Rural-specific identity and associations with lifestyle behaviors and well-being among rural cancer survivors.

BACKGROUND: Disparities in rural cancer survivors' health outcomes are well-documented, yet the role of sociocultural aspects of rurality, such as rural identity, attitudes toward rurality, and social standing on health beliefs and behaviors remain unclear. This study aimed to address these gaps. METHODS: Rural cancer survivors (N = 188) completed a mailed/online survey. Regression analyses identified relationships among rural identity, negative attitudes toward rurality, and social standing with health outcomes, quality of life, cancer fatalism, and cancer information overload. RESULTS: Higher rural identity was associated with believing everything causes cancer (OR = 1.58, p = 0.048), believing "there's not much you can do to lower your chances of getting cancer" (OR = 2.22, p = 0.002), and higher odds of being overloaded with cancer information (OR = 2.05, p  = 0.008). Negative attitudes toward rurality was linked with higher levels of perceived stress (B = 0.83, p = 0.001), and chronic pain (OR = 1.47, p = 0.039). Higher subjective social status was associated with perceived social support (B = 0.09, p = 0.016), better overall health (B = 0.13, p < 0.001), lower levels of perceived stress (B = -0.38, p = 0.007), and chronic pain (OR = 0.80, p = 0.027). CONCLUSION: Sociocultural factors of rurality were associated with indicators of quality of life, cancer fatalism, and information overload. Further exploration of the underlying mechanisms that drive these associations can help improve intervention targets for rural cancer survivors.

Sociodemographic and Clinical Factors Associated With Radiation Treatment Nonadherence and Survival Among Rural and Nonrural Patients With Cancer.

PURPOSE: Cancer treatment nonadherence is associated with higher rates of cancer recurrence and decreased survival. Rural patients with cancer experience a 10% higher mortality rate compared with their nonrural counterparts; geographic differences in nonadherence may contribute to this increased mortality. The goal of this study was to assess for geographic disparities and determine sociodemographic and clinical factors associated with radiation therapy (RT) nonadherence and survival among rural and nonrural patients with cancer. METHODS AND MATERIALS: We examined cancer registry, medical records, and billing claims data at a safety net academic medical center. Geographic residence was defined as rural versus nonrural by US Department of Agriculture 2013 Rural-Urban Continuum Codes. Other factors assessed were age, sex, race, marital status, insurance type, employment, area median household income, residential distance to cancer treatment center, clinical stage, cancer type, treatment modality, total radiation dose received, and radiation dose per fraction. We used Cox proportional hazards modeling to examine 7 ways of operationalizing nonadherence and selected the definition that resulted in the best model fit statistics and prediction of mortality. Overall survival rates were estimated with the Kaplan-Meier method. We then examined nonadherence as the main exposure along with additional covariates in least absolute shrinkage and selection operator penalized survival analyses and as the outcome in our multivariable generalized linear regression analyses predicting nonadherence. We considered 2-way interaction terms with the main exposure, geographic residence. RESULTS: We identified 3,077 patients with cancer who averaged 62 years old, were 59% female, 34% Black, and 14% rural. Twenty-two percent of patients missed at least 2 fractions and missed an average of 10% of their treatment plan. Rural patients experienced a higher mortality rate than nonrural patients (53% vs 42%, P < .0001). Survival was assessed through December 31, 2021, with a mean follow-up of 4.5 years. Proportion of missed fractions as the indicator of nonadherence provided the best model fit statistics and prediction of survival. Marital status, employment status, tumor, nodes, metastases stage, cancer type, and age at diagnosis significantly affected survival, in addition to a treatment delay by geographic residence interaction effect. Specifically, patients residing in rural areas who experienced a treatment delay were more than twice as likely to die as nonrural residents who also experienced a treatment delay, and nearly twice as likely to die as rural residents who did not experience a treatment delay. The 2-year survival rate was 76% for nonrural residents who did not experience a treatment delay versus 27% for rural residents who experienced a treatment delay. Patients who were widowed, had stage 4 cancer, or lung cancer were more likely to be nonadherent. Finally, patients residing in rural areas who experienced a treatment delay were more likely to subsequently be nonadherent. CONCLUSIONS: In a geographically and racially diverse population, RT nonadherence is a significant concern that affects survival, yet it is a modifiable risk factor. We demonstrated that rural residence was associated with both RT nonadherence and poorer overall survival. Rural patients with a treatment delay had the lowest overall survival, compared with both nonrural survivors and rural survivors without delay. Rural residents who are delayed in starting treatment are at heightened risk for poor outcomes and should receive targeted support to mitigate the observed disparities. Additional patient populations that may benefit from targeted treatment adherence support include widowed patients and those with stage 4 cancer or lung cancer.

Factors Associated with Delaying and Forgoing Care Due to Cost among Long-term, Appalachian Cancer Survivors in Rural North Carolina.

Background: Little research exists on delayed and forgone health and mental health care due to cost among rural cancer survivors. Methods: We surveyed survivors in 7 primarily rural, Appalachian counties February to May 2020. Univariable analyses examined the distribution and prevalence of delayed/forgone care due to cost in the past year by independent variables. Chi-square or Fisher's tests examined bivariable differences. Logistic regressions assessed the odds of delayed/forgone care due to cost. Results: Respondents (n=428), aged 68.6 years on average (SD: 12.0), were 96.3% non-Hispanic white and 49.8% female; 25.0% reported delayed/forgone care due to cost. The response rate was 18.5%. The proportion of delayed/forgone care for those aged 18-64 years was 46.7% and 15.0% for those aged 65+ years (P<0.0001). Females aged 65+ years (OR: 2.00; CI: 1.02-3.93) had double the odds of delayed/forgone care due to cost compared to males aged 65+ years. Conclusion: About one in four rural cancer survivors reported delayed/forgone care due to cost, with rates approaching 50% in survivors aged <65 years. Impact: Clinical implications indicate the need to: 1) ask about the impact of care costs, and 2) provide supportive services to mitigate effects of treatment costs, particularly for younger and female survivors.

PTCH1 mutant small cell glioblastoma in a patient with Gorlin syndrome: A case report.

Gorlin syndrome or nevoid basal cell carcinoma syndrome is a rare genetic disease characterized by predisposition to congenital defects, basal cell carcinomas and medulloblastoma. The syndrome results from a heritable mutation in PATCHED1 (PTCH1), causing constitutive activation of the Hedgehog pathway. The present study described a patient with Gorlin syndrome who presented early in life with characteristic basal cell carcinomas and later developed a small cell glioblastoma (GBM), World Health Organization grade IV, associated with a Patched 1 (PTCH1) N97fs*43 mutation. Comprehensive genomic profiling of GBM tissues also revealed multiple co-occurring alterations including cyclin-dependent kinase 4 (CDK4) amplification, receptor tyrosine-protein kinase 3 (ERBB3) amplification, a fibroblast growth factor receptor 1 and transforming acidic coiled-coil containing protein 1 (FGFR1-TACC1) fusion, zinc finger protein (GLI1) amplification, E3 ubiquitin-protein ligase (MDM2) amplification and spectrin α chain, erythrocytic 1 (SPTA1) T1151fs*24. After the biopsy, imaging revealed extensive leptomeningeal enhancement intracranially and around the cervical spinal cord due to leptomeningeal disease. The patient underwent craniospinal radiation followed by 6 months of adjuvant temozolomide (150 mg/m2) with good response. She was then treated with vismodegib for 11 months, first combined with temozolomide and then with bevacizumab, until disease progression was noted on MRI, with no significant toxicities associated with the combination therapy. She received additional therapies but ultimately succumbed to the disease four months later. The current study presents the first documentation in the literature of a primary (non-radiation induced) glioblastoma secondary to Gorlin syndrome. Based on this clinical experience, vismodegib should be considered in combination with standard-of-care therapies for patients with known Gorlin syndrome-associated glioblastomas and sonic hedgehog pathway mutations.

Recreational and occupational physical activity in relation to prostate cancer aggressiveness: the North Carolina-Louisiana Prostate Cancer Project (PCaP).

PURPOSE: To examine associations between recreational and occupational physical activity and prostate cancer aggressiveness in a population-based, case-only, incident prostate cancer study. METHODS: Data were analyzed from the cross-sectional North Carolina-Louisiana Prostate Cancer Project of African-American (n = 1,023) and European-American (n = 1,079) men newly diagnosed with prostate cancer (CaP). High-aggressive CaP was defined as Gleason sum ≥ 8, or prostate-specific antigen > 20 ng/ml, or Gleason sum ≥ 7 and clinical stage T3-T4. Metabolic equivalent tasks (MET) were estimated from self-reported recreational physical activity in the year prior to diagnosis assessed retrospectively via a validated questionnaire and from occupational physical activity based on job titles. Associations between physical activity variables and high-aggressive prostate cancer were estimated using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple confounders. RESULTS: There was suggestive evidence that walking for 75-150 min/week for exercise is associated with lower odds of high-aggressive prostate cancer compared to no walking (OR = 0.69, 95% CI 0.47-1.01). Physical activity at the current job was associated with 24% lower odds of high-aggressive prostate cancer (highest vs. lowest tertile OR = 0.76, 95% CI 0.56-1.04). However, total MET-h/week of recreational physical activity and accumulation of high-level physical activity at the longest-held job were not associated with high-aggressive prostate cancer. Results did not vary by race. CONCLUSIONS: The odds of high-aggressive prostate cancer were lower among men who walk for exercise and those engaged in occupations with high activity levels.

The role of digital health technology in rural cancer care delivery: A systematic review.

PURPOSE: Rural residents face higher cancer incidence rates and mortality rates, disparities that could be mitigated with health technology interventions, yet a digital divide is also apparent. This paper systematically and critically examines existing literature to understand how digital technologies have been used to support rural oncology care. METHODS: PubMed, CINAHL Complete, PsycINFO, and Embase were searched using Medical Subject Headings terms and keywords. Studies were eligible if they presented empirical data investigating the use of technology in rural oncology and were published in English in a peer-reviewed journal within the last decade. The Mixed Methods Appraisal Tool was used to assess methodological quality. FINDINGS: Digital health has been less extensively utilized in rural oncology compared with the general cancer population and other chronic diseases. We identified 54 studies that used technology in rural cancer care delivery, a comparatively small number, representing a significant gap in the literature. Studies were classified into 4 categories: Telemedicine (n = 32), phone calls (n = 11), Internet (n = 9), and mobile phone (n = 2). Of the 54 articles, 12 were RCTs, 17 were quasi-experimental, 3 were descriptive, 12 were mixed methods, and 10 were qualitative. Most of the studies involved patients only (n = 31) and were not specific to a cancer type (n = 41). CONCLUSIONS: Further implementation and expansion of telemedicine and phone-based strategies in rural cancer care delivery are warranted. Rural cancer survivors value digital approaches to their care. However, social and behavioral determinants of health and access to technology must be considered.

Patient access to clinical notes in oncology: A mixed method analysis of oncologists' attitudes and linguistic characteristics towards notes.

BACKGROUND: Providers have expressed concern about patient access to clinical notes. There is the possibility that providers may linguistically censor notes knowing that patients have access. PURPOSE: Qualitative interviews and a pre- and post- linguistic analysis of the implementation of OpenNotes was performed to determine whether oncologists changed the content and style of their notes. METHODS: Mixed methods were utilized, including 13 semi-structured interviews with oncologists and random effects modeling of over 500 clinical notes. The Linguistic Inquiry and Word Count program was used to evaluate notes for emotions, thinking styles, and social concerns. RESULTS: No significant differences from pre- and post-implementation of OpenNotes was found. Thematic analysis revealed that oncologists were concerned that changing their notes would negatively impact multidisciplinary communication. However, oncologists acknowledged that notes could be more patient-friendly and may stimulate patient-provider communication. CONCLUSIONS: Although oncologists were aware that patients could have access, they felt strongly about not changing the content of notes. A comparison between pre- and post-implementation confirmed this view and found that notes did not change. PRACTICE IMPLICATIONS: Patient access to oncologist's notes may serve as an opportunity to reinforce important aspects of the consultation.

OpenNotes in oncology: oncologists' perceptions and a baseline of the content and style of their clinician notes.

Patients' ability to access their provider's clinical notes (OpenNotes) has been well received and has led to greater transparency in health systems. However, the majority of this research has occurred in primary care, and little is known about how patients' access to notes is used in oncology. This study aims to understand oncologists' perceptions of OpenNotes, while also establishing a baseline of the linguistic characteristics and patterns used in notes. Data from 13 in-depth, semistructured interviews with oncologists were thematically analyzed. In addition, the Linguistic Inquiry and Word Count (LIWC) program evaluated over 200 clinician notes, measuring variables encompassing emotions, thinking styles, social concerns, and parts of speech. Analysis from LIWC revealed that notes contained negative emotional tone, low authenticity, high clout, and high analytical writing. Oncologists' use of stigmatized and sensitive words, such as "obese" and "distress," was mainly absent. Themes from interviews revealed that oncologists were uncertain about patients' access to their notes and may edit their notes to avoid problematic terminology. Despite their reluctance to embrace OpenNotes, they envisioned opportunities for an improved patient-provider relationship due to patients initiating interactions from viewing notes. Oncologists believe notes are not intended for patients and altering their content may compromise the integrity of the note. This study established a baseline for further study to compare notes pre-implementation to post-implementation. Further analysis will clarify whether oncologists are altering the style and content of their notes and determine the presence of patient-centered language.

Identifying How Patient Portals Impact Communication in Oncology.

Patient portals are becoming widespread throughout health-care systems. Initial research has demonstrated that they positively impact patient-provider communication and patients' health knowledge, but little is known about the impact of patient portals in the cancer setting, where highly complex and uncertain medical data are available for patients to view. To better understand communicative behaviors and perceptions of the patient portal and how it is utilized in oncology, in-depth, semi-structured interviews were conducted with 48 participants: 35 patients and 13 oncologists. Thematic analysis identified that portals help to enhance participation during in-person consultations, increase patients' self-advocacy, and build rapport with providers. However, patients' comfort level with reviewing information via the portal depended upon the severity of the test. Oncologists worried about patient anxiety and widening health disparities, but acknowledged that the portal can motivate them to expedite communication about laboratory and scan results. As patient portals become more widely used in all medical settings, oncologists should become more engaged with how patients are viewing their medical information and consider the portal within the framework of patient-centered care by valuing patients' communication preferences.

Implications of Patient Portal Transparency in Oncology: Qualitative Interview Study on the Experiences of Patients, Oncologists, and Medical Informaticists.

BACKGROUND: Providing patients with unrestricted access to their electronic medical records through patient portals has impacted patient-provider communication and patients' personal health knowledge. However, little is known about how patient portals are used in oncology. OBJECTIVE: The aim of this study was to understand attitudes of the portal's adoption for oncology and to identify the advantages and disadvantages of using the portal to communicate and view medical information. METHODS: In-depth semistructured interviews were conducted with 60 participants: 35 patients, 13 oncologists, and 12 medical informaticists. Interviews were recorded, transcribed, and thematically analyzed to identify critical incidents and general attitudes encountered by participants. RESULTS: Two primary themes were discovered: (1) implementation practices influence attitudes, in which the decision-making and execution process of introducing portals throughout the hospital did not include the input of oncologists. Lack of oncologists' involvement led to a lack of knowledge about portal functionality, such as not knowing the time period when test results would be disclosed to patients; (2) perceptions of portals as communication tools varies by user type, meaning that each participant group (patients, oncologists, and medical informaticists) had varied opinions about how the portal should be used to transmit and receive information. Oncologists and medical informaticists had difficulty understanding one another's culture and communication processes in their fields, while patients had preferences for how they would like to receive communication, but it largely depended upon the type of test being disclosed. CONCLUSIONS: The majority of patients (54%, 19/35) who participated in this study viewed lab results or scan reports via the portal before being contacted by a clinician. Most were relatively comfortable with this manner of disclosure but still preferred face-to-face or telephone communication. Findings from this study indicate that portal education is needed for both patients and oncologists, especially when portals are implemented across entire health systems since highly specialized areas of medicine may have unique needs and uses. Patient portals in oncology can potentially alter the way diagnoses are delivered and how patients and oncologists communicate. Therefore, communication about the portal should be established during initial consultations so patients can decide whether they want to be informed in such a manner.

Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial.

BACKGROUND: Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. METHODS: In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m2, leucovorin at 400 mg/m2, irinotecan at 140 mg/m2, and fluorouracil 400 mg/m2 bolus followed by 2400 mg/m2 over 46 h). We applied a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m2 per day; the dose level was then escalated by doubling the previous dose if there were no adverse events worse than grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxic effects attributed as probably or definitely related to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. The primary objective was to establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting toxicities). This trial is registered with ClinicalTrials.gov, number NCT01835041, and is closed to recruitment. FINDINGS: Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m2. The median number of treatment cycles given at the maximum tolerated dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a higher dose of 1000 mg/m2, and both had a dose-limiting toxicity. Two unexpected serious adverse events occurred, both for the first patient enrolled. Expected serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for patient number 2; anaemia and lymphopenia were dose-limiting toxicities); hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis (patient number 11); and neutropenia (patient number 20). No deaths due to adverse events were reported. For the 18 patients given the maximum tolerated dose, the most common grade 3-4 non-haematological adverse events were hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]). The most common grade 3-4 haematological adverse events were neutropenia (five [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded in 17 (94%) of the 18 patients and was managed with dose de-escalation or discontinuation per standard of care. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Of the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective (complete or partial) response. INTERPRETATION: A maximum tolerated dose of CPI-613 was established at 500 mg/m2 when used in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of clinical activity will require validation in a phase 2 trial. FUNDING: Comprehensive Cancer Center of Wake Forest Baptist Medical Center.

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (EPOCH) With or Without Rituximab as First-Line Therapy for Aggressive Non-Hodgkin Lymphoma.

INTRODUCTION: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) was developed in an effort to overcome inadequate drug concentrations and compensate for increased drug clearance. The goal of the present study was to examine the risk factors and outcomes of patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH. PATIENTS AND METHODS: We report the data from 136 patients with previously untreated aNHL who received infusional DA-EPOCH chemotherapy with or without rituximab from 2005 to 2013. Overall survival was estimated using Kaplan-Meier methods. Univariate and multivariate logistic regression was used to determine the factors associated with death, progression, or relapse at 2 years. RESULTS: The overall response rate was 82%. The relapse-free survival rate at 1, 3, and 5 years was 68%, 63%, and 52% with 95% confidence intervals (CIs) of 0.59% to 0.85%, 0.54% to 0.70%, and 0.31% to 0.70%, respectively. Patients with T-cell aNHL had an increased risk of death, progression, or relapse (Odds Ratio, 3.5; 95% CI, 1.4-8.8) compared with those with B-cell aNHL. In multivariate analysis, current smoking, disease in the bone marrow, and the number of cycles completed were independent predictors of death and relapse. CONCLUSION: Our data suggest that EPOCH with or without rituximab is active in both B- and T-cell aNHL. Toxicity did not significantly affect timing of treatment delivery or treatment outcomes. Dose adjustment by hematopoietic nadir similarly had no effect. The effect of smoking during chemotherapy should be evaluated further.

Treatment decisional regret among men with prostate cancer: Racial differences and influential factors in the North Carolina Health Access and Prostate Cancer Treatment Project (HCaP-NC).

BACKGROUND: It has been demonstrated that treatment decisional regret affects quality of life in patients with prostate cancer (CaP); however, there are limited studies that identify factors associated with treatment decisional regret, particularly within a racially diverse patient population that has extended follow-up. METHODS: Logistic regression analysis was used to determine associations between decisional regret and potential predictors in a population-based cohort of 348 African American men and 446 Caucasian American men approximately 3 years after CaP diagnosis. RESULTS: Of 794 research participants, 12% experienced treatment decisional regret. Decisional regret was associated with androgen-deprivation therapy (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.1-4.0), recent urinary bother (OR, 3.4; 95% CI, 1.6-7.3), satisfaction with understanding potential treatment side effects (very unsatisfied: OR, 13.3; 95% CI, 5.5-32.2; somewhat unsatisfied: OR, 5.0; 95% CI, 2.3-11.2; neutral: OR, 3.8; 95% CI, 1.9-7.6), and CaP treatment effect on the spousal relationship (very affected: OR, 3.9; 95% CI, 2.0-7.6; somewhat affected: OR, 3.1; 95% CI, 1.4-7.3; neutral: OR, 2.4; 95% CI, 1.9-7.6). Younger African Americans were more likely to experience regret than older African Americans (OR, 3.0; 95% CI, 1.1-8.1), and older African Americans were less likely to experience regret than older Caucasian Americans (OR, 0.2; 95% CI, 0.1-0.7). CONCLUSIONS: Treatment decisional regret remains an important issue in CaP survivors beyond initial treatment. Potential interventions should involve younger African Americans and patient spouses. Increased regret may reflect the unexpected influence of treatment side effects on the patient's everyday life; helping the patient relate potential side effects to his individual situation could improve patient satisfaction.