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.
Chetna Malhotra, Ling En Koh, Irene Teo, Semra Ozdemir, Isha Chaudhry, Eric Finkelstein, and on behalf of the COMPASS Study Team
Jake S. Jacob, Barbara E. Dutra, Victor Garcia-Rodriguez, Kavea Panneerselvam, Fiyinfoluwa O. Abraham, Fangwen Zou, Weijie Ma, Petros Grivas, John A. Thompson, Mehmet Altan, Isabella C. Glitza Oliva, Hao Chi Zhang, Anusha S. Thomas, and Yinghong Wang
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.
Dong Ding, Huabin Hu, Shuosha Li, Youwen Zhu, Yin Shi, Mengting Liao, Jin Liu, Xu Tian, Aiting Liu, and Jin Huang
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.
Jessica S.W. Borgers, Richard P. Tobin, Robert J. Torphy, Victoria M. Vorwald, Robert J. Van Gulick, Carol M. Amato, Dasha T. Cogswell, Tugs-Saikhan Chimed, Kasey L. Couts, Adrie Van Bokhoven, Christopher D. Raeburn, Karl D. Lewis, Joshua Wisell, Martin D. McCarter, Rao R. Mushtaq, and William A. Robinson
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.
Rongbo Lin, Sunzhi Lin, Shuitu Feng, Qingyi Wu, Jianqian Fu, Fang Wang, Hui Li, Xiaofeng Li, Gaowang Zhang, Yongzhi Yao, Min Xin, Tianyang Lai, Xia Lv, Yigui Chen, Shangwang Yang, Yubiao Lin, Lixia Hong, Zhenyu Cai, Jianfeng Wang, Gen Lin, Shaowei Lin, Shen Zhao, Jinfeng Zhu, and Cheng Huang
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.
Courtney Lawhn Heath, Laura J. Esserman, Robert R. Flavell, and Michelle E. Melisko
Daniel J. Boffa, Keith B. Churchwell, and Richard C. Maduka
Jeffrey S. Dome, Elizabeth A. Mullen, David B. Dix, Eric J. Gratias, Peter F. Ehrlich, Najat C. Daw, James I. Geller, Murali Chintagumpala, Geetika Khanna, John A. Kalapurakal, Lindsay A. Renfro, Elizabeth J. Perlman, Paul E. Grundy, and Conrad V. Fernandez
Refinements in surgery, radiation therapy, and chemotherapy since the mid-20th century have resulted in a survival rate exceeding 90% for patients with Wilms tumor (WT). Although this figure is remarkable, a significant proportion of patients continue to have event-free survival (EFS) estimates of <75%, and nearly 25% of survivors experience severe chronic medical conditions. The first-generation Children’s Oncology Group (COG) renal tumor trials (AREN ‘0’), which opened to enrollment in 2006, focused on augmenting treatment regimens for WT subgroups with predicted EFS <75% to 80%, including those with the adverse prognostic marker of combined loss of heterozygosity (LOH) at chromosomes 1p/16q, pulmonary metastasis with incomplete lung nodule response after 6 weeks of chemotherapy, bilateral disease, and anaplastic histology. Conversely, therapy was reduced for patient subgroups with good outcomes and potential for long-term toxicity, such as those with lung metastasis with complete lung nodule response after 6 weeks of chemotherapy. This article summarizes the key findings of the first-generation COG renal tumor studies and their implications for clinical practice.