Assessment of Laparoscopic Indocyanine Green Tracer-guided Lymphadenectomy After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of indocyanine green (ICG)-guided lymph node (LN) dissection during laparoscopic radical gastrectomy after neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC). BACKGROUND: Studies on ICG imaging use in patients with LAGC on NAC are rare. METHODS: Patients with gastric adenocarcinoma (clinical T2-4NanyM0) who received NAC were randomly assigned to receive ICG-guided laparoscopic radical gastrectomy or laparoscopic radical gastrectomy alone. Here, we reported the secondary endpoints including the quality of lymphadenectomy (total retrieved LNs and LN noncompliance) and surgical outcomes. RESULTS: Overall, 240 patients were randomized. Of whom, 236 patients were included in the primary analysis (118 in the ICG group and 118 in the non-ICG group). In the ICG group, the mean number of LNs retrieved was significantly higher than in the non-ICG group within the D2 dissection (48.2 vs 38.3, P < 0.001). The ICG fluorescence guidance significantly decreased the LN noncompliance rates (33.9% vs 55.1%, P = 0.001). In 165 patients without baseline measurable LNs, ICG significantly increased the number of retrieved LNs and decreased the LN noncompliance rate ( P < 0.05). For 71 patients with baseline measurable LNs, the quality of lymphadenectomy significantly improved in those who had a complete response ( P < 0.05) but not in those who did not ( P > 0.05). Surgical outcomes were comparable between the groups ( P > 0.05). CONCLUSIONS: ICG can effectively improve the quality of lymphadenectomy in patients with LAGC who underwent laparoscopic radical gastrectomy after NAC.

Incidence, clinical management and prognosis of patients with small intestinal adenocarcinomas from 1999 through 2019: A nationwide Dutch cohort study.

BACKGROUND: Small intestinal adenocarcinomas (SIAs) are rare. Hence, randomized controlled trials are lacking and understanding of the disease features is limited. This nationwide cohort investigates incidence, treatment and prognosis of SIA patients, to improve disease outcome. PATIENTS AND METHODS: Data of 2697 SIA patients diagnosed from January 1999 through December 2019 were retrieved from the Netherlands Cancer Registry and Pathology Archive. Incidence was calculated using the revised European Standardized Rate. The influence of patient and tumor characteristics on overall survival (OS) was studied using survival analyses. RESULTS: The age-standardized incidence rate almost doubled from 0.58 to 1.06 per 100,000 person-years, exclusively caused by an increase in duodenal adenocarcinomas. OS did not improve over time. Independent factors for a better OS were a younger age, jejunal tumors, Lynch syndrome and systemic therapy. Only 13.8% of resected patients was treated with adjuvant chemotherapy, which improved OS compared to surgery alone in stage III disease (HR 0.47 (0.35-0.61)), but not in the limited group of deficient mismatch repair (MMR) patients (n = 53, HR 0.93 (0.25-3.47)). In the first-line setting, CAPOX was associated with improved OS compared to FOLFOX (HR 0.51 (0.36-0.72)). For oligometastatic patients, a metastasectomy significantly improved OS (HR 0.54 (0.36-0.80)). CONCLUSIONS: The incidence of SIAs almost doubled in the past 20 years, with no improvement in OS. This retrospective non-randomized study suggests the use of adjuvant chemotherapy for stage III disease and first-line CAPOX for metastatic patients. For selected oligometastatic patients, a metastasectomy may be considered. MMR-status testing could aid in clinical decision-making.

Cost-effectiveness analysis of nivolumab plus chemotherapy vs chemotherapy for patients with unresectable advanced or metastatic HER2-negative gastric or gastroesophageal junction or esophageal adenocarcinoma in Japan.

BACKGROUND: This study aimed to evaluate the cost-effectiveness of nivolumab plus chemotherapy (NIVO + Chemo) compared with chemotherapy monotherapy (Chemo) for patients with advanced or metastatic HER2-negative gastric or gastroesophageal junction or esophageal adenocarcinoma (GC/GEJC/EAC) in Japan from the perspective of healthcare payer. METHODS: A partitioned survival analysis model was developed to predict costs and quality-adjusted life years (QALYs) for NIVO + Chemo and Chemo. The time horizon of the model was set to 38 years. An annual discount rate of 2% for both costs and QALYs was applied. Data on overall survival and progression-free survival were derived from the CheckMate649 trial. Cost parameters were estimated from a Japanese medical claims database. The incremental cost-effectiveness ratio (ICER) of NIVO + Chemo compared with Chemo was estimated. A subgroup analysis on the level of PD-L1 CPS expression was conducted. In addition, sensitivity analysis was performed to assess the uncertainty in the parameter settings. RESULTS: The incremental cost and QALY of NIVO + Chemo compared with Chemo were USD99,416 and 0.30 QALY, respectively. The ICER of NIVO + Chemo was estimated to be USD327,161 per QALY gained. The results of the subgroup analysis showed that ICER was USD247,403/QALY and USD302,183/QALY for PD-L1 CPS ≧ 5 and ≧ 1, respectively. Sensitivity analyses showed a relatively robust result that the ICER remained higher than the Japanese cancer threshold of USD75,000-150,000/QALY. CONCLUSIONS: Applying the Japanese cancer threshold of USD75,000-150,000/QALY, NIVO + Chemo was not cost-effective for patients with advanced or metastatic HER2-negative GC/GEJC/EAC in Japan from the perspective of healthcare payer.

In Vitro Assessment of the Synergistic Effect of Aspirin and 5-Fluorouracil in Colorectal Adenocarcinoma Cells.

Although remarkable progress has been made, colorectal cancer remains a significant global health issue. One of the most challenging aspects of cancer treatment is the resistance of tumor cells to classical chemotherapy. Conventional therapy for colorectal cancer often involves the use of 5-fluorouracil as a chemotherapeutic agent. Aspirin, a drug used primarily to prevent cardiovascular complications, became a focus of attention due to its potential use as an antitumor agent. The purpose of the study was to evaluate the potential synergistic cytotoxic effects of aspirin and 5-fluorouracil on colorectal adenocarcinoma cells. The viability of cells, the impact on the morphology and nuclei of cells, the potential antimigratory effect, and the impact on the expression of the major genes associated with cell apoptosis (Bcl-2, Bax, Bad), as well as caspases 3 and 8, were evaluated. The results indicated that the two compounds exerted a synergistic effect, causing a reduction in cell viability accompanied by changes characteristic of the apoptosis process-the condensation of nuclei and the reorganization of actin filaments in cells, the reduction in the expression of the Bcl-2 gene, and the increase in the expression of Bax and Bad genes, along with caspases 3 and 8. Considering all these findings, it appears that aspirin may be investigated in depth in order to be used in conjunction with 5-fluorouracil to increase antitumor activity.

Association of County-level Upward Economic Mobility with Stage at Diagnosis and Receipt of Treatment Among Patients Diagnosed with Pancreatic Adenocarcinoma.

OBJECTIVE: Determining the impact of county-level upward economic mobility on stage at diagnosis and receipt of treatment among Medicare beneficiaries with pancreatic adenocarcinoma. SUMMARY BACKGROUND DATA: The extent to which economic mobility contributes to socioeconomic disparities in health outcomes remains largely unknown. METHODS: Pancreatic adenocarcinoma patients diagnosed in 2004-2015 were identified from the SEER-Medicare linked database. Information on countylevel upward economic mobility was obtained from the Opportunity Atlas. Its impact on early-stage diagnosis (stage I or II), as well as receipt of chemotherapy or surgery was analyzed, stratified by patient race/ethnicity. RESULTS: Among 25,233 patients with pancreatic adenocarcinoma, 37.1% (n = 9349) were diagnosed at an early stage; only 16.7% (n = 4218) underwent resection, whereas 31.7% (n = 7996) received chemotherapy. In turn, 10,073 (39.9%) patients received any treatment. Individuals from counties with high upward economic mobility were more likely to be diagnosed at an earlier stage (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07-1.25), as well as to receive surgery (OR 1.58, 95% CI 1.41-1.77) or chemotherapy (OR 1.51, 95% CI 1.39-1.63). White patients and patients who identified as neither White or Black had increased odds of being diagnosed at an early stage (OR 1.12, 95% CI 1.02-1.22 and OR 1.35, 95% CI 1.02-1.80, respectively) and of receiving treatment (OR 1.73, 95% CI 1.59-1.88 and OR 1.49, 95% CI 1.13-1.98, respectively) when they resided in a county of high vs low upward economic mobility. The impact of economic mobility on stage at diagnosis and receipt of treatment was much less pronounced among Black patients (high vs low, OR 1.28, 95% CI 0.96-1.71 and OR 1.30, 95% CI 0.99-1.72, respectively). CONCLUSIONS: Pancreatic adenocarcinoma patients from higher upward mobility areas were more likely to be diagnosed at an earlier stage, as well as to receive surgery or chemotherapy. The impact of county-level upward mobility was less pronounced among Black patients.

Economic evaluation of FLOT and ECF/ECX perioperative chemotherapy in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma.

OBJECTIVE: The perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin plus docetaxel (FLOT) was recommended by the Chinese Society of Clinical Oncology Guidelines for gastric cancer (2018 edition) for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (class IIA). However, the economic impact of FLOT chemotherapy in China remains unclear. The analysis aimed to compare the cost-effectiveness of FLOT versus epirubicin, cisplatin plus fluorouracil or capecitabine (ECF/ECX) in patients with locally advanced resectable tumours. DESIGN: We developed a Markov model to compare the healthcare and economic outcomes of FLOT and ECF/ECX in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. Costs were estimated from the perspective of Chinese healthcare system. Clinical and utility inputs were derived from the FLOT4 phase II/III clinical trial and published literature. Sensitivity analyses were employed to assess the robustness of our result. The annual discount rate for costs and health outcomes was set at 5%. OUTCOME MEASURES: The primary outcome of incremental cost-effectiveness ratios (ICERs) was calculated as the cost per quality-adjusted life years (QALYs). RESULTS: The base-case analysis found that compared with ECF/ECX, the use of FLOT chemotherapy was associated with an additional 1.08 QALYs, resulting in an ICER of US$851/QALY. One-way sensitivity analysis results suggested that the HR of overall survival and progression-free survival had the greatest impact on the ICER. Probabilistic sensitivity analysis demonstrated that FLOT was more likely to be cost-effective compared with ECF/ECX at a willingness-to-pay threshold of US$31 513/QALY. CONCLUSIONS: For patients with locally advanced resectable tumours, the FLOT chemotherapy is a cost-effective treatment option compared with ECF/ECX in China. TRIAL REGISTRATION NUMBER: NCT01216644.

Prognostic risk assessment model and drug sensitivity analysis of colon adenocarcinoma (COAD) based on immune-related lncRNA pairs.

PURPOSE: The aim of this study was to identify and screen long non-coding RNA (lncRNA) associated with immune genes in colon cancer, construct immune-related lncRNA pairs, establish a prognostic risk assessment model for colon adenocarcinoma (COAD), and explore prognostic factors and drug sensitivity. METHOD: Our method was based on data from The Cancer Genome Atlas (TCGA). To begin, we obtained all pertinent demographic and clinical information on 385 patients with COAD. All lncRNAs significantly related to immune genes and with differential expression were identified to construct immune lncRNA pairs. Subsequently, least absolute shrinkage and selection operator and Cox models were used to screen out prognostic-related immune lncRNAs for the establishment of a prognostic risk scoring formula. Finally, We analysed the functional differences between subgroups and screened the drugs, and establish an individual prediction nomogram model. RESULTS: Our final analysis confirmed eight lncRNA pairs to construct prognostic risk assessment model. Results showed that the high-risk and low-risk groups had significant differences (training (n = 249): p < 0.001, validation (n = 114): p = 0.022). The prognostic model was certified as an independent prognosis model. Compared with the common clinicopathological indicators, the prognostic model had better predictive efficiency (area under the curve (AUC) = 0.805). Finally, We have analysed highly differentiated cellular pathways such as mucosal immune response, identified 9 differential immune cells, 10 sensitive drugs, and establish an individual prediction nomogram model (C-index = 0.820). CONCLUSION: Our study verified that the eight lncRNA pairs mentioned can be used as biomarkers to predict the prognosis of COAD patients. Identified cells, drugs may have an positive effect on colon cancer prognosis.

Vascular Endothelial Growth Factor Receptor Inhibitors in Chinese Patients With Advanced Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Network Meta-Analysis and Cost-Effectiveness Analysis.

Introduction: Two targeted drugs (apatinib and lenvatinib) show clinical efficacy in first-line treatment of Chinese patients with radioactive advanced iodine-refractory differentiated thyroid cancer (RAIR-DTC) and are recommended by the Chinese Society of Clinical Oncology guidelines. Considering the high clinical cost of long-term vascular endothelial growth factor receptor inhibitor administration and to determine which of the two targeted drugs is preferable, we opted to conduct a cost-effectiveness analysis (CEA) and network meta-analysis (NMA). Material and Methods: The results of NMA and CEA included in the two phase III randomized clinical trials REALITY (NCT03048877) and Study-308 (NCT02966093), in which Bayesian NMA and CEA were performed on 243 and 149 Chinese patients, respectively, were retrieved. Overall survival and progression-free survival (PFS) for apatinib versus lenvatinib were determined by NMA. CEA involved the development of a 20-year Markov model to obtain the total cost and quality-adjusted life-years (QALYs), and this was followed by sensitivity and subgroup analyses. Results: Compared with lenvatinib, apatinib therapy provided a 0.837 improvement in QALY and $6,975 reduction in costs. The hazard ratio of apatinib versus lenvatinib and the cost of the targeted drugs had a significant impact on the model. According to the sensitivity analysis, apatinib was more cost-effective and had no correlation with willingness-to-pay in China. Subgroup analysis showed that apatinib maintained PFS more economically. Conclusion: NMA and CEA demonstrated that apatinib was more cost-effective compared to lenvatinib in the first-line treatment of Chinese RAIR-DTC patients.

Patterns of care amongst older adults diagnosed with locally advanced esophageal cancer: A cohort study.

INTRODUCTION: Since the early 2010s, neoadjuvant chemoradiation followed by esophagectomy (trimodal therapy) has been a recommended treatment for patients diagnosed with locally advanced esophageal cancer. However, it may also add treatment-related toxicity, particularly for older adults with significant comorbidity and frailty burdens. We examined contemporary patterns of care in older adults, which have not been well characterized. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results-Medicare database to identify a cohort of US adults aged 66 years and older diagnosed with incident locally advanced esophageal cancer between 2004 and 2017. Calendar year age-standardized percentages of treatment receipt were calculated. Joinpoint regression was used to detect temporal trends in treatment receipt. Descriptive associations between patient factors and treatment were assessed. Trend analyses quantified how the percentage of trimodal and definitive chemoradiation (no surgery) patients receiving cisplatin-based, carboplatin-based, and other chemotherapy regimens evolved over time. RESULTS: In total, 4332 adults aged ≥66 years with locally advanced esophageal cancer were included. The age-standardized percentage of patients receiving trimodal therapy increased from 16.7% in 2004 to 26.1% in 2017 (annual percent change = 3.5%; 95% confidence interval [CI], 0.7%-6.4%) in adenocarcinomas and from 7.3% in 2004 to 9.1% in 2017 (annual percent change = 0.4%; 95% CI, -4.1%-5.1%) in squamous cell carcinomas. By 2017, definitive chemoradiation became the most frequently used treatment modality for adenocarcinomas (49.8%; 95% CI, 43.5-56.0) and squamous cell carcinomas (59.5%; 95% CI, 50.8-68.2). Patients with higher comorbidity and frailty burdens were less likely to be treated with trimodal therapy. Amongst patients receiving chemoradiation as part of their treatment, a large and swift channeling away from cisplatin and towards carboplatin-based regimens was observed. DISCUSSION: In practice, definitive chemoradiation is the most commonly received treatment by older adults with locally advanced esophageal cancer. Four out of five older adults do not receive trimodal therapy, some of whom are potentially undertreated.

Intraoperative Pancreatic Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Adenocarcinoma in the Era of Neoadjuvant Therapy: A Multi-institutional Analysis from the Central Pancreatic Consortium.

BACKGROUND: Data regarding the survival impact of converting frozen-section (FS):R1 pancreatic neck margins to permanent section (PS):R0 by additional resection (i.e., converted-R0) during upfront pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) are conflicting. The impact of neoadjuvant therapy on this practice and its relationship with overall survival (OS) is incompletely understood. METHODS: We reviewed PDAC patients (80% borderline resectable/locally advanced [BR/LA]) undergoing pancreaticoduodenectomy after neoadjuvant therapy at seven, academic, high-volume centers (2010-2018). Multivariable models examined the association of PS:R0, PS:R1, and converted-R0 margins with OS. RESULTS: Of 272 patients receiving at least 2 (median 4) cycles of neoadjuvant chemotherapy (71% mFOLFIRINOX or gemcitabine/nab-paclitaxel) and undergoing pancreaticoduodenectomy with intraoperative frozen-section assessment of the transected pancreatic neck margin, PS:R0 (n = 220, 80.9%) was observed in a majority of patients; 18 patients (6.6%) had converted-R0 margins following additional resection, whereas 34 patients (12.5%) had persistently positive PS:R1 margins. At a median follow-up of 42 months, PS:R0 resection was associated with improved OS compared with either converted-R0 or PS:R1 resection (median 25 vs. 14 vs. 16 months, respectively; p = 0.023), with no survival difference between the converted-R0 and PS:R1 groups (p = 0.9). On Cox regression, SMA margin positivity (hazard ratio 2.2, p = 0.012), but not neck margin positivity (hazard ratio 1.2, p = 0.65), was associated with worse OS. CONCLUSIONS: In this multi-institutional cohort of predominantly BR/LA PDAC patients undergoing pancreaticoduodenectomy following modern neoadjuvant therapy, pursuing a negative neck margin intraoperatively if the initial margin is positive does not appear to be associated with improved survival.

Opioid use and associated factors among pancreatic cancer patients diagnosed between 2007 and 2015.

BACKGROUND: Opioid therapy provides essential pain relief for cancer patients. We used the population-based Surveillance Epidemiology and End Results (SEER) linked with Medicare database to identify the patterns of opioid use and associated factors in pancreatic adenocarcinoma cancer patients 66 years or older. PATIENTS AND METHODS: We assessed opioid types, dispensed days, opioid uptake rates, and factors associated with opioid use after pancreatic adenocarcinoma cancer diagnosis in Medicare beneficiaries between 2007 and 2015 from the SEER-Medicare data. Multivariable regression analysis was used to adjust for a variety of patient-related factors. RESULTS: We identified a cohort of 10,745 pancreatic cancer patients with a median age of 76 years old and median survival of 7 months; 75% of patients-initiated opioids after cancer diagnosis. African Americans had the lowest rate of opioid use of 69.1% compared with all other race/ethnicity groups at around 75%. No significant yearly trend of prescribing opioids was detected. Hydrocodone was the most frequently prescribed opioid type. Regression analysis revealed that age ≤80 years, residing in Southern or Western SEER registries, residing in urban/less urban versus big metro areas, having stage IV cancer at diagnosis, longer survival time, and undertaking cancer-directed treatment or using palliative care were positively associated with opioid initiation, more prescribed opioid types, and higher opioid doses. DISCUSSION: While a range of sociodemographic variables were associated with opioid use in unadjusted analysis, the associations between race/ethnicity, gender, and socioeconomic status with opioid initiation disappeared when sociodemographic factors, tumor characteristics, and cancer treatment were adjusted. CONCLUSION: Health care professionals' opioid prescription pattern for pancreatic cancer patients does not parallel the U.S. opioid epidemic. Racial/ethnic disparities in opioid treatment were not identified.

Cost-effectiveness analysis of nivolumab plus standard chemotherapy versus chemotherapy alone for the first-line treatment of unresectable advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

Background Nivolumab plus standard chemotherapy has significant clinical benefits for unresectable advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC). However, nivolumab is expensive, necessitating a cost-effectiveness evaluation. Aim This study aimed to evaluate the cost-effectiveness of nivolumab plus standard chemotherapy vs. chemotherapy alone for unresectable advanced or metastatic GC/GEJC/EAC from the Chinese healthcare system perspective. This study was based on randomized clinical trial data from the CheckMate-649 clinical trial (NCT02872116) published in Lancet (June 2021). Method A Markov model was used to assess the cost-effectiveness of nivolumab plus standard chemotherapy versus chemotherapy alone for unresectable advanced or metastatic GC/GEJC/EAC. Drug costs were collected from Tianjin Medical Purchasing Center in 2021, and utility values of health states were obtained from the literature. The reliability of model was assessed with one-way and probabilistic sensitivity analyses. Main outcome measure The main outcomes were costs, quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). Results Over a 10-year horizon, the outputs were 1.19 QALYs at a cost of $78,814.9 and 0.88 QALYs at a cost of $19,522.3 with nivolumab plus chemotherapy and chemotherapy alone, respectively. The ICER for nivolumab plus chemotherapy versus chemotherapy alone was $191,266/QALY, exceeding the willingness-to-pay (WTP) threshold ($33,436/QALY). One-way sensitivity analysis revealed nivolumab cost was the most influential parameter. Conclusion Adding nivolumab is not cost-effective for unresectable advanced or metastatic GC/GEJC/EAC in the current Chinese healthcare environment.

Black race is independently associated with underutilization of preoperative chemotherapy in clinical stage T2 or higher gastric adenocarcinoma.

BACKGROUND: Consensus guidelines recommend for perioperative chemotherapy and surgery for patients with clinical stage (cT) T2 or greater gastric adenocarcinoma. We compared adherence to guidelines in these patients stratified by race. METHODS: Non-Hispanic White and Black patients with resected ≥cT2 gastric adenocarcinoma were identified within the National Cancer Database (2008-2017). We compared administration of preoperative chemotherapy by race, adjusting for clinicodemographic variables. We performed marginal standardization of logistic regression to calculate adjusted probabilities of administration of preoperative chemotherapy in patients under the age of 80 years with insurance. RESULTS: A total of 13,850 patients were identified (White = 12,161; Black = 1,689). Black race was associated with lower likelihood of receiving preoperative chemotherapy than White race (odds ratio = 0.46, 95% confidence interval: 0.39-0.54). Other factors associated with lower likelihood of preoperative chemotherapy included age ≥70 years, female sex, treatment at community facilities, non-private or no health insurance, and cT4 disease. Factors associated with higher likelihood of preoperative chemotherapy included treatment at high-volume facilities, longer distance to facility, higher education and income levels, cT3 disease, and cN+ disease. In patients <80 years with insurance, marginal standardization models demonstrated that Black race was associated with a lower adjusted probability of receiving preoperative chemotherapy regardless of age, insurance payor, facility type/volume, distance to facility, cT stage, cN stage, sex, and education/income levels. CONCLUSION: Black race was associated with underutilization of preoperative chemotherapy for cT2 or greater gastric cancer, in discordance to published guidelines. The etiology of these disparities is multifactorial, and correcting the root causes represents a critical area for improvement.

Neglected geriatric assessment and overtreatment of older patients with pancreatic cancer - Results from a prospective phase IV clinical trial.

BACKGROUND: Older patients with metastatic pancreatic cancer may suffer increased toxicity from intensive chemotherapy. Treatment individualization by geriatric assessment (GA) might improve functional outcome. METHODS: We performed a multicenter, phase IV, open label trial in patients ≥70 years with metastatic pancreatic adenocarcinoma. Patients underwent GA and were assigned to one of three categories based on their scores: Go-Go, Slow-Go, or Frail. These categories were intended to guide physician's treatment decisions when choosing to treat patients with nab-paclitaxel/gemcitabine (arm A), gemcitabine (arm B), or best supportive care (arm C). Primary objective was a stable (loss of five points or less) Barthel's Activities of Daily Living (ADL) score during chemotherapy; secondary endpoints included GA scores during therapy, safety, quality of life, response and survival rates. RESULTS: Thirty-two patients were enrolled in the trial in six centers in Germany (out of 135 planned), resulting in termination due to low recruitment. Fifteen patients were allocated to nab-paclitaxel/gemcitabine, fifteen to gemcitabine, and two to best supportive care by their physicians, although according to their GA scores 29 patients (91%) were categorized as Slow-Go and three (9%) as Go-Go. Thus, fifteen of 32 (47%) patients were misclassified and given a course of treatment inconsistent with their GA scores. Median progression-free survival (PFS) were 3.3 months and 9.1 months and median time to quality-of-life deterioration 13 days and 29 days in the nab-paclitaxel/gemcitabine and gemcitabine monotherapy arms, respectively. Serious adverse events were reported in 11 (78.6%) patients in the nab-paclitaxel/gemcitabine and 8 (53.3%) patients in the gemcitabine arm. CONCLUSIONS: Clinical evaluations by investigators differed markedly from geriatric assessments, leading to potential overtreatment. In our modest sample size study, those patients undergoing more intensive therapy had a less favorable course.

Patient and caregiver socioeconomic burden of first-line systemic therapy for advanced gastroesophageal adenocarcinoma.

Aim: This study assessed the work productivity and financial impact of advanced gastroesophageal adenocarcinomas, comprising gastric, esophageal and gastroesophageal junction cancers, on patients of working age and their caregivers. Patients & methods: A multicenter medical chart review and surveys of patients with advanced gastroesophageal adenocarcinoma and their caregivers was conducted in France, Germany, the UK, China, Japan and the USA. Results: Across differing regions, the study highlighted the impact of cancer on patients' ability to work, to function normally and on their wellbeing, as well as the economic burden placed on patients and their caregivers. Conclusion: Advanced gastroesophageal adenocarcinomas have a significant impact on patients' and caregivers' well-being and are associated with reduced work productivity, and income loss.

Opportunity Costs of Surgical Resection and Perioperative Chemotherapy for Locoregional Pancreatic Adenocarcinoma.

PURPOSE: Given the perioperative morbidity and intensity of multimodality treatment, patients with resected pancreatic ductal adenocarcinoma (PDAC) spend a substantial amount of time in clinical care. The primary aim was to determine total time spent in multimodality care for patients with locoregional PDAC. METHODS: A cohort study of all patients who underwent curative-intent resection for PDAC at a single-institution, tertiary care center was performed (2015-2019). Exact times for all relevant visits were abstracted from the primary medical record, and travel time was calculated. Care time was divided into preoperative, surgical, radiation, and systemic therapy phases of care. Primary outcome measures were the percentage of total survival time (TST) and percentage of overall survival (OS) days spent in receipt of care. RESULTS: One hundred seven patients were included. Patients spent a median of 5.0% (interquartile range [IQR] 2.4%-10.1%) of TST and 11.0% (IQR, 5.7%-20.4%) of OS days in receipt of clinical care. Preoperative, surgical, radiation, and systemic therapy phases of care comprised a median of 0.9% (IQR, 0.4%-2.2%), 3.0% (IQR, 1.9%-6.8%), 4.4% (IQR, 3.6%-6.3%), and 10.0% (IQR, 6.2%-14.1%) of OS days. The median per-visit travel time was 60 minutes (IQR, 32-120), and the median cumulative travel time was 22.0 hours (IQR, 12.0-51.5). 12.1% (n = 13) and 7.8% (n = 4) of patients spent > 10% of TST in receipt of surgical and systemic therapy care, respectively. CONCLUSION: Patients with locoregional pancreatic cancer spend a considerable percentage of their survival time in receipt of oncologic care. Further research to determine predictors of increased time burden is warranted to better inform shared decision making.

Perioperative chemotherapy versus adjuvant chemotherapy strategies in resectable gastric and gastroesophageal cancer: A Markov decision analysis.

BACKGROUND: Perioperative chemotherapy has been shown to improve overall survival (OS) for operable gastric and gastroesophageal cancer. However, optimal sequence of surgery and chemotherapy has not been clearly identified. Markov models are useful for analyzing the outcomes of different treatment strategies in the absence of adequately powered randomized clinical trials. In this study, we use Markov decision analysis models to compare median OS (mOS), quality-adjusted mOS, life expectancy (LE), and quality-adjusted life expectancy (QALE) of perioperative chemotherapy with adjuvant chemotherapy strategies in resectable gastric and gastroesophageal cancer patients. METHODS: Markov models are constructed to compare two strategies: adjuvant chemotherapy after surgery and preoperative chemotherapy followed by cancer resection and postoperative chemotherapy. LE and QALE are calculated analytically, and mOS are obtained by simulation. Parameters used in the models are computed from prospective clinical trial data published in PUBMED from January 2000 to July 2020. RESULTS: Total of 8088 patients from 25 prospective studies were included in this analysis. Regardless of R0 resection ratio, the analyses of the models show a higher mOS for patients in the perioperative therapy arm compared to adjuvant chemotherapy. For R0 resected patients, the perioperative therapy arm provided an additional 11.0 mOS months (61.3 months vs. 50.3 months). For R1 resected patients, the perioperative therapy arm had mOS of 17.0 months vs. 10.7 months in adjuvant therapy. CONCLUSIONS: The Markov models indicate that perioperative chemotherapy improves mOS, quality-adjusted mOS, LE, and QALE for resectable gastric and gastroesophageal cancer patients compared to adjuvant chemotherapy strategies.

Cost-effectiveness of trifluridine/tipiracil as a third-line treatment of metastatic gastric cancer, including adenocarcinoma of the gastrohesophageal junction, among patients previously treated in Greece.

OBJECTIVE: To evaluate the cost-effectiveness of trifluridine/tipiracil (FTD/TPI) compared with best supportive care (BSC) for the treatment of patients with metastatic gastric cancer(mGC), including gastroesophageal junction adenocarcinoma(GEJ), who have received at least two prior therapies for metastatic disease and are eligible for third-line treatment, in Greece. METHODS: A partitioned survival model was locally adapted from a public payer perspective over a 10-year time horizon. Clinical, safety and utility data were extracted from literature. Resource consumption data obtained from a panel of local experts using a questionnaire developed for the study was combined with unit costs obtained from official sources. All costs reflect the year 2020 (€). Outcomes of the model were patients' life years (LYs) and quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratio (ICER) per QALY and LY gained. RESULTS: The total cost per patient was estimated to be €6,965 for FTD/TPI and €1,906 for BSC, while FTD/TPI was associated with 0.180 and 0.107 increments in LYs and QALYs, respectively, compared with BSC, resulting in an ICER of €47,144 per QALY gained and €28,112 per LY gained. CONCLUSION: FTD/TPI was estimated to be a cost-effective treatment option for eligible third line mGC patients, including GEJ in Greece.

Cost-effectiveness analysis of pembrolizumab for treatment of US patients with persistent, recurrent, or metastatic cervical cancer.

OBJECTIVE: The effectiveness of pembrolizumab for persistent, recurrent, or metastatic cervical cancer has been demonstrated. We aimed to evaluate its cost-effectiveness from the United States (US) healthcare payers perspective. METHODS: A partitioned survival model over a 30-year lifetime horizon was developed to compare the cost and effectiveness of pembrolizumab versus placebo based on clinical data from the KEYNOTE-826 phase 3 randomized trial. Costs and health state utilities were obtained from literature and publicly available databases. The incremental cost-effectiveness ratio (ICER) was measured. One-way and probabilistic sensitivity analyses were conducted. RESULTS: For the Intention-to-Treat patients, pembrolizumab was associated with an additional 0.74 quality-adjusted life-year (QALY) at an additional cost of $182,271 when compared with placebo. The ICER was $247,663/QALY. For patients with a programmed death-ligand 1 combined positive score ≥ 1 and 10, the ICER was $253,322/QALY and $214,212/QALY, respectively. One-way sensitivity analyses showed that pembrolizumab had the greatest impact on the ICER. Probabilistic sensitivity analyses showed that the probability of pembrolizumab being cost-effective was zero at the current willingness-to-pay threshold of $150,000/QALY. The price of pembrolizumab had to reduce at least to $28.336 (55.8% of the current price) for it to be cost-effective in a 50% of chance. CONCLUSION: The addition of pembrolizumab to chemotherapy is costly and might not be cost-effective for persistent, recurrent, or metastatic cervical cancer at the current price in the US.

Cost-Effectiveness of Nab-Paclitaxel and Gemcitabine Versus Gemcitabine Monotherapy for Patients with Unresectable Metastatic Pancreatic Cancer in Japan.

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of nab-paclitaxel and gemcitabine (GnP) compared with gemcitabine monotherapy (G) for patients with unresectable metastatic pancreatic cancer in Japan from the perspective of healthcare payer. METHODS: A partitioned survival analysis model was developed to predict costs and quality-adjusted life years (QALYs) for GnP and G. The time horizon of the model was set at 20 years. An annual discount rate of 2% for both costs and QALYs was applied. Data on overall survival and progression-free survival were derived from the Metastatic Pancreatic Adenocarcinoma Clinical Trial. Cost parameters were estimated from a Japanese medical claims database. The incremental cost-effectiveness ratio (ICER) of GnP compared with G was estimated. One-way sensitivity analysis was performed to assess the uncertainty in the parameter settings. In addition, scenario and probability sensitivity analyses were performed. RESULTS: The incremental cost and QALY of GnP compared with G were US$25 089 and 0.13 QALY, respectively. The ICER of GnP was estimated to be US$192 992 per QALY gained. Although the ICER was influenced by utility parameters and the survival curves, the ICERs remained higher than the willingness to pay (WTP) threshold of US$68 000 (JPY 7.5 million). The probability that GnP becomes cost-effective compared with G was estimated to be 29.2%. CONCLUSIONS: Applying the WTP threshold of US$68 000 per QALY, GnP was not cost-effective for patients with unresectable metastatic pancreatic cancer in Japan from the perspective of healthcare payer. Further research is needed to obtain utility data from Japanese patients with pancreatic cancer.