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Background: Optimal treatment of nonoperative patients with large, node-negative non–small cell lung cancer (NSCLC) is poorly defined. Current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend definitive radiotherapy (RT) with or without sequential chemotherapy and do not include concurrent chemoradiotherapy (chemoRT) as a treatment option. In this study, we identified factors that predict nonadherence to NCCN Guidelines. Patients and Methods: Patients who received definitive RT for nonmetastatic, node-negative NSCLC with tumor size of 5 to 7 cm were identified in the National Cancer Database from 2004 through 2016. Patients were evaluated by RT type (stereotactic body RT [SBRT], hypofractionated RT [HFRT], or conventionally fractionated RT [CFRT]) and chemotherapy use (none, sequential, or concurrent with RT). Patients were classified as receiving NCCN-adherent (RT with or without sequential chemotherapy) or NCCN-nonadherent (concurrent chemoRT) treatment. Demographic and clinical factors were assessed with logistic regression modeling. Overall survival was evaluated with Kaplan-Meier, log-rank, and univariable/multivariable Cox proportional hazards regression analyses. Results: Among 2,020 patients in our cohort, 32% received NCCN-nonadherent concurrent chemoRT, whereas others received NCCN-adherent RT alone (51%) or sequential RT and chemotherapy (17%). CFRT was most widely used (64% CFRT vs 22% SBRT vs 14% HFRT). Multivariable analysis revealed multiple factors to be associated with NCCN-nonadherent chemoRT: age ≤70 versus >70 years (odds ratio [OR] , 2.72; P<.001), treatment at a nonacademic facility (OR, 1.65; P<.001), and tumor size 6 to 7 cm versus 5 to 6 cm (OR, 1.27; P=.026). Survival was similar between the NCCN-nonadherent chemoRT and NCCN-adherent groups (hazard ratio, 1.00; P=.992) in multivariable analysis. Conclusions: A substantial proportion of inoperable patients with large, node-negative NSCLC are not treated according to NCCN Guidelines and receive concurrent chemoRT. Younger patients with larger tumors receiving treatment at nonacademic medical centers were more likely to receive NCCN-nonadherent therapy, but adherence to NCCN Guidelines was not associated with differences in overall survival.

Background: Psychological distress is common in patients with cancer. Distress can affect patients’ engagement with treatment. We examined the relationship between psychological distress and treatment timeliness in a sample of adult oncology patients at a safety-net hospital. Methods: A retrospective review was conducted of all patients screened for distress at a first outpatient oncology visit between March 1, 2014, and December 31, 2015 (n=500). The analytic sample (n=96) included patients with a new cancer diagnosis and a curative-intent treatment plan for lymphoma (stage I–IV), solid tumor malignancy (stage I–III), or head and neck cancer (stage I–IVb). Distress was measured using the Hospital Anxiety and Depression Scale. Using Poisson regression, we determined the effects of depression and anxiety on treatment timeliness. Patient age, sex, race/ethnicity, insurance type, cancer site, and cancer stage were included as covariates. Results: Mean patient age was 54 years. The median treatment initiation interval was 28 days. Clinically significant anxiety was present in 34% of the sample, and clinically significant depression in 15%. Greater symptom severity in both anxiety and depression were associated with a longer treatment initiation interval after controlling for demographics and disease factors. The average days to treatment (DTT) was 4 days longer for patients with elevated anxiety scores and for those with elevated depression scores compared with those without. Overall survival was not associated with anxiety, depression, or DTT. Conclusions: In this safety-net patient sample, greater psychological distress was associated with slower time to treatment. As of writing, this is a new finding in the literature, and as such, replication studies utilizing diverse samples and distress measurement tools are needed.

Background: Breast cancer care requires coordination between multiple diagnostic and treatment modalities. Disparities such as age, race/ethnicity, and socioeconomic status are associated with delays in care. This study investigates whether primary language is associated with delays in breast cancer diagnosis and treatment before and through radiotherapy (RT). Patients and Methods: This study was an institutional retrospective matched-cohort analysis of women treated with breast RT over 2 years. A total of 65 non–English-speaking (NES) patients were matched with 195 English-speaking (ES) patients according to stage, age, and chemotherapy delivery. Key time intervals along the breast cancer care path from initial findings through RT were recorded. Data were analyzed in a mixed model with matching as the random effect. The impact of race and insurance status was analyzed in addition to language. Results: Significant delays were found for NES patients, which varied by race. NES Latina patients experienced the longest delay, with a mean total care-path time of 13.53 months (from initial findings to end of RT) versus 8.18 months for all ES patients (P<.0001). Specifically, their mean total care-path time was 5.97 months longer than that of ES Latina patients (P=.001) and 5.80 months longer than that of ES White patients (P<.0001). In addition, NES Latina patients had a significantly longer total care-path time than NES patients of other races/ethnicities (P=.001). Delays were specifically seen between initial clinical or radiographic findings and diagnostic mammogram (P=.001) and between biopsy and resection (P=.044). Beyond language, race/ethnicity was itself associated with delays between resection and start of RT (P=.032) and between start and end of RT (P=.022). Conclusions: Language is associated with pre-RT delays in breast cancer care, especially for NES Latina patients. Delays are most pronounced before diagnostic mammograms, but they also exist before resection and RT. Future work should target NES patients to assist their progress along the care path.

Background: This study used a linked dataset consisting of all childhood cancers recorded over the course of 10 years in New South Wales (NSW), Australia, to evaluate the hospital and emergency department costs (from a payer perspective) and resources used by patients with childhood cancer. We also analyzed determinants responsible for high-frequency hospital admissions, hospital length of stay (LoS), and hospital costs. Methods: We analyzed linked data at the individual patient level for a retrospective cohort of 2,966 patients with cancer aged <18 years with a diagnosis date between 2001 and 2012 from the NSW Central Cancer Registry, Australia. We reported costs and use of hospitalization and emergency department presentation 1 year before the date of diagnosis, 1 year after diagnosis, and 2 to 5 years after diagnosis. We also examined the association between cancer types and hospital admission and hospital costs from the payer perspective. Patient characteristics associated with the frequency of hospital admissions, hospital LoS, and hospital costs were also determined using a generalized linear model. Results: Most hospital admission costs occurred in the first year after diagnosis, accounting for >70% of hospital costs within 5 years after diagnosis. The estimated median annual cost of hospitalization in the first year after diagnosis was A$88,964 (interquartile range [IQR], A$34,399–A$163,968) for patients diagnosed at age 0 to 14 years and A$23,384 (IQR, A$5,585–A$91,565) for those diagnosed at age 15 to 17 years. Higher frequency of hospital admissions, hospital LoS, and hospital costs were significantly associated with younger age at cancer diagnosis, cancer metastases, and living in remote/disadvantaged socioeconomic areas. Conclusions: Our study represents one of the first in Australia to include detailed hospitalization cost information for all childhood cancer cases. This study highlights the high hospital use by pediatric patients and the importance of early diagnosis. Our findings also demonstrate the health inequities experienced by patients from remote areas and the lowest socioeconomic areas.

Background: Advance care planning (ACP) involves documentation of patients’ preferred place of death (PoD). This assumes that patients’ preferred PoD will not change over time; yet, evidence for this is inconclusive. We aimed to assess the extent and correlates of change in patients’ preferred PoD over time. Materials and Methods: Using data from a cohort study of patients with advanced cancer in Singapore, we analyzed preferred PoD (home vs institution including hospital, hospice, and nursing home vs unclear) among 466 patients every 6 months for a period of 2 years. At each time point, we assessed the proportion of patients who changed their preferred PoD from the previous time point. Using a multinomial logistic regression model, we assessed patient factors (demographics, understanding of disease stage, ACP, recent hospitalization, quality of life, symptom burden, psychologic distress, financial difficulty, prognosis) associated with change in their preferred PoD. Results: More than 25% of patients changed their preferred PoD every 6 months, with no clear trend in change toward home or institution. Patients psychologically distressed at the time of the survey had increased likelihood of changing their preferred PoD to home (relative risk ratio [RRR], 1.02; 95% CI, 1.00–1.05) and to an institution (RRR, 1.06; 95% CI, 1.02–1.10) relative to no change in preference. Patients hospitalized in the past 6 months were more likely to change their preferred PoD to home (RRR, 1.56; 95% CI, 1.07–2.29) and less likely to change to an institution (RRR, 0.50; 95% CI, 0.28–0.88) relative to no change in preference. Conclusions: The present study provides evidence of instability in the preferred PoD of patients with advanced cancer. ACP documents need to be updated regularly to ensure they accurately reflect patients’ current preference.

Background: Advance care planning (ACP) involves documentation of patients’ preferred place of death (PoD). This assumes that patients’ preferred PoD will not change over time; yet, evidence for this is inconclusive. We aimed to assess the extent and correlates of change in patients’ preferred PoD over time. Materials and Methods: Using data from a cohort study of patients with advanced cancer in Singapore, we analyzed preferred PoD (home vs institution including hospital, hospice, and nursing home vs unclear) among 466 patients every 6 months for a period of 2 years. At each time point, we assessed the proportion of patients who changed their preferred PoD from the previous time point. Using a multinomial logistic regression model, we assessed patient factors (demographics, understanding of disease stage, ACP, recent hospitalization, quality of life, symptom burden, psychologic distress, financial difficulty, prognosis) associated with change in their preferred PoD. Results: More than 25% of patients changed their preferred PoD every 6 months, with no clear trend in change toward home or institution. Patients psychologically distressed at the time of the survey had increased likelihood of changing their preferred PoD to home (relative risk ratio [RRR], 1.02; 95% CI, 1.00–1.05) and to an institution (RRR, 1.06; 95% CI, 1.02–1.10) relative to no change in preference. Patients hospitalized in the past 6 months were more likely to change their preferred PoD to home (RRR, 1.56; 95% CI, 1.07–2.29) and less likely to change to an institution (RRR, 0.50; 95% CI, 0.28–0.88) relative to no change in preference. Conclusions: The present study provides evidence of instability in the preferred PoD of patients with advanced cancer. ACP documents need to be updated regularly to ensure they accurately reflect patients’ current preference.

Background: Immune checkpoint inhibitor (ICI) therapy predisposes patients to immune-related adverse events (irAEs). Data are limited regarding the incidence, management, and outcomes of one such irAE: mucositis. In this study, we evaluated the clinical characteristics, disease course, treatment, and outcomes of ICI-mediated mucositis. Methods: This was a retrospective, single-center study of patients who received ICI therapy and developed oral mucositis at The University of Texas MD Anderson Cancer Center from January 2009 to September 2019. Inclusion criteria included age ≥18 years, a diagnosis of oral mucositis and/or stomatitis based on ICD-9 and ICD-10 codes, and therapy using CTLA-4 or PD-1/L1 inhibitors alone or combined with other agents. Results: We identified 152 patients with a mean age of 60 years, 51% of whom were men. Of the sample patients, 73% had stage IV cancer, with melanoma the most common (28%). Median time from ICI initiation to mucositis was 91 days. The most common clinical presentation of mucositis was odynophagia and/or oral pain (89%), 91% developed CTCAE grade 1–2 mucositis, and 78% received anti–PD-1/L1 monotherapy. Compared with anti–PD-1/L1–based therapy, anti–CTLA-4–based therapy was more frequently associated with earlier onset of mucositis (73 vs 96 days; P=.077) and a lower rate of symptom resolution (76% vs 92%; P=.029); 24% of patients required immunosuppressive therapy, which was associated with longer symptom duration (84 vs 34 days; P=.002) and higher mucositis recurrence rate (61% vs 32%; P=.006). ICI interruption was associated with worse survival (P=.037). Mucositis recurrence, immunosuppressant use, and presence of other irAEs did not affect survival. Conclusions: For ICI-mediated mucositis, a diagnosis of exclusion has not been well recognized and is understudied. Although the clinical symptoms of mucositis are mostly mild, approximately 25% of patients require immunosuppression. Mucositis recurrence can occur in approximately 39% patients. Our results showed that ICI interruption compromises overall survival.

Background: In the CASPIAN trial, durvalumab + chemotherapy demonstrated significant improvements in overall survival compared with chemotherapy alone in patients with extensive-stage small cell lung cancer (SCLC). We aimed to assess the cost-effectiveness of durvalumab in patients with extensive-stage SCLC from the US healthcare system perspective. Patients and Methods: A comprehensive Markov model was adapted to evaluate cost and effectiveness of durvalumab combination versus platinum/etoposide alone in the first-line therapy of extensive-stage SCLC based on data from the CASPIAN study. The main endpoints included total costs, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-e-ectiveness ratios (ICERs). Model robustness was assessed with sensitivity analysis, and additional subgroup analyses were also performed. Results: Durvalumab + chemotherapy therapy resulted in an additional 0.27 LYs and 0.20 QALYs, resulting in an ICER of $464,711.90 per QALY versus the chemotherapy treatment. The cost of durvalumab has the greatest influence on this model. Subgroup analyses showed that the ICER remained higher than $150,000/QALY (the willingness-to-pay threshold in the United States) across all patient subgroups. Conclusions: Durvalumab in combination with platinum/etoposide is not a cost-effective option in the first-line treatment of patients with extensive-stage SCLC.

Background: Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites. We sought to investigate whether having an AGM is associated with altered outcomes and whether ICI responses are dampened in the adrenal glands. Patients and Methods: We retrospectively compared ICI responses and overall survival (OS) in 68 patients with melanoma who were diagnosed with an AGM and a control group of 100 patients without AGMs at a single institution. Response was determined using RECIST 1.1. OS was calculated from time of ICI initiation, anti–PD-1 initiation, initial melanoma diagnosis, and stage IV disease diagnosis. Tumor-infiltrating immune cells were characterized in 9 resected AGMs using immunohistochemical analysis. Results: Response rates of AGMs were significantly lower compared with other metastatic sites in patients with AGMs (16% vs 22%) and compared with those without AGMs (55%). Patients with AGMs also had significantly lower median OS compared with those without AGMs (3.1 years vs not reached, respectively). We further observed that despite this, AGMs exhibited high levels of tumor-infiltrating immune cells. Conclusions: In this cohort of patients with melanoma, those diagnosed with an AGM had lower ICI response rates and OS. These results suggest that tissue-specific microenvironments of AGMs present unique challenges that may require novel, adrenal gland–directed therapies or surgical resection.

Background: Opioid titration is necessary to achieve rapid, safe pain relief. Medication can be administered via patient-controlled analgesia (PCA) or by a healthcare provider (non-PCA). We evaluated the efficacy of intravenous PCA versus non-PCA hydromorphone titration for severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]). Patients and Methods: Patients with severe cancer pain were randomized 1:1 to PCA or non-PCA titration, stratified by opioid-tolerant or opioid-naïve status. The PCA pump was set to no continuous dose, with a hydromorphone bolus dose 10% to 20% of the total previous 24-hour equianalgesic (for opioid-tolerant patients) or 0.5 mg (for opioid-naïve patients). For the non-PCA group, the initial hydromorphone bolus dose was identical to that in the PCA group, with the subsequent dose increased by 50% to 100% (for NRS unchanged or increased) or repeated at the current dose (for NRS 4–6). Hydromorphone delivery was initiated every 15 minutes (for NRS ≥4) or as needed (for NRS ≤3). The primary endpoint was time to successful titration (TST; time from first hydromorphone dose to first occurrence of NRS ≤3 in 2 consecutive 15-minute intervals). Results: Among 214 patients (PCA, n=106; non-PCA, n=108), median TSTs (95% CI) were 0.50 hours (0.25–0.50) and 0.79 hours (0.50–1.42) for the PCA and non-PCA groups, respectively (hazard ratio [HR], 1.64; 95% CI, 1.23–2.17; P=.001). TSTs in opioid-tolerant patients were 0.50 hours (0.25–0.75) and 1.00 hours (0.50–2.00) for the PCA and non-PCA groups, respectively (HR, 1.92; 95% CI, 1.32–2.78; P=.003); in opioid-naive patients, TST was not significantly different for the PCA versus non-PCA groups (HR, 1.35; 95% CI, 0.88–2.04; P=.162). Pain score (median NRS; interquartile range) over 24 hours was significantly lower in the PCA group (2.80; 2.15–3.22) than in the non-PCA group (3.00; 2.47–3.53; P=.020). PCA administration produces significantly higher patient satisfaction with pain control than non-PCA administration (P<.001). Conclusions: Intravenous hydromorphone titration for severe cancer pain was achieved more effectively with PCA than with non-PCA administration.