Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data.

PURPOSE: Medications regulating immune homeostasis and gut microbiota could affect the efficacy of immune checkpoint inhibitors (ICIs). This study aimed to investigate the impact of concurrent medications on the clinical outcomes of patients with cancer receiving ICI therapy in South Korea. METHODS: We identified patients newly treated with ICI for non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and malignant melanoma (MM) between August 2017 and June 2020 from a nationwide database in Korea. The effect of concurrent antibiotics (ATBs), corticosteroids (CSs), proton-pump inhibitors (PPIs), and opioids prescribed within 30 days before ICI initiation on the treatment duration and survival was assessed. RESULTS: In all, 8870 patients were included in the ICI cohort (NSCLC, 7,128; UC, 960; MM, 782). The patients were prescribed ATBs (33.8%), CSs (47.8%), PPIs (28.5%), and opioids (53.1%) at the baseline. The median overall survival durations were 11.1, 12.2, and 22.1 months in NSCLC, UC, and MM subgroups, respectively, since starting the ICI mostly as second-line (NSCLC and UC) and first-line (MM) therapy. Early progression was observed in 34.2% of the patients. Opioids and CS were strongly associated with poor survival across all cancer types. A high number of concurrent medications was associated with early progression and short survival. Opioid and CS use was associated with poor prognosis in all patients treated with ICIs. However, ATBs and PPIs had a cancer-specific effect on survival. CONCLUSION: A high number of concurrent medications was associated with poor clinical outcomes.

The impact of systematic assessment for adverse events on unscheduled hospital utilization in patients receiving neoadjuvant or adjuvant chemotherapy: A retrospective multicenter study.

BACKGROUND: This study was conducted to compare the reported adverse event (AE) profiles and unexpected use of medical services during chemotherapy between before and after the healthcare reimbursement of AE evaluation in patients with cancer. PATIENTS AND METHODS: Using the electronic medical record database system, extracted patients with breast, lung, gastric, and colorectal cancers receiving neoadjuvant or adjuvant chemotherapy between September 2013 and December 2016 at four centers in Korea were matched using the 1:1 greedy method: pre-reimbursement group (n = 1084) and post-reimbursement group (n = 1084). Unexpected outpatient department (OPD), emergency room (ER) visit, hospitalization rates, and chemotherapy completion rates were compared between the groups. RESULTS: The baseline characteristics were well-balanced between the groups. By chemotherapy cycle, hospitalization (1.8% vs. 2.3%; p = 0.039), and ER visit rates (3.3% vs. 3.9%; p = 0.064) were lower in the post-reimbursement group than that in the pre-reimbursement group. In particular, since cycle 2, ER visit and hospitalization rates were significantly lower in the post-reimbursement group than those in the pre-reimbursement group (2.6% vs. 3.3%; p = 0.020 and 1.4% vs. 2.0%; p = 0.007, respectively), although no significant differences were observed during cycle 1. The OPD visit rates were similar between both groups, regardless of cycles. The post-reimbursement group had a higher proportion of patients who completed chemotherapy as planned than the pre-reimbursement group (93.5% vs. 90.1%; p = 0.006). Post-reimbursement group had more AEs reported, including alopecia, fatigue, diarrhea, anorexia, and peripheral neuropathy, during cycle 1 than the pre-reimbursement group, which significantly decreased after cycle 2. CONCLUSION: The introduction of healthcare reimbursement for AE evaluation may help physicians capture and appropriately manage AEs, consequently, decreasing hospital utilization and increasing chemotherapy completion rates.

Pilot study for the Psychometric Validation of the Sheffield Profile for Assessment and Referral to Care (SPARC) in Korean Cancer Patients.

PURPOSE: This study aimed to validate the Sheffield Profile for Assessment and Referral to Care (SPARC) as an effective tool for screening palliative care needs among Korean cancer patients. MATERIALS AND METHODS: The English version of the SPARC was translated by four Korean oncologists and reconciled by a Korean language specialist and a medical oncologist fluent in English. After the first version of the Korean SPARC (K-SPARC) was developed, back-translation into English was performed by a professional translator and bilingual oncologist. The back-translated version was reviewed by the original author (S.H.A.), and modifications were made (ver. 2). The second version of the K-SPARC was tested against other questionnaires, including the Functional Assessment of Cancer Therapy-General (FACT-G) and the Edmonton Symptom Assessment System (ESAS). RESULTS: Thirty patients were enrolled in the pilot trial. Fifteen were male, and the median age was 64.5 years. Six patients had an Eastern Cooperative Oncology Group performance status of 2 or more. All patients except one were receiving chemotherapy. Regarding internal consistency, the Cronbach's α scores for physical symptoms, psychological issues, religious and spiritual issues, independency and activity, family and social issues, and treatment issues were 0.812, 0.804, 0.589, 0.843, 0.754, and 0.822, respectively. The correlation coefficients between the SPARC and FACT-G were 0.479 (p=0.007) for the physical domain and -0.130 (p=0.493) for the social domain. CONCLUSION: This pilot study indicates that the K-SPARC could be a reliable tool to screen for palliative care needs among Korean cancer patients. A further study to validate our findings is ongoing.

Delirium and its consequences in the specialized palliative care unit: Validation of the Korean version of Memorial Delirium Assessment Scale.

OBJECTIVES: Delirium is highly prevalent in patients with advanced cancer. This study aimed to investigate delirium rates and potential associated factors such as mortality in patients admitted to an acute palliative care unit (APCU). Our second aim was to validate the Korean version of the Memorial Delirium Assessment Scale (K-MDAS). METHODS: A total of 102 patients with advanced cancer, and who were admitted to the APCU, were assessed. Demographic data were collected alongside clinical diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, clinical symptoms according to the Edmonton Symptom Assessment System, history of smoking, alcohol use, hypnotic use, and daily dose of morphine were collected. The Confusion Assessment Method, the Delirium Rating Scale-Revised 98, and the K-MDAS were measured at admission and 1 week later. RESULTS: Twenty-four patients (23.52%) were diagnosed with delirium, and associated factors were old age (P = 0.007), higher ECOG (P = 0.011), and drowsiness (P < 0.001). The presence of delirium was an independent predictor of 1-month mortality; male gender, higher body mass index, and hypnotic use were also related to 1-month mortality. The K-MDAS had reliable internal consistency (α = 0.942) and showed sensitivity of 0.958 and specificity of 0.921 at the optimal cutoff score for diagnosing delirium of 9. CONCLUSIONS: Delirium was prevalent in patients admitted to the APCU and was associated with 1-month mortality. The K-MDAS showed acceptable reliability and validity and can be used to screen for delirium in a palliative care setting.

A population-based outcomes study of patients with metastatic gastric cancer receiving second-line chemotherapy: A nationwide health insurance database study.

PURPOSE: The survival benefit of second-line chemotherapy in patients with metastatic gastric cancer (MGC) has recently been established. We conducted a nationwide population-based outcomes study of patients with MGC receiving second-line chemotherapy to better understand real-world treatment patterns and outcomes. MATERIALS AND METHODS: Data were collected from the Health Insurance Review and Assessment Service database. We identified 509 newly diagnosed patients with MGC in 2010 who received second-line chemotherapy. These patients were divided into three groups for analyses: Group A comprised all patients who received second-line chemotherapy (N = 509); Group B comprised those who received fluoropyrimidine (Fp) plus platinum as first-line treatment, followed by irinotecan-based or taxane-based regimens as second-line chemotherapy (N = 284); and Group C comprised those who received Fp plus cisplatin as first-line treatment, followed by 5-fluorouracil (5-FU)/oxaliplatin, irinotecan-based, or taxane-based regimens as second-line chemotherapy (N = 184). RESULTS: Among patients who received first-line chemotherapy, 47.2% (509/1,078) continued to receive second-line chemotherapy. The most commonly used second-line chemotherapy regimens were 5-FU/irinotecan, 5-FU/oxaliplatin, and docetaxel. The median overall survival (OS) of all 509 patients was 5.2 months. The time from the start date of first-line chemotherapy to the start date of second-line chemotherapy > 6.1 months was an independent prognostic factor for improved OS. The type of chemotherapy regimen was not a significant factor affecting OS. CONCLUSION: The findings provide a better understanding of second-line treatment patterns and outcomes in patients with MGC and will help guide treatment decisions in real-world clinical practice.

Low-dose nivolumab can be effective in non-small cell lung cancer: alternative option for financial toxicity.

OBJECTIVES: Nivolumab is used at 3 mg/kg or fixed doses of 240 mg every 2 weeks. There was no dose-response/toxicity relationship of nivolumab. This study evaluated the efficacy of low-dose nivolumab as an alternative to the financial toxicity of standard-dose nivolumab in treatment of non-small cell lung cancer (NSCLC). METHODS: Outcomes of patients with NSCLC treated with nivolumab as a routine practice at two tertiary hospitals in Korea were retrospectively analysed. Patients who could not afford standard nivolumab treatment received low-dose nivolumab (20 or 100 mg fixed dose every 3 weeks). Others received standard dose of 3 mg/kg every 2 weeks. Progression-free survival (PFS) and overall survival (OS) were measured and compared between low-dose and standard-dose groups in overall and stratified analyses according to programmed death-ligand 1 (PD-L1) status. RESULTS: Among the 47 patients with NSCLC, 18 received low-dose nivolumab. PD-L1 positivity was observed in 13 (27.7%) patients and did not differ between the groups. During 5.2 months of follow-up, the objective response rate was 13.8% in the standard-dose group and 16.7% in the low-dose group (p=0.788). Dosing of nivolumab or PD-L1 expression did not significantly affect PFS or OS. CONCLUSION: Low-dose nivolumab can be effective in NSCLC and is worth considering as an alternative option to reducing financial toxicity. The efficacy of low-dose nivolumab requires study.

Attitudes toward early palliative care in cancer patients and caregivers: a Korean nationwide survey.

Integrated early palliative care (EPC) improves quality of life and reduces psychological distress in adult patients with cancer and caregivers, but attitudes toward EPC have been poorly studied. We aimed to investigate attitudes toward EPC in a nationwide survey of patients with cancer and caregivers. From July to October 2016, we administered nationwide questionnaires examining attitudes toward EPC in patients with cancer (n = 1001) and their families (n = 1006) from 12 Korean hospitals. When an individual considered EPC unnecessary, the reasons were collected and analyzed. Factors associated with perception of EPC were examined. A majority of patients (84.5%) and caregivers (89.5%) had positive attitudes toward EPC. The most common reasons for deeming EPC unnecessary were that EPC may be an obstacle to cancer treatment (patients: 37%; caregivers: 23%; respectively) or that they were not sure if EPC is beneficial (patients: 21%; caregivers: 24%; respectively). Financial burden as a reason was more evident in caregivers (23%) than in patients (17%). Male gender, age <50, early stage, intensive care unit admission, and not believing that dying people should prepare to practice charity were associated with patients' negative attitudes. In caregivers, opposition to EPC was associated with not thinking death should be feared, not thinking people should be remembered, and lower educational level. Our findings showed that significant numbers of patients with advanced cancer and family caregivers showed positive attitudes toward EPC. However, more than 10% of participants did not consider EPC necessary. Physicians' communication with patients and caregivers and financial support could help overcome the barriers of EPC.

Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to the primary brain tumor: the result of dosimetric study and neurocognitive function assessment.

BACKGROUND: We hypothesized that hippocampal-sparing radiotherapy via volumetric modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of patients with primary brain tumors treated with radiotherapy. METHODS: We reviewed data from patients with primary brain tumors who underwent hippocampal-sparing brain radiotherapy via VMAT between February 2014 and December 2015. The optimization criteria for the contralateral hippocampus was a maximum dose (Dmax) of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was performed at baseline and at seven months after radiotherapy. RESULTS: A total of 26 patients underwent NCF testing seven months after radiotherapy. Their median age was 49.5 years (range 26-77 years), and 14 (53.8%) had grade III/IV tumors. The median Dmax to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4). The median mean dose to the contralateral hippocampus, expressed as equivalent to a 2-Gy dose (EQD2/2), was 7.4 Gy2 (0.7-13.1). The mean relative changes in SVLT-TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were - 7.7% (95% confidence interval [CI], - 19.6% to 4.2%), - 9.2% (95% CI, - 25.4% to 7.0%), and - 3.4% (- 12.7% to 5.8%), respectively. Two patients (7.7%) showed deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT-Recognition. The mean dose of the left hippocampus and bilateral hippocampi were significantly higher in patients showing deterioration of the SVLT-TR and SVLT-Recognition than in those without deterioration. CONCLUSIONS: The contralateral hippocampus could be effectively spared in patients with primary brain tumor via VMAT to preserve the verbal memory function. Further investigation is needed to identify those patients who will most benefit from hippocampal-sparing radiotherapy of the primary brain tumor.

Epidemiology and management of primary immune thrombocytopenia: A nationwide population-based study in Korea.

INTRODUCTION: The epidemiology of immune thrombocytopenia (ITP) is not well characterized in an Asian population. MATERIALS AND METHODS: From July 2010 to June 2014, ITP patients were identified using the Korean Health Insurance Review and Assessment Service database. RESULTS: The overall incidence rate of ITP was 5.3 per 100,000 person-years (95% CI: 5.1-5.5). The overall incidence rate ratios of children under 15years old to adults and females to males were 3.8 (95% CI: 3.7-3.9) and 1.3 (95% CI: 1.2-1.4), respectively. Of the total 10,814 patients, 3388 patients (31%) needed treatment for ITP; of these, 54% continued treatment for more than three months. First-line therapy consisted of corticosteroids (CS) in 42%, immunoglobulin (IVIg) in 35%, CS with IVIg in 19%, and other immunosuppressive agents (ISA) in 4%. Among treated patients, 75% of adults and 33% of children continued treatment for more than three months. After three months, the most frequently used drug was CS alone in 63% of patients. Only 104 patients underwent splenectomy; of these, 51% received salvage treatment after a median of one month after surgery (range: 0-27). The proportion of patients who received platelet transfusions of 12units or more per month for at least two consecutive months was significantly higher among patients treated for more than three months compared with patients who completed treatment within three months. CONCLUSIONS: This population-based study is the first to describe the incidence of ITP and its treatment reality for patients in Korea.

Differences in Performance Status Assessment Among Palliative Care Specialists, Nurses, and Medical Oncologists.

CONTEXT: The Eastern Cooperative Oncology Group performance status (ECOG PS) is one of the most commonly used assessments in oncology and palliative care (PC). However, the interobserver differences between medical oncologists and PC specialists have never been reported. OBJECTIVES: To determine the interobserver differences in ECOG PS assessment among PC specialists, PC nurses, and medical oncologists in patients with advanced cancer. METHODS: We retrospectively reviewed the medical records of all patients who had an outpatient PC consultation in 2013 and identified 278 eligible patients. We retrieved the ECOG PS scores and symptom burden assessed by the Edmonton Symptom Assessment System (ESAS). RESULTS: PC specialists (median +0.5, P < 0.0001) and nurses (median +1.0, P < 0.0001) rated the ECOG PS significantly higher than medical oncologists. The weighted kappa values were 0.26 between PC specialists and medical oncologists and 0.61 between PC specialists and nurses. PC specialists' assessments correlated with ESAS fatigue, dyspnea, anorexia, feeling of well-being, and symptom distress score. The ECOG PS assessments by all three groups were significantly associated with survival (P < 0.001). However, patients with ECOG PS 2 and 3-4 rated by their medical oncologists had similar survival (P = 0.67). Predictors of discordance in ECOG PS assessments between PC specialists and medical oncologists were the presence of a potentially effective treatment (odds ratio [OR] 2.39; 95% CI 1.09-5.23) and poor feeling of well-being (≥4) (OR 2.38, 95% CI 1.34-4.21). CONCLUSION: ECOG PS assessments by PC specialists and nurses were significantly higher than those of medical oncologists. Systematic efforts to increase regular interdisciplinary communications may help to bridge this gap.

Pseudoprogression and pseudoresponse in the management of high-grade glioma : optimal decision timing according to the response assessment of the neuro-oncology working group.

OBJECTIVE: We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. METHODS: Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. RESULTS: Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). CONCLUSION: Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

Comprehensive geriatric assessment in Korean elderly cancer patients receiving chemotherapy.

BACKGROUND: Growing evidence suggests that a comprehensive geriatric assessment (CGA) in older patients with cancer can detect unsuspected health problems, predict survival, and predict tolerance to chemotherapy. However, studies regarding CGA in cancer patients are scarce in Asia. METHODS: We prospectively enrolled 65 elderly cancer patients who were candidates of systemic chemotherapy between July 2006 and March 2008. Baseline CGA data including demographic information, comorbidity, functional status by means of Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL), cognition, psychological state, nutritional status, and medication were collected and analyzed. Quality of life (QoL) was assessed by the EORTC questionnaire QLQ-C30. RESULTS: Of the 65 patients, the median age was 71 years (range, 65-80), 49 (75%) were males, and 58 (89%) had Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. All patients had solid tumor, 74% received palliative chemotherapy, and 18% received adjuvant chemotherapy. Twenty-five percent of patients had Charlson's comorbidity index score of 2 or more, 23% were ADL dependent, and 14% were IADL dependent. Using Mini-Mental Status Exam (MMSE), it was found that 51% of patients had mild cognitive impairment (MMSE score 17-24), and 5% had cognitive impairment (≤ 16). Forty percent of patients had depression by Short form Geriatric Depression Scale (SGDS), 19% had malnutrition by Mini-Nutritional Assessment (MNA), and 23% had body mass index (BMI) less than 19.4 kg/m(2) (lowest 10%). Global health status/quality of life (QoL) was less than 50% in 39% of patients. Frail patients according to the Balducci classification had significantly poor ECOG PS and worse global health status/QoL. CONCLUSION: CGA was feasible and could detect multiple unsuspected health problems including functional impairment and malnutrition in Korean elderly cancer patients receiving chemotherapy.