Study Protocol for a Prospective Self-Controlled Trial on Success in Meeting Comprehensive Genomic Profiling Analysis Criteria for Specimens Obtained by Endoscopic Ultrasound-Guided Tissue Acquisition Using a 19G Needle from Primary and Metastatic Lesions in Pancreatic Cancer with Metastatic Lesions: The PRIMATE Study.

EUS-TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS-TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS-TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS-TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity of ≥20% and a tissue area of ≥4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.

Utility of Transpapillary Biopsy and Endoscopic Ultrasound-Guided Tissue Acquisition for Comprehensive Genome Profiling of Unresectable Biliary Tract Cancer.

Tissue sampling in biliary tract cancer (BTC) is generally performed through transpapillary biopsy (TPB) or endoscopic ultrasound-guided tissue acquisition (EUS-TA). For the first time, we compared the suitability of specimens obtained using TPB and EUS-TA to determine the optimal tissue-sampling method for comprehensive genome profiling (CGP) analysis in patients with unresectable BTC (UR-BTC). Pathology precheck criteria for CGP analysis comprised the OncoGuide NCC Oncopanel System (NCCOP) and FoundationOne CDx (F1CDx). Seventy-eight patients with UR-BTC (35 TPB and 43 EUS-TA) were included. The NCCOP analysis suitability achievement rate was higher in EUS-TA specimens than in TPB specimens (34.9% vs. 8.6%, p = 0.007), whereas that of F1CDx was 0% in both groups. EUS-TA was identified as an independent factor that contributed to the suitability of the NCCOP analysis. The suitability of the NCCOP analysis of EUS-TA specimens showed a tendency to be higher for mass lesions (43.8% vs. 9.1%, p = 0.065), especially for target size ≥ 18.5 mm, and lower for perihilar cholangiocarcinoma (0% vs. 41.7%, p = 0.077). In TPB, papillary-type lesions (66.7% vs. 3.2%, p = 0.016) and peroral cholangioscopy-assisted biopsies (50.0% vs. 3.3%, p = 0.029) showed better potential for successful NCCOP analysis. EUS-TA is suitable for NCCOP analysis in UR-BTC and may be partially complemented by TPB.

Diagnostic performance of EUS-guided tissue acquisition for solid pancreatic lesions ≤10 mm.

Background and Objectives: EUS tissue acquisition (EUS-TA) is the standard diagnostic method for solid pancreatic lesions (SPLs); however, there are few reports on EUS-TA results for SPLs ≤10 mm. Furthermore, given the recent advent of fine-needle biopsy, the current diagnostic accuracy of EUS-TA for SPLs ≤10 mm is unknown. This study aimed to evaluate the diagnostic accuracy and efficacy of EUS-TA for SPLs ≤10 mm. Methods: We retrospectively analyzed the data of 109 patients with SPLs ≤10 mm who underwent EUS-TA. All patients underwent rapid on-site specimen evaluation. Results: The median tumor diameter was 8 mm (range, 2.5-10 mm), and the technical success rate was 99.1% (108/109). Adverse events were observed in 3 patients (2.8%). The diagnostic performance was as follows: sensitivity, 90.1% (64/71); specificity, 97.3% (36/37); accuracy, 92.6% (100/108); positive predictive value, 98.5% (64/65); and negative predictive value, 83.7% (36/43). Multivariate analysis revealed that the number of punctures (odds ratio, 7.03; 95% confidence interval, 1.32-37.5; P = 0.023) and tumor type (odds ratio, 11.90; 95% confidence interval, 1.38-102.0; P = 0.024) were independent risk factors for inaccurate EUS-TA results. The diagnostic accuracy of EUS-TA for pancreatic ductal adenocarcinoma was 87.5% (14/16). No EUS-TA-related needle-tract seeding was observed in patients with pancreatic ductal adenocarcinoma during the observation period. Conclusions: EUS-TA for SPLs ≤10 mm showed adequate diagnostic accuracy and was safe for use with rapid on-site specimen evaluation in all cases.

Comparison of stent patency between EUS-guided hepaticogastrostomy with bridging and endoscopic transpapillary biliary drainage for hilar obstruction.

Background and study aims Endoscopic ultrasound-guided hepaticogastrostomy with bridging between the left and right bile ducts is an alternative to endoscopic transpapillary drainage for malignant hilar biliary obstruction. We aimed to analyze the long-term stent patency of endoscopic ultrasound-guided hepaticogastrostomy with bridging. Patients and methods Patients who underwent endoscopic ultrasound-guided hepaticogastrostomy with bridging between April 2018 and July 2023 were retrospectively analyzed. We retrospectively compared the stent patency of these patients with that of the individuals who underwent endoscopic transpapillary drainage-multi-stenting using unmatched (entire) and propensity score-matched cohorts. Results Endoscopic ultrasound-guided hepaticogastrostomy with bridging had a technical success rate of 90% (18/20). Adverse events were minimal. The number of clinical success cases was 17 and 82 for endoscopic ultrasound-guided hepaticogastrostomy with bridging using metallic stent and endoscopic transpapillary drainage-multi-stenting, respectively. The recurrent biliary obstruction rate was 17.6% and 58.5% for endoscopic ultrasound-guided hepaticogastrostomy with bridging and endoscopic transpapillary drainage-multi-stenting, respectively; the median time to recurrent biliary obstruction (days) was significantly longer for endoscopic ultrasound-guided hepaticogastrostomy with bridging in the entire (not reached vs. 104, P =0.03) and propensity score-matched (183 vs. 79, P =0.05) cohorts. The non-recurrent biliary obstruction rate for endoscopic ultrasound-guided hepaticogastrostomy with bridging was 91.6% at 3 and 6 months and 57% at 12 months. Multivariate analyses revealed that endoscopic ultrasound-guided hepaticogastrostomy with bridging contributed to a lower recurrent biliary obstruction incidence (hazard ratio, 0.31, P =0.05) without significant difference. Conclusions Stent patency was significantly better for endoscopic ultrasound-guided hepaticogastrostomy with bridging. However, future prospective studies are needed.

Efficacy of endoscopic ultrasound-guided gastroenterostomy using self-expandable metallic stent for afferent loop syndrome: A single-center retrospective study.

BACKGROUND AND AIM: Endoscopic ultrasound-guided gastroenterostomy is a procedure used to connect the stomach and dilated afferent loop using a stent under endoscopic ultrasound for afferent loop syndrome. However, the actual efficacy and safety of this procedure remain unclear. Therefore, this retrospective study aimed to evaluate the efficacy and safety of endoscopic ultrasound-guided gastroenterostomy using a laser-cut-type fully covered self-expandable metallic stent and an anchoring plastic stent for afferent loop syndrome. METHODS: Technical and clinical success rates, adverse events, recurrent intestinal obstruction rates, time to recurrent intestinal obstruction, and technical and clinical success rates of re-intervention were evaluated in intended patients who underwent endoscopic ultrasound-guided gastroenterostomy for afferent loop syndrome from October 2018 to August 2022. RESULTS: In 25 intended patients with afferent loop syndrome who intended endoscopic ultrasound-guided gastroenterostomy, the technical success rate was 100% (25/25), whereas the clinical success rate was 96% (24/25). Two patients experienced grade ≥ 3 early adverse events, including one with intra-abdominal abscess and one with hypotension. Both events were attributed to intestinal fluid leakage. No late adverse events were observed. The recurrent intestinal obstruction rate was 32% (8/25), and the median time to recurrent intestinal obstruction was 6.5 months (95% confidence interval: 2.8-not available). The technical and clinical success rates of re-intervention were both 100% (8/8). CONCLUSIONS: Endoscopic ultrasound-guided gastroenterostomy using a fully covered self-expandable metallic stent and an anchoring plastic stent is effective and safe as a treatment procedure for afferent loop syndrome.

Feasibility and safety of a novel plastic stent designed specifically for endoscopic ultrasound-guided pancreatic duct drainage.

Background and study aims Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) is emerging as an effective alternative treatment for obstructive pancreatitis after unsuccessful endoscopic retrograde pancreatography (ERP). However, the high incidence of adverse events associated with EUS-PD (approximately 20%) remains an issue. Recently, we developed a novel plastic stent for EUS-PD, with a radiopaque marker positioned at approximately one-third of the length from the distal end of the stent and side holes positioned exclusively distal to the marker. This study aimed to evaluate the feasibility and safety of using this stent in EUS-PD. Patients and methods We retrospectively reviewed data from 10 patients who underwent EUS-PD with the novel plastic stent at the National Cancer Center Hospital between March 2021 and October 2023. Technical and clinical success, procedure times, adverse events (AEs), recurrent pancreatic duct obstruction (RPO), and time to RPO were assessed. Results Of the 10 patients, five had postoperative benign pancreaticojejunal anastomotic strictures and five had malignant pancreatic duct obstruction. The technical and clinical success rates were both 100% (10/10). An AE (self-limited abdominal pain) occurred in one patient (10.0%). Two patients (20.0%) died of their primary disease during the follow-up period (median, 44 days; range, 25-272 days). The incidence of RPO was 10.0% (1/10), and the 3-month non-RPO rate was 83.3%. Conclusions The novel plastic stent shows potential as a useful and safe tool in EUS-PD.

Incidence and factors associated with stent dysfunction and pancreatitis after gastroduodenal stenting for malignant gastric outlet obstruction.

Background and study aims Endoscopic gastroduodenal stent (GDS) deployment is currently a standard treatment for malignant gastric outlet obstruction (mGOO) in patients with limited life expectancy; however, stent dysfunction (SD) and complicated pancreatitis often occur after GDS deployment. We investigated incidence and contributing factors of SD and complicated pancreatitis. Patients and methods We retrospectively reviewed 203 patients who underwent initial GDS deployment for palliation of mGOO symptoms between October 2017 and July 2022, including 109 who underwent GDS deployment across the duodenal papilla (sub-cohort). Results SDs, including tumor ingrowth (n = 26), kinking (n = 14), and migration (n = 13), occurred in 68 patients (33.5%). Cumulative SD incidence was 41.1% (95% confidence interval, 32.6-49.4%). SD incidence increased to 0.4%, 0.16%, and 0.06% per day at < 8, 8-16, and>16 weeks, respectively. On multivariate analysis, Niti-S pyloric/duodenal stent deployment (sub-distribution hazard ratio [sHR] 0.26, P = 0.01) and survival length ≥ 90 days (sHR 2.5, P = 0.01) were respectively identified as favorable and risk factors significantly associated with SD. Pancreatitis developed in 14 patients (12.8%) in the sub-cohort, which had significantly higher parenchymal diameter ( P < 0.01) and lower main pancreatic duct (MPD) caliber ( P < 0.01) than the non-pancreatitis cohort. On multivariate analysis, MPD caliber < 3 mm independently predicted pancreatitis (odds ratio 6.8, P = 0.03). Conclusions Deployment of the Niti-S pyloric/duodenal stent, with conformability even for angulated strictures, significantly reduced the incidence of SD. Stent selection, life expectancy, and MPD caliber should be taken into consideration during decision-making for GDS deployment for mGOO.

Study protocol for a prospective, multicentre, phase II trial on endoscopic treatment using two fully covered self-expandable metallic stents for benign strictures after hepaticojejunostomy.

INTRODUCTION: The current endoscopic treatment for postoperative benign hepaticojejunostomy anastomotic stricture (HJAS) has a high technical success rate and is highly effective in the short term. However, long-term results have shown a high rate of stenosis recurrence, which indicates an insufficient response to treatment. Three prospective studies on fully covered self-expandable metallic stent (FC-SEMS) treatment for benign HJAS used the stenosis resolution rate as the primary endpoint, and no study has yet used the long-term non-stenosis rate (at 12 months) as the primary endpoint. METHODS AND ANALYSIS: We launched the 'saddle-cross study', which will be conducted as a multicentre, prospective intervention of endoscopic treatment using two modified FC-SEMSs (BONASTENT️ M-Intraductal) that have been improved for benign stenosis in patients with benign HJAS, with the long-term non-restenosis rate (at 12 months) as the primary endpoint. This study aims to evaluate the long-term non-restenosis rate (at 12 months) and safety of the saddle-cross technique for benign HJAS. We plan to enrol 50 participants. ETHICS AND DISSEMINATION: This study has been approved by the Certified Review Board of the National Cancer Center, Japan (CRB3180009). The results will be reported at various conferences and published in international peer-reviewed journals.

Efficacy of endoscopic ultrasound-guided tissue acquisition for solid pancreatic lesions 20 mm or less in diameter suspected as neuroendocrine tumors or requiring differentiation.

BACKGROUND: For non-functioning pancreatic neuroendocrine tumors (pNETs) ≤ 20 mm, most guidelines consider follow-up observations as an option; however, the various treatment strategies are defined by size alone, even though the Ki-67 index is important for malignancy grading. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is the standard for the histopathological diagnosis of solid pancreatic lesions; however, recent results for small lesions remain unclear. Therefore, we examined the efficacy of EUS-TA for solid pancreatic lesions ≤ 20 mm suspected as pNETs or requiring differentiation and the non-increase rate in tumor size in follow-up cases. METHODS: We retrospectively analyzed data of 111 patients (median age = 58 years) with lesions ≤ 20 mm suspected as pNETs or requiring differentiation who underwent EUS-TA. All patients underwent specimen evaluation by rapid onsite evaluation (ROSE). RESULTS: EUS-TA led to a diagnosis of pNETs in 77 patients (69.4%) and tumors other than pNETs in 22 patients (19.8%). The histopathological diagnostic accuracy of EUS-TA was 89.2% (99/111) overall, 94.3% (50/53) for 10-20 mm lesions, and 84.5% (49/58) for ≤ 10 mm lesions, with no significant difference in diagnostic accuracy (p = 0.13). The Ki-67 index was measurable in all patients with a histopathological diagnosis of pNETs. Among 49 patients with a diagnosis of pNETs who were followed up, one patient (2.0%) showed tumor enlargement. CONCLUSIONS: EUS-TA for solid pancreatic lesions ≤ 20 mm suspected as pNETs or requiring differentiation is safe and has adequate histopathological diagnostic accuracy, suggesting that follow-up observations of pNETs with a histological pathologic diagnosis are acceptable in the short term.

Relationship Between Safety and Cumulative Bevacizumab Dose in Patients With Metastatic Colorectal Cancer Who Received Long-term Bevacizumab Treatment.

BACKGROUND/AIM: Bevacizumab-based chemotherapy is the standard treatment for metastatic colorectal cancer (mCRC) but has several specific adverse events. The cumulative bevacizumab dose (CBD) increases with long-term treatment as it is often used beyond the first disease progression, based on existing evidence. However, the association between CBD and the frequency and severity of adverse events in mCRC patients who received bevacizumab for long-term treatment remains unclear. PATIENTS AND METHODS: Among the mCRC patients who received bevacizumab-based chemotherapy between March 2007 and December 2017 at the University of Tsukuba Hospital, those who continued treatment for more than 2 years were eligible for the study. The onset and worsening of proteinuria, hypertension, bleeding, and thromboembolic events were assessed to determine their relationship with CBD. RESULTS: Of the 109 patients who received bevacizumab-based chemotherapy, 24 were included in the study. Grade 3 proteinuria was observed in 21 (88%) and 9 (38%) patients. The severity of proteinuria markedly increased after administering >100 mg/kg of CBD and progressed to grade 3 at concentrations exceeding 200 mg/kg. Thromboembolic events were observed in three (13%) patients, and two of them developed acute myocardial infarction after receiving a CBD of >300 mg/kg. Grade 2 or higher hypertension and grade 1 bleeding were observed in 9 (38%) patients and in 6 (25%) patients, respectively, regardless of the CBD. CONCLUSION: Proteinuria and thromboembolic events occurred and worsened in mCRC patients when the bevacizumab dose exceeded the threshold dose.

Diagnostic Ability of Endoscopic Ultrasound-Guided Tissue Acquisition Using 19-Gauge Fine-Needle Biopsy Needle for Abdominal Lesions.

Attempts at performing endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a 19G needle are increasing because histological diagnosis and comprehensive genomic profiling are a necessity. However, the diagnostic ability of the 19G fine-needle biopsy (FNB) needle, especially the third-generation FNB needle, is unclear and has been retrospectively reviewed. The 19G TopGain needle was used in 147 patients and 160 lesions between September 2020 and December 2021. The technical success rate of the biopsies was 99.4% (159/160). The early adverse event rate was 4.1% (6/147), and moderate or severe adverse event rate occurrence was 2.0% (3/147). The sensitivity, specificity, and accuracy of the 19G TopGain needle for 157 lesions with a confirmed diagnosis were 96.7%, 100%, and 96.8%, respectively. Rescue EUS-TA using the 19G TopGain needle was performed for nine lesions, and a successful diagnosis was made in six of these lesions (66.7%). The diagnostic ability of EUS-TA using the third-generation 19G TopGain needle was favorable. However, the use of 19G FNB needles may increase adverse events. Therefore, EUS-TA with a 19G FNB needle is mainly indicated in lesions where comprehensive genomic profiling may be necessary or the diagnosis could not be determined via EUS-TA using the 22G needle.

Palliative Care and End-of-Life Outcomes in Patients Considered for Liver Transplantation: A Single-Center Experience in the US Midwest.

Introduction: Previous research has shown limited palliative care (PC) utilization among patients evaluated for liver transplantation (LT) despite the cohort's significant symptom burden, high frequency of hospitalization and risk of rapid decompensation. Our aim was to evaluate patient characteristics and end-of-life (EOL) outcomes (i.e. ICU utilization, code status, advance care planning) associated with the use of PC services in patients who were evaluated for LT. Methods: We performed a single-center cross-sectional study comprised of 223 deceased patients evaluated for LT between 1/1/2017 and 12/31/2021. We evaluated demographic characteristics and EOL outcomes for differences between patients who received PC consultation and those who did not. EOL outcomes associated with PC use were assessed using logistic and linear regression analysis adjusted for patient demographics. Results: Patients who received PC consultation were younger (mean 57 vs. 61; P = 0.048), had higher Model for end-stage Liver Disease (MELD) scores (27.5 vs. 22; P = 0.001), higher rates of hepatic encephalopathy (96% vs. 84%, P = 0.005), and were more frequently declined for LT (77% vs. 57%; P = 0.008). Patients who received PC services were less likely to die in the ICU (OR = 0.07 [0.02-0.18]) and were more likely to have documented advance care planning (OR = 3.16 [1.47-6.97]), family meetings (OR = 6.58 [2.72-17.08]), and goals-of-care discussions (OR = 14.83 [4.39-69.29]). Conclusion: For patients being evaluated for LT, PC utilization differed based on demographics, disease complications and severity, and transplant status. Those who received PC services had higher quality EOL care planning and fewer ICU admissions.

Fine-needle biopsy with 19G needle is effective in combination with endoscopic ultrasound-guided tissue acquisition for genomic profiling of unresectable pancreatic cancer.

OBJECTIVES: Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC). METHODS: Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route. RESULTS: In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30). CONCLUSION: In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.

Family Caregivers' Challenges in Cancer Pain Management for Patients Receiving Palliative Care.

CONTEXT: Family caregivers (FCs) of cancer patients play a crucial role in managing their care partner's pain, but little research has examined FCs' specific challenges regarding the provision of pain management (PM) to cancer patients receiving palliative care. OBJECTIVES: To determine the demographic and clinical characteristics of FCs who encounter challenges in PM and to elucidate the specific challenges that FCs face when managing pain for their care partner with cancer. METHODS: We conducted a secondary analysis of 40 interview transcripts of FCs who were caring for persons with cancer. Interviews were audio-recorded, transcribed verbatim, and analyzed using deductive thematic analysis. RESULTS: The three major identified challenges to PM for FCs of persons with cancer were: (1) communication and teamwork issues, (2) caregiver-related issues, and (3) patient-related issues. Communication and teamwork issues encompassed caregivers' receipt of inadequate information regarding PM, and inappropriate and ineffective communication from the healthcare team. Caregiver issues pertained to caregivers' fear and beliefs, concurrent responsibilities, and lack of pain-related knowledge and skills. Patient issues related to their own fear and beliefs, psychological and physiological well-being, adherence to medications, and reluctance to report pain. CONCLUSION: Findings of this study have implications for future research and practice related to cancer PM in palliative care. Results suggest the need for FC training in PM as well as clear clinical practice guidelines and resources to help providers prepare, educate, and communicate with FCs regarding PM.

Severe Gastrointestinal Disorder Due to Capecitabine Associated with Dihydropyrimidine Dehydrogenase Deficiency: A Case Report and Literature Review.

Dihydropyrimidine dehydrogenase (DPD) deficiency induces severe adverse events in patients receiving fluoropyrimidines. We encountered a 64-year-old DPD-deficient man with a severe capecitabine-related gastrointestinal disorder. He received capecitabine-containing chemotherapy after rectal cancer resection. During the first course of chemotherapy, he developed severe diarrhea, a fever, and hematochezia. Endoscopy revealed mucosal shedding with bleeding throughout the gastrointestinal tract. DPD deficiency was suspected because he developed many severe adverse events of capecitabine early and was finally confirmed based on the finding of a low DPD activity level in peripheral blood mononuclear cells. After one month of intensive care, hemostasis and mucosal healing were noted, although his gastrointestinal function did not improve, and he had persistent nutritional management issues.

Nanoparticle albumin-bound paclitaxel and ramucirumab versus paclitaxel and ramucirumab as second-line chemotherapy for unresectable advanced or recurrent gastric cancer: a multicenter, propensity score-matched analysis (CROSS SELL study).

BACKGROUND: Paclitaxel plus ramucirumab (PTX + RAM) is the standard second-line chemotherapy for unresectable advanced or recurrent gastric cancer (AGC). Nanoparticle albumin-bound paclitaxel (nab-PTX) is an improved, more convenient form of PTX and is non-inferior to PTX. Although some retrospective and single-arm phase II studies regarding nab-PTX + RAM have been reported, comparative studies are lacking. Here, we compared the efficacy and toxicity of nab-PTX + RAM and PTX + RAM using propensity score matching. METHODS: Clinical data of 265 patients treated for AGC with nab-PTX + RAM or PTX + RAM were retrospectively collected. Nab-PTX was administered at dosages of 100 mg/m2, replacing PTX in the standard PTX + RAM regimen. Progression-free survival (PFS), overall survival (OS), and toxicity were compared using 1:1 propensity score matching. RESULTS: In total, 190 (72%) patients were matched. The median PFS was 5.3 [95% confidence interval (CI) 4.4-6.3] and 4.7 (95% CI 3.2-5.3) months in the nab-PTX + RAM and PTX + RAM groups, respectively [hazard ratio (HR) = 0.76, 95% CI 0.56-1.03, p = 0.07]. The median OS was 11.5 (95% CI 9.2-15.0) and 9.9 (95% CI 8.0-12.7) months, respectively (HR = 0.78, 95% CI 0.56-1.07, p = 0.12). Grade 3 and 4 neutropenia was observed more frequently in the nab-PTX + RAM group (72% vs. 56%, p = 0.03). No treatment-related deaths occurred. CONCLUSIONS: Nab-PTX + RAM exhibited more favorable trends in terms of PFS and OS but was more myelosuppressive than PTX + RAM. As neutropenia is commonly manageable toxicity, nab-PTX + RAM presents a treatment alternative for AGC. Further studies including randomized, controlled studies are warranted.

Risk factors and efficacy outcomes of early-onset severe neutropenia due to paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab in advanced gastric cancer: a multicenter retrospective cohort study.

Background: Paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab (PTX/nab-PTX + RAM) is widely used as second-line chemotherapy for advanced gastric cancer (AGC), but severe neutropenia often develops with this regimen. Although previous studies have reported that severe neutropenia is a favorable prognostic factor in cancer chemotherapy, it is unclear in AGC patients receiving PTX/nab-PTX + RAM. In addition, the risk factors for early-onset of severe neutropenia (EOSN) still remain unknown. Methods: Among patients with AGC treated with PTX/nab-PTX (on day 1, 8, and 15) + RAM (on day 1 and 15) every 4 weeks as second-line therapy from January 2017 to June 2020, those with grade 0 or 1 neutropenia before the treatment were retrospectively studied. Blood tests were performed on the day of treatment each time, and disease progression was primarily determined by computed tomography every 8±2 weeks. EOSN was defined as grade 4 neutropenia that occurred during the first 28 days. The risk factors for EOSN were investigated using multivariate logistic regression analysis. Progression-free survival (PFS) and overall survival (OS) in patients with and without EOSN were investigated using multivariate analysis with a Cox proportional hazards model. Results: The clinical data of 244 patients were analyzed. EOSN was observed in 51 (20.9%) patients. Multivariate analysis identified the following five risk factors for EOSN: age ≥65 years [odds ratio (OR), 2.75], presence of primary tumor (OR, 2.82), presence of peritoneal metastasis (OR, 2.52), grade 1 neutropenia (OR, 3.32), and high serum level of alkaline phosphatase (OR, 2.34). The PFS was significantly longer in patients with EOSN than in those without EOSN [adjusted hazard ratio (HR), 0.61; 95% CI, 0.41-0.92] and the OS tended to be longer in patients with EOSN than in those without EOSN (adjusted HR, 0.73; 95% CI, 0.47-1.12). HR was adjusted with patient background factors and blood test data considered important as predictive or prognostic factors. Conclusions: EOSN may be associated with favorable outcomes in patients with AGC treated with PTX/nab-PTX + RAM. We should carefully try to treat them keeping the risk factors in mind.

The Impact of Food on Bioavailability of Oxycodone Myristate: A Case Report.

BACKGROUND: In efforts to reduce misuse of opioids, new abuse deterrent formulations of medications have been developed. Insurers increasingly give abuse-deterrent opioid formulations preferred formulary status, which can result in required formulation rotation for patients. Xtampza® (oxycodone myristate extended-release) is an abuse-deterrent opioid formulation that maintains its extended-release properties with any physical manipulation. Blood levels of oxycodone myristate extended-release (OxyM-ER) may vary with dietary caloric and fat intake. CASE DESCRIPTION: A woman with metastatic breast carcinoma had severe myalgias and arthralgias well-managed with oxycodone hydrochloride extended-release (OxyHCl-ER) and hydrocodone/acetaminophen. A switch from OxyHCl-ER to OxyM-ER resulted in worsened pain management, decreased functional status, and a referral to palliative care (PC). Recognizing calorie-depending pharmacokinetic variability with OxyM-ER, the interdisciplinary PC team obtained a detailed dietary history from the patient, which revealed a low-fat, low-calorie healthy diet with inconsistent meals. After repeated education, the patient changed her diet and had improved pain and functional status without increasing her total daily opioid dose. CONCLUSION: The efficacy of OxyM-ER may be compromised in patients with cancer experiencing anorexia, decreased or inconsistent food intake, or low-fat/low-calorie diets. An interdisciplinary team approach can improve pain control in the setting of "forced" formulary switches to OxyM-ER.

Immune Checkpoint Inhibitor Use Near the End of Life: A Single-Center Retrospective Study.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for many patients with advanced cancer. Little is known about ICI use near the end of life. Objective: To describe ICI use near the end of life. Design: Retrospective study of patients who received ICIs and died. Setting/Subjects: Patients treated with ICIs who died between August 2014 and December 2018 (N = 441) at the University of Iowa. Measurements: Comparisons were made between patients who received ICIs ≤30 days versus patients who received ICIs >30 days before death. The same analysis was done using a cutoff of 90 days. Results: Two hundred ninety-four (67%) patients received ICIs in the last 90 days of life and 117 (27%) patients received ICIs in the last 30 days of life. Patients who received ICIs in the last 30 days of life received fewer mean doses and more often ≤3 total doses. They also had higher mean Eastern Cooperative Oncology Group (ECOG) scores, more patients with ECOG ≥3, higher rates of dying in the hospital, and lower hospice enrollment. Patients treated with ICIs in the last 90 days of life received fewer doses, more often ≤3 total doses, had a higher mean ECOG score, more patients with ECOG ≥3, and lower hospice enrollment. $7.1 million USD was spent on ICI medications in the last 90 days of life. Conclusion: ICI use near the end of life is associated with poor performance status, lower hospice enrollment, dying in the hospital, financial toxicity, and minimal clinical benefit.

Immune Checkpoint Inhibitor Use Near the End of Life Is Associated With Poor Performance Status, Lower Hospice Enrollment, and Dying in the Hospital.

BACKGROUND: Immune checkpoint inhibitors have changed the landscape of cancer care by increasing progression-free and overall survival in some patients with cancer. We evaluated use and variables contributing to immune checkpoint inhibitor treatment near the end of life. METHODS: We studied 157 patients who received immune checkpoint inhibitors and died between January 2015 and December 2018. All patients had a palliative care consult any time between starting an immune checkpoint inhibitor and death. Univariate and multivariate models were used to examine variables related to immune checkpoint inhibitor use near the end of life. RESULTS: Among 157 patients studied, 42 (27%) received a dose of immune checkpoint inhibitor in the last 30 days of life. Those who received treatment in the last 30 days of life had lower hospice enrollment (19 [45%] vs 78 [69%], P = .007) and higher rates of dying in the hospital (23 [56%] vs 33 [29%], P = .002). The percentage of patients with Eastern Cooperative Oncology Group (ECOG) ≥3 at the time of last immune checkpoint inhibitor dose was higher in the group that received immune checkpoint inhibitor treatment in the last 30 days of life (11 [26%] vs 9 [8%], P = .003). Lack of traditional chemotherapy after immune checkpoint inhibitor, ECOG ≥3, and lack of hospice enrollment were independently associated with receiving immune checkpoint inhibitor in the last 30 days of life. CONCLUSION: Immune checkpoint inhibitor use in the last 30 days of life is common and associated with poor performance status, lower hospice enrollment, and dying in the hospital.