Appraisals of cancer, religious/spiritual coping, and hope in patients with colorectal cancer.

PURPOSE/OBJECTIVES: To examine the extent to which religious/spiritual coping moderates the association between stress appraisals and hope among patients with colorectal cancer. DESIGN/RESEARCH APPROACH: A longitudinal, prospective examination of hope, stress appraisals of cancer, and religious/spiritual coping through self-report questionnaires at baseline, 6-months, and 12-months post-surgery. SAMPLE/PARTICIPANTS: One hundred thirty-nine newly diagnosed patients with colorectal cancer recruited from tertiary medical centers. FINDINGS: Challenge and threat appraisals predicted hope. Only the relationship between hope and challenge appraisals was significantly moderated by coping through religion/spirituality, such that those who were both low on challenge and low in religious/spiritual coping reported the lowest hope. CONCLUSIONS/INTERPRETATION: Hope is predicted by how people appraise their cancer. Hope was lowest among participants who reported both low challenge appraisals and religious/spiritual coping. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Understanding how patients appraise their cancer and use religion/spirituality to cope may help providers understand which patients are at risk for low hope.

Change in cancer-related fatigue over time predicts health-related quality of life in ovarian cancer patients.

OBJECTIVE: There is limited research examining how change in cancer-related fatigue (CRF) over time predicts change in health-related quality of life (HRQOL), and no studies have examined this relationship in ovarian cancer patients, specifically. The purpose of this study was to explore the prevalence and trajectory of CRF over time and examine how change in CRF over time predicts change in HRQOL in ovarian cancer patients. METHODS: Ovarian cancer patients (N = 202) were recruited from Princess Margaret Cancer Centre in Toronto, Canada. Consenting participants completed measures at baseline (beginning of study) and again three months later. Data were analyzed using a longitudinal multilevel mixed model design. RESULTS: Four groups of CRF trajectories emerged. Fifty-four percent reported CRF as always present, 16% reported CRF subsided, 21% reported CRF developed, and 9% reported CRF as never present. As CRF developed, functional and physical wellbeing decreased. As CRF subsided, functional, physical, and emotional wellbeing improved. CRF trajectory was not associated with change in social wellbeing over time. CONCLUSIONS: Our findings suggest CRF negatively impacts all domains of HRQOL except for social wellbeing in ovarian cancer patients. Among patients who reported that CRF improved over time, all HRQOL domains impacted by CRF showed recovery to normal endorsement rates. Among patients who reported development of CRF, impacted HRQOL domains significantly declined over time. Implications from this research indicate that fatigue management should be prioritized during and after cancer treatment to ensure optimal physical, functional, and emotional wellbeing.

Brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed non-serous, non-mucinous ovarian cancers.

OBJECTIVES: While ovarian cancer is the third most common Lynch syndrome-associated cancer in women, there is no established screening strategy to identify Lynch syndrome in this population. The objective of this study was to assess whether the 4-item brief Family History Questionnaire can be used as a screening tool to identify women with ovarian cancer at risk of Lynch syndrome. METHODS: In this prospective cohort study, participants with newly diagnosed non-serous, non-mucinous ovarian cancer completed the brief Family History Questionnaire, extended Family History Questionnaire, and had tumors assessed with immunohistochemistry for mismatch repair proteins, MLH1 methylation, and microsatellite instability testing. All underwent universal germline testing for Lynch syndrome. Performance characteristics were compared between the brief Family History Questionnaire, extended Family History Questionnaire, immunohistochemistry±MLH1 methylation, and microsatellite instability testing. RESULTS: Of 215 participants, 169 (79%) were evaluable with both the brief Family History Questionnaire and germline mutation status; 12 of these 169 were confirmed to have Lynch syndrome (7%). 10 of 12 patients (83%) with Lynch syndrome were correctly identified by the brief Family History Questionnaire, compared with 6 of 11 (55%) by the extended Family History Questionnaire, 11 of 13 (85%) by immunohistochemistry±MLH1 methylation, and 9 of 11 (82%) by microsatellite instability testing. The sensitivity, specificity, positive predictive values, and negative predictive values of the brief Family History Questionnaire were 83%, 65%, 15%, and 98%, respectively. A combined approach with immunohistochemistry and the brief Family History Questionnaire correctly identified all 12 patients with Lynch syndrome. The brief Family History Questionnaire was more sensitive than the extended Family History Questionnaire and took <10 min for each patient to complete. CONCLUSIONS: The brief Family History Questionnaire alone or combined with immunohistochemistry may serve as an adequate screening strategy, especially in centers without access to universal tumor testing.

Maximizing cancer prevention through genetic navigation for Lynch syndrome detection in women with newly diagnosed endometrial and nonserous/nonmucinous epithelial ovarian cancer.

BACKGROUND: Despite recommendations for reflex immunohistochemistry (IHC) for mismatch repair (MMR) proteins to identify Lynch syndrome (LS), the uptake of genetic assessment by those who meet referral criteria is low. The authors implemented a comprehensive genetic navigation program to increase the uptake of genetic testing for LS in patients with endometrial cancer (EC) or nonserous/nonmucinous ovarian cancer (OC). METHODS: Participants with newly diagnosed EC or OC were prospectively recruited from 3 cancer centers in Ontario, Canada. Family history questionnaires were used to assess LS-specific family history. Reflex IHC for MMR proteins was performed with the inclusion of clinical directives in pathology reports. A trained genetic navigator initiated a genetic referral on behalf of the treating physician and facilitated genetic referrals to the closest genetics center. RESULTS: A total of 841 participants (642 with EC, 172 with OC, and 27 with synchronous EC/OC) consented to the study; 194 (23%) were MMR-deficient by IHC. Overall, 170 women (20%) were eligible for a genetic assessment for LS: 35 on the basis of their family history alone, 24 on the basis of their family history and IHC, 82 on the basis of IHC alone, and 29 on the basis of clinical discretion. After adjustments for participants who died (n = 6), 149 of 164 patients (91%) completed a genetic assessment, and 111 were offered and completed genetic testing. Thirty-four women (4.0% of the total cohort and 30.6% of those with genetic testing) were diagnosed with LS: 5 with mutL homolog 1 (MLH1), 9 with mutS homolog 2 (MSH2), 15 with mutS homolog 6 (MSH6), and 5 with PMS2. CONCLUSIONS: The introduction of a navigated genetic program resulted in a high rate of genetic assessment (>90%) in patients with gynecologic cancer at risk for LS.

Understanding the clinical implication of mismatch repair deficiency in endometrioid endometrial cancer through a prospective study.

OBJECTIVES: Findings on impact of mismatch repair deficiency (MMRd) on patient outcomes in endometrial cancer (EC) have been inconsistent to date. The objective of this study was to compare the oncologic outcomes and recurrence patterns between MMRd and MMR-intact (MMRi) endometrioid EC (EEC). METHODS: Between 2015 and 2018, we prospectively recruited 492 EEC cases from three cancer centers in Ontario, Canada. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry (IHC). Clinicopathological, survival and recurrence patterns were compared between MMRd and MMRi cases. RESULTS: Of 492 EEC, 348 were MMRi (71%) and 144 were MMRd (29%) with median follow-up of 16.8 months (0-69.6). MMRd tumors tended to be grade 2 or 3 (56% vs. 29%, p < 0.001), with propensity for lymphovascular space invasion (28% vs. 18%, p = 0.024), lymph node involvement (7% vs. 5%, p < 0.001) and received more adjuvant treatment (46% vs. 33%, p = 0.027). This group also had significantly lower 3-year recurrence-free survival (78% vs. 90%, p = 0.014) although there was no difference in OS (p = 0.603). MMRd cases were more likely to recur in retroperitoneal lymph nodes (p = 0.045). Upon subgroup analysis, MLH1 methylated tumors had the worst prognostic features and survival outcomes. CONCLUSIONS: MLH1 methylated EECs exhibit more aggressive features compared to other MMRd and MMRi EECs. This may indicate an inherent difference in tumor biology, suggesting the importance of individualized management based on EC molecular phenotype.

Barriers and facilitators to CDH1 carriers contemplating or undergoing prophylactic total gastrectomy.

Hereditary diffuse gastric cancer (HDGC) is an inherited cancer syndrome associated with high lifetime risk of diffuse-type gastric cancer. Current guidelines recommend individuals with HDGC undergo prophylactic total gastrectomy (PTG) to eliminate this risk. However, PTG is associated with significant lifestyle changes, post-surgical recovery, and symptom burden. This study examined factors related to decision-making about PTG in three groups of individuals who: (1) underwent PTG immediately after receiving genetic testing results; (2) delayed PTG by ≥ 1 year or; (3) declined PTG. Participants were recruited from a familial gastric cancer registry at a tertiary care hospital. Patients with CDH1 pathogenic or likely pathogenic variants who contemplated and/or underwent PTG were eligible. 24 individuals contemplated PTG: 9 had immediate surgery (within a year), 8 delayed surgery, and 7 declined surgery. Data on PTG barriers and facilitators were obtained on all participants using quantitative surveys (n = 7), qualitative interviews (n = 8) or both methods (n = 9). PTG barriers included age, positive beliefs about screening, close relatives with negative PTG experiences, fertility-related concerns, and life stress. Facilitators included social support, trust in healthcare providers, understanding risk, negative beliefs about screening, family-related factors, positive or abnormal screening results, and positive attitude toward PTG. This study highlights factors related to the PTG decision-making process among individuals with HDGC from three distinct groups. Future research should explore educational interventions aimed at addressing surgery-related concerns and the limitations of screening, and might also consider incorporating close relatives as informational supports.

Tumor site discordance in mismatch repair deficiency in synchronous endometrial and ovarian cancers.

OBJECTIVES: For synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests. METHODS: 30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing. RESULTS: Of 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with a PMS2 pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium. CONCLUSIONS: There was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.

Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer.

BACKGROUND: For women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In the current study, the authors compared the performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for the detection of LS. METHODS: Women with nonserous and/or nonmucinous ovarian cancer were recruited prospectively from 3 cancer centers in Ontario, Canada. All underwent germline testing for LS and completed a family history assessment. Tumors were assessed using MMR IHC and MSI. The sensitivity, specificity, and positive and negative predictive values of screening strategies were compared with the gold standard of a germline result. RESULTS: Of 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (MSH6); 3 women with mutL homolog 1 (MLH1); 2 women with PMS1 homolog 2, mismatch repair system component (PMS2); and 1 woman with mutS homolog 2 (MSH2). A total of 28 women had MMR-deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (with MLH1 promoter methylation analysis on MLH1-deficient tumors) followed by MSI for nonmethylated and/or MMR-intact patients was the most sensitive (92.3%; 95% confidence interval, 64%-99.8%) and specific (97.7%; 95% confidence interval, 94.2%-99.4%) approach, missing 1 case of LS. IHC with MLH1 promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%. CONCLUSIONS: Sequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter methylation analysis also performed well and is likely more cost-effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS.

Awkward Choreographies from Cancer's Margins: Incommensurabilities of Biographical and Biomedical Knowledge in Sexual and/or Gender Minority Cancer Patients' Treatment.

Canadian and American population-based research concerning sexual and/or gender minority populations provides evidence of persistent breast and gynecologic cancer-related health disparities and knowledge divides. The Cancer's Margins research investigates the complex intersections of sexual and/or gender marginality and incommensurabilities and improvisation in engagements with biographical and biomedical cancer knowledge. The study examines how sexuality and gender are intersectionally constitutive of complex biopolitical mappings of cancer health knowledge that shape knowledge access and its mobilization in health and treatment decision-making. Interviews were conducted with a diverse group (n=81) of sexual and/or gender minority breast or gynecologic cancer patients. The LGBQ//T2 cancer patient narratives we have analyzed document in fine grain detail how it is that sexual and/or gender minority cancer patients punctuate the otherwise lockstep assemblage of their cancer treatment decision-making with a persistent engagement in creative attempts to resist, thwart and otherwise manage the possibility of discrimination and likewise, the probability of institutional erasure in care settings. Our findings illustrate the demands that cancer places on LGBQ//T2 patients to choreograph access to, and mobilization of knowledge and care, across significantly distinct and sometimes incommensurable systems of knowledge.

Dyadic coping mediates the effects of attachment on quality of life among couples facing ovarian cancer.

Cancer is an interpersonal stressor affecting both patient and spouse. To examine the pathways that insecure adult attachment can impact health outcomes by way of dyadic processes, this cross-sectional study used the actor-partner interdependence mediation model to examine whether common dyadic coping (CDC) mediated the associations between attachment and quality of life (QOL). Couples (N = 106) facing ovarian cancer were recruited from a comprehensive cancer center and completed self-report questionnaires. Results indicated that worse social and functional QOL were associated with both one's own and one's partner's greater insecure attachment, by way of one's own use of less CDC. Unexpectedly, greater CDC reported by one's partner was associated with one's own lower functional QOL. Although CDC has beneficial effects on QOL, CDC may also be experienced as draining. Effects of adult attachment on dyadic coping are a significant contributor to subjective health outcomes among couples facing ovarian cancer.