT treatment on overall survival was assessed using multivariable Cox regression and stratified propensity score analysis. RESULTS: A series of 409 gastric cancer patients who had undergone an R1 resection were studied (no-CRT, N = 369; CRT, N = 40). In the no-CRT group, median age was higher (70 vs. 57 years; p < 0.001) and the percentage of patients with diffuse-type tumors was lower (43 vs. 80 %; p < 0.001). There were no significant differences in pathological T- and N-classification. There was a significant difference in median overall survival between the no-CRT and CRT group (13 vs. 24 months; p = 0.003). In a multivariable analysis, adjuvant CRT was an independent prognostic factor for improved overall survival (hazard ratio 0.54; 95 % confidence interval 0.35-0.84). This effect of CRT was further supported by propensity score analysis. CONCLUSIONS: Adjuvant CRT was associated with an improved survival in patients who had undergone an R1 resection for gastric cancer.

Presence and Number of Positive Surgical Margins after Radical Prostatectomy for Prostate Cancer: Effect on Oncological Outcome in a Population-Based Cohort.

INTRODUCTION: Additional insight in the occurrence and number of positive surgical margins (PSM) and the potential consequences is needed, since earlier studies show divergent results. This study aims at investigating the effect of the presence and number of PSM on oncological outcomes. METHODS: Retrospective population-based cohort study including 648 consecutive prostate cancer patients who underwent RP in the Southern Netherlands in 2006-2008. The effect of PSM on risk of treatment failure, defined by either biochemical recurrence or necessity of any additional therapy (Cox regression), was evaluated. RESULTS: PSM were observed in 39%; 11% had multiple PSM. Treatment failure was observed in 26% of all patients. Multivariably, the presence (hazard ratio 2.5) and number of PSM (hazard ratios: single 2.3; multiple 3.1) were independently associated with higher treatment failure rates, unlike location of PSM. CONCLUSIONS: Treatment failure rates are high among patients with PSM, especially in those with multiple PSM. This needs to be taken into account when decisions are made on the applicability of the adjuvant and salvage therapy.

Burden of disease caused by keratinocyte cancer has increased in The Netherlands since 1989.

BACKGROUND: Keratinocyte cancer is the most common cancer among Caucasians. OBJECTIVE: We sought to study time trends of the burden of disease attributable to keratinocyte cancer in The Netherlands. METHODS: Data of all patients with newly diagnosed keratinocyte cancer (ie, squamous cell carcinoma and basal cell carcinoma) were obtained from the population-based Netherlands Cancer Registry and the Eindhoven Cancer Registry (1989-2008). Population structure, mortality data, and life expectancy data were extracted from Statistics Netherlands. The disability-adjusted life-years (DALY) was the sum of the years of life lived with disability and the years of life lost. RESULTS: The world standardized rate of keratinocyte cancer has doubled and was 103 and 94 per 100,000 person-years for males and females in 2004 to 2008, respectively. DALYs as a result of basal cell carcinoma increased by 124% and DALYs as a result of squamous cell carcinoma increased by 66% from 1989 to 1993. Keratinocyte cancer accounted for a total loss of 19,913 DALYs (15,369 years of life lived with disability and 4544 years of life lost) between 2004 and 2008. LIMITATIONS: Only the first keratinocyte cancer was included in this study. CONCLUSION: Keratinocyte cancer is a large burden to the Dutch society. Because incidence rates of keratinocyte cancer continue to increase, the management becomes even more challenging.

Low socioeconomic status and mental health outcomes in colorectal cancer survivors: disadvantage? advantage?... or both?

OBJECTIVE: The goal of this study is to examine the relationship between socioeconomic status (SES) and both positive and negative mental health (MH) outcomes in a population-based sample of colorectal cancer survivors. On the basis of theoretical conceptualizations of trauma and posttraumatic growth, low SES was hypothesized to be positively associated with both greater negative MH outcomes (e.g., distress) and greater positive MH outcomes (e.g., growth). METHODS: Colorectal cancer survivors (n = 1300; 57% male; mean age 69.4 and 4.0 years post-diagnosis) were recruited using a regional, population-based cancer registry in the Netherlands and completed a questionnaire assessing current negative and positive MH outcomes. Low, medium, and high SES respondents were identified using an area-level indicator of SES based on aggregated individual fiscal data on monetary home value and household income. RESULTS: Analysis of covariance and logistic regression analyses indicated that low SES was a risk factor for greater negative MH outcomes. Relative to high SES survivors, low SES survivors reported poorer status on nine indices of MH, and high SES survivors were about 50% less likely to report clinically important levels of anxiety and depression. Results provided partial support for the hypothesis low SES was a 'risk' factor for greater positive MH outcomes. Relative to high SES survivors, low SES survivors reported greater positive MH outcomes on 2 of 5 positive MH indices examined (Positive Self-Evaluation, Meaning of Cancer). CONCLUSIONS: Study findings are the first to suggest that low SES might increase the likelihood of both greater negative as well as positive MH outcomes in cancer survivors.

Trends in the epidemiology of small-cell lung cancer: a Dutch nationwide population-based study over 1989-2020.

INTRODUCTION: This study describes the evolving characteristics of patients with small-cell lung cancer (SCLC) from 1989 to 2020 in the Netherlands to analyse how the population of patients with SCLC has changed in the last decades, hypothesising that this might explain the little progress made in SCLC. METHODS: Patients with SCLC diagnosed from 1989 to 2020 were selected from the Dutch cancer registry. Incidence, patient and disease characteristics, treatments, and overall survival (OS) were analysed. Joinpoint analyses were used to test annual percentage changes for statistical significance. RESULTS: A total of 52,527 patients were diagnosed with SCLC. The absolute numbers of patients with SCLC remained equal over the years; however, the incidence rates decreased from 15.01 to 8.93 per 100,000 person-years. The proportion of women increased from 22% to 50%, and those aged ≥75 years increased from 20% to 25%. The latter coincided with a higher proportion receiving only the best supportive care (BSC) over the years (18-24%). The use of surgery in stage I increased from 2% to 37%. The proportion of patients diagnosed with stage IV increased from 46% to 70% due to better staging. The OS improved for all stages, with a 2-year OS rate for stage IV doubling from 3% to 6%. CONCLUSION: The incidence of SCLC has significantly decreased over the last 30 years, with an increasing proportion of elderly and women. The male-female ratio became similar, and the OS improved. As a consequence of more elderly and probably more vulnerable patients, more patients received only the BSC.

Socioeconomic differences in health-related quality of life among cancer survivors and comparison with a cancer-free population: a PROFILES study.

PURPOSE: This study investigates the association between socioeconomic position (SEP) and health-related quality of life (HRQoL) in a cross-sectional cohort among cancer survivors and compares with cancer-free people. METHODS: Survivors of colorectal, hematological, gynecological, prostate, thyroid cancer, and melanoma diagnosed 2000-2014 were identified in the PROFILES registry, and an age- and sex-matched cancer-free population were identified in the CentER panel. HRQoL, education, and comorbidity were self-reported. Street-level income and clinical factors were obtained from Statistics Netherlands and the Netherlands Cancer Registry. Multivariable logistic regression was used to examine associations of SEP (measured by education and income) and impaired HRQoL among cancer survivors and the cancer-free population, adjusting for age, sex, and time since diagnosis. RESULTS: We included 6693 cancer survivors and 565 cancer-free people. Cancer survivors with low versus medium SEP more frequently reported impaired HRQoL (odds ratio (OR) range for all HRQoL outcomes, 1.06-1.78 for short education and 0.94-1.56 for low income). Survivors with high compared to medium SEP reported impaired HRQoL less frequently (OR range for all HRQoL outcomes, 0.46-0.81 for short education and 0.60-0.84 for low income). The association between SEP and HRQoL was similar in the matched cancer-free population. CONCLUSION: Low SEP was associated with impaired HRQoL in both cancer survivors and cancer-free people. IMPLICATIONS FOR CANCER SURVIVORS: Targeted care is warranted for cancer survivors with impaired HRQoL, especially among those with low SEP.

Impact of time-to-treatment on survival for early-stage non-small cell lung cancer in The Netherlands-a nationwide observational cohort study.

Background: Varied outcomes on the relation between time-to-treatment and survival in early-stage non-small cell lung cancer (NSCLC) patients are reported. We examined this relation in a large multicentric retrospective cohort study and identified factors associated with extended time-to-treatment. Methods: We included 9,536 patients with clinical stage I-II NSCLC, diagnosed and treated in 2014-2019, from the Netherlands Cancer Registry that includes nation-wide data. Time-to-treatment was defined as the number of days between first outpatient visit for suspected lung cancer and start of treatment. The effect of extended time-to-treatment beyond the first quartile and survival was studied with Cox proportional hazard regression. Analyses were stratified for stage and type of therapy. Time-to-treatment was adjusted for multiple covariates including performance status and socioeconomic status. Factors associated with treatment delay were identified by multilevel logistic regression. Results: Median time-to-treatment was 47 days [interquartile range (IQR): 34-65] for stage I and 46 days (IQR: 34-62) for stage II. The first quartile extended to 33 days for both stages. Risk of death increased significantly with extended time-to-treatment for surgical treatment of clinical stage II patients [adjusted hazard ratio (aHR) >33 days: 1.36, 95% confidence intervals (CI): 1.09-1.70], but not in stage II patients treated with radiotherapy or in stage I patients. Causes of prolonged time-to-treatment were multifactorial including diagnostic tests, such as endoscopic ultrasound (EUS) or endobronchial ultrasound (EBUS). Conclusions: Clinical stage II patients benefit from fast initiation of surgical treatment. Surprisingly this appears to be accounted for by patients who are clinically stage II but pathologically stage I. Further study is needed on characterizing these patients and the significance of lymph node- or distant micrometastasis in guiding time-to-treatment and treatment strategy.

Prognostic Implication of KRAS G12C Mutation in a Real-World KRAS-Mutated Stage IV NSCLC Cohort Treated With Immunotherapy in The Netherlands.

Introduction: With the approval of G12C inhibitors as the second line of treatment for KRAS G12C-mutated NSCLC, and the expanding research regarding targeting KRAS, it is key to understand the prognostic implication of KRAS G12C in the current first line of treatment. We compared overall survival (OS) of patients with stage IV KRAS G12C-mutated NSCLC to those with a KRAS non-G12C mutation in a first-line setting of (chemo)immunotherapy. Methods: This nationwide population-based study used real-world data from The Netherlands Cancer Registry. We selected patients with stage IV KRAS-mutated lung adenocarcinoma diagnosed in 2019 to 2020 who received first-line (chemo-)immunotherapy. Primary outcome was OS. Results: From 28,120 registered patients with lung cancer, 1185 were selected with a KRAS mutation, of which 494 had a KRAS G12C mutation. Median OS was 15.5 months (95% confidence interval [CI]: 13.6-18.4) for KRAS G12C versus 14.0 months (95% CI:11.2-15.7) for KRAS non-G12C (p = 0.67). In multivariable analysis, KRAS subtype was not associated with OS (hazard ratio = 0.95, 95% CI: 0.82-1.10). For the subgroup with programmed death-ligand 1 at 0% to 49% who received chemoimmunotherapy, median OS was 13.3 months (95% CI: 10.5-15.2) for G12C and 9.8 months (95% CI: 8.6-11.3) for non-G12C (p = 0.48). For the subgroup with programmed death-ligand 1 more than or equal to 50% who received monoimmunotherapy, the median OS was 22.0 months (95% CI: 18.4-27.3) for G12C and 18.9 months (95% CI: 14.9-25.2) for non-G12C (p = 0.36). Conclusions: There was no influence of KRAS subtype (G12C versus non-G12C) on OS in patients with KRAS-mutated stage IV NSCLC treated with first-line (chemo)immunotherapy.

Survival of patients with KRAS G12C mutated stage IV non-small cell lung cancer with and without brain metastases treated with immune checkpoint inhibitors.

INTRODUCTION: Few data is available on whether brain metastases (BM) influence survival in patients with stage IV KRAS G12C mutated (KRAS G12C+ ) non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitor (ICI) +/- chemotherapy ([chemo]-ICI). METHODS: Data was retrospectively collected from the population-based Netherlands Cancer Registry. The cumulative incidence of intracranial progression, overall survival (OS) and progression free survival (PFS) was determined for patients with KRAS G12C+ stage IV NSCLC diagnosed January 1 - June 30, 2019, treated with first-line (chemo)-ICI. OS and PFS were estimated using Kaplan-Meier methods and BM+ and BM- groups were compared using log-rank tests. RESULTS: Of 2489 patients with stage IV NSCLC, 153 patients had KRAS G12C+ and received first-line (chemo)-ICI. Of those patients, 35% (54/153) underwent brain imaging (CT and/or MRI), of which 85% (46/54) MRI. Half of the patients with brain imaging (56%; 30/54) had BM, concerning one-fifth (20%; 30/153) of all patients, of which 67% was symptomatic. Compared to BM-, patients with BM+ were younger and had more organs affected with metastasis. Around one-third (30%) of patients with BM+ had ≥5 BM at diagnosis. Three quarters of patients with BM+ received cranial radiotherapy prior to start of (chemo)-ICI. The 1-year cumulative incidence of intracranial progression was 33% for patients with known baseline BM and 7% for those without (p = 0.0001). Median PFS was 6.6 (95% CI 3.0-15.9) and 6.7 (95% CI 5.1-8.5) months for BM+ and BM- (p = 0.80), respectively. Median OS was 15.7 (95% CI 6.2-27.3) and 17.8 (95% CI 13.4-22.0) months for BM+ and BM- (p = 0.77), respectively. CONCLUSION: Baseline BM are common in patients with metastatic KRAS G12C+ NSCLC. During (chemo)-ICI treatment, intracranial progression was more frequent in patients with known baseline BM, justifying regular imaging during treatment. In our study, presence of known baseline BM did not influence OS or PFS.

The effect of socioeconomic status on staging and treatment decisions in esophageal cancer.

BACKGROUND: Optimal treatment choice for patients with esophageal cancer (EC) is complex and largely determined by tumor characteristics, comorbidity, and age. GOALS: This study describes the role of patient characteristics, among which is socioeconomic status (SES), in EC treatment. STUDY: Patients diagnosed with primary EC between 1990 and 2008 in the southern part of the Netherlands were identified using the Eindhoven Cancer Registry. Multivariable logistic and proportional hazard regression analyses were used to identify determinants of treatment and survival. RESULTS: We included 1914 patients, and 37% of them underwent intentionally curative treatment. Low-SES patients were diagnosed at older age (16% vs. 9%, age more than or equal to 80) and with more advanced tumor stages (13% vs. 10%, stage T4) than high-SES patients. Age less than 60 compared with 70 to 79 years [adjusted odds ratio, 4.51; 95% confidence interval (CI), 2.98-6.84] and high SES compared with low SES (adjusted odds ratio 1.59; 95% CI, 1.07-2.37) were independent predictors for curative treatment. Probability of death for high-SES patients undergoing palliative treatment was decreased compared with low-SES patients (hazard ratio, 0.84; 95% CI, 0.71-0.99). CONCLUSIONS: SES is an important factor in treatment choice of EC. As health care is equally accessible to the whole population in the Netherlands, this suggests that both patient-related and physician-related factors are involved in this phenomenon.