Primary ovarian cancer after colorectal cancer: a Dutch nationwide population-based study.

BACKGROUND AND PURPOSE: Women with colorectal cancer (CRC) are at risk not only of developing ovarian metastases, but also of developing a primary ovarian malignancy. Several earlier studies have in fact shown a link between the development of primary ovarian cancer and CRC. The purpose of this study was therefore to determine the risk of developing a primary ovarian cancer in women with prior CRC compared to the general population. METHODS: Data from the Netherlands Cancer Registry were used. All women diagnosed with invasive CRC between 1989 and 2017 were included. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10,000 person-years were calculated. RESULTS: During the study period, 410 (0.3%) CRC patients were diagnosed with primary ovarian cancer. Women with CRC had a 20% increased risk of developing ovarian cancer compared to the general population (SIR = 1.2, 95% CI: 1.1-1.3). The AER of ovarian cancer was 0.9 per 10,000 person-years. The risk was especially increased within the first year of a CRC diagnosis (SIR = 3.3, 95% CI: 2.8-3.8) and in women aged ≤ 55 years (SIR = 2.0, 95% CI: 1.6-2.6). CONCLUSION: This study found a slightly increased risk of primary ovarian cancer in women diagnosed with CRC compared to the general population. However, this may be partly attributable to surveillance or detection bias. Nevertheless, our findings could be helpful for patient counseling, as CRC patients do not currently receive information concerning the increased risk of ovarian cancer.

Treatment Strategies and Prognosis of Patients With Synchronous or Metachronous Colorectal Peritoneal Metastases: A Population-Based Study.

BACKGROUND: This study aimed to compare treatment strategies and survival of patients with synchronous colorectal peritoneal metastases (CPM) and patients with metachronous CPM in a nationwide cohort. METHODS: All patients from the Netherlands Cancer Registry with synchronous or metachronous CPM whose primary colorectal cancer (CRC) was diagnosed between 1 January and 30 June 2015 were included in the study. Treatments were categorized as (A) cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [CRS-HIPEC]; (B) palliative treatment; or (C) best supportive care. Overall survival (OS) for all the patients and disease-free survival (DFS) for those who underwent CRS-HIPEC were compared between the two groups. RESULTS: Of 7233 patients, 743 had a diagnosis of CPM, including 409 patients with synchronous CPM and 334 patients with metachronous CPM. The median OS was 8.1 months for the patients with synchronous CPM versus 12 months for the patients with metachronous CPM (p = 0.003). After multivariable correction, OS no longer differed between the patients with synchronous CPM and those with metachronous CPM (HR 1.03 [0.83-1.27]). The patients with metachronous CPM more often underwent CRS-HIPEC than the patients with synchronous CPM (16 % vs 8 %; p = 0.001). The two groups did not differ statistically in terms of DFS and OS (median DFS, 21.5 vs 14.1 months, respectively; p = 0.094; median OS, 37.8 vs. 35.8 months, respectively; p = 0.553). CONCLUSION: This population-based study showed that survival for the patients with synchronous CPM and patients with metachronous CPM did not significantly differ. This suggests that a similar prognosis may be expected for patients selected for treatment regardless of the onset of CPM.

Incidence, risk factors, treatment, and survival of ovarian metastases of colorectal origin: a Dutch population-based study.

OBJECTIVE: The aim of this nationwide study was to provide insight in the incidence, risk factors, treatment, and survival of patients with ovarian metastases from colorectal cancer (CRC). METHODS: Data from the Netherlands Cancer Registry were used. All newly diagnosed female CRC patients between 2008 and 2016 were included. Treatment was categorized as follows: cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC); resection of the primary tumor; palliative treatment; and no treatment. Overall survival (OS) was investigated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: Of 53,883 female CRC patients, 11,343 (21.1%) had metastases at time of diagnosis. Among them, 471 (4.2%) had ovarian metastases. Within latter group, 27.2% received CRS-HIPEC; 38.4% underwent resection of the primary tumor; 25.3% received palliative treatment; and 9.1% received no treatment. Median OS of all patients with ovarian metastases was 17.5 months. In patients receiving CRS-HIPEC, OS was significantly longer than in patients undergoing resection only (median OS 34.1 vs. 17.5 months, adjusted HR 0.44 [0.33-0.66]). Five-year OS was 28.5% for patients having underwent CRS-HIPEC, 11.0% for patients having underwent resection of the primary tumor, 1.2% for patients having underwent palliative treatment, and 0.0% for patients without treatment. CONCLUSIONS: Synchronous ovarian metastases are diagnosed in 4.2% of female colorectal patients presenting with metastatic disease. Risk factors are young age, T4/N+ tumor and histology of signet ring cell carcinoma. Median OS of the entire cohort was 17.5 months, ranging from 3.1 months in patients without treatment to 34.1 months in patients undergoing CRS-HIPEC.

Treatment and Outcome of Synchronous Colorectal Carcinomas: A Nationwide Study.

BACKGROUND: Synchronous colorectal carcinomas (CRC) occur in 1-8% of patients diagnosed with CRC. This study evaluated treatment patterns and patient outcomes in synchronous CRCs compared with solitary CRC patients. METHODS: All patients diagnosed with primary CRC between 2008 and 2013, who underwent elective surgery, were selected from the Netherlands Cancer Registry. Using multivariable regressions, the effects of synchronous CRC were assessed for both short-term outcomes (prolonged postoperative hospital admission, anastomotic leakage, postoperative 30-day mortality, administration of neoadjuvant or adjuvant treatment), and 5-year relative survival (RS). RESULTS: Of 41,060 CRC patients, 1969 patients (5%) had synchronous CRC. Patients with synchronous CRC were older (mean age 71 ± 10.6 vs. 69 ± 11.4 years), more often male (61 vs. 54%), and diagnosed with more advanced tumour stage (stage III-IV 54 vs. 49%) compared with solitary CRC (all p < 0.0001). In 50% of the synchronous CRCs, an extended surgery was conducted (n = 934). Synchronous CRCs with at least one stage II-III rectal tumour less likely received neoadjuvant (chemo)radiation [78 vs. 86%; adjusted OR 0.6 (0.48-0.84)], and synchronous CRCs with at least one stage III colon tumour less likely received adjuvant chemotherapy [49 vs. 63%; adjusted OR 0.7 (0.55-0.89)]. Synchronous CRCs were independently associated with decreased survival [RS 77 vs. 71%; adjusted RER 1.1 (1.01-1.23)]. CONCLUSIONS: The incidence of synchronous CRCs in the Dutch population is 5%. Synchronous CRCs were associated with decreased survival compared with solitary CRC. The results emphasize the importance of identifying synchronous tumours, preferably before surgery to provide optimal treatment.

Recurrence-free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy.

The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence-free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non-)completion. Patients aged ≥70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non-academic hospitals were included. RFS and OS were analyzed with Kaplan-Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five-year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p = 0.91), adjusted HR = 0.99 (95%CI 0.68-1.44); OS: 66% vs. 66% (p = 0.76), adjusted HR = 0.93 (95%CI 0.64-1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three-year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p = 0.21), adjusted HR = 1.42 (95%CI 0.85-2.37); OS: 68% vs. 78% (p = 0.41), adjusted HR = 1.17 (95%CI 0.70-1.97)). Three-year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p = 0.01), adjusted HR = 2.07 (95%CI 1.11-3.84); OS: 65% vs. 80% (p = 0.01), adjusted HR = 2.00 (95%CI 1.12-3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients.

Adjuvant chemotherapy is not associated with improved survival for all high-risk factors in stage II colon cancer.

Adjuvant chemotherapy can be considered in high-risk stage II colon cancer comprising pT4, poor/undifferentiated grade, vascular invasion, emergency surgery and/or <10 evaluated lymph nodes (LNs). Adjuvant chemotherapy administration and its effect on survival was evaluated for each known risk factor. All patients with high-risk stage II colon cancer who underwent resection and were diagnosed in the Netherlands between 2008 and 2012 were included. After stratification by risk factor(s) (vascular invasion could not be included), Cox regression was used to discriminate the independent association of adjuvant chemotherapy with the probability of death. Relative survival was used to estimate disease-specific survival. A total of 4,940 of 10,935 patients with stage II colon cancer were identified as high risk, of whom 790 (16%) patients received adjuvant chemotherapy. Patients with a pT4 received adjuvant chemotherapy more often (37%). Probability of death in pT4 patients receiving chemotherapy was lower compared to non-recipients (3-year overall survival 91% vs. 73%, HR 0.43, 95% CI 0.28-0.66). The relative excess risk (RER) of dying was also lower for pT4 patients receiving chemotherapy compared to non-recipients (3-year relative survival 94% vs. 85%, RER 0.36, 95% CI 0.17-0.74). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between receipt of adjuvant chemotherapy and survival was observed. In high-risk stage II colon cancer, adjuvant chemotherapy was associated with higher survival in pT4 only. To prevent unnecessary chemotherapy-induced toxicity, further refinement of patient subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated.

Drug dispensings among elderly in the year before colon cancer diagnosis versus matched cancer-free controls.

WHAT IS KNOWN AND OBJECTIVE: The concomitant use of multiple drugs is common among the general population of elderly. The aim of this study was to provide an overview of which drugs are dispensed to elderly in the year before colon cancer diagnosis and to compare this with cancer-free controls. METHODS: Data from the Eindhoven Cancer Registry were linked to the PHARMO Database Network. Patients with colon cancer aged ≥70 years were included and matched with controls on gender, year of birth and postal code. Proportions of cases and controls with ≥1 dispensing of each WHO ATC-2-level drug during the total year and during each quarter of the year were calculated and differences between cases and controls tested. RESULTS AND DISCUSSION: Proportion of cases with ≥1 drug dispensing was highest for drugs for constipation (cases vs. controls 58% vs. 10%), antithrombotics (42% vs. 33%), drugs for acid-related disorders (35% vs. 22%), antibacterials (34% vs. 24%), agents acting on the renin-angiotensin system (33% vs. 27%), beta-blockers (33% vs. 23%), lipid-modifying agents (29% vs. 22%), diuretics (29% vs. 21%), psycholeptics (25% vs. 18%) and antianaemics (23% vs. 6%). The proportion of cases with ≥1 drug dispensing increased from the first to the last quarter of the year for drugs for constipation (7%-53%), drugs for acid-related disorders (16%-27%), antibacterials (12%-16%), beta-blockers (26%-28%), psycholeptics (15%-19%) and antianaemics (6%-18%). Elevated proportions of cases with ≥1 drug dispensing for several drugs are mostly related to comorbidity, although increasing proportions of cases with ≥1 drug dispensing for certain drugs during the year can be attributed to the incidence of colon cancer. WHAT IS NEW AND CONCLUSION: We have provided insight into which drugs are commonly used in the year preceding colon cancer diagnosis. This may trigger general practitioners and medical specialists to further evaluate the patient.

Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis.

BACKGROUND: Many patients with non-small cell lung cancer (NSCLC) die within the first few years of diagnosis, and considerable excess mortality remains even after 5 years. We investigated the death rate and the distribution of causes of death for NSCLC patients by age and stage at diagnosis during long-term follow-up. PATIENTS AND METHODS: All 72 021 patients aged 45-89 years diagnosed with stage I-III NSCLC between 1989 and 2008 in the Netherlands and who died up till 2011 were derived from the Netherlands Cancer Registry and linked with the database of Statistics Netherlands for underlying causes of death. Mortality ratios and proportional distribution of causes of death were calculated during 5 time periods after diagnosis of NSCLC (up to 15 years). RESULTS: Median follow-up was 9.6 years (range: 0-23 years). Lung cancer was the predominant cause of death in the first 6 years after diagnosis (being 80%-85% and ∼90% up to 3 years for localized and locally advanced disease, respectively, and ∼60%-75% and ∼75%-85% during years 4-6 for both stage groups, respectively). Thereafter, lung cancer as cause of death proportionally decreased with time since diagnosis, but remained over 30%. Hence, cardiovascular diseases and chronic obstructive pulmonary diseases (COPD) became more important causes of death, especially for patients aged >60 years at diagnosis (up to 34% for cardiovascular diseases and up to 19% for COPD). CONCLUSIONS: With time, the relative contribution of cardiovascular and COPD causes of death increased, although the absolute contribution of lung cancer remained high in non-metastatic NSCLC. Therefore, managing morbidity of these diseases remains relevant.

Reduced risk of distant recurrence after adjuvant chemotherapy in patients with stage III colon cancer aged 75 years or older.

BACKGROUND: Little is known about the effects of adjuvant chemotherapy on the risk of distant recurrence in elderly with stage III colon cancer, treated in daily practice. PATIENTS AND METHODS: One thousand two hundred and ninety-one stage III colon cancer patients diagnosed in the southern Netherlands between 2003 and 2008 were included. Propensity score matching was applied to create a subsample to reduce bias caused by differences between patients receiving adjuvant chemotherapy and patients not receiving adjuvant chemotherapy. For both the total study population and the propensity score matched sample, Cox regression analysis was used to discriminate independent risk factors for distant recurrence. RESULTS: Adjuvant chemotherapy (CT) was correlated with a reduced risk of distant recurrence in both the total study population [hazard ratio (HR) CT versus nCT 0.55, 95% confidence interval (CI) 0.42-0.70] and in the propensity score matched sample (HR CT versus nCT 0.46, 95% CI 0.33-0.63). In separate analyses for patients aged <75 and ≥75 years, the effect of adjuvant chemotherapy on the risk of distant recurrence remained comparable for both age groups (HR CT versus nCT 0.50, 95% CI 0.37-0.68 and 0.57, 95% CI 0.36-0.90, respectively). CONCLUSION: Distant recurrence risks at higher age definitely warrant consideration of adjuvant chemotherapy for elderly stage III colon cancer patients. This decision should be based on a multidisciplinary and functional assessment of the patient, not on age.

Increase in the incidence of synchronous and metachronous peritoneal metastases in patients with colorectal cancer: A nationwide study.

INTRODUCTION: - To investigate the incidence of, factors associated with, and differences between synchronous and metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. METHODS: - Data from the Netherlands Cancer Registry were used. All patients diagnosed with colorectal cancer (CRC) between 1 January and June 30, 2015 were evaluated for synchronous or metachronous CPM (diagnosis ≤90 or >90 days after surgery for primary CRC), and survival in 2019 (median follow-up 38.4 months). RESULTS: - Of 7233 included patients, 409 (5.7%) were diagnosed with synchronous CPM. Factors associated with synchronous CPM were mucinous (OR 2.72 [1.90-3.90]) or signet ring cell (SRC) histology (OR 6.58 [3.66-11.81]), T4 (OR 4.82 [3.68-6.32]), N1 (OR 1.66 [1.20-2.30]), or N2 stage (OR 3.27 [2.36-4.52]), and synchronous systemic metastases (SM) (OR 3.13 [2.37-4.14]). After surgery for primary CRC, 326 patients developed metachronous CPM after a median time of 14.7 months (3-year cumulative incidence: 5.5%). Factors associated with metachronous CPM were younger age (HR 1.63 [1.10-2.42]), mucinous (HR 1.84 [1.20-2.82]) or SRC histology (HR 2.43 [1.11-5.32]), T4 (HR 2.77 [2.07-3.70]), N1 (HR 2.90 [2.18-3.85]), N2 (HR 3.19 [2.26-4.50]), and synchronous SM (HR 1.95 [1.43-2.66]). CONCLUSION: - This population-based study found the highest incidence of CPM currently reported in literature and a strong association between the presence of synchronous SM and both synchronous and metachronous CPM. These findings may contribute to a tailored approach in the follow-up after primary CRC surgery and guide future clinical trials investigating new strategies regarding risk-reduction or early detection of metachronous CPM.

Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer?

BACKGROUND: Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer. METHODS: Retrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN <20ms or RMSSD <19ms) and normal HRV (SDNN ≥20ms or RMSSD ≥19ms). Primary endpoints were overall and cancer free survival. RESULTS: A total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN <20ms vs SDNN ≥20ms:24.4% vs 22.8%, adjusted HR = 0.952 (0.607-1.493), p = 0.829; RMSSD <19ms vs RMSSD ≥19ms:27.0% vs 19.5%, adjusted HR = 1.321 (0.802-2.178), p = 0.274) or cancer recurrence (SDNN <20ms vs ≥20ms:20.1% vs 18.7%, adjusted HR = 0.976 (0.599-1.592), p = 0.924; RMSSD <19ms vs ≥19ms, 21.5% vs 16.9%, adjusted HR = 1.192 (0.706-2.011), p = 0.511). There was no significant association between HRV and CEA-level at one year follow-up, or between HRV and occurrence of a post-operative complication or the severity of post-operative complications. CONCLUSIONS: Heart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.

Long-term survival after hyperthermic intraperitoneal chemotherapy using mitomycin C or oxaliplatin in colorectal cancer patients with synchronous peritoneal metastases: A nationwide comparative study.

OBJECTIVES: In the Netherlands, limited variability exists in performance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) among centers treating colorectal peritoneal metastases (PM), except for the intraperitoneal drug administration. This offers a unique opportunity to investigate any disparities in survival between the two most frequently used HIPEC regimens worldwide: mitomycin C (MMC) and oxaliplatin. METHODS: This was a comparative, population-based cohort study of all Dutch patients diagnosed with synchronous colorectal PM who underwent CRS-HIPEC between 2014 and 2017. They were retrieved from the Netherlands Cancer Registry. Main outcome was overall survival (OS). The effect of the intraperitoneal drug on OS was investigated using multivariable Cox regression analysis. RESULTS: In total, 297 patients treated between 2014 and 2017 were included. Among them, 177 (59.6%) received MMC and 120 (40.4%) received oxaliplatin. Only primary tumor location was different between the two groups: more left-sided colon in the Oxaliplatin group (47.5% vs. 33.3%, respectively, p=0.048). The 1-, 2- and 3-year OS were 84.6% vs. 85.8%, 61.6% vs. 63.9% and 44.7% vs. 53.5% in patients treated with MMC and oxaliplatin, respectively. Median OS was 30.7 months in the MMC group vs. 46.6 months in the oxaliplatin group (p=0.181). In multivariable analysis, no influence of intraperitoneal drug on survival was observed (adjusted HR 0.77 [0.53-1.13]). CONCLUSIONS: Long-term survival between patients treated with either MMC or oxaliplatin during CRS-HIPEC was not significantly different.

The association between body mass index and postoperative complications, 30-day mortality and long-term survival in Dutch patients with colorectal cancer.

INTRODUCTION: This retrospective study aims to examine the association between body mass index (BMI) and serious postoperative complications, 30-day mortality and overall survival in colorectal cancer (CRC) patients. MATERIALS AND METHODS: All CRC patients diagnosed between 2008 and 2013 in the south-eastern part of the Netherlands were included. Patients were categorized into four BMI groups: underweight (<18.5), normal weight (18.5 ≥ BMI<25), overweight (25 ≥ BMI<30), and obese (≥30). RESULTS: A total of 7371 CRC patients were included (underweight 133 (1.8%); normal weight 2054 (41.4%); overweight 2955 (40.1%); obesity 1229 (16.7%)). Underweight patients were more likely to have postoperative complications (18.8% vs. 11.7%, adjusted OR 1.95, 95% CI 1.08-3.49) and had a worse 30-day mortality (9.8% vs. 3.3%, adjusted OR 4.37, 95% CI 2.03-9.42) compared to normal weight patients. After stratification for stage (stage I-III and stage IV), underweight was associated with a worse overall survival in both groups compared to normal weight (stage I-III: HR 2.06, 95%CI 1.51-2.80; stage IV: HR 1.65, 95% CI 1.11-2.45). Overweight was associated with an improved overall survival compared to normal weight in both stage groups. Only in stage IV patients obesity was associated with a significant better overall survival compared to stage IV normal weight patients. CONCLUSION: Underweight CRC patients were more likely to have postoperative complications and a worse 30-day mortality compared to patients in other BMI categories. The underweight population also has a worse long-term survival while overweight CRC patients and obese stage IV CRC patients were associated with an improved survival compared to normal weight patients.

Inter-hospital variation in resection rates of colon cancer in the Netherlands: A nationwide study.

INTRODUCTION: Hospital of diagnosis is shown to have an impact on the probability of undergoing a resection in different types of gastrointestinal cancer. The aim of this study was to investigate the inter-hospital variation in resection rates and its impact on survival among patients with non-metastatic colon cancer. METHODS: All patients diagnosed with non-metastatic colon cancer between 2009 and 2014 were selected from the Netherlands Cancer Registry. Multilevel logistic regression was used to examine the variation in resection rates among hospitals. The effect of variation in surgical resection on overall survival was assessed using Cox regression analyses. Relative survival was used as an estimate for disease-specific survival. RESULTS: 38164 patients, treated in 95 different hospitals, were included in the analysis. After adjustments, resection rates varied between hospitals from 88 to 99%. This variation increased among patients older than 75 years, from 79 to 98%. Crude overall 5-year survival was 64%. After adjustment, no significant difference in overall or relative survival between hospitals with higher and lower resection rates was observed. CONCLUSION: Resection rates are important to consider when interpreting hospital outcomes. There is a significant variation in resection rates in patients with non-metastatic colon cancer among hospitals in the Netherlands. This variation increases in the elderly. No significant effect on survival was found. This could imply that undertreatment may play a role as well as that some patients might not benefit from surgery.

Postoperative mortality in elderly patients with colorectal cancer: The impact of age, time-trends and competing risks of dying.

BACKGROUND: Worse prognosis in elderly colorectal cancer (CRC) patients may be cancer or treatment related, or death from other causes. This population-based study aimed to compare survival among non-metastatic CRC patients between age groups and notice time trends in mortality rates. METHODS: Primary stage I-III CRC patients who underwent resection between 2008 and 2013 were selected from the Netherlands Cancer Registry. Patients were divided into three equally distributed age groups and a separated group including the oldest old (<65, 65-74, 75-84 and ≥ 85 years). Survival rates were calculated by age groups and tumour localization. Relative excess risks of death, 30-day, 1-year mortality and 1-year excess mortality were calculated. RESULTS: 52296 patients were included. Age-related differences in 5-year overall survival were observed (colon cancer: 82%, 73%, 56% and 35%; rectal cancer: 82%, 74%, 56% and 38%; p < 0.0001). Age-related differences were less prominent in relative survival and disappeared in conditional relative survival (condition of surviving 1 year). Thirty-day mortality rates decreased over time (colon cancer: 4.9%-3.4%; rectal cancer: 3.0%-1.7%); 1-year mortality rates decreased from 11.9% to 9.6% in colon cancer and from 8.0% to 6.4% in rectal cancer. One-year excess mortality increased with age (17.3% and 12.9% in patients with colon or rectal cancer aged ≥85 years). CONCLUSION: One-year mortality rates remain high in elderly patients. Age-related differences in survival disappeared after adjustment for expected death from other causes and first-year mortality. Beneficial time trends in 1-year mortality rates underline that survival in elderly after CRC surgery is modifiable.

Intensity of adjuvant chemotherapy regimens and grade III-V toxicities among elderly stage III colon cancer patients.

PURPOSE: The aim of this study was to provide insight in the use, intensity and toxicity of therapy with capecitabine and oxaliplatin (CAPOX) and capecitabine monotherapy (CapMono) among elderly stage III colon cancer patients treated in everyday clinical practice. METHODS: Data from the Netherlands Cancer Registry were used. All stage III colon cancer patients aged ≥70 years diagnosed in the southeastern part between 2005 and 2012 and treated with CAPOX or CapMono were included. Differences in completion of all planned cycles, cumulative dosages and toxicity between both regimens were evaluated. RESULTS: One hundred ninety-three patients received CAPOX and 164 patients received CapMono; 33% (n = 63) of the patients receiving CAPOX completed all planned cycles of both agents, whereas 55% (n = 90) of the patients receiving CapMono completed all planned cycles (P < 0.0001). The median cumulative dosage capecitabine was lower for patients treated with CAPOX (163,744 mg/m(2), interquartile range [IQR] 83,397-202,858 mg/m(2)) than for patients treated with CapMono (189,195 mg/m(2), IQR 111,667-228,125 mg/m(2), P = 0.0003); 54% (n = 105) of the patients treated with CAPOX developed grade III-V toxicity, whereas 38% (n = 63) of the patients treated with CapMono developed grade III-V toxicity (P = 0.0026). After adjustment for patient and tumour characteristics, CapMono was associated with a lower odds of developing grade III-V toxicity than CAPOX (odds ratio 0.54, 95% confidence interval 0.33-0.89). For patients treated with CAPOX, the most common toxicities were gastrointestinal (29%), haematological (14%), neurological (11%) and other toxicity (13%). For patients treated with CapMono, dermatological (17%), gastrointestinal (13%) and other toxicity (11%) were the most common. CONCLUSION: CAPOX is associated with significantly more grade III-V toxicities than CapMono, which had a pronounced impact on the cumulative dosage received and completion of all planned cycles. In this light, CapMono seems preferable over CAPOX.

Effect of adjuvant chemotherapy on recurrence-free survival varies by neo-adjuvant treatment in patients with stage III rectal cancer.

INTRODUCTION: Adjuvant chemotherapy still is a controversial therapy for rectal cancer patients. The aim of this study was to analyze the effect of adjuvant chemotherapy on recurrence-free survival (RFS) for patients with stage III rectal cancer treated in clinical practice, taking into account which neo-adjuvant treatment patients received. METHODS: Patients from regions in the Netherlands diagnosed between 1996 and 2013 with pathological stage III rectal cancer who received short-course radiotherapy, chemoradiation or no neo-adjuvant treatment and who underwent surgery were included. After stratification by neo-adjuvant treatment, 5-year RFS according to adjuvant chemotherapy receipt was calculated using Kaplan-Meier curves. Cox regression was used to discriminate the independent effect of adjuvant chemotherapy on the risk of recurrence/death. RESULTS: The study population consisted of 829 patients, of whom 537 (65%) patients received short-course radiotherapy, 128 (15%) patients received chemoradiation and 164 (20%) patients received no neo-adjuvant treatment. Adjuvant chemotherapy was administered to 152 (18%) patients. Adjuvant chemotherapy was associated with improved 5-year RFS for patients who received short-course radiotherapy (61% vs. 46%, p = 0.005) and for patients who did not receive any neo-adjuvant treatment (70% vs. 28%, p < 0.0001). In multivariable analyses, adjuvant chemotherapy was associated with a reduced risk of recurrence/death for patients treated with short-course radiotherapy (HR 0.65, 95% CI 0.46-0.93) and for patients without neo-adjuvant treatment (HR 0.35, 95% CI 0.18-0.71), but not for patients treated with chemoradiation (HR 1.11, 95% CI 0.51-2.41). CONCLUSION: Among patients with stage III rectal cancer, the effect of adjuvant chemotherapy on RFS seems to vary by neo-adjuvant treatment.

Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer.

BACKGROUND: Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). PATIENTS AND METHODS: Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: ⩽ 4, 5-6, 7-8, 9-10, 11-12 and 13-16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. RESULTS: 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus < 65 years 1.3 (95% confidence interval (CI): 1.14-1.58); OR ⩾ 75 versus < 65 years 1.6 (1.25-1.94)), emergency resection (OR 1.8 (1.41-2.32)), anastomotic leakage (OR 8.1 (6.14-10.62)), referral to another hospital for adjuvant chemotherapy (OR 1.9 (1.36-2.57)) and prolonged postoperative hospital admission (OR 4.7 (3.30-6.68)). Starting 5-8 weeks post-surgery showed no decrease in OS compared to initiation within 4 weeks (Hazard ratio (HR) 5-6 weeks 0.9 (0.79-1.11); HR 7-8 weeks 1.1 (0.91-1.30)). However, commencing beyond 8 weeks was associated with decreased OS compared to initiation within 8 weeks (HR 9-10 weeks 1.4 (1.21-1.68); HR 11-12 weeks 1.3 (1.06-1.59); HR 13-16 weeks 1.7 (1.23-2.23)). CONCLUSION: Our data support initiating adjuvant chemotherapy in stage III colon cancer patients within 8 weeks post-surgery.