Days alive and out of hospital after surgical treatment of epithelial ovarian cancer: A Danish nationwide cohort study.

OBJECTIVE: Days alive and out of hospital (DAOH) is a validated outcome measure in perioperative trials integrating information on primary hospitalization, readmissions, and mortality. It is negatively associated with advanced age. However, DAOH has not been described for surgical treatment of epithelial ovarian cancer (EOC), primarily diagnosed in older patients. METHODS: We conducted a Danish nationwide cohort study including patients undergoing debulking surgery for EOC from 2013 to 2018. DAOH was explored for 30 (DAOH30), 90 (DAOH90), and 180 (DAOH180) postoperative days in younger (<70 years) and older (≥70 years) patients with advanced-stage disease stratified by surgical modality (primary (PDS) or interval debulking surgery (IDS)). We examined the associations between patient- and surgical outcomes and low or high DAOH30. RESULTS: Overall, 1168 patients had stage IIIC-IV disease and underwent debulking surgery. DAOH30 was 22 days [interquartile range (IQR): 18, 25] and 23 days [IQR: 18, 25] for younger and older patients treated with PDS, respectively. For IDS, DAOH30 was 25 days [IQR: 22, 26] for younger and 25 days[IQR: 21, 26] for older patients. We found no significant differences between age cohorts regarding DAOH30, DAOH90, and DAOH180. Low DAOH30 was associated with poor performance status, PDS, extensive surgery, and long duration of surgery in adjusted analysis. CONCLUSIONS: DAOH did not differ significantly between age cohorts. Surgical rather than patient-related factors were associated with low DAOH30. Our results likely reflect a high selection of fit older patients for surgery, reducing the patient-related differences between younger and older patients receiving surgical treatment.

Secondary validation of an ovarian cancer-specific comorbidity index in a US population.

OBJECTIVES: The Ovarian Cancer Comorbidity Index (OCCI) is an age-specific index developed and previously found to be more predictive of overall and cancer-specific survival than the Charlson Comorbidity Index (CCI). The objective was to perform secondary validation of the OCCI in a US population. METHODS: A cohort of ovarian cancer patients undergoing primary or interval cytoreductive surgery from January 2005 to January 2012 was identified in SEER-Medicare. OCCI scores were calculated with the regression coefficients determined from the original developmental cohort for five comorbidities. Cox regression analyses were used to calculate associations between the OCCI risk groups and 5-year overall survival and 5-year cancer-specific survival in comparison to the CCI. RESULTS: A total of 5052 patients were included. Median age was 74 (range 66-82) years. 47% (n=2375) had stage III and 24% (n=1197) had stage IV disease at diagnosis. 67% had a serous histology subtype (n=3403). All patients were categorized as moderate (48.4%) or high risk (51.6%). The prevalence of the five predictive comorbidities were: coronary artery disease 3.7%, hypertension 67.5%, chronic obstructive pulmonary disease 16.7%, diabetes 21.8%, and dementia 1.2%. Controlling for histology, grade, and age-stratification, worse overall survival was associated with both a higher OCCI (hazard ratio (HR) 1.57; 95% confidence interval (CI) 1.46 to 1.69) and CCI (HR 1.96; 95% CI 1.66 to 2.32). Cancer-specific survival was associated with the OCCI (HR 1.33; 95% CI 1.22 to 1.44) but was not associated with the CCI (HR 1.15; 95% CI 0.93 to 1.43). CONCLUSIONS: This internationally developed comorbidity score for ovarian cancer patients is predictive for both overall and cancer-specific survival in a US population. CCI was not predictive for cancer-specific survival. This score may have research applications when utilizing large administrative datasets.

Impact of surgery and chemotherapy timing on outcomes in older versus younger epithelial ovarian cancer patients: A nationwide Danish cohort study.

INTRODUCTION: To explore differences in surgical complexity, chemotherapy administration, and treatment delays between younger and older Danish patients with epithelial ovarian cancer (EOC). MATERIALS AND METHODS: We included a nationwide cohort diagnosed with EOC from 2013 to 2018. We described surgical complexity and outcomes, the extent of chemotherapy and treatment delays stratified by age (<70 and ≥ 70 years), and surgical modality (primary, interval, or no debulking surgery). RESULTS: In total, we included 2946 patients. For patients with advanced-stage disease, 52% of the older patients versus 25% of the younger patients did not undergo primary debulking surgery (PDS) or interval debulking surgery (IDS). For patients undergoing PDS or IDS, older patients underwent less extensive surgery and more often had residual disease after surgery >0 cm compared to younger patients. Furthermore, older patients were less often treated with chemotherapy. Older patients had PDS later than younger. We did not find any differences between age groups concerning treatment delays. Two-year cancer-specific survival differed significantly between age groups regardless of curatively intended treatment. DISCUSSION: This study demonstrates that older patients are treated less actively concerning surgical and oncological treatment than younger patients, leading to worse cancer-specific survival. Older patients do not experience more treatment delays than younger ones.

Incidence, treatment, and survival trends in older versus younger women with epithelial ovarian cancer from 2005 to 2018: A nationwide Danish study.

OBJECTIVE: To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. METHODS: We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (<70 and ≥ 70 years), stage, and period (2005-09, 2010-13, 2014-18). RESULTS: We included 7522 patients. The incidence decreased from 16.3 (2005) to 11.4 (2018) per 100,000 woman-years, driven by the younger cohort. While the proportion of patients with stage IIIC-IV disease undergoing primary debulking surgery (PDS) decreased, the proportion of patients having interval debulking surgery (IDS) and no debulking surgery increased significantly. In 2014-18, 36% and 24% had PDS for younger and older patients, respectively, compared to 72% and 62% in 2005-09. In both age cohorts, the proportion of patients debulked to no residual disease increased significantly among patients with stage IIIC-IV and in the total cohort. Two-year cancer-specific survival increased from 75% (2005-09) to 84% (2014-18) for younger patients and from 53% to 66% for older patients. After adjusting for potential confounders, age ≥ 70 was associated with a 1.4-fold increased risk of cancer-specific death (95% confidence interval: 1.2,1.5). CONCLUSIONS: The proportion of patients with advanced EOC not undergoing PDS or IDS increased significantly. During the same period, patients debulked to no residual disease, and cancer-specific survival increased. However, a survival gap in favor of the younger patients remains after adjusting for potential confounders.

Risk factors for early death among ovarian cancer patients: a nationwide cohort study.

OBJECTIVE: To characterize ovarian cancer patients who die within 6 months of diagnosis and to identify prognostic factors for these early deaths. METHODS: A nationwide cohort study covering ovarian cancer in Denmark in 2005-2016. Tumor and patient characteristics including comorbidity and socioeconomic factors were obtained from the comprehensive Danish national registers. RESULTS: A total of 5,570 patients were included in the study. Three months after ovarian cancer diagnosis 456 (8.2%) had died and 664 (11.9%) died within 6 months of diagnosis. Adjusted for age and comorbidity, patients who died early were admitted to hospital significantly more often in a 6-month period before the diagnosis (odds ratio [OR]=1.61 [1.29-2.00], and OR=1.47 [1.21-1.78]), for patients who died within 3 and 6 months respectively). Low educational level (OR=2.11), low income (OR=2.50) and singlehood (OR=1.90) were factors significantly associated with higher risk of early death. The discriminative ability of risk factors in identifying early death was assessed by cross-validated area under the receiver operating characteristic curve (AUC). The AUC was found to be 0.91 (0.88-0.93) and 0.90 (0.87-0.92) for death within 3 and 6 months, respectively. CONCLUSIONS: Despite several admissions to hospital, the ovarian cancer diagnosis is delayed for a subgroup of patients, who end up dying early, probably due to physical deterioration in the ineffective waiting time. Up to 90% of high-risk patients might be identified significantly earlier to improve the prognosis. The admittance of the patients having risk symptoms should include fast track investigation for ovarian cancer.

Confounders other than comorbidity explain survival differences in Danish and Swedish ovarian cancer patients - a comparative cohort study.

OBJECTIVE: Danish ovarian cancer (OC) patients have previously been found to have worse prognosis than Swedish patients, and comorbidity has been suggested as a possible explanation for this survival difference. We aimed to investigate the prognostic impact of comorbidity in surgically treated OC patients in Denmark and Sweden. METHODS: This comparative cohort study was based on data from 3118 surgically treated OC patients diagnosed in 2012-2015. The Swedish subcohort (n = 1472) was identified through the Swedish National Quality Register of Gynecological Surgery, whereas the Danish subcohort (n = 1646) originated from the Danish Gynecological Cancer Database. The clinical databases have high coverage and similar variables included. Comorbidity was classified according to the Ovarian Cancer Comorbidity Index and overall survival was the primary outcome. Data were analyzed using Kaplan Meier and Cox regression analyses. Multiple imputation was used to handle missing data. RESULTS: We found comparable frequencies of the following comorbidities: Hypertension, diabetes and 'Any comorbidity'. Arteriosclerotic cardiac disease and chronic pulmonary disease were more common among Swedish patients. Univariable survival analysis revealed a significant better prognosis for Swedish than for Danish patients (HR 0.84 [95% CI 0.74-0.95], p < .01). In adjusted multivariable analysis, Swedish patients had nonsignificant better prognosis compared to Danish patients (HR 0.91 [95% CI 0.80-1.04], p = .16). Comorbidity was associated with survival (p = .02) but comorbidity did not explain the survival difference between the two countries. CONCLUSIONS: Danish OC patients have a poorer prognosis than patients in Sweden but the difference in survival seems to be explained by other factors than comorbidity.

Type I Versus Type II Endometrial Cancer: Differential Impact of Comorbidity.

OBJECTIVE: Two distinct types of endometrial carcinoma (EC) with different etiology, tumor characteristics, and prognosis are recognized. We investigated if the prognostic impact of comorbidity varies between these 2 types of EC. Furthermore, we studied if the recently developed ovarian cancer comorbidity index (OCCI) is useful for prediction of survival in EC. MATERIALS AND METHODS: This nationwide register-based cohort study was based on data from 6487 EC patients diagnosed in Denmark between 2005 and 2015. Patients were assigned a comorbidity index score according to the Charlson comorbidity index (CCI) and the OCCI. Kaplan-Meier survival statistics and adjusted multivariate Cox regression analyses were used to investigate the differential association between comorbidity and overall survival in types I and II EC. RESULTS: The distribution of comorbidities varied between the 2 EC types. A consistent association between increasing levels of comorbidity and poorer survival was observed for both types. Cox regression analyses revealed a significant interaction between cancer stage and comorbidity indicating that the impact of comorbidity varied with stage. In contrast, the interaction between comorbidity and EC type was not significant. Both the CCI and the OCCI were useful measurements of comorbidity, but the CCI was the strongest predictor in this patient population. CONCLUSIONS: Comorbidity is an important prognostic factor in type I as well as in type II EC although the overall prognosis differs significantly between the 2 types of EC. The prognostic impact of comorbidity varies with stage but not with type of EC.

Ovarian Cancer and Comorbidity: Is Poor Survival Explained by Choice of Primary Treatment or System Delay?

OBJECTIVES: Comorbidity influences survival in ovarian cancer, but the causal relations between prognosis and comorbidity are not well characterized. The aim of this study was to investigate the associations between comorbidity, system delay, the choice of primary treatment, and survival in Danish ovarian cancer patients. METHODS: This population-based study was conducted on data from 5317 ovarian cancer patients registered in the Danish Gynecological Cancer Database. Comorbidity was classified according to the Charlson Comorbidity Index and the Ovarian Cancer Comorbidity Index. Pearson χ test and multivariate logistic regression analyses were used to investigate the association between comorbidity and primary outcome measures: primary treatment ("primary debulking surgery" vs "no primary surgery") and system delay (more vs less than required by the National Cancer Patient Pathways [NCPPs]). Cox regression analyses, including hypothesized mediators stepwise, were used to investigate if the impact of comorbidity on overall survival is mediated by the choice of treatment or system delay. RESULTS: A total of 3945 patients (74.2%) underwent primary debulking surgery, whereas 1160 (21.8%) received neoadjuvant chemotherapy. When adjusting for confounders, comorbidity was not significantly associated to the choice of treatment. Surgically treated patients with moderate/severe comorbidity were more often experiencing system delay longer than required by the NCPP. No association between comorbidity and system delay was observed for patients treated with neoadjuvant chemotherapy. Survival analyses demonstrated that system delay longer than NCPP requirement positively impacts survival (hazard ratio, 0.90 [95% confidence interval, 0.82-0.98]), whereas primary treatment modality has no significant impact on survival. CONCLUSIONS: Patients with moderate/severe comorbidity experience often a longer system delay than patients with no or mild comorbidity. Age, stage, and comorbidity are factors influencing the choice of treatment, with stage being the most important factor and comorbidity of lesser importance. The impact of comorbidity on survival does not seem to be mediated by the choice of treatment or system delay.

Vaginal vault suspension during hysterectomy for benign indications: a prospective register study of agreement on terminology and surgical procedure.

INTRODUCTION AND HYPOTHESIS: Several suspension methods are used to try to prevent pelvic organ prolapse (POP) after hysterectomy. We aimed to evaluate agreement on terminology and surgical procedure of these methods. METHODS: We randomly chose 532 medical records of women with a history of hysterectomy from the Danish Hysterectomy and Hysteroscopy Database (DHHD). Additionally, we video-recorded 36 randomly chosen hysterectomies. The hysterectomies were registered in the DHHD. The material was categorized according to predefined suspension methods. Agreement compared suspension codes in DHHD (gynecologists' registrations) with medical records (gynecologists' descriptions) and with videos (reviewers' categorizations) respectively. Whether the vaginal vault was suspended (pooled suspension) or not (no suspension method + not described) was analyzed, in addition to each suspension method. RESULTS: Regarding medical records, agreement on terminology was good among patients undergoing pooled suspension in cases of hysterectomy via the abdominal and vaginal route (agreement 78.7, 92.3%). Regarding videos, agreement on surgical procedure was good among pooled suspension patients in cases of hysterectomy via the abdominal, laparoscopic, and vaginal routes (agreement 88.9, 97.8, 100%). Agreement on individual suspension methods differed regarding both medical records (agreement 0-90.1%) and videos (agreement 0-100%). CONCLUSIONS: Agreement on terminology and surgical procedure regarding suspension method was good in respect of pooled suspension. However, disagreement was observed when individual suspension methods and operative details were scrutinized. Better consensus of terminology and surgical procedure is warranted to enable further research aimed at preventing POP among women undergoing hysterectomy.

[Acute mackerel-induced sleep in a young researcher].

Sleeping disorders are common and they are associated with substantial psychological and physical strain in those affected. We report a case of sudden onset of deep sleep in a 29-year-old Danish woman just after intake of mackerel in tomato sauce. There were no abnormal findings in the physical examination and no suspicion of underlying neurological disease. We hypothesize that the observed association between mackerel intake and deep sleep is causal and we suggest that more research is conducted in order to establish the potential of mackerel in treatment of sleeping disorders.

Survival of ovarian cancer patients in Denmark: Results from the Danish gynaecological cancer group (DGCG) database, 1995-2012.

BACKGROUND: Ovarian cancer has a high mortality rate, especially in Denmark where mortality rates have been reported higher than in adjacent countries with similar demographics. This study therefore examined recent survival and mortality among Danish ovarian cancer patients over an 18-year study period. METHODS: This nationwide registry-based observational study used data from the Danish Gynecology Cancer Database, Danish Pathology Registry, and Danish National Patient Registry. All patients with ovarian cancer diagnosed between 1995 and 2012 were included in the study. The data sources were linked via the patients' personal identification number and the analyses included data on cancer stage, age, survival, surgery status and comorbidity. The computed outcome measures were age-adjusted mortality rates and age-adjusted overall and relative survival rates for one and five years. RESULTS: We identified 9972 patients diagnosed with ovarian cancer in the period 1995-2012. The absolute one-year mortality rate decreased from 42.8 (CI 40.3-45.6) in 1995-1999 to 28.3 (CI 25.9-30.9) in 2010-2012, and the five-year mortality rate decreased from 28.2 (CI 27.0-29.5) in 1995-1999 to 23.9 (CI 22.9-25.0) in 2005-2009. After stratification by age, comorbidity and cancer stage, the decrease in one-year mortality was most substantial in the 65-74 year old age group 41.1 (CI 38.8-43.5) to 26.5 (CI 24.4-28.7) and for stage III 39.1 (CI 35.1-43.6) to 22.9 (CI 19.9-26.5) and stage IV 91.3 (CI 80.8-103.2) to 41.9 (CI 35.5-49.5). For overall survival, we showed an increase in one-year survival from 68% (CI 66-69%) in 1995-1999 to 76% (CI 74-78%) in 2010-2012 and an increase in five-year survival from 33% (CI 32-35%) in 1995-1999 to 36% (CI 34-38%) in 2005-2009. Relative survival showed similar increases through the period. CONCLUSIONS: Ovarian cancer survival in Denmark has improved substantially from 1995 to 2012, bringing Denmark closer to the standards set by adjacent countries.

A new clinically applicable age-specific comorbidity index for preoperative risk assessment of ovarian cancer patients.

OBJECTIVE: To develop and validate a new feasible comorbidity index based on self-reported information suited for preoperative risk assessment of ovarian cancer patients. METHODS: The study was based on patient self-reported data from ovarian cancer patients registered in the Danish Gynecological Cancer Database between January 1, 2005 and December 31, 2012. The study population was divided into a development cohort (n=2020) and a validation cohort (n=1975). Age-stratified multivariate Cox regression analyses were conducted to identify comorbidities significantly impacting five-year overall survival in the development cohort, and regression coefficients were used to construct a new weighted comorbidity index. The index was applied to the validation cohort, and its predictive ability in regard to overall and cancer-specific five-year-survival was investigated. Finally, the performance of the new index was compared to that of the Charlson Comorbidity Index. RESULTS: Regression coefficients of age and five comorbidities (atherosclerotic cardiac disease, chronic obstructive pulmonary disease, diabetes, dementia and hypertension) were included in the new comorbidity index. The validation study found the new index to be significantly associated to both overall survival (HR 1.44, p=0.013) and cancer-specific survival (HR 1.51, p=0.017) in multivariate analyses adjusted for other prognostic factors. The index was a significantly better predictor than the Charlson Comorbidity Index. CONCLUSION: This new age-specific comorbidity index based on self-reported information is a significant predictor of overall and cancer-specific survival in ovarian cancer. It can be used to quickly identify those ovarian cancer patients requiring special attention in terms of preoperative optimization and postoperative care.

Comorbidity is an independent prognostic factor for the survival of ovarian cancer: a Danish register-based cohort study from a clinical database.

OBJECTIVE: The aim of the study was to examine whether comorbidity is an independent prognostic factor for 3129 women diagnosed with ovarian cancer from 2005 to 2011. As Performance status (PS) might capture the impact of comorbidity we addressed whether comorbidity can be explained by PS or whether comorbidity has an independent impact on survival. METHODS: The Danish Gynecological Cancer Database (DGCD) is a national clinical database including information on comorbidity and a large number of tumor-related and patient-related factors. The Charlson Comorbidity Index was used to measure the patients' comorbidity based on the registration in DGCD. The overall mortality (OS) from the date of surgery to death or censoring was the outcome measure. RESULTS: The hazard ratio (HR) for patients with comorbidity was 3.31 (1.14-1.50) compared to patients without comorbidity after adjustment for age, stage, residual tumor, histology and grade. After including PS in the model, comorbidity remained significant for OS. Age, stage, residual tumor, histology and PS prove to be independent prognostic factors as well. No association is found between comorbidity and receiving surgery or not. CONCLUSION: Comorbidity is an independent prognostic factor, and has a negative impact on the survival of ovarian cancer patients. However, comorbidity has a smaller impact on survival compared with the other prognostic factors considered.