Characterization of ovarian cancer survival by histotype and stage: A nationwide study in Norway.

Contemporary population-based data on ovarian cancer survival using current subtype classifications and by surgical status are sparse. We evaluated 1-, 3-, 5- and 7-year relative (and overall) survival, and excess hazards in patients with borderline tumors or invasive epithelial ovarian cancer diagnosed 2012 to 2021 in a nationwide registry-based cohort in Norway. Outcomes were evaluated by histotype, FIGO stage, cytoreduction surgery and residual disease. Overall survival was evaluated for non-epithelial ovarian cancer. Survival of women with borderline ovarian tumors was excellent (≥98.0% 7-year relative survival). Across all evaluated invasive epithelial ovarian cancer histotypes, 7-year relative survival for cases diagnosed with stages I or II disease was ≥78.3% (stage II high-grade serous). Survival for ovarian cancers diagnosed at stage ≥III differed substantially by histotype and time since diagnosis (eg, stage III, 5-year relative survival from 27.7% [carcinosarcomas] to 76.2% [endometrioid]). Overall survival for non-epithelial cases was good (91.8% 5-year overall survival). Women diagnosed with stage III or IV invasive epithelial ovarian cancer and with residual disease following cytoreduction surgery had substantially better survival than women not operated. These findings were robust to restriction to women with high reported functional status scores. Patterns for overall survival were similar to those for relative survival. We observed relatively good survival with early stage at diagnosis even for the high grade serous histotype. Survival for patients diagnosed at stage ≥III invasive epithelial ovarian cancer was poor for all but endometrioid disease. There remains an urgent need for strategies for risk reduction and earlier detection, together with effective targeted treatments.

Early referral to a palliative team improves end-of-life care among gynecological cancer patients: a retrospective, population-based study.

OBJECTIVE: To assess end-of-life care among patients with gynecological cancer, and to describe the association between timing of palliative care referral and patterns of care. METHODS: All women with residence in Oslo, Norway, who died of gynecological cancer between January 1, 2015 and December 30, 2017 (36 months), were identified. Patients were primarily treated at the Norwegian Radium Hospital and clinical data on end-of-life care were retrospectively extracted from the medical records. RESULTS: We identified 163 patients with median age 70.1 years at death (range 26-100) with the following diagnoses: ovarian (n=100), uterine (n=40), cervical (n=21), and vulvar cancer (n=2). 53 (33%) of patients died in a palliative care unit, 34 patients (21%) died in nursing homes without palliative care, and 48 (29%) patients died in hospital. Only 15 (9%) patients died at home. 25 (15%) patients received chemotherapy in the last 30 days before death, especially ovarian cancer patients (n=21, 21%). 103 patients (61%) were referred to a palliative team prior to death. Referral to a palliative team was associated with a significantly reduced risk of intensive care unit admission (OR 0.11, 95% CI 0.02 to 0.62) and higher likelihood of a structured end-of-life discussion (OR 2.91, 95% CI 1.03 to 8.25). Palliative care referral also seemed to be associated with other quality indicators of end-of-life care (less chemotherapy use, more home deaths). CONCLUSIONS: End-of-life care in patients with gynecological cancer suffers from underuse of palliative care. Chemotherapy is still commonly used towards end-of-life. Early palliative care referral in the disease trajectory may be an important step towards improved end-of-life care.

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.

Survival after secondary cytoreductive surgery and chemotherapy compared with chemotherapy alone for first recurrence in patients with platinum-sensitive epithelial ovarian cancer and no residuals after primary treatment. A registry-based study.

INTRODUCTION: The aim of this study was to investigate whether secondary cytoreductive surgery and platinum-based chemotherapy improved survival among patients with recurrent, platinum-sensitive epithelial ovarian cancer compared with those who received platinum-based chemotherapy alone, and to identify possible predictors for selection to secondary cytoreductive surgery. MATERIAL AND METHODS: We included 397 patients who had a primary diagnosis of FIGO stage I-IV epithelial ovarian cancer recorded in the Cancer Registry of Norway between 1 January 2002 and 31 December 2012, received primary surgery with no residuals followed by platinum-based chemotherapy, had first recurrence six or more months after completion of primary platinum-based chemotherapy, and received secondary treatment with either secondary cytoreductive surgery and platinum-based chemotherapy (secondary cytoreductive surgery+platinum-based chemotherapy group) or platinum-based chemotherapy alone (platinum-based chemotherapy group). Outcomes were progression-free survival to second recurrence or death and overall survival. Hazard ratios were estimated using multivariable Cox regression. RESULTS: There were 75 patients in the secondary cytoreductive surgery+platinum-based chemotherapy group in whom complete resection was achieved for 60 (80%), and 322 patients in the platinum-based chemotherapy group. Both progression-free survival (hazard ratio 0.45, 95% confidence interval 0.32-0.62) and overall survival (hazard ratio 0.50, 95% confidence interval 0.32-0.70) were improved in the secondary cytoreductive surgery+platinum-based chemotherapy compared with the platinum-based chemotherapy group. A survival benefit was only seen in patients with no residuals at secondary cytoreductive surgery. CONCLUSIONS: In selected epithelial ovarian cancer patients with no residuals after primary surgery and a recurrent, platinum-sensitive tumor, the complete resection of recurrent tumor at secondary cytoreductive surgery improves progression-free survival and overall survival. Our results suggest that a long treatment-free interval and non-disseminated lesions (three or fewer lesions) on radiological images could be useful predictors for complete resection at secondary cytoreductive surgery.

Physical dormancy in seeds: a game of hide and seek?

Historically, 'physical dormancy', or 'hard seededness', where seeds are prevented from germinating by a water-impermeable seed coat, is viewed as a dormancy mechanism. However, upon water uptake, resumption of metabolism leads to the unavoidable release of volatile by-products, olfactory cues that are perceived by seed predators. Here, we examine the hypothesis that hard seeds are an anti-predator trait that evolved in response to powerful selection by small mammal seed predators. Seeds of two legume species with dimorphic seeds ('hard' and 'soft'), Robinia pseudoacacia and Vicia sativa, were offered to desert hamsters (Phodopus roborovskii) in a series of seed removal studies examining the differences in seed harvest between hard and soft seeds. Volatile compounds emitted by dry and imbibed soft seeds were identified by headspace gas chromatography-mass spectrometry (GC-MS). Fourteen main volatile compounds were identified, and hamsters readily detected both buried imbibed seeds and an artificial 'volatile cocktail' that mimicked the scent of imbibed seeds, but could not detect buried hard or dry soft seeds. We argue that physical dormancy has evolved to hide seeds from mammalian predators. This hypothesis also helps to explain some otherwise puzzling features of hard seeds and has implications for seed dispersal.

High risk for ovarian cancer in a prospective series is restricted to BRCA1/2 mutation carriers.

PURPOSE: Inherited ovarian cancer carries a serious prognosis. Prophylactic oophorectomy has been advocated. The degree to which inherited ovarian cancer is restricted to BRCA mutation carriers is not fully known. We wanted to determine the prevalence of BRCA mutation carriers in women at high risk from ovarian cancer. EXPERIMENTAL DESIGN: Healthy women who were found to be at increased risk judged by family history were followed prospectively. Full BRCA1/2 mutation analysis was conducted on all patients who contracted pelvic cancer. RESULTS: We identified 1,582 women at risk during 5,674 person-years. Forty infiltrating epithelial ovarian cancers, six peritoneal cancers, and one fallopian tube cancer were diagnosed. All but one of these patients (98%) had a BRCA mutation, a frequency that was significantly higher than for the 3 patients with borderline ovarian cancers, who were all mutation negative (P = 0.0002). Eighty-two percent of the detected mutations belonged to one of the 10 Norwegian founder mutations previously reported. At prophylactic bilateral salpingo-oophorectomy, cancer was found in 18 of 345 (5.2%) of mutation carriers compared with none in the 446 mutation negative (P = 0.0000). CONCLUSIONS: In healthy women with a family history of ovarian cancer, high risk for ovarian cancer was restricted to BRCA1/2 mutation carriers. A woman at risk for ovarian cancer according to her family history should have access to full BRCA1/2 mutation testing before deciding on prophylactic bilateral salpingo-oophorectomy.

Conditions favouring hard seededness as a dispersal and predator escape strategy.

SUMMERY: The water-impermeable seed coat of 'hard' seeds is commonly considered a dormancy trait. Seed smell is, however, strongly correlated with seed water content, and hard seeds are therefore olfactionally cryptic to foraging rodents. This is the rationale for the crypsis hypothesis, which proposes that the primary functions of hard seeds are to reduce seed predation and promote rodent seed dispersal. We use a mechanistic model to describe seed survival success of plants with different dimorphic soft and hard seed strategies. The model is based on established empirical-ecological relationships of moisture requirements for germination and benefits of seed dispersal, and on experimentally demonstrated relationships between seed volatile emission, predation and predator escape. We find that water-impermeable seed coats can reduce seed predation under a wide range of natural humidity conditions. Plants with rodent dispersed seeds benefit from producing dimorphic soft and hard seeds at ratios where the anti-predator advantages of hard seeds are balanced by the dispersal benefits gained by producing some soft seeds. The seed pathway predicted from the model is similar to those of experimental seed-tracking studies. This validates the relevance and realism of the ecological mechanisms and relationships incorporated in the model. Synthesis. Rodent seed predators are often also important seed dispersers and have the potential to exert strong selective pressures on seeds to evolve methods of avoiding detection, and hard seeds seem to do just that. This work suggests that water-impermeable hard seeds may evolve in the absence of a dormancy function and that optimal seed survival in many environments with rodent seed predators is obtained by plants having a dimorphic soft and hard seed strategy.

Influence of interval between primary surgery and chemotherapy on short-term survival of patients with advanced ovarian, tubal or peritoneal cancer.

OBJECTIVE: To investigate the impact on short-term survival of time between surgery and start of first chemotherapy cycle in patients with advanced ovarian cancer. METHODS: This prospective, population-based study comprised 371 patients with epithelial ovarian, tubal or peritoneal cancer diagnosed in 2002-2003. All patients underwent primary surgery, followed at different intervals by chemotherapy. The data were derived from notifications to the Norwegian Cancer Registry and included medical, surgical and histopathological records. Kaplan-Meier plots were used to show differences in survival, and Cox regression analysis was used to show the effect of prognostic factors on survival, expressed as hazard ratios (HRs). RESULTS: No difference in survival between patient groups was seen when time between surgery and start of chemotherapy was divided into quartiles. The group of patients with no residual disease and an interval between surgery and start of chemotherapy equal to or more than 6 weeks had non-significantly worse survival (unadjusted HR = 1.86; adjusted HR = 1.35) than those with an interval of less than 6 weeks. Patients with residual disease after surgery and chemotherapy at an interval of less than 6 weeks had worse short-term survival than patients without residual disease and the same interval before chemotherapy: unadjusted HR = 3.66 (95% CI, 2.09-6.40) and adjusted HR = 2.36 (95% CI, 1.22-4.57). CONCLUSIONS: The interval between surgery and start of chemotherapy had no major impact on short-term survival after ovarian cancer. Patients might be included in chemotherapy trials when interval between surgery and start of chemotherapy is more than 6 weeks. Any further investigation of a possible effect of interval between surgery and start of chemotherapy should be performed as a randomized trial.

Research note: Avian gut passage reduces seed exit costs in Sorbus aucuparia (Rosaceae) as measured by a diametral compression test.

Reduced seed exit costs have been suggested to explain advanced seedling emergence and increased seedling growth in Sorbus aucuparia L. (Rosaceae; rowan) following Turdus spp. (Turdidae; thrush) gut passage. In the present study, seed coat tension strength of Turdus merula L. (Turdidae; blackbird) gut-passed and non-ingested control seeds were tested with a diametral compression test. Both maximum load (N) and work (mJ) required for opening the seeds were reduced in gut-passed seeds, although scanning electron microscopy showed no visible differences in seed coat surface structure between treatments. In addition, gut passage increased dry seed weight by 0.64 mg (22%), weight of hydrated seeds by 0.62 mg (16%) and width of hydrated seeds by 0.1 mm (9%). Absorption causing the seed coat to yield more easily to the germinating seedling is proposed as an explanation for the reduction in seed exit costs. For the emerging seedling, the time and force needed to open the seed coat was reduced, thus lowering dispersal and germination costs of S. aucuparia.

Corrigendum to: Avian gut passage reduces seed exit costs in Sorbus aucuparia (Rosaceae) as measured by a diametral compression test.

Reduced seed exit costs have been suggested to explain advanced seedling emergence and increased seedling growth in Sorbus aucuparia L. (Rosaceae; rowan) following Turdus spp. (Turdidae; thrush) gut passage. In the present study, seed coat tension strength of Turdus merula L. (Turdidae; blackbird) gut-passed and non-ingested control seeds were tested with a diametral compression test. Both maximum load (N) and work (mJ) required for opening the seeds were reduced in gut-passed seeds, although scanning electron microscopy showed no visible differences in seed coat surface structure between treatments. In addition, gut passage increased dry seed weight by 0.64mg (22%), weight of hydrated seeds by 0.62mg (16%) and width of hydrated seeds by 0.1mm (9%). Absorption causing the seed coat to yield more easily to the germinating seedling is proposed as an explanation for the reduction in seed exit costs. For the emerging seedling, the time and force needed to open the seed coat was reduced, thus lowering dispersal and germination costs of S. aucuparia.