Feasibility of a Serious Illness Communication Program for Pediatric Advance Care Planning.

Importance: Pediatric advance care planning (ACP), which aims to ensure care is aligned with family goals and values, is associated with better end-of-life outcomes; however, ACP in pediatrics remains uncommon. Objectives: To determine the feasibility and acceptability of the Pediatric Serious Illness Communication Program (PediSICP) and explore family-centered outcomes. Design, Setting, and Participants: This cohort study was a single-group pilot study of the PediSICP in adolescents and young adults (AYAs; age ≥13 y) with serious illness, parents of seriously ill children, and interprofessional clinicians from April 2021 to March 2023 in a quaternary care pediatric hospital. Duration of follow-up was 1 month. Data were analyzed from January 2022 to March 2023. Exposure: The PediSICP includes clinician training preceding an ACP communication occasion supported by communication guides and a template for electronic medical record documentation. Main Outcomes and Measures: Outcomes of interest were parent, patient, and clinician experiences with and perceptions of the PediSICP. Feasibility was defined a priori as at least 70% clinician intervention completion rates. Results: A total of 10 virtual trainings were conducted among 40 clinicians, including 27 physicians, 7 nurse practitioners, 5 nurses, and 1 respiratory therapist, and 30 trained clinicians (75%) conducted and documented 42 ACP conversations with 33 parents (median [IQR] age, 43 [35-51] years; 25 [76%] female) and 5 AYAs (median [IQR] age, 19 [17-19] years; 3 [60%] female) who completed the intervention. The median (IQR) conversation duration was 27 (10-45) minutes. Most clinicians (29 clinicians [97%]) agreed that they felt prepared for the conversation, and all clinicians recommended the PediSICP. Parents reported participation was worthwhile (27 parents [84%]), they felt listened to (31 parents [94%]), and would recommend the PediSICP (28 parents [85%]). Parents endorsed higher therapeutic alliance after the PediSICP intervention compared with before (The Human Connection scale mean [SD] score, 57.6 [6.4] vs 55.3 [7.8]; P = .03) and decreased anxiety immediately after the intervention (Generalized Anxiety Disorder-7-item mean [SD] score, 10.1 [7.3] vs 8.4 [6.9]; P = .003), which persisted at the 1-month follow-up (mean [SD] score, 7.7 [6.8]; P = .03). Conclusions and Relevance: This pilot cohort study found that the PediSICP was feasible, acceptable, and highly valued by clinicians and parents of children with serious illness. These findings suggest that the PediSICP may empower interprofessional clinicians and improve ACP with families of children and AYAs who are seriously ill.

A phase 2 trial exploring the significance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib.

OBJECTIVE: Combination cediranib/olaparib has reported activity in relapsed ovarian cancer. This phase 2 trial investigated the activity of cediranib/olaparib in relapsed ovarian cancer and its association with homologous recombination deficiency (HRD). METHODS: Seventy patients were enrolled to cohorts of either platinum-sensitive or platinum-resistant ovarian cancer and received olaparib tablets 200 mg twice daily and cediranib tablets 30 mg once daily under a continuous dosing schedule. HRD testing was performed on pre-treatment, on-treatment and archival biopsies by sequencing key homologous recombination repair (HRR) genes and by genomic LOH analysis. The primary objective for the platinum-sensitive cohort was the association of HRD, defined as presence of HRR gene mutation, with progression-free survival (PFS). The primary objective for the platinum-resistant cohort was objective response rate (ORR), with a key secondary endpoint evaluating the association of HRD status with activity. RESULTS: In platinum-sensitive ovarian cancer (N = 35), ORR was 77.1% (95% CI 59.9-89.6%) and median PFS was 16.4 months (95% CI 13.2-18.6). Median PFS in platinum-sensitive HRR-HRD cancers (N = 22) was 16.8 months (95% CI 11.3-18.6), and 16.4 months (95% CI 9.4-NA) in HRR-HR proficient cancers (N = 13; p = 0.57). In platinum-resistant ovarian cancer (N = 35), ORR was 22.9% (95% CI 10.4-40.1%) with median PFS 6.8 months (95% CI 4.2-9.1). Median PFS in platinum-resistant HRR-HRD cancers (N = 7) was 10.5 months (95% CI 3.6-NA) and 5.6 months (95% CI 3.6-7.6) in HRR-HR proficient cancers (N = 18; p = 0.23). CONCLUSIONS: Cediranib/olaparib had clinical activity in both platinum-sensitive and -resistant ovarian cancer. Presence of HRR gene mutations was not associated with cediranib/olaparib activity in either setting.

Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.

PURPOSE: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi. PATIENTS AND METHODS: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non-small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations. Paired pretreatment and day 15 tumor biopsies and serial cell-free (cf)DNA were analyzed. RESULTS: A total of 91 patients initiated treatment, with 38 in dose escalation. Fifty-eight percent had ≥3 prior therapies. A total of 15 patients (17%) had colorectal cancer, 19 (11%) pancreatic, 15 (17%) NSCLC, and 32 (35%) GYN cancers. The recommended phase II dose (RP2D) was established as trametinib 2 mg daily days 1 to 14 and navitoclax 250 mg daily days 1 to 28 of each cycle. Most common adverse events included diarrhea, thrombocytopenia, increased AST/ALT, and acneiform rash. At RP2D, 8 of 49 (16%) evaluable patients achieved partial response (PR). Disease-specific differences in efficacy were noted. In patients with GYN at the RP2D, 7 of 21 (33%) achieved a PR and median duration of response 8.2 months. No PRs occurred in patients with colorectal cancer, NSCLC, or pancreatic cancer. MAPK pathway inhibition was observed in on-treatment tumor biopsies. Reductions in KRAS/NRAS mutation levels in cfDNA correlated with clinical benefit. CONCLUSIONS: Navitoclax in combination with trametinib was tolerable. Durable clinical responses were observed in patients with RAS-mutant GYN cancers, warranting further evaluation in this population.

Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer.

Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming de novo and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in recurrent endometrial cancer (EC). This study was terminated prematurely after 5 patients initiated protocol therapy due to discontinuation of further development of LY3023414. We report our findings from these patients, including one with recurrent endometrioid EC with AKT1, CTNNB1 and ESR1 hotspot mutations who had previously progressed through letrozole/everolimus and achieved a partial response to letrozole/abemaciclib/LY3023414.

Mixed-methods analysis of decisional regret in parents following a child's death from cancer.

BACKGROUND AND OBJECTIVES: Decisional regret is common in bereaved parents. We aimed to identify factors associated with and to explain patterns of parental decisional regret. METHODS: We used a convergent mixed-methods design including quantitative items and free-text responses from a survey of parents 6-24 months from their child's death from cancer. Parents expressed whether they had regrets about decisions during the end of their child's life (Yes/No/I don't know) and elaborated with free text. Results of qualitative content analysis of free-text responses guided development and interpretation of quantitative multinomial models. RESULTS: Parents (N = 123 surveys, N = 84 free text) primarily identified as White (84%), mothers (63%), and primary caregivers (69%) for their children. Forty-seven (38%) parents reported decisional regret, 61 (49%) indicated no regret, and 15 (12%) were unsure. Mothers (relative risk [RR]: 10.3, 95%CI: [1.3, 81.3], p = .03) and parents who perceived greater suffering at the end of their child's life (RR = 3.8, 95%CI: [1.2, 11.7], p = .02) were at increased risk of regret; qualitative evaluation revealed elements of self-blame and difficulty reconciling treatment choices with the ultimate outcome. Preparation for symptoms was associated with decreased risk of regret (RR = 0.1, 95%CI: [0, .3], p < .01) with qualitative reflections focused on balanced teamwork that alerted parents for what to expect and how to make meaningful final memories. CONCLUSIONS: Though decisional regret is common among cancer-bereaved parents, mothers and those who perceive more suffering in their children may be at particular risk. Close collaboration between families and clinicians to prepare for symptoms and proactively attend to and minimize suffering may help alleviate decisional regret.

"It's a lot of things": Household material hardship among Black and Hispanic parents of children with cancer.

Household material hardship (HMH)-housing, food, transportation, or utility insecurity-is an adverse social determinant of health that is modifiable in the clinical setting. This mixed-methods, single-center study explored the experiences of HMH among Black and Hispanic pediatric oncology parents utilizing a single timepoint survey (N = 60) and semi-structured interviews (N = 20 purposively sampled subcohort). Forty-four (73%) parents reported HMH. Qualitatively, participants expressed stress, anxiety, and embarrassment due to unmet basic resource needs, and childcare emerged as an additional important domain of HMH. Participants recommend a standardized approach to HMH screening and resource allocation, offering insight into targets for future intervention.

A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor-Positive Recurrent Endometrial Cancer.

PURPOSE: Estrogen receptor (ER)-positive endometrial cancers (ECs) are characterized by phosphatidylinositol 3-kinase (PI3K) and receptor tyrosine kinase (RTK)/RAS/ß-catenin (CTNNB1) pathway alterations in approximately 90% and 80% of cases, respectively. Extensive cross-talk between ER, PI3K, and RTK/RAS/CTNNB1 pathways leads to both ligand-dependent and ligand-independent ER transcriptional activity as well as upregulation of cyclin D1 which, in complex with cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), is a critical regulator of cell cycle progression and a key mediator of resistance to hormonal therapy. We hypothesized that the combination of the aromatase inhibitor letrozole and CDK4/6 inhibitor abemaciclib would demonstrate promising activity in this setting. METHODS: We conducted a phase II, two-stage study of letrozole/abemaciclib in recurrent ER-positive EC. Eligibility criteria included measurable disease, no limit on prior therapies, and all EC histologies; prior hormonal therapy was allowed. Primary end points were objective response rate by RECIST 1.1 and progression-free survival (PFS) rate at 6 months. RESULTS: At the data cutoff date (December 03, 2021), 30 patients (28 with endometrioid EC) initiated protocol therapy; 15 (50%) patients had prior hormonal therapy. There were nine total responses (eight confirmed), for an objective response rate of 30% (95% CI, 14.7 to 49.4), all in endometrioid adenocarcinomas. Median PFS was 9.1 months, PFS at 6 months was 55.6% (95% CI, 35.1 to 72), and median duration of response was 7.4 months. Most common ≥ grade 3 treatment-related adverse events were neutropenia (20%) and anemia (17%). Responses were observed regardless of grade, prior hormonal therapy, mismatch repair, and progesterone receptor status. Exploratory tumor profiling revealed several mechanistically relevant candidate predictors of response (CTNNB1, KRAS, and CDKN2A mutations) or absence of response (TP53 mutations), which require independent validation. CONCLUSION: Letrozole/abemaciclib demonstrated encouraging and durable evidence of activity in recurrent ER positive endometrioid EC.

Health-related quality of life, patient-centred communication and self-efficacy in ovarian cancer: a mediation analysis.

OBJECTIVE: To assess the role of self-efficacy as a mediator of the association between patient-centred communication (PCC) and health-related quality of life (HRQoL) in a sample of participants with ovarian cancer. METHODS: English-speaking adults with ovarian cancer completed a cross-sectional survey. We assessed self-efficacy with the Self-Efficacy for Managing Chronic Disease scale, PCC with the Patient-Centred Communication in Cancer Care-36, and HRQoL with the Functional Assessment of Cancer Therapy-General. We used the PROCESS macro to calculate regression coefficients for the total effect of PCC on HRQoL and direct effect of PCC on HRQoL. We calculated a 95% CI for the indirect effect of PCC on HRQoL using 10 000 bootstrapped samples. RESULTS: The total effect of PCC on HRQoL (9.47, 95% CI 6.21 to 12.74) was greater than the direct effect of PCC on HRQoL (3.47, 95% CI 0.73 to 6.21). The indirect effect of PCC on HRQoL was 6.00 (95% CI 3.56 to 8.95). Self-efficacy explained approximately 63.4% of the association between PCC and HRQoL. CONCLUSIONS: Self-efficacy partially mediated the association between PCC and HRQoL. Self-efficacy is a potential target for communication interventions that aim to improve HRQoL. Research to validate this finding in the setting of a randomised trial is warranted.

Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers.

PURPOSE: The identification of patients with homologous recombination deficiency (HRD) beyond BRCA1/2 mutations is an urgent task, as they may benefit from PARP inhibitors. We have previously developed a method to detect mutational signature 3 (Sig3), termed SigMA, associated with HRD from clinical panel sequencing data, that is able to reliably detect HRD from the limited sequencing data derived from gene-focused panel sequencing. EXPERIMENTAL DESIGN: We apply this method to patients from two independent datasets: (i) high-grade serous ovarian cancer and triple-negative breast cancer (TNBC) from a phase Ib trial of the PARP inhibitor olaparib in combination with the PI3K inhibitor buparlisib (BKM120; NCT01623349), and (ii) TNBC patients who received neoadjuvant olaparib in the phase II PETREMAC trial (NCT02624973). RESULTS: We find that Sig3 as detected by SigMA is positively associated with improved progression-free survival and objective responses. In addition, comparison of Sig3 detection in panel and exome-sequencing data from the same patient samples demonstrated highly concordant results and superior performance in comparison with the genomic instability score. CONCLUSIONS: Our analyses demonstrate that HRD can be detected reliably from panel-sequencing data that are obtained as part of routine clinical care, and that this approach can identify patients beyond those with germline BRCA1/2mut who might benefit from PARP inhibitors. Prospective clinical utility testing is warranted.

How does patient-centered communication in ovarian cancer care enhance patient well-being? A mixed methods study.

OBJECTIVE: Greater perceived patient-centered communication (PCC) is associated with better health-related quality of life (HRQoL) in patients with ovarian cancer. Quantitative measures of PCC and HRQoL do little to explain this association. We interviewed patients with high and low ratings of PCC to understand how it is associated with HRQoL. METHODS: Explanatory sequential mixed methods study. Participants were English-speaking U.S. adults with ovarian cancer. We assessed PCC with the Patient-Centered Communication - Cancer (PCC-Ca)-36 (possible score range 1-5; higher scores represent greater patient-centeredness), and purposively sampled 14 participants with total scores in the top and bottom quartiles. Participants completed individual, semi-structured interviews about their communication experiences. Guided by the National Cancer Institute Framework for PCC in Cancer Care, we analyzed interview transcripts using directed content analysis. We integrated survey and interview findings in a joint display. RESULTS: Among 176 survey respondents, PCC-Ca-36 total scores ranged from 1.7 to 5.0. Participants with scores in the top quartile (4.8-5.0) perceived clinicians as proactive and attentive to psychosocial concerns. Those with scores in the bottom quartile (1.7-3.5) described not feeling known as an individual and receiving limited support for self-management. CONCLUSIONS: The association between PCC and QoL may be partially explained by differences in perceived support for psychosocial concerns and self-management. PCC may facilitate receipt of proactive, personalized care.

Concordance between influential adverse treatment outcomes and localized prostate cancer treatment decisions.

BACKGROUND: Although treatment decisions for localized prostate cancer (LPC) are preference-sensitive, the extent to which individuals with LPC receive preference-concordant treatment is unclear. In a sample of individuals with LPC, the purpose of this study was to (a) assess concordance between the influence of potential adverse treatment outcomes and treatment choice; (b) determine whether receipt of a decision aid predicts higher odds of concordance; and (c) identify predictors of concordance from a set of participant characteristics and influential personal factors. METHODS: Participants reported the influence of potential adverse treatment outcomes and personal factors on treatment decisions at baseline. Preference-concordant treatment was defined as (a) any treatment if risk of adverse outcomes did not have a lot of influence, (b) active surveillance if risk of adverse outcomes had a lot of influence, or (c) radical prostatectomy or active surveillance if risk of adverse bowel outcomes had a lot of influence and risk of other adverse outcomes did not have a lot of influence. Data were analyzed using descriptive statistics and logistic regression. RESULTS: Of 224 participants, 137 (61%) pursued treatment concordant with preferences related to adverse treatment outcomes. Receipt of a decision aid did not predict higher odds of concordance. Low tumor risk and age ≥ 60 years predicted higher odds of concordance, while attributing a lot of influence to the impact of treatment on recreation predicted lower odds of concordance. CONCLUSIONS: Risk of potential adverse treatment outcomes may not be the foremost consideration of some patients with LPC. Assessment of the relative importance of patients' stated values and preferences is warranted in the setting of LPC treatment decision making. CLINICAL TRIAL REGISTRATION: NCT01844999 ( www. CLINICALTRIALS: gov ).

Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer.

Importance: Although the activity of pembrolizumab and lenvatinib (the only US Food and Drug Administration-approved immunotherapy for mismatch repair proficient endometrial cancer [MMRP EC]) is compelling, there are no biomarkers of response and most patients do not tolerate, do not respond to, or develop resistance to this regimen, highlighting the need for additional, potentially biomarker-driven therapeutic approaches for patients with recurrent MMRP EC. Objective: To assess the potential positive outcomes and safety of the combination of the polyadenosine diphosphate-ribose polymerase inhibitor talazoparib and the programmed cell death ligand 1 (PD-L1) inhibitor avelumab in recurrent MMRP EC. Design, Settings, and Participants: This investigator-initiated, open-label, single-arm, 2-stage, phase 2 study nonrandomized controlled trial patients at 4 institutions in the US. Key eligibility criteria included measurable disease, unlimited prior therapies, and all endometrial cancer histologies. Interventions: Talazoparib, 1 mg, orally, daily, and avelumab, 10 mg/kg, intravenously, every 2 weeks, were administered until disease progression or unacceptable toxic effects. Main Outcomes and Measures: Statistical considerations were developed for 2 coprimary objectives of objective response rate and rate of progression-free survival at 6 months, with a 2-stage design that allowed for early discontinuation for futility. Prespecified exploratory objectives included the association of immunogenomic features (determined by targeted-panel next-generation sequencing and immunohistochemistry) with activity. Results: Thirty-five female patients (mean [SD] age, 67.9 [8.41] years) received protocol therapy; 9 (25.7%) derived clinical benefit after meeting at least 1 of the 2 coprimary end points. Four patients (11.4%) exhibited confirmed objective response rates (4 partial responses), and 8 (22.9%) survived progression free at 6 months. The most common grade 3 and 4 treatment-related toxic effects were anemia (16 [46%]), thrombocytopenia (10 [29%]), and neutropenia (4 [11%]); no patient discontinued receipt of therapy because of toxic effects. Tumors with homologous recombination repair alterations were associated with clinical benefit from treatment with avelumab and talazoparib. Tumor mutational burden, tumor-infiltrating lymphocytes, and PD-L1 status were not associated with clinical benefit. Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that treatment with avelumab and talazoparib demonstrated a favorable toxic effect profile and met the predetermined criteria to be considered worthy of further evaluation in MMRP EC. Immunogenomic profiling provided insights that may inform ongoing and future studies of polyadenosine diphosphate-ribose polymerase and PD-L1 inhibitor combinations in endometrial cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02912572.

Transitioning from heparin to saline locks for central venous access devices in oncology: An evidence-based practice approach.

Central vascular access devices (CVADs) are often essential to the care of patients undergoing long-term cancer treatment. CVAD maintenance is an essential oncology nurse competency. Evidence-based practice (EBP) in flushing and locking help to prevent intraluminal occlusion, a common complication. Heparinized saline (HS) has been the standard locking solution for CVADs. However, research indicates no superiority of HS over normal saline (NS). The objectives of this EBP project were 1) to evaluate whether a significant difference in intraluminal occlusion was associated with the change from HS to NS use for locking CVADs in ambulatory oncology care, and 2) to evaluate the effects of peer nurse mentoring on nurses' and patients' perspectives about the practice change. Analysis of data revealed decreases in alteplase usage after transitioning to NS locking. Patient and nurse surveys indicated that peer nurse mentoring increased nurse and patient confidence and competence in making the practice transition.

A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma.

Uterine serous carcinoma (USC) is an uncommon subtype of endometrial cancer with a poor prognosis. USCs have genomic alterations in the PI3K pathway. A prior phase II study of AKT inhibitor MK-2206 (an allosteric AKT inhibitor, primarily affecting AKT1 and AKT2) in endometrial cancers resulted in progression-free survival (PFS) of ≥6 months in five out of seven patients with USC. To further assess the activity of MK-2206 in USC, we designed a phase II, single-stage assessment of MK-2206 in patients with advanced or recurrent high-grade serous endometrial cancer, who had received up to two lines of prior therapy. MK-2206 (135 mg) was administered orally once per week, in continuous 28-day cycles. Fourteen patients received treatment. The most common treatment-related adverse events were diarrhea (36%), acneiform rash (36%), nausea (29%), fatigue (29%), and hyperglycemia (21%); most events were grade 1-2. One confirmed partial response was observed in a patient who was also alive and progression-free at 6 months. One additional patient was alive and progression-free at 6 months. The clinical benefit rate was 14.3% (95% CI: 1.8 to 42.8). Five patients had stable disease (35.7%) and seven had progressive disease (50%); one was unevaluable. Median PFS was 2 months (95% CI: 1.6 to 4.4) and median overall survival was 6.4 months (95% CI: 5.1 to not reached). In summary, MK-2206 had limited activity in USC, although a few patients achieved sustained progression-free intervals in this study and in the previously reported phase II trial of MK-2206. Further investigations are needed to identify features associated with response.

Phase 1b Clinical Trial with Alpelisib plus Olaparib for Patients with Advanced Triple-Negative Breast Cancer.

PURPOSE: We had previously reported on the safety and the recommended phase 2 dose (RP2D) of olaparib in combination with the PI3Kα-specific inhibitor alpelisib in patients with high-grade serous ovarian cancer as studied in a phase 1b trial (NCT01623349). Here, we report on the breast cancer cohort from that study. PATIENTS AND METHODS: Eligible patients had recurrent triple-negative breast cancer (TNBC) or recurrent breast cancer of any subtype with a germline BRCA mutation and were enrolled to a dose-escalation or -expansion cohort. After definition of the RP2D, secondary end points included safety and objective response rate (ORR). Exploratory analyses were performed using circulating-free DNA (cfDNA). RESULTS: Seventeen patients with TNBC were enrolled with a median of three prior lines of chemotherapy. The most common treatment-related grade 3-4 adverse events were hyperglycemia (18%) and rash (12%). The ORR was 18% (23% for patients treated at the RP2D) and 59% had disease control. The median duration of response was 7.4 months. Analysis of cfDNA tumor fractions (TFx) revealed that patients with TFx < 15% after completion of the first cycle had a longer progression-free survival compared with those with TFx ≥ 15% (6.0 vs. 0.9 months; P = 0.0001). CONCLUSIONS: Alpelisib in combination with olaparib is tolerable in patients with pre-treated TNBC, with evidence of activity in non-BRCA carriers. cfDNA provided important prognostic information. Results highlight potential synergistic use of a PI3K inhibitor to sensitize HR-proficient (BRCA wild-type) TNBC to PARP inhibition and suggest the potential to expand the use of PARP inhibition beyond BRCA-mutant tumors.

Association of Operability With Post-Treatment Mortality in Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: Operability is both a crucial determinant in treatment selection and a potential confounder in analyses comparing surgery with non-surgical approaches such as stereotactic body radiotherapy (SBRT). We aimed to assess the association between operability status and intervention with post-treatment mortality in early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We defined four groups of patients with cT1-T2N0M0 NSCLC diagnosed 2010 to 2014 from the National Cancer Database: SBRT patients deemed operable vs. inoperable and surgery patients receiving open vs. minimally-invasive approaches. Mortality rates at 30, 60, and 90 days post-treatment were calculated and compared. RESULTS: We abstracted 80,108 patients, 0.8% undergoing SBRT and operable, 13.2% undergoing SBRT and inoperable, 52.4% undergoing open surgery, and 33.7% undergoing minimally-invasive surgery. Mortality rates were highest among open surgery patients and lowest among operable SBRT patients (2.0% vs. 0.2% at 30 days and 3.7% vs. 0.7% at 90 days), with intermediate results in the other two groups. These findings persisted on multivariate Cox regression: compared to patients undergoing minimally-invasive surgery, mortality risk was highest among open surgery patients (30 days HR 1.32, 95%CI 1.16-1.51; 90 days HR 1.36, 95%CI 1.24-1.50; both P < .001) and lowest among operable SBRT patients (30 days HR 0.09, 95%CI 0.01-0.64; 90 days HR 0.15, 95%CI 0.05-0.46; both P ≤ .016). These associations were maintained in a propensity score-matched subset. CONCLUSION: Operable patients undergoing SBRT experience minimal post-treatment mortality compared to their inoperable counterparts. These findings illustrate the potential for confounding by operability to bias results in cohort studies that compare surgical vs. non-surgical approaches in early-stage NSCLC.

Clinical Decision Support for Symptom Management in Lung Cancer Patients: A Group RCT.

CONTEXT: Clinical guidelines are available to enhance symptom management during cancer treatment but often are not used in the practice setting. Clinical decision support can facilitate the implementation and adherence to clinical guidelines. and improve the quality of cancer care. OBJECTIVES: Clinical decision support offers an innovative approach to integrate guideline-based symptom management into oncology care. This study evaluated the effect of clinical decision support-based recommendations on clinical management of symptoms and health-related quality of life (HR-QOL) among outpatients with lung cancer. METHODS: Twenty providers and 179 patients were allotted in group randomization to attention control (AC) or Symptom Assessment and Management Intervention (SAMI) arms. SAMI entailed patient-report of symptoms and delivery of recommendations to manage pain, fatigue, dyspnea, depression, and anxiety; AC entailed symptom reporting prior to the visit. Outcomes were collected at baseline, two, four and six-months. Adherence to recommendations was assessed through masked chart review. HR-QOL was measured by the Functional Assessment of Cancer Therapy-Lung questionnaire. Descriptive statistics with linear and logistic regression accounting for the clustering structure of the design and a modified chi-square test were used for analyses. RESULTS: Median age of patients was 63 years, 58% female, 88% white, and 32% ≤high school education. Significant differences in clinical management were evident in SAMI vs. AC for all target symptoms that passed threshold. Patients in SAMI were more likely to receive sustained-release opioids for constant pain, adjuvant medications for neuropathic pain, opioids for dyspnea, stimulants for fatigue and mental health referrals for anxiety. However, there were no statistically significant differences in HR-QOL at any time point. CONCLUSION: SAMI improved clinical management for all target symptoms but did not improve patient outcomes. A larger study is warranted to evaluate effectiveness.

Knowledge and psychosocial impact of genetic counseling and multigene panel testing among individuals with ovarian cancer.

In a sample of individuals with ovarian cancer, we aimed to (a) identify factors associated with the psychosocial impact of genetic counseling and multigene panel testing, (b) identify factors associated with cancer genetics knowledge, and (c) summarize patient-reported recommendations to improve the genetic counseling and multigene panel testing process. Eligible participants in this secondary analysis of quantitative and qualitative survey data were English-speaking adults with ovarian cancer. Psychosocial impact was assessed using the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire. Knowledge of cancer genetics was assessed using the KnowGene scale. Significant predictors of MICRA and KnowGene scores were identified using multiple regression. Open-ended survey item responses were analyzed using conventional content analysis. Eighty-seven participants met eligibility criteria. A positive genetic test result was associated with greater adverse psychosocial impact (B = 1.13, p = 0.002). Older age (B = - 0.07, p = 0.044) and being a member of a minority racial or ethnic group (B = - 3.075, p = 0.033) were associated with lower knowledge, while a personal history of at least one other type of cancer (B = 1.975, p = 0.015) was associated with higher knowledge. In open-ended item responses, participants wanted clinicians to assist with family communication, improve result disclosure, and enhance patient and family understanding of results. A subset of individuals with ovarian cancer who receive a positive genetic test result may be at risk for adverse psychosocial outcomes. Tailored cancer genetics education is necessary to promote the equitable uptake of targeted ovarian cancer treatment and risk-reducing therapies. Interventions to enhance patient-clinician communication in this setting are a research priority.

Perceived patient-centered communication, quality of life, and symptom burden in individuals with ovarian cancer.

OBJECTIVE: To describe perceptions of patient-centered communication (PCC); assess whether physician specialty, patient characteristics, or health system characteristics are associated with PCC; and identify associations between PCC, health-related quality of life (HRQoL), and symptom burden among individuals with ovarian cancer. METHODS: Cross-sectional, descriptive survey of English-speaking adults with ovarian cancer. PCC, HRQoL, and ovarian cancer symptom burden were assessed with the PCC-Ca-36, the FACT-G, and the FOSI-18, respectively. PCC-Ca-36 scores were summarized using descriptive statistics. Predictors of PCC-Ca-36, FACT-G, and FOSI-18 scores were identified using multiple linear regression. RESULTS: Participants (n = 176) had a mean age of 59.4 years (SD = 12.1). The majority (65.9%) had advanced-stage disease, while 42.0% were receiving treatment. The mean PCC-Ca-36 total score was 4.09 (SD = 0.78) out of a possible 5, indicating participants often perceived that clinicians engaged in PCC. Among the PCC functions, participants reported that clinicians least often enabled patient self-management (M = 3.65, SD = 0.99), responded to emotions (M = 3.84, SD = 1.04), and managed uncertainty (M = 3.91, SD = 0.93). In multivariable analyses, neither physician specialty nor patient and health system characteristics were significantly associated with overall PCC. Greater overall PCC predicted better overall HRQoL; better social/family, emotional, and functional well-being; and lower overall and physical symptom burden (all p ≤ 0.05). CONCLUSION: Greater PCC is significantly associated with better HRQoL and lower symptom burden among individuals with ovarian cancer. PRACTICE IMPLICATIONS: Promotion of PCC is a promising strategy to improve patient-reported outcomes in the ovarian cancer care setting.