Quality of Medication Cost Conversations and Interest in Future Cost Conversations Among Older Adults.

BACKGROUND: Medication cost conversations occur less frequently than patients prefer, and it is unclear whether patients have positive experiences with them when they do occur. OBJECTIVE: To describe patients' experiences discussing their medication costs with their health care team. DESIGN: Cross-sectional survey. SETTING: Nationally representative survey fielded in the United States in 2022 (response rate = 48.5%). PATIENTS: 1020 adults over age 65. MEASUREMENTS: Primary measures were adapted from Clinician and Group Consumer Assessment of Healthcare Providers Survey visit survey v4.0 and captured patients' experiences of medication cost conversations. Additional measures captured patients' interest in future cost conversations, the type of clinicians with whom they would be comfortable discussing costs, and sociodemographic characteristics. RESULTS: Among 1020 respondents who discussed medication prices with their health care team, 39.3% were 75 or older and 78.6% were non-Hispanic White. Forty-three percent of respondents indicated that their prior medication cost conversation was not easy to understand; 3% indicated their health care team was not respectful and 26% indicated their health care team was somewhat respectful during their last conversation; 48% indicated that there was not enough time. Those reporting that their prior discussion was not easy to understand or that their clinician was not definitely respectful were less likely to be interested in future discussions. Only 6% and 10% of respondents indicated being comfortable discussing medication prices with financial counselors or social workers, respectively. Few differences in responses were observed by survey participant characteristics. LIMITATIONS: This cross-sectional survey of prior experiences may be subject to recall bias. CONCLUSION: Among older adults who engaged in prior medication cost conversations, many report that these conversations are not easy to understand and that almost one-third of clinicians were somewhat or not respectful. Efforts to increase the frequency of medication cost conversations should consider parallel interventions to ensure the discussions are effective at informing prescribing decisions and reducing cost-related medication nonadherence.

Cost-Related Medication Nonadherence and Desire for Medication Cost Information Among Adults Aged 65 Years and Older in the US in 2022.

Importance: Rising prescription drug costs and increasing prices for consumer goods may increase cost-related medication nonadherence. Cost-conscious prescribing can be supported by real-time benefit tools, but patient views on real-time benefit tool use and their potential benefits and harms are largely unexplored. Objective: To assess older adults' cost-related medication nonadherence, cost-coping strategies, and views on the use of real-time benefit tools in clinical practice. Design, Setting, and Participants: A weighted, nationally representative survey of adults aged 65 years and older administered via the internet and telephone from June 2022 to September 2022. Main Outcomes and Measures: Cost-related medication nonadherence; cost coping strategies; desire for cost conversations; potential benefits and harms from real-time benefit tool use. Results: Among 2005 respondents, most were female (54.7%) and partnered (59.7%); 40.4% were 75 years or older. Cost-related medication nonadherence was reported by 20.2% of participants. Some respondents used extreme forms of cost-coping, including foregoing basic needs (8.5%) or going into debt (4.8%) to afford medications. Of respondents, 89.0% reported being comfortable or neutral about being screened before a physician's visit for wanting to have medication cost conversations and 89.5% indicated a desire for their physician to use a real-time benefit tool. Respondents expressed concern if prices were inaccurate, with 49.9% of those with cost-related nonadherence and 39.3% of those without reporting they would be extremely upset if their actual medication price was more than what their physician estimated with a real-time benefit tool. If the actual price was much more than the estimated real-time benefit tool price, nearly 80% of respondents with cost-related nonadherence reported that it would affect their decision to start or keep taking a medication. Furthermore, 54.2% of those with any cost-related nonadherence and 30% of those without reported they would be moderately or extremely upset if their physicians used a medication price tool but chose not to discuss prices with them. Conclusions and Relevance: In 2022, approximately 1 in 5 older adults reported cost-related nonadherence. Real-time benefit tools may support medication cost conversations and cost-conscious prescribing, and patients are enthusiastic about their use. However, if disclosed prices are inaccurate, there is potential for harm through loss of confidence in the physician and nonadherence to prescribed medications.

A Large-Scale Proteomics Resource of Circulating Extracellular Vesicles for Biomarker Discovery in Pancreatic Cancer.

Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy earlier. Analyzing circulating extracellular vesicles (cEVs) using 'liquid biopsies' offers an attractive approach to diagnose and monitor disease status. However, it is important to differentiate EV-associated proteins enriched in patients with pancreatic ductal adenocarcinoma (PDAC) from those with benign pancreatic diseases such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). To meet this need, we combined the novel EVtrap method for highly efficient isolation of EVs from plasma and conducted proteomics analysis of samples from 124 individuals, including patients with PDAC, benign pancreatic diseases and controls. On average, 912 EV proteins were identified per 100µL of plasma. EVs containing high levels of PDCD6IP, SERPINA12 and RUVBL2 were associated with PDAC compared to the benign diseases in both discovery and validation cohorts. EVs with PSMB4, RUVBL2 and ANKAR were associated with metastasis, and those with CRP, RALB and CD55 correlated with poor clinical prognosis. Finally, we validated a 7-EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC.

"Worth it if you could afford it": Patient perspectives on integrating real-time benefit tools into drug cost conversations.

BACKGROUND: Medication costs can lead to financial burdens for patients, creating barriers to effective medication use. Health care provider use of real-time benefit tools (RTBTs) may facilitate cost conversations with patients. We sought to explicate patient views on how RTBTs could be used to improve cost considerations in prescribing decisions. METHODS: We conducted focus groups to characterize patient perspectives on holding cost conversations with their physicians and to identify factors that would influence the value of RTBTs. We focused on adults aged 50+ who reported trouble paying for their prescriptions. Three groups included patients with conditions requiring high-cost treatments and one group included lower-income patients independent of their medical conditions. Focus groups were recorded, transcribed, coded, and categorized to salient themes employing inductive and deductive approaches using the Health Equity Implementation Framework. RESULTS: Focus groups were conducted from 09/2020-12/2020 including 18 participants representing cancer (n = 6), diabetes (n = 6), rheumatoid arthritis (n = 3), and lower income (n = 3). Participants were between 50-74, eight self-identified as Black, 10 as White, and eight reported earning <$50,000/year. We identified five themes regarding cost conversations (medication cost importance, past experiences with cost/cost conversations, perception of physician's role and knowledge, knowledge of existing resources, and influence on decision-making) and four RTBT-use-specific themes (advantages/disadvantages, perceived relevance, data quality concerns, and implementation considerations). CONCLUSION: Approaches that envision RTBTs as one-size-fits-all technological interventions may underestimate the complexity of incorporating price information into prescribing decisions. Nevertheless, patients highlighted the potential value of accurate, real-time information on medication costs to inform decision-making.

Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Keratinocyte carcinomas (KCs) are the most diagnosed cancers worldwide and are commonly excised via complete margin assessment (CMA) or excision with sectional assessment (SA). National Comprehensive Cancer Network guidelines encourage CMA for KC with high-risk features. OBJECTIVE: To systematically compare recurrence outcomes for CMA vs SA in high-risk KC based on National Comprehensive Cancer Network guidelines criteria. MATERIALS AND METHODS: EMBASE and MEDLINE were searched for articles reporting recurrences of high-risk KC undergoing excision using CMA or SA. High-risk KCs were defined as recurrent, having perineural invasion (PNI), or basal cell carcinomas (BCC) with aggressive histology. Chi-squared tests and risk ratios evaluated differences between CMA and SA groups, and a random-effects meta-analysis was performed. RESULTS: Twenty-eight studies met inclusion criteria. Pooled percentages of locoregional recurrences were significantly lower with CMA vs SA for all KCs (3.9% [95% CI: 2.9-4.9] vs 13.5% [7.7, 19.2, p = .001]), cutaneous squamous cell carcinoma with PNI (9.8% [5.4-14.1] vs 32.0% [25.0-39.0], p < .001), and recurrent BCC (4.4% [2.9-5.9] vs 11.9% [8.0-15.8], p < .001). CONCLUSION: For high-risk KCs, recurrence risk was over 3-times greater with SA compared with CMA. Expanded access to CMA for high-risk KC is likely to reduce recurrence risk and improve clinical outcomes.

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes. EXPERIMENTAL DESIGN: PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes. RESULTS: A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients. CONCLUSIONS: These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.

Different Associations Between Inpatient or Outpatient Palliative Care and End-of-Life Outcomes for Hospitalized Patients With Cancer.

PURPOSE: Palliative care (PC) improves outcomes in advanced cancer, and guidelines recommend early outpatient referral. However, many PC teams see more inpatient than outpatient consults. We conducted a retrospective study of hospitalized patients with cancer to quantify exposure to inpatient and outpatient PC and describe associations between PC and end-of-life (EOL) quality measures. METHODS: We identified all decedents admitted to an inpatient oncology unit in 1 year (October 1, 2017-September 30, 2018) and abstracted hospitalization statistics, inpatient and outpatient PC visits, and EOL outcomes. Descriptive statistics, univariate tests, and multivariate analysis evaluated associations between PC and patient outcomes. RESULTS: In total, 522 decedents were identified. 50% saw PC; only 21% had an outpatient PC visit. Decedents seen by PC were more likely to enroll in hospice (78% v 44%; P < .001), have do-not-resuscitate status (87% v 55%; P < .001), have advance care planning documents (53% v 31%; P < .001), and die at home or inpatient hospice instead of in hospital (67% v 40%; P < .01). Decedents seen by PC had longer hospital length-of-stay (LOS; 8.4 v 7.0 days; P = .03), but this association reversed for decedents seen by outpatient PC (6.3 v 8.3 days; P < .001), who also had longer hospice LOS (46.5 v 27.1 days; P < .01) and less EOL intensive care (6% v 15%; P < .05). CONCLUSION: PC was associated with significantly more hospice utilization and advance care planning. Patients seen specifically by outpatient PC had shorter hospital LOS and longer hospice LOS. These findings suggest different effects of inpatient and outpatient PC, underscoring the importance of robust outpatient PC.

Durable Response to PD-1 Blockade in a Patient With Metastatic Pancreatic Undifferentiated Carcinoma With Osteoclast-Like Giant Cells.

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare and potentially aggressive variant of pancreatic ductal adenocarcinoma. Data on this disease are sparse, and despite genetic similarities to pancreatic ductal adenocarcinoma, UCOGC clinical outcomes can be markedly different. We report on a female patient aged 62 years who presented with UCOGC with pulmonary metastases initially treated with 2 lines of cytotoxic chemotherapy. After rapid disease progression with both cytotoxic treatments, the patient's tissue was sent for next-generation sequencing, which revealed a high tumor mutation burden (32 mutations per megabase), as well as somatic mutations in BRAF, NF1, PIK3CA, CDKN2A, TERT, and TP53. Pancreatic cancers have previously demonstrated suboptimal responses to immunotherapeutic approaches. However, given the high tumor mutation burden and distinctiveness of the tumor class, the patient began third-line pembrolizumab monotherapy after palliative radiation to the rapidly progressing and painful abdominal mass from her primary tumor. She had a marked response in her primary UCOGC tumor and metastatic sites, and she remains on pembrolizumab monotherapy with ongoing response after 32 months of therapy. Recent evidence showing significant PD-L1 enrichment on neoplastic cells of undifferentiated carcinomas (including UCOGC) may indicate a role for immunotherapeutic approaches in these patients. Rare cancers such as UCOGC and other undifferentiated carcinomas may benefit from next-generation sequencing to inform treatment decisions when standards of care are absent, as in this report.

Diagnostic Biopsy via In-Office Frozen Sections for Clinical Nonmelanoma Skin Cancer.

BACKGROUND: Treatment of nonmelanoma skin cancer (NMSC) by Mohs surgery has traditionally relied on previous pathologic evaluation of paraffin-embedded tissue. Tissue processing by frozen sections allows for expedited diagnosis and treatment; however, data on its accuracy are limited. OBJECTIVE: To measure the accuracy and outcomes of biopsy via frozen sections for clinical NMSC. METHODS: Biopsies of clinical NMSCs processed via frozen sections with in-office diagnosis rendered by one Mohs surgeon were retrospectively reviewed by one board-certified dermatopathologist. Discordant diagnoses were re-read in blinded fashion by both physicians. If still discordant, final diagnosis was determined by consensus discussion. Inter-rater reliability was calculated using Cohen's kappa statistic. RESULTS: Two hundred ninety-seven lesions from 208 patients were included. Correlation between in-office and final diagnosis was 0.876 indicating "almost perfect" concordance. Sensitivity and specificity of in-office diagnosis for detecting malignancy were 98.1% and 94.4%. Seven cases (2.0%) had a clinically relevant change in final diagnosis, but appropriate treatment had been rendered. Two benign lesions (0.7%) initially diagnosed as malignant underwent excision. CONCLUSION: In-office biopsy via frozen sections is highly accurate in confirming NMSC. This practice may speed diagnosis and treatment thus improving outcomes and patient satisfaction.

Brigham and Women's Hospital tumor classification system for basal cell carcinoma identifies patients with risk of metastasis and death.

BACKGROUND: Despite approximately 4400 locally advanced US cases annually, high-stage basal cell carcinoma (BCC) is ill-defined. OBJECTIVE: To develop a tumor (T) staging system for BCC that will predict metastasis/death and compare its performance with that of the American Joint Committee on Cancer 8th edition (AJCC8) T-staging system. METHODS: Brigham and Women's Hospital (BWH) T staging was developed from a previously published nested cohort of 488 primary BCCs. Tumors were staged via BWH and AJCC8 T-staging systems, and predictions of metastasis and/or death were compared. RESULTS: The BWH and AJCC8 T-staging systems both captured all metastases/deaths in high T stages (BWH, T2; AJCC8, T3/T4). BWH T2 included 54% fewer cases ≥2 cm than AJCC8 T3/T4. BWH had a higher specificity (0.92 vs 0.80; P < .001) and positive predictive value (24% vs 11%, P < .001) for identifying cases at risk for metastasis/death, and the C-statistic was superior for BWH (P < .001). The BWH T2 10-year cumulative incidence of metastasis/death was 37% (95% confidence interval, 21%-60%). LIMITATIONS: Two-center cohort. CONCLUSIONS: BWH and AJCC 8 BCC staging both capture all metastases and deaths in the upper stages. However, BWH staging does so in half the number of cases, thus minimizing inappropriate up-staging. The risk of metastasis or death in BWH T2 BCC is sufficient to warrant surveillance for recurrence and clinical trials of adjuvant therapy.

Factors predictive of recurrence, metastasis, and death from primary basal cell carcinoma 2 cm or larger in diameter.

BACKGROUND: Basal cell carcinoma (BCC) recurrence and metastatic rates are known to be very low. The risk factors for these rare outcomes are subsequently not well studied. OBJECTIVE: To identify risk factors independently associated with local recurrence (LR) and metastasis and/or death (M/D) in large (≥2 cm) BCC. METHODS: BCCs histologically confirmed between 2000 and 2009 were retrospectively screened for tumor diameter at 2 academic centers. Medical records of all large BCCs and an equal number of randomly selected small BCCs were reviewed for LR and M/D. RESULTS: Included were 248 large BCC and 248 small BCC tumors. Large BCCs had a significantly higher risk of LR and M/D than small BCCs (LR: 8.9% vs 0.8%, P < .001; M/D: 6.5% vs. 0%, P < .001). Because the risks were so low in small BCCs, they were excluded from further analysis. On multivariable logistic regression, head/neck location (odds ratio [OR], 9.7; 95% confidence interval [CI], 3.0-31.3) and depth beyond fat (OR, 3.1; 95% CI, 1.0-9.6) were associated with LR in large BCCs. Risk of LR was lower with Mohs micrographic surgery (OR, 0.14; 95% CI, 0.04-0.5). Head/neck location (OR, 5.3; 95% CI, 1.2-23.2), tumor diameter ≥4 cm (OR, 11.9; 95% CI, 2.4-59.4), and depth beyond fat (OR, 28.6; 95% CI, 6.7-121) were significant predictors of M/D in large BCCs. LIMITATIONS: Retrospective cohort design. CONCLUSIONS: Large BCCs, particularly those with additional risk factors, have a high enough risk of recurrence and metastasis to warrant further investigation to optimize management.

Chronic intestinal pseudo-obstruction in a patient with metastatic gastro-oesophageal junction cancer receiving treatment with pembrolizumab.

Acute gastrointestinal (GI) immune-related adverse events (irAE) are commonly reported by patients with cancer undergoing treatment with immune checkpoint inhibitors (CPI); however chronic irAEs are rare. We present a case of a 71-year-old woman with metastatic gastro-oesophageal junction (GOJ) adenocarcinoma who developed delayed-onset chronic intestinal pseudo-obstruction (CIPO) while receiving second-line pembrolizumab. Repeated CT scans of the abdomen/pelvis found no small bowel obstruction, and evaluations for bowel inflammation, infection and paraneoplastic syndrome were negative. Bowel rest and glucocorticoids were associated with transient symptom resolution; however, symptoms recurred within 1 month. The patient was ultimately supported with total parenteral nutrition and intestinal motility agents. After 4 months, the GOJ cancer remained stable with no signs of progression. As CPI use expands, the incidence of rare irAEs, such as CIPO, may increase.

Performance of the American Joint Committee on Cancer Staging Manual, 8th Edition vs the Brigham and Women's Hospital Tumor Classification System for Cutaneous Squamous Cell Carcinoma.

Importance: Brigham and Women's tumor classification (BWH) better predicts poor outcomes than American Joint Committee on Cancer (AJCC) 7th edition (AJCC 7). AJCC 8th edition (AJCC 8) has not been evaluated. Objectives: To compare BWH and AJCC 8 tumor classifications for head and neck cutaneous squamous cell carcinoma (HNCSCC). Design, Setting, and Participants: A total of 459 patients with 680 HNCSCCs in this cohort study were staged via BWH and AJCC 8 classifications and poor outcomes (ie, local recurrence [LR], nodal metastasis [NM], disease specific death [DSD], and overall survival [OS]) were compared. The study was carried out at a single academic tertiary care center in Boston, Massachusetts. Main Outcomes and Measures: Distinctiveness (outcome differences between tumor class), homogeneity (outcome similarity within tumor class), monotonicity (outcome worsening with increasing tumor class), and C statistic. Results: A total of 680 HNCSCCs in 459 patients were included in this study, of which 313 (68%) were men with the mean (SD) age of 70.2 (12.7) years. The AJCC 8 (T3/T4) and BWH (T2b/T3) high tumor classes accounted for 121 (18%) vs 63 (9%), 17 (71%) vs 16 (70%), and 11 (85%) vs 12 (92%) of total cases, metastases, and deaths, respectively. The AJCC 8 T2 and T3 comprised 23% of cases and had statistically indistinguishable outcomes. The BWH had higher specificity (93%) and positive predictive value (30%) for identifying cases at risk for metastasis or death. C statistics showed BWH to be superior in predicting NM and DSD (P = .01 and P = .005, respectively), but there was no difference for LR and OS. Conclusions and Relevance: Lack of distinction between AJCC T2 and T3 resulted in a 23% subset of HNCSCCs with significant risk of metastasis and death-too large of a group for routine nodal staging or consideration of adjuvant therapy. The BWH identifies the same number of poor outcomes in a 9% subset of HNCSCCs, thus minimizing inappropriate upstaging of low-risk disease.

Association of Nodal Metastasis and Mortality With Vermilion vs Cutaneous Lip Location in Cutaneous Squamous Cell Carcinoma of the Lip.

Importance: Although the lip is considered a high-risk location in cutaneous squamous cell carcinoma (cSCC), it has not been established whether this risk stems from vermilion or cutaneous locations or both. Objective: To compare differences in risks of recurrence, metastasis, and death from cSCCs on the vermilion vs cutaneous lip. Design, Setting, and Participants: Retrospective cohort study of 303 patients with 310 primary cSCCs of the lip (138 cutaneous, 172 vermilion) diagnosed between 2000 and 2015 at 2 academic tertiary care centers in Boston, Massachusetts. Main Outcomes and Measures: Development of local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death. Results: Of the 303 study participants with 310 SCCs of the lip, 153 (50.5%) were men, and 150 (49.5%) were women; median age at diagnosis, 68 years (range, 27-93 years). Outcomes were as follows for vermilion vs cutaneous locations: local recurrence, 6.4% (11 of 172) vs 2.9% (4 of 138); nodal metastasis, 7.6% (13 of 172) vs 1.5% (2 of 138); distant metastasis, 0.6% (1 of 172) vs 0.7% (1 of 138); disease-specific death, 3.5% (6 of 172) vs 2.9% (4 of 138); and all-cause death, 26.7% (46 of 172) vs 29.0% (40 of 138). The difference was statistically significant for nodal metastasis (P = .01). In multivariable analysis, nodal metastasis was associated with vermilion lip location (subhazard ratio, 5.0; 95% CI, 1.1-23.8) and invasion beyond fat (fascia or beyond for vermilion lip) (subhazard ratio, 4.4; 95% CI, 1.3-14.9). Conclusions and Relevance: The risk of nodal metastasis is 5-fold greater for cSCCs on the vermilion lip compared with those on the cutaneous lip. Squamous cell carcinomas of the cutaneous lip have a nodal metastasis risk similar to cSCCs in general (1.5%). Thus, vermilion involvement appears responsible for the increased risk associated with cSCC of lip. Vermilion involvement may merit radiologic nodal staging and inclusion in future tumor staging, since it was independently associated with higher-risk cSCC of the lip region.