Swedish Cancer Registry Research Articles

Types of second primary cancer influence overall survival in cutaneous melanoma

BackgroundFavorable survival in malignant cutaneous melanoma (melanoma) has increased the likelihood of second primary cancer (SPC). We assess the influence of patient characteristics at diagnosis of first melanoma and the type of SPC (second melanoma and other SPC) on overall survival.MethodsWe used the Swedish Cancer Registry data to assess overall survival in melanoma for the period 1990 to 2015. Kaplan-Meier curves were plotted and hazard ratios (HRs) were estimated with Cox regression models by considering SPC diagnosis as a time-dependent variable.ResultsA total of 46,726 patients were diagnosed with melanoma, and 15.3% of them developed SPC, among which, two thirds were other SPCs. Second melanomas were diagnosed early (31% during the first year) compared to non-melanoma SPCs (9.5%). Survival for women with second melanoma or other SPC (56 and 21% alive after 25 years of follow-up, respectively) exceeded the male rates (21 and 10%, respectively) but all these figures were lower than for females (60% alive) or males (48%) without SPC. Time dependent analysis showed vastly increased HRs for cancer types that are fatal also as first cancers, but SPC-specific HRs remained relatively uniform, irrespective of SPC diagnosed soon or late after first melanoma. In early-onset melanoma, SPC diagnosis after 10 years may not negatively influence overall survival.ConclusionsAs the overall survival of patients with many types of SPCs is unfavorable, advice about health lifestyle should benefit smoking patients and early detection methods may be recommended for SPCs of the breast, prostate and colorectum.

Cancer incidence in a Swedish cohort with high exposure to perfluoroalkyl substances in drinking water

BackgroundThe use of firefighting foams at a military airport resulted in high levels of perfluorinated substances (PFAS) in the drinking water distributed to one-third of households in the Swedish municipality of Ronneby between the mid-1980s and the end of 2013. MethodThe Ronneby Register Cohort, a large cohort comprising all individuals (N = 60,507) who ever lived in the Ronneby municipality during the period of drinking water contamination, was linked to the Swedish Cancer Register 1985–2016. Individual exposure was classified based on comprehensive data on yearly residential address and water distribution. External analysis explored standardized cancer incidence ratios (SIR) for residents never, or ever, residing in the contaminated water district, compared with those residing in other towns in the same county as reference population. Cox models provided hazard ratios (HR) for different exposure groups within the cohort. Results5,702 individuals with cancer were identified. SIR for overall cancer was 1.04 for men (95%CI 0.96–1.12) and 0.89 for women (95%CI 0.82–0.96) who ever lived in the contaminated drinking water area. Kidney cancer, which was reported with increased risk in C8 study, showed somewhat elevated HR in this study (HR 1.27; 95%CI 0.85–1.89). The HR was modestly elevated for bladder cancer (HR 1.32; 95%CI 1.01–1.72), and reduced for prostate cancer (HR 0.83; 95%CI 0.71–0.98). In subjects who ever lived in the contaminated water area during 2005–2013, when exposure was estimated to be highest, higher risks for kidney cancer (HR 1.84; 95%CI 1.00–3.37) but lower for prostate cancer (HR 0.76; 95%CI 0.59–0.98) were observed. ConclusionAnalysis of this large cohort exposed to high levels of PFAS, dominated by PFHxS and PFOS, revealed no evidence for an overall increased risk of cancer. A moderately increased risk of kidney cancer was observed, in accordance with previous findings after PFAS exposure dominated by PFOA.

The Association Between Revised Cardiac Risk Index and Postoperative Mortality Following Elective Colon Cancer Surgery: A Retrospective Nationwide Cohort Study.

Despite improvements in the perioperative care during the last decades for oncologic colon resection, there is still a substantial risk for postoperative complications and mortality. Opportunities exist for improvement in preoperative risk stratification in this patient population. We hypothesize that the Revised Cardiac Risk Index, a user-friendly tool, could better identify patients with high postoperative mortality risks. A retrospective analysis of operated patients between the years 2007 and 2017 was undertaken, using the prospectively recorded Swedish Colorectal Cancer Registry, which has a 99.5% national coverage for all cases of colon cancer. Patients were cross-referenced with the Swedish National Board of Health and Welfare dataset, a government registry of mortality and comorbidity data. Revised Cardiac Risk Index (RCRI) scores were calculated for each patient and stratified into four groups (RCRI 1, 2, 3, ⩾ 4). A Poisson regression model with robust standard errors of variance was employed to correlate the 90-day postoperative survival with each level of the Revised Cardiac Risk Index. A total of 24,198 patients met the study inclusion criteria. 90-day postoperative mortality increased from 2.4% in patients with RCRI 1 to 10.1% in patients with RCRI ⩾ 4 (p < 0.001). Adjusted 90-day postoperative mortality increased linearly with an increasing RCRI, where an RCRI of 2, 3, and ≥ 4 respectively led to a 46%, 80%, and 167% increased risk of mortality compared to RCRI 1 (p < 0.001). A strong association between an increasing Revised Cardiac Risk Index score and increased 90-day postoperative mortality risk was detected. The Revised Cardiac Risk Index may facilitate risk stratification of patients undergoing elective colon cancer surgery.

Accuracy of magnetic resonance imaging staging of tumour and nodal stage in rectal cancer treated by primary surgery: a population-based study.

The preoperative stage of rectal cancer is an important prognostic factor affecting treatment recommendations. Currently, magnetic resonance imaging (MRI) is used for clinical staging to identify patients who should be recommended for neoadjuvant oncological treatment. The aim of this work was to investigate the accuracy of the preoperative T- and N-stage and also involvement of the mesorectal fascia (MRF) as determined by MRI in a Swedish national cohort. Patients who had undergone resectional surgery for rectal cancer without neoadjuvant treatment in Sweden in the period 2013-2017 were identified through the Swedish Colorectal Cancer Registry (n=2062). The T- and N-stage determined by preoperative MRI were compared with the histopathological results. The MRI-assessed MRF status was compared with the circumferential resection margin. Sensitivity for differentiating T1-2 from T3-4 was 69% and specificity 77%. Sensitivity to detect N1-2 was 42% and specificity 81%. Sensitivity for MRF positivity was 50% and specificity 92%. Agreement analysed by weighted kappa analysis was 0.47 for T-stage [confidence interval (CI) 0.44-0.51], 0.24 for N-stage (CI 0.19-0.24) and 0.20 for MRF status (CI 0.12-0.29). In this study, accuracy of the preoperative MRI was lower than expected for rectal cancers. Overstaging might lead to potentially harmful neoadjuvant treatment and understaging can lead to a higher risk of tumour recurrence. The results of this study show that efforts should be made to increase the accuracy of the preoperative evaluation in order to optimize treatment recommendations.

Permanent stoma rates after anterior resection for rectal cancer: risk prediction scoring using preoperative variables.

A permanent stoma after anterior resection for rectal cancer is common. Preoperative counselling could be improved by providing individualized accurate prediction modelling. Patients who underwent anterior resection between 2007 and 2015 were identified from the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine presence of a stoma 2 years after surgery. A training set based on the years 2007-2013 was employed in an ensemble of prediction models. Judged by the area under the receiving operating characteristic curve (AUROC), data from the years 2014-2015 were used to evaluate the predictive ability of all models. The best performing model was subsequently implemented in typical clinical scenarios and in an online calculator to predict the permanent stoma risk. Patients in the training set (n = 3512) and the test set (n = 1136) had similar permanent stoma rates (13.6 and 15.2 per cent). The logistic regression model with a forward/backward procedure was the most parsimonious among several similarly performing models (AUROC 0.67, 95 per cent c.i. 0.63 to 0.72). Key predictors included co-morbidity, local tumour category, presence of metastasis, neoadjuvant therapy, defunctioning stoma use, tumour height, and hospital volume; the interaction between age and metastasis was also predictive. Using routinely available preoperative data, the stoma outcome at 2 years after anterior resection for rectal cancer can be predicted fairly accurately.

Statin therapy and its association with long-term survival after colon cancer surgery

BackgroundThe current study aimed to address the clinical equipoise regarding the association of ongoing statin therapy at time of surgery with long-term postoperative mortality rates after elective, curative, surgical resections of colon cancer by analyzing data from a large validated national register. MethodsAll adults with stage I to III colon cancer who underwent elective surgery with curative intent between January 2007 and October 2016 were retrieved from the Swedish Colorectal Cancer Register, a prospectively collected national register. Patients were identified as having ongoing statin therapy if they filled a prescription within 12 months pre- and postoperatively. Study outcomes included 5-year all-cause and cancer-specific postoperative mortality. To reduce the impact of confounding from covariates owing to nonrandomization, the inverse probability of treatment weighting method was used. Subsequently, Cox proportional hazards models were fitted to the weighted cohorts. ResultsIn total, 19,118 patients underwent elective surgery for colon cancer in the specified period, of whom 31% (5,896) had ongoing statin therapy. Despite being older, having a higher preoperative risk, and having more comorbidities, patients with statin therapy had a higher postoperative survival. After inverse probability of treatment weighting, patients with statin therapy displayed a significantly lower mortality risk up to 5 years after surgery for both all-cause (hazard ratio 0.68, 95% confidence interval 0.63–0.74, P < .001) and cancer-specific mortality (hazard ratio 0.76, 95% confidence interval 0.66–0.89, P < .001). ConclusionThe results of this study indicate that statin therapy is associated with a sustained reduction in all-cause and cancer-specific mortality up to 5 years after elective colon cancer surgery. The findings warrant validation in future prospective clinical trials.

Management, treatment and prognostic significance of lateral lymph node metastases in rectal cancer\u2014a regional cohort study

PurposeLateral lymph node metastases in rectal cancer remain a clinical challenge. Different treatment regimens have been suggested. This retrospective regional cohort study examines outcome after combined oncological and surgical treatment of MRI-positive lateral lymph nodes (LLN).MethodsData from the Swedish Colorectal Cancer Registry (SCRCR) and patient records were used for retrospective analysis of resected high-risk rectal cancers between 2009 and 2014. The aim was to compare tumour characteristics, neoadjuvant therapy, recurrence and outcome after lateral lymph node dissection.ResultsOne thousand and one hundred nineteen cases were identified and after exclusion 344 patients with cT3–T4 ≤ 10 cm from the anal verge were analysed. Thirty (8.7%) patients with MRI-positive LLN were identified. Synchronous distant metastases were associated with MRI-positive LLN (p-value 0.019). Long-course chemoradiotherapy was clinical practice in cases of MRI-positive LLN. No differences in local (p-value 0.154) or distant (p-value 0.343) recurrence rates between MRI-positive LLN patients and MRI-negative patients were detected. Only four patients underwent lateral lymph node dissection (LLND). There was no significant difference in overall survival during follow-up between the MRI-negative (CI at 95%; 99–109 months) and MRI-positive group (CI at 95%; 69–108 months; p-value 0.14).ConclusionLateral lymph node metastases present a challenging clinical situation. The present study shows that combination of neoadjuvant therapy and selective LLND is an applicable strategy in cases of MRI-positive LLN.

Incidence, detection and outcome of differentiated thyroid cancer in Western Sweden.

BackgroundIt is unclear whether the increasing incidence of thyroid cancer (TC) due to increased diagnosis of small and indolent tumours might mask a real increase of clinically significant cancers. The aim of this study was to correlate surgery, pathology and outcome data of individual patients to the mode of primary detection (palpation, by imaging or incidental) to assess if TC incidence has increased.MethodsThe Swedish Cancer Registry identified all patients with TC in Västra Götaland County representing approximately 1.6 million inhabitants. Clinical information was retrieved from medical records of patient cohorts from three study intervals (2001–2002, 2006–2007 and 2011–2014) comprising 60 per cent of all TC patients. Data were also obtained from the NORDCAN registry to compare of TC incidence with other Nordic countries.ResultsBetween 2001 and 2014, the annualized standard incidence rate/100 000 population (ASR) of TC increased from 3.14 to 10.71 in women and from 1.12 to 3.77 in men. This was higher than the mean incidence for Sweden but similar to that in Norway and Finland. Differentiated TC (DTC) increased more than threefold. The majority of tumours (64 per cent) were detected by palpation. Larger tumours (10–20, 21–40 and greater than 40 mm) increased as much as microcarcinomas (less than 10 mm). Only 5 per cent of the tumours were detected by imaging. All disease-specific deaths (8.5 per cent of DTC in the first two cohorts) and most patients with recurrent or persistent disease (6.6 per cent of DTC cases) were diagnosed due to tumour-related symptoms.ConclusionDTC in Western Sweden gradually increased between 2001 and 2014. The majority of tumours were detected by palpation suggesting a real increase in the incidence of clinically significant thyroid malignancies.

Familial Risks and Proportions Describing Population Landscape of Familial Cancer

Simple SummaryFamilial cancer can be defined through the occurrence of the same cancer in two or more family members. Hereditary cancer is a narrower definition of high-risk familial aggregation through identified predisposing genes. The absence of correlation between spouses for risk of most cancers, particularly those not related to tobacco smoking or solar exposure, suggests that familial cancers are mainly due to genetic causes. The aim of the present study was to define the frequency and increased risk for familial cancer. Data on 31 of the most common cancers were obtained from the Swedish Family-Cancer Database and familial relative risks (SIRs) were estimated between persons with or without family history of the same cancer in first-degree relatives. Practically all cancers showed a familial risk, with an SIR most commonly around two, or a doubling of the risk because of family history.Background: Familial cancer can be defined through the occurrence of the same cancer in two or more family members. We describe a nationwide landscape of familial cancer, including its frequency and the risk that it conveys, by using the largest family database in the world with complete family structures and medically confirmed cancers. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for concordant cancer among first-degree relatives using the Swedish Cancer Registry from years 1958 through 2016. Results: Cancer risks in a 20–84 year old population conferred by affected parents or siblings were about two-fold compared to the risk for individuals with unaffected relatives. For small intestinal, testicular, thyroid and bone cancers and Hodgkin disease, risks were higher, five-to-eight-fold. Novel familial associations included adult bone, lip, pharyngeal, and connective tissue cancers. Familial cancers were found in 13.2% of families with cancer; for prostate cancer, the proportion was 26.4%. High-risk families accounted for 6.6% of all cancer families. Discussion/Conclusion: High-risk family history should be exceedingly considered for management, including targeted genetic testing. For the major proportion of familial clustering, where genetic testing may not be feasible, medical and behavioral intervention should be indicated for the patient and their family members, including screening recommendations and avoidance of carcinogenic exposure.

Center-Level Procedure Volume Does Not Predict Failure-to-Rescue After Severe Complications of Oncologic Colon and Rectal Surgery

BackgroundThe relationship between hospital surgical volume and outcome after colorectal cancer surgery has thoroughly been studied. However, few studies have assessed hospital surgical volume and failure-to-rescue (FTR) after colon and rectal cancer surgery. The aim of the current study is to evaluate FTR following colorectal cancer surgery between clinics based on procedure volume.MethodsPatients undergoing colorectal cancer surgery in Sweden from January 2015 to January 2020 were recruited through the Swedish Colorectal Cancer Registry. The primary endpoint was FTR, defined as the proportion of patients with 30-day mortality after severe postoperative complications in colorectal cancer surgery. Severe postoperative complications were defined as Clavien–Dindo ≥ 3. FTR incidence rate ratios (IRR) were calculated comparing center volume stratified in low-volume (≤ 200 cases/year) and high-volume centers (> 200 cases/year), as well as with an alternative stratification comparing low-volume (< 50 cases/year), medium-volume (50–150 cases/year) and high-volume centers (> 150 cases/year).ResultsA total of 23,351 patients were included in this study, of whom 2964 suffered severe postoperative complication(s). Adjusted IRR showed no significant differences between high- and low-volume centers with an IRR of 0.97 (0.75–1.26, p = 0.844) in high-volume centers in the first stratification and an IRR of 2.06 (0.80–5.31, p = 0.134) for high-volume centers and 2.15 (0.83–5.56, p = 0.116) for medium-volume centers in the second stratification.ConclusionThis nationwide retrospectively analyzed cohort study fails to demonstrate a significant association between hospital surgical volume and FTR after colorectal cancer surgery. Future studies should explore alternative characteristics and their correlation with FTR to identify possible interventions for the improvement of quality of care after colorectal cancer surgery.

Statin Use and Long-Term Mortality after Rectal Cancer Surgery.

Simple SummaryA diagnosis of locally advanced rectal cancer and succeeding surgery remains an area of high postoperative risk for adverse outcomes. The current investigation aims to clarify uncertainty regarding the impact of ongoing statin therapy on postoperative long-term mortality rates after curative surgical resections of rectal cancer by examining data from a large validated national register. It is the first to date to investigate the impact of statin therapy on long-term mortality following curative rectal cancer surgery. Having an ongoing statin prescription was associated with a lower risk of mortality up to five years after surgery. The results should be confirmed in future large, randomized clinical trials.Background: The current study aimed to assess the association between regular statin therapy and postoperative long-term all-cause and cancer-specific mortality following curative surgery for rectal cancer. The hypothesis was that statin exposure would be associated with better survival. Methods: Patients with stage I–III rectal cancer undergoing surgical resection with curative intent were extracted from the nationwide, prospectively collected, Swedish Colorectal Cancer Register (SCRCR) for the period from January 2007 and October 2016. Patients were defined as having ongoing statin therapy if they had filled a statin prescription within 12 months before and after surgery. Cox proportional hazards models were employed to investigate the association between statin use and postoperative five-year all-cause and cancer-specific mortality. Results: The cohort consisted of 10,743 patients who underwent a surgical resection with curative intent for rectal cancer. Twenty-six percent (n = 2797) were classified as having ongoing statin therapy. Statin users had a considerably decreased risk of all-cause (adjusted hazard ratio (HR) 0.66, 95% confidence interval (CI): 0.60–0.73, p < 0.001) and cancer-specific (adjusted HR 0.60, 95% CI: 0.47–0.75, p < 0.001) mortality up to five years following surgery. Conclusions: Statin use was associated with a lower risk of both all-cause and rectal cancer-specific mortality following curative surgical resections for rectal cancer. The findings should be confirmed in future prospective clinical trials.

Family History of Head and Neck Cancers.

Simple SummaryHead and neck cancers are cancers that arise between the mouth and larynx. Risk factors for these include smoking, alcohol, human papilloma virus (HPV) infection and family history. Because families can be identified for the whole Swedish population, we wanted to analyzed familial risks for HNC with same and different cancers among first-degree relatives. When a parent or sibling was diagnosed with HNC, other family members had a two-fold risk of being diagnosed with HNC, but the risk was higher when specific types of HNC, such as oral or nasopharyngeal cancers, were analyzed. Husbands of wives with cervical cancer had an increased risk of oropharyngeal cancer which may be related to shared HPV infection. In the Swedish population with low smoking levels, HPV is becoming a dominant risk factor, emphasizing the need for sexual hygiene and HPV vaccination.Background: Head and neck cancers (HNCs) encompass a heterogeneous group of cancers between the mouth and larynx. Familial clustering in HNCs has been described, but how it influences individual sites and to which extent known risk factors, such as human papilloma virus (HPV) infection, may contribute is not well established. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for HNC with same (concordant) and different (discordant) cancers among first-degree relatives using data from the Swedish Cancer Registry from 1958 to 2018. Results: Incidence for male and female oropharyngeal cancer increased close to four-fold in the past 39 years. Familial HNC was found in 3.4% of the study population, with an overall familial SIR of 1.78. Patients with concordant nasopharyngeal cancer showed a high risk of 23.97, followed by hypopharyngeal cancer (5.43). The husbands of wives with cervical cancer had an increased risk of oropharyngeal cancer. Discussion/Conclusion: Nasopharyngeal cancers lacked associations with lifestyle or HPV associated cancers, suggesting a role for germline genetics, which was also true for the high-risk families of three HNC patients. In the Swedish population with low smoking levels, HPV is becoming a dominant risk factor, emphasizing the need for sexual hygiene and HPV vaccination.

Defunctioning stomas may reduce chances of a stoma-free outcome after anterior resection for rectal cancer.

To investigate the conflicting consequences of faecal diversion on stoma outcomes and anastomotic leakage in anterior resection for rectal cancer, including interaction effects determined by the extent of mesorectal excision. Anterior resections between 2007 and 2016 were identified using the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine stoma outcome 2years after surgery. Tumour distance from the anal verge constituted a proxy for extent of mesorectal excision [total mesorectal excision (TME): ≤10cm; partial mesorectal excision (PME): 13-15cm]. With confounder-adjusted probit regression, the total effect of defunctioning stoma on permanent stoma, and the interaction effect of extent of mesorectal excision, were estimated together with the indirect effect through anastomotic leakage. Baseline risks, risk differences (RDs) and relative risks (RRs) were reported. The main study cohort included 4529 patients. Defunctioning stomas influenced the absolute permanent stoma risk (TME: RD 0.11 [95% CI 0.09-0.13]; PME: RD 0.15 [95% CI 0.13-0.16]). The baseline risk was higher in TME, with a resulting greater RR in PME (2.23 [95% CI 1.43-3.02] vs 4.36 [95% CI 3.05-5.68]). The indirect reduction in permanent stoma rates, due to the alleviating effect of faecal diversion on anastomotic leakage, was small (TME: 0.89 [95% CI 0.81-0.96]; PME: 0.96 [95% CI 0.91-1.00]). In anterior resection for rectal cancer, defunctioning stomas may reduce chances of a stoma-free outcome. Considering leakage reduction benefits, consequences of routine diversion in TME might be fairly balanced, while this seems questionable in PME.

Second Primary Cancers After Liver, Gallbladder and Bile Duct Cancers, and These Cancers as Second Primary Cancers.

BackgroundSecond primary cancers (SPCs) are important clinically as they may negatively influence patient survival and they may tell about therapeutic side effects and general causes of cancer. Population-based literature concerning SPCs after hepatobiliary cancers is limited and here we assess risks of SPCs after hepatocellular cancer (HCC), and cancers of the gallbladder, bile ducts and ampulla of Vater. In reverse order, we consider the risk of hepatobiliary cancers as SPCs after any cancer.MethodsWe used standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancers associated with hepatobiliary cancers. Cancer diagnoses were obtained from the Swedish Cancer Registry from years 1990 through 2015.ResultsWe identified 9997 primary HCCs, 1365 gallbladder cancers and 4721 bile duct cancers. After HCC, risks of four SPCs were increased: gallbladder (SIR = 4.38; 95% confidence interval 1.87–8.67), thyroid (4.13; 1.30–9.70), kidney (2.92; 1.66–4.47) and squamous cell skin (1.55; 1.02–2.26) cancers. In reverse order, HCC as SPC, in addition to the above cancers, associations included upper aerodigestive tract, esophageal, small intestinal and bladder cancers and non-Hodgkin lymphoma. For gallbladder and bile duct cancers, associations were found with small intestinal and pancreatic cancers.ConclusionThe results suggested that HCC is associated with two types of SPC, one related to shared environmental risk factors, such as alcohol, exemplified by upper aerodigestive tract and esophageal cancer, and the other related to immune dysfunction, exemplified by squamous cell skin cancer. SPCs associated with gallbladder and bile duct cancers suggest predisposition to mutations in the mismatch repair gene MLH1.

Statin use and survival in 16 098 patients with non-Hodgkin lymphoma or chronic lymphocytic leukaemia treated in the rituximab era.

Statin use has been associated with reduced mortality from several cancers but also suggested, invitro, to diminish the effectiveness of lymphoma treatments including rituximab. The present study aimed to assess the association of statin use with mortality in patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). We identified all incident NHLs and CLLs in Sweden from 2007 to 2013 with subtype information in the Swedish Lymphoma and Cancer Registers. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pre- or post-diagnosis statin use (yes/no, intensity) with lymphoma-specific, cardiovascular, or all-cause mortality; and for follicular lymphoma (FL) by initial treatment strategy (active/watch-and-wait). Among 16 098 incident NHL/CLL patients, 20% used statins at diagnosis. Pre- and post-diagnosis statin use, and statin intensity were not consistently associated with any mortality outcome in patients with NHL, overall or for any subtype. For actively treated patients with FL, statin use did not appear to increase lymphoma-specific mortality (vs. non-users, HR [95% CI]after diagnosis 0·87 [0·45-1·67]). For CLL, statin use was associated with all-cause and cardiovascular but not consistently with lymphoma-specific mortality. In conclusion, statin use was not associated with improved lymphoma survival but appears safe to use during lymphoma treatment.

Short- and longer-term cancer risks with biologic and targeted synthetic disease-modifying antirheumatic drugs as used against rheumatoid arthritis in clinical practice.

ObjectiveTo estimate the occurrence and relative risks of first-ever-incident non-cutaneous cancer overall and for 16 sites in patients with RA treated with biologic and targeted synthetic DMARDs (b/tsDMARDs), by time since treatment start, attained age, and duration of active treatment.MethodsThis is an observational nationwide and population-based cohort study of patients with RA (n = 69 308), treated with TNF inhibitors (TNFi; adalimumab, certolizumab, etanercept, golimumab, infliximab) or other b/tsDMARDs (abatacept, rituximab, baricitinib, tofacitinib and tocilizumab) compared with RA patients not treated with b/tsDMARDs, and matched general population referents (n = 109 532), 2001–2018. The study was based on prospectively collected data from the Swedish Rheumatology Quality Register and from other registers, linked to the national Swedish Cancer Register. Incidence rates and hazard ratios were estimated via Cox regression adjusted for co-morbidities and other health characteristics.ResultsBased on 8633 incident cancers among RA patients, the overall relative risk of cancer with TNFi [hazard ratio (HR) = 1.0] was neither increased nor did it change with time since treatment start, duration of active treatment, or attained age, when compared with b/tsDMARD-naïve RA. For other b/tsDMARDs, we noted no consistent signal of increased overall risks (HRs ranged from 1.0 to 1.2), but there were statistically significant estimates above 1 for abatacept with 2–5 years of active treatment, for older age groups, and between several of the bDMARDs and urinary tract cancer.ConclusionTNFis, as used long term in clinical practice against RA, are not linked to increased risks for cancer overall. For other b/tsDMARDs, and for site-specific risks, our results are generally reassuring but contain signals that call for replication.

Younger age at onset of colorectal cancer is associated with increased patient’s delay

AimThis study aimed to investigate if younger age at diagnosis of colorectal cancer was associated with a diagnostic delay. The secondary objective was to evaluate if symptomatology varied with age. MethodThe study population consisted of the cohorts from two prospective multicentre studies conducted in Sweden and Denmark, the QoLiRECT and QoLiCOL studies. These studies investigated the quality of life in patients with colorectal cancer. Participants responded to the validated questionnaires used to extract information on patient’s and doctor’s delay as well as first presenting symptoms. Clinical variables were retrieved from the Swedish Colorectal Cancer Registry and the Danish Colorectal Cancer Group Database. Results2574 patients were included, 1085 from QoLiRECT and 1489 from QoLiCOL. The probability of an increased patient’s delay was higher when age decreased by 10 years (the SD in both QoLiRECT and QoLiCOL), adjusted OR 1.19 (95%CI: 1.10; 1.30), p < 0.001. A similar effect was found for doctor’s delay, but the age effect was smaller in this case, adjusted OR 1.05 (95%CI: 0.97; 1.15), p = 0.177. When the age effect was analysed non-linearly, an increased probability of a delay was seen for patients from around 60 years and below. Younger patients were equally or more likely to report the symptoms of blood in stool, diarrhoea, constipation, mucus in faeces, faecal urgency, faecal emptying difficulties and pain compared to older patients. ConclusionYounger patients were more likely to have an increased patient’s delay, probably contributing to a delayed diagnosis of colorectal cancer. Symptomatology at diagnosis was similar irrespective of age.

Early postoperative pain as a marker of anastomotic leakage in colorectal cancer surgery

PurposeEven though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient’s early postoperative pain is an independent marker of anastomotic leakage.MethodsBy combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014–2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data.ResultsIn total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4–10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21–2.38), as well as reoperation (OR 2.17, 95% CI 1.41–3.32). Severe pain (NRS 8–10) was more strongly related to leakage (OR 2.38, 95% CI 1.44–3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome.ConclusionIn this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.

Cohort Selection In Utero against Male Twins and Childhood Cancers: A Population-Based Register Study.

Cancer ranks as the second leading cause of death among children ages 1 to 14 years in the United States. Previous research finds that strong cohort selection in utero against males precedes a reduction in live-born males considered frail. We examine whether such cohort selection in utero may similarly affect the frequency of childhood cancers among male live births. We examined 1,368 childhood cancers among males born in Sweden over 144 months, from January 1990 to December 2001, and followed to age 15 in the Swedish Cancer Registry. We retrieved the count of male twins by birth month from the Swedish Birth Registry. We applied autoregressive, integrated, moving average time-series methods to identify and control for temporal patterns in monthly childhood cancers and to evaluate robustness of results. Fewer childhood cancers occur among monthly male birth cohorts with elevated selection in utero (i.e., a low count of live-born male twins). This association appears in the concurrent month (coef = 0.04; 95% CI, 0.001-0.079) as well as in the following month in which most births from the twin's conception cohort are "scheduled" to be born (coef = 0.055; 95% CI, 0.017-0.094). Elevated cohort selection in utero may reduce the number of frail male gestations that would otherwise have survived to birth and received a cancer diagnosis during childhood. This novel result warrants further investigation of prenatal exposures, including those at the population level, that may induce cohort selection in utero for some cancer types but not others.

Accurate population-based model for individual prediction of colon cancer recurrence

Background Prediction models are useful tools in the clinical management of colon cancer patients, particularly when estimating the recurrence rate and, thus, the need for adjuvant treatment. However, the most used models (MSKCC, ACCENT) are based on several decades-old patient series from clinical trials, likely overestimating the current risk of recurrence, especially in low-risk groups, as outcomes have improved over time. The aim was to develop and validate an updated model for the prediction of recurrence within 5 years after surgery using routinely collected clinicopathologic variables. Material and methods A population-based cohort from the Swedish Colorectal Cancer Registry of 16,134 stage I–III colon cancer cases was used. A multivariable model was constructed using Cox proportional hazards regression. Three-quarters of the cases were used for model development and one quarter for internal validation. External validation was performed using 12,769 stage II–III patients from the Norwegian Colorectal Cancer Registry. The model was compared to previous nomograms. Results The nomogram consisted of eight variables: sex, sidedness, pT-substages, number of positive and found lymph nodes, emergency surgery, lymphovascular and perineural invasion. The area under the curve (AUC) was 0.78 in the model, 0.76 in internal validation, and 0.70 in external validation. The model calibrated well, especially in low-risk patients, and performed better than existing nomograms in the Swedish registry data. The new nomogram’s AUC was equal to that of the MSKCC but the calibration was better. Conclusion The nomogram based on recently operated patients from a population registry predicts recurrence risk more accurately than previous nomograms. It performs best in the low-risk groups where the risk-benefit ratio of adjuvant treatment is debatable and the need for an accurate prediction model is the largest.