Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

BACKGROUND AND AIM: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. METHODS: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. RESULTS: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. CONCLUSION: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

Effect of metformin on outcomes of patients treated with immune checkpoint inhibitors: a retrospective cohort study.

BACKGROUND: Immune checkpoint inhibitors have transformed the treatment landscape of cancer treatment, but only a fraction of patients responds to treatment, leading to an increasing effort to repurpose clinically approved medications to augment ICI therapy. Metformin has been associated with improved survival outcomes in patients undergoing conventional chemotherapy. However, whether metformin provides survival benefits in patients receiving immune checkpoint inhibitors (ICIs) is unknown. METHODS: We performed a retrospective cohort study at two tertiary referral centers in Taiwan. All adult diabetes mellitus patients who were treated with ICIs between January 2015 and December 2021 were included. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: In total, 878 patients were enrolled in our study, of which 86 patients used metformin and 78 patients used non-metformin diabetes medications. Compared with non-users, metformin users had a longer median OS (15.4 [IQR 5.6-not reached] vs. 6.1 [IQR, 0.8-21.0] months, P = 0.003) and PFS (5.1 [IQR 2.0-14.3] vs. 1.9 [IQR 0.7-8.6] months, P = 0.041). In a univariate Cox proportional hazard analysis, the use of metformin was associated with a reduction in the risk of mortality (HR: 0.53 [95% confidence interval: 0.35-0.81], P = 0.004) and disease progression (HR: 0.69 [95% CI 0.49-0.99], P = 0.042). The use of metformin remained associated with a lower risk of mortality after adjusting for baseline variables such as age, cancer stage, and underlying comorbidities (OS, HR: 0.55 [95% CI 0.34-0.87], P = 0.011). Similarly, the use of metformin was associated with a lower risk of disease progression. Importantly, the use of metformin before ICI initiation was not associated with a reduction in mortality (HR: 0.61 [95% CI 0.27-1.42], P = 0.25) or disease progression (HR: 0.69 [95% CI 0.33-1.43], P = 0.32). CONCLUSION: The use of metformin is associated with survival benefits in patients undergoing immunotherapy. Prospective clinical trials are warranted to define the role of metformin in augmenting immunotherapy.

Efficacy of Lipophilic Statins on Outcomes of Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Statins are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the impact of lipophilic and hydrophilic statin properties on patient outcomes is unknown. OBJECTIVES: We aim to investigate if statins with lipophilic properties are associated with clinical outcomes in patients receiving ICIs. METHOD: We conducted a retrospective cohort study at two tertiary referral centers in Taiwan comprising patients receiving ICIs between January 2015 and December 2021. We compared the comparative effect of lipophilic and hydrophilic statins on patient outcomes. The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS). RESULTS: Among 734 patients receiving ICIs, there were 51 lipophilic statin users, 25 hydrophilic statin users, and 658 nonusers. Lipophilic statin users had a longer median OS (38.0 [IQR, 16.7-not reached] vs. 15.2 [IQR, 8.2-not reached] months vs. 18.9 [IQR, 5.4 51.6] months) and PFS (13.0 [IQR, 4.7-41.5] vs. 8.2 [IQR, 2.2-14.7] months vs. 5.6 [2.3-18.7] months) than hydrophilic statin users and non-statin users. In Cox proportional hazard analyses, the use of lipophilic statins was associated with a 40-50% lower risk of mortality and disease progression compared with hydrophilic statin or non-statin users. CONCLUSIONS: The use of lipophilic statins seems to be associated with survival benefits in patients undergoing immunotherapy.

Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of replacing doxorubicin with tirapazamine in conventional transarterial chemoembolization (TACE) in an Asian population with hepatocellular carcinoma (HCC), and to determine the optimal tirapazamine dose for phase II studies. MATERIALS AND METHODS: This was a phase I, 3 + 3 dose-escalation study for patients with unresectable early- and intermediate-stage HCC who received 5, 10, or 20 mg/m2 of intra-arterial (IA) tirapazamine followed by ethiodized oil/gelatin sponge-based embolization. Key eligibilities included HCCs no more than 10 cm in diameter, prior embolization allowed, Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of 5-7, and platelet count of ≥60,000 µL. Dose-limiting toxicity (DLT) was defined as any grade 3 nonhematological or grade 4 hematological toxicity, with the exception of transient elevation of aminotransferase levels after the procedure. RESULTS: Seventeen patients were enrolled, 59% of whom had progression from a prior HCC therapy and 35% of whom had progression or recurrence after TACE. All patients tolerated the tirapazamine TACE well without any DLT or serious adverse event. Using the modified Response Evaluation Criteria in Solid Tumors, the complete response (CR) rate was 47%, and the CR + partial response rate was 65%. The median duration of response was not reached. The median time to progression was 12.6 months (95% confidence interval, 5.1-not reached). The median overall survival was 29.3 months. The selected phase II dose was set at a fixed dose of 35 mg of IA tirapazamine. CONCLUSIONS: IA tirapazamine with transarterial embolization was well tolerated and showed promising efficacy signals in intermediate-stage HCC, justifying pursuit of a phase II study.

The incidence and risk of cardiovascular events associated with immune checkpoint inhibitors in Asian populations.

OBJECTIVES: Immune checkpoint inhibitors are associated with adverse cardiovascular events. However, there are no data characterizing cardiovascular events among Asians on immune checkpoint inhibitors. We aim to determine the incidence and risk of cardiac events associated with immune checkpoint inhibitors in an Asian population. METHODS: We performed a retrospective, propensity score-matched cohort study at two tertiary referral centers in Taiwan. Immune checkpoint inhibitor users were matched with non-immune checkpoint inhibitor users based on predetermined clinical variables. The primary outcome was major adverse cardiovascular events, defined as a composite of myocardial infarction, ischemic stroke, acute peripheral occlusive disease, pulmonary embolism, deep venous thrombosis, heart failure, pericardial disease, myocarditis, cardiac arrhythmias and conduction block. RESULTS: Between January 2010 and November 2021, 868 immune checkpoint inhibitor users were matched 1:1 with non-immune checkpoint inhibitor users. Among immune checkpoint inhibitor users, 67 (7.7%) patients developed major adverse cardiovascular events. During a median follow-up period of 188 days, the incidence rate of major adverse cardiovascular events for immune checkpoint inhibitor and non-immune checkpoint inhibitor users was 94.8 and 46.2 per 1000 patient-years, respectively, resulting in an incidence rate ratio of 2.1 [95% confidence interval: 1.5-2.9]. In multivariate Cox proportional hazard models, immune checkpoint inhibitor users had a 60% increased risk for major adverse cardiovascular events [hazard ratio, 1.6 (95% confidence interval: 1.1-2.3)]. Immune checkpoint inhibitors use was independently associated with increased risk of ischemic stroke [hazard ratio, 3.0 (95% confidence interval: 1.0-9.0)] and pulmonary embolism [hazard ratio, 5.5 (95% confidence interval: 1.4-21.3)]. In multivariate logistic regression analysis, age > 65, metastatic disease, hypertension and baseline platelet-to-lymphocyte ratio < 180 were risk factors for major adverse cardiovascular events. CONCLUSIONS: Among Asians, immune checkpoint inhibitors were associated with an increased risk of major adverse cardiovascular events, particularly ischemic stroke and pulmonary embolism.

Reduced-port robotic pancreaticoduodenectomy versus open pancreaticoduodenectomy: a single-surgeon experience.

BACKGROUND AND OBJECTIVES: Multiple-port robotic pancreaticoduodenectomy (RPD) has been increasingly used as an alternative to open pancreaticoduodenectomy (OPD) in pancreatic cancer. However, the comparative safety and efficacy of reduced-port RPD versus OPD are unknown. METHODS: This was a prospective cohort study comprising adult patients who underwent reduced-port RPD (single-port or single-site plus one port) or OPD for malignant tumors of the pancreas and periampullary region from July 2015 to October 2020 at a single center. We collected data on the patient demographics, perioperative results, oncologic outcomes, and one-year survival. RESULTS: Forty-five patients underwent reduced-port RPD, and 13 underwent OPD. There were no significant differences in the age, sex, body mass index, ASA score, tumor location, or occurrences of postoperative complications between the two groups. Compared with OPD, reduced-port RPD was associated with less blood loss (300 ml [95% confidence interval {CI} 155-700] vs. 650 ml [95% CI 300-850], p value = 0.11) but a longer operative time (325 min [95% CI 290-370] vs. 215 min [95% CI 180-270], p value < 0.001). Compared with patients who underwent OPD, patients who underwent reduced-port RPD had a higher 1-year survival rate (68% [95% CI 49-81] vs. 22% [95% CI 3-51], log-rank, p value = 0.007). CONCLUSIONS: Reduced-port RPD can be safely performed in experienced surgeons and is associated with better perioperative and oncologic outcomes than OPD.

Abdominal Ultrasound in the Detection of an Incidental Paraganglioma.

Paraganglioma is a tumor that originates from neuroendocrine cells of the sympathetic or parasympathetic systems. Patients may suffer from headaches, palpitations, diaphoresis, and hypertension due to catecholamine excess or symptoms from the mass effect of the tumor. In the absence of typical symptoms of catecholamine excess, the diagnosis of a nonfunctional paraganglioma is often delayed. Herein, we report a case of a 63-year-old female patient with a nonfunctional paraganglioma which is an accidental finding during investigation of a fever. Abdominal ultrasonography incidentally detected this lesion as a complex, solid, cystic mass in the left suprarenal retroperitoneum.

Favorable gallbladder cancer mortality-to-incidence ratios of countries with good ranking of world's health system and high expenditures on health.

BACKGROUND: The mortality-to-incidence ratio (MIR) is a marker that reflects the clinical outcome of cancer treatment. MIR as a prognostic marker is more accessible when compared with long-term follow-up survival surveys. Theoretically, countries with good health care systems would have favorable outcomes for cancer; however, no report has yet demonstrated an association between gallbladder cancer MIR and the World's Health System ranking. METHODS: We used linear regression to analyze the correlation of MIRs with the World Health Organization (WHO) rankings and total expenditures on health/gross domestic product (e/GDP) in 57 countries selected according to the data quality. RESULTS: The results showed high crude rates of incidence/mortality but low MIR in more developed regions. Among continents, Europe had the highest crude rates of incidence/mortality, whereas the highest age-standardized rates (ASR) of incidence/mortality were in Asia. The MIR was lowest in North America and highest in Africa (0.40 and 1.00, respectively). Furthermore, favorable MIRs were correlated with good WHO rankings and high e/GDP (p = 0.01 and p = 0.030, respectively). CONCLUSIONS: The MIR variation for gallbladder cancer is therefore associated with the ranking of the health system and the expenditure on health.

Application of a commercial single-port device for robotic single-incision distal pancreatectomy: initial experience.

PURPOSE: Laparoscopic distal pancreatectomy has proven to be feasible and safe. Moreover, robotic surgery provides unique advantages for pancreatic procedures, although single-incision robotic pancreatic surgery is rarely discussed. We applied the single-port modified platform to accomplish robotic distal pancreatectomy in a series of patients. METHODS: The subjects of this study were ten patients who underwent robotic distal pancreatectomy in our hospital between July 1, 2015 and Dec 31, 2016. All patients were placed supine in the reverse Trendelenburg position with the legs abducted. Surgery was performed via a trans-umbilical 5.0-cm incision, using a modified single-port platform (LAGIPORT®) combined with the da Vinci Si Surgical System. The three arms and scope (30-degree up) were inserted through the LAGIPORT® and positioned in a triangle. Endoscopic ultrasound was used to localize the tumor and plan the resection margin. We recorded the surgical time, operation time, blood loss, postoperative pain score, hospital stay, and complications. RESULTS: The surgical time was 236 ± 32 min, the operation time was 172 ± 30 min, and the blood loss was 149 ± 65 ml. All patients underwent robot-assisted distal pancreatectomy without conversion. The average pain score on postoperative day (POD) 3 was 4.5 ± 1. Complications included subsplenic hematoma (n = 1) and minor pancreatic leakage (n = 2). There was no surgical mortality. CONCLUSIONS: Our results demonstrate the safety and efficiency of robotic single-incision distal pancreatectomy via the modified platform (LAGIPORT®).

EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?

Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 functions as a double-facet molecule in regulation of gene expression via repression or activation mechanisms, depending on the different cellular contexts. EZH2 interacts with both histone and non-histone proteins to modulate diverse physiological functions including cancer progression and malignancy. In this review article, we focused on the updated information regarding microRNAs (miRNAs) and long non coding RNAs (lncRNAs) in regulation of EZH2, the oncogenic and tumor suppressive roles of EZH2 in cancer progression and malignancy, as well as current pre-clinical and clinical trials of EZH2 inhibitors.

Insulinoma in a young female patient with systemic lupus erythematosus: a case report.

OBJECTIVE: Fasting hypoglycemia may occur in subjects with systemic lupus erythematosus (SLE) when accompanied with insulin-binding antibodies or insulin-receptor antibodies. However, insulinoma has not been reported in SLE subjects with hypoglycemia. METHODS: We present a case report and review the relevant literature. RESULTS: A 26-year-old female with underlying SLE experienced several episodes of neuropsychiatric symptoms in a fasting state. The steroid dosage was titrated up, but in vain. Timely imaging studies showed a pancreatic tumor, and insulinoma was proven by pathology. Hypoglycemia did not recur after surgery. CONCLUSION: Physicians should distinguish insulinoma from autoimmunity-mediated hypoglycemia in SLE patients with fasting hypoglycemia.

Periodontitis is an immune-related adverse event associated with immune checkpoint inhibitors: A multi-center cohort study.

Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7%) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio=2.14, 95% CI=1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR=2.5, 95%CI=1.3-4.7) and PD-1 inhibitors (multivariate HR=2.0, 95%CI=1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value=0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs.

Spleen-preserving distal pancreatectomy from multi-port to reduced-port surgery approach.

BACKGROUND: Minimally invasive pancreatic surgery via the multi-port approach has become a primary surgical method for distal pancreatectomy (DP) due to its advantages of lower wound pain and superior cosmetic results. Some studies have applied reduced-port techniques for DP in an attempt to enhance cosmetic outcomes due to the minimally invasive effects. Numerous recent review studies have compared multi-port laparoscopic DP (LDP) and multi-port robotic DP (RDP); most of these studies concluded multi-port RDP is more beneficial than multi-port LDP for spleen preservation. However, there have been no comprehensive reviews of the value of reduced-port LDP and reduced-port RDP. AIM: To search for and review the studies on spleen preservation and the clinical outcomes of minimally invasive DP that compared reduced-port DP surgery with multi-port DP surgery. METHODS: The PubMed medical database was searched for articles published between 2013 and 2022. The search terms were implemented using the following Boolean search algorithm: ("distal pancreatectomy" OR "left pancreatectomy" OR "peripheral pancreatic resection") AND ("reduced-port" OR "single-site" OR "single-port" OR "dual-incision" OR "single-incision") AND ("spleen-preserving" OR "spleen preservation" OR "splenic preservation"). A literature review was conducted to identify studies that compared the perioperative outcomes of reduced-port LDP and reduced-port RDP. RESULTS: Fifteen articles published in the period from 2013 to 2022 were retrieved using three groups of search terms. Two studies were added after manually searching the related papers. Finally, 10 papers were selected after removing case reports (n = 3), non-English language papers (n = 1), technique papers (n = 1), reviews (n = 1), and animal studies (n = 1). The common items were defined as items reported in more than five papers, and data on these common items were extracted from all papers. The ten studies included a total of 337 patients (females/males: 231/106) who underwent DP. In total, 166 patients (females/males, 106/60) received multi-port LDP, 126 (females/males, 90/36) received reduced-port LDP, and 45 (females/males, 35/10) received reduced-port RDP. CONCLUSION: Reduced-port RDP leads to a lower intraoperative blood loss, a lower postoperative pancreatic fistula rate, and shorter hospital stay and follow-up duration, but has a lower spleen preservation rate.

The Efficacy of Cationic Amphiphilic Antihistamines on Outcomes of Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Cationic amphiphilic H1-antihistamines have demonstrated antitumor effects in preclinical studies. We conducted a retrospective cohort study to investigate their impact on patients with pancreatic adenocarcinoma (PDAC). METHODS: We performed a matched cohort study involving PDAC patients from two tertiary centers in Taiwan using criteria including age, sex, and cancer stage. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response rates (ORR). RESULTS: We matched 28 cationic amphiphilic antihistamine users with 56 non-cationic amphiphilic antihistamine users. Cationic amphiphilic antihistamine users showed significantly longer OS (median 16.4 [IQR, 2.8 - 89.0] vs.5.8 [IQR, 2.0 - 9.8] months; p<0.001) and PFS (median 12.2 [IQR, 2.2 - 83.3] vs. 5.2 [IQR, 1.7 - 8.4] months; p=0.002) compared to non-users. In the Cox proportional hazard models, the use of cationic amphiphilic antihistamines was associated with approximately 60% lower risk of all-cause mortality and disease progression. Additionally, cationic amphiphilic antihistamine users exhibited a significantly greater ORR than non-users (39% vs. 7%, p=0.004). CONCLUSION: Our study suggests that cationic amphiphilic antihistamines are associated with improved survival outcomes in PDAC patients.

The relationship between statin administration timing and survival outcomes in patients with cancer receiving immune checkpoint blockade.

OBJECTIVE: Statins have been demonstrated to improve outcomes in patients receiving immune checkpoint blockade (ICB). This study aimed to investigate whether the timing of statin administration influences the outcomes of patients receiving ICB. METHODS: We conducted a retrospective cohort study utilizing electronic health records from two tertiary referral centers in Taiwan. We compared the overall survival (OS) and progression-free survival (PFS) of patients who received statins before and after ICB initiation. RESULTS: We included 734 patients who received ICB. Among them, 606 were non-statin users, 76 started statins after ICB initiation, and 52 started statins before ICB initiation. Post-ICB statin users demonstrated significantly prolonged OS (median 37.6 versus 10.3 versus 11.3 months, p = 0.009) and PFS (median 10.5 versus 6.3 versus 5.6 months, p = 0.024) compared to pre-ICB statin and non-statin users. Statin use after ICB initiation had a reduced risk of all-cause mortality (HR, 0.65 [95% CI: 0.45-0.94], p = 0.022) and progressive disease (HR, 0.71 [95% CI: 0.53-0.95], p = 0.021) by approximately 30-35%, compared to non-statin users. However, statin use prior to ICB initiation did not affect the risk of all-cause mortality or progressive disease. Similar results were observed after controlling for potential cofounders such as age, sex, cancer stage, and cancer type. CONCLUSIONS: These findings suggest that initiating statin therapy after the initiation of ICB, regardless of indication, is associated with improved patient prognosis.

The impact of peroxisome proliferator-activated receptor-γ activating angiotensin receptor blocker on outcomes of patients receiving immunotherapy.

BACKGROUND: Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator-activated receptor-γ (PPAR-γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte-mediated antitumor activity. METHODS: We conducted a retrospective cohort study to investigate the impact of PPAR-γ-activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers. RESULTS: A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non-PPAR-γ-ARB users (n = 102), PPAR-γ-ARB users (n = 65) had a longer median overall survival (not reached [IQR, 16.0-not reached] vs. 18.6 [IQR, 6.1-38.6] months) and progression-free survival (17.3 [IQR, 5.1-not reached] vs. 8.2 [IQR, 2.4-18.6] months). In Cox regression analysis, the use of PPAR-γ-activating ARBs had an approximately 50% reduction in all-cause mortality and disease progression. Patients who received PPAR-γ-activating ARBs also had higher clinical benefit rates than non-PPAR-γ-ARB users (82% vs. 61%, p = 0.005). CONCLUSION: The use of ARBs with PPAR-γ-activating property is linked with better survival among patients receiving ICIs.

Real-World Data Validation of NAPOLI-1 Nomogram for the Prediction of Overall Survival in Metastatic Pancreatic Cancer.

BACKGROUND: The nomogram derived from the pivotal phase III NAPOLI-1 study demonstrated a significant ability to predict median overall survival (OS) in gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (PDAC) treated with liposomal irinotecan plus fluorouracil and leucovorin (nal-IRI+5-FU/LV). However, the NAPOLI-1 nomogram has not been validated in a real-world setting and therefore the applicability of the NAPOLI-1 nomogram in daily practice remains unknown. This study aims to evaluate the NAPOLI-1 nomogram in a multicenter real-world cohort. METHODS: The NAPOLI-1 nomogram was applied to a previously established cohort of metastatic PDAC patients treated with nal-IRI+5-FU/LV in nine participating centers in Taiwan. Patients were divided into three risk groups according to the NAPOLI-1 nomogram. The survival impact of relative dose intensity at 6 weeks (RDI at 6 weeks) in different risk groups was also investigated. RESULTS: Of the 473 included patients, the median OSs of patients classified as low (n = 156), medium (n = 186), and high (n = 131) risk were 10.9, 6.3, and 4.3 months, respectively (p < 0.0001). The survival impact of RDI at 6 weeks remained significant after stratification by risk groups, adjustment with Cox regression, inverse probability weighting, or propensity score matching. CONCLUSIONS: Our results support the usefulness of the NAPOLI-1 nomogram for risk stratification in gemcitabine-refractory metastatic PDAC treated with nal-IRI+5-FU/LV in daily practice. We further showed that the RDI at 6 weeks is an independent prognostic factor beyond the NAPOLI-1 nomogram.

Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer.

OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce heart failure (HF) in at-risk patients and may possess antitumour effects. We examined the effect of SGLT2i on HF and mortality among patients with cancer and diabetes. METHODS: This was a retrospective propensity score-matched cohort study involving adult patients with type 2 diabetes mellitus diagnosed with cancer between January 2010 and December 2021. The primary outcomes were hospitalisation for incident HF and all-cause mortality. The secondary outcomes were serious adverse events associated with SGLT2i. RESULTS: From a total of 8640 patients, 878 SGLT2i recipients were matched to non-recipients. During a median follow-up of 18.8 months, SGLT2i recipients had a threefold lower rate of hospitalisation for incident HF compared with non-SGLT2i recipients (2.92 vs 8.95 per 1000 patient-years, p=0.018). In Cox regression and competing regression models, SGLT2i were associated with a 72% reduction in the risk of hospitalisation for HF (HR 0.28 (95% CI: 0.11 to 0.77), p=0.013; subdistribution HR 0.32 (95% CI: 0.12 to 0.84), p=0.021). The use of SGLT2i was also associated with a higher overall survival (85.3% vs 63.0% at 2 years, p<0.001). The risk of serious adverse events such as hypoglycaemia and sepsis was similar between the two groups. CONCLUSIONS: The use of SGLT2i was associated with a lower rate of incident HF and prolonged overall survival in patients with cancer with diabetes mellitus.