Browse Articles

Validation of PDACai v2.0 in predicting relative benefit from frontline FOLFIRINOX (FFX) and gemcitabine/nab-paclitaxel (GA) for patients (pts) with metastatic pancreatic cancer (mPDAC).

776 Background: Novel biomarkers beyond genomic alterations in DDR pathway genes (e.g. BRCA1/2 ) have the potential to optimize frontline and subsequent treatment decisions for mPDAC. This real-world evidence (RWE) study validates PDACai v2.0, a machine learning framework that leverages clinical NGS data to predict progression-free survival (PFS) on FFX vs GA in individual pts with mPDAC. Methods: We analyzed outcomes from 774 pts with mPDAC who underwent genomic profiling via the Know Your Tumor program or were referred to Perthera by treating oncologists. Independent training and validation cohorts receiving either 1st line FFX or GA were split (60:40). PDACai v2.0 integrates an updated set of clinical (age < 63, sex) and lab-agnostic molecular features derived from genomic testing reports (specific KRAS variants, TP53 GOF vs LOF, DDR pathway redefined). Relative benefit scores predicted by FFX or GA models were evenly binned into three PDACai signature categories representing lower, middle, and upper tertiles for each independent cohort. Statistical differences in median PFS were evaluated using ordinal Cox regression. Results: Median PFS followed PDACai predicted trends for each therapy’s training and validation cohorts. The predictive utility of PDACai was confirmed in the independent validation cohorts when comparing PFS on FFX (p = 0.01637; HR = 0.73 [95% CI: 0.56-0.94]) and GA (p = 0.0007506; HR = 0.62 [95% CI: 0.47-0.82]) across tertiles. Conclusions: Using RWE, the PDACai v2.0 signature successfully predicted PFS differences in pts treated with 1st line FFX or GA in mPDAC. Prospective validation efforts and additional data-driven insights into 2nd line PFS on FOLFOX vs 5FU/nal-irinotecan are underway. Summary of actual PFS in months on 1st line therapies in pts assigned to lower, middle, and upper thirds based on relative PDACai v2.0 scores. Independent Cohort (# Pts) Lower TertilemPFS [95% CI] Middle TertilemPFS [95% CI] Upper TertilemPFS [95% CI] 1st line FFX Training (243) 6.5 [5.5-8.1] 9.3 [6.5-13.3] 15.8 [14.1-N/R] 1st line FFX Validation (165) 9.4 [7-13.3] 8.6 [5.6-11.4] 13.2 [9.9-39.6] 1st line GA Training (218) 5.6 [4.7-6.3] 6.9 [5.2-8.2] 11.2 [8.8-13.4] 1st line GA Validation (148) 5.6 [4.2-8.4] 7.5 [6.5-13.1] 8.5 [7.7-11.5]

The changing treatment landscape of EGFR-mutant non-small-cell lung cancer

Trace Adsorptive Removal of PFAS from Water by Optimizing the UiO‐66 MOF Interface (Adv. Mater. 6/2025)

Passive Isothermal Flexible Sensor Enabled by Smart Thermal‐Regulating Aerogels

Abstract Environmentally induced sensor temperature fluctuations can distort the outputs of a sensor, reducing their stability during long‐term health monitoring. Here, a passive isothermal flexible sensor is proposed by using hierarchical cellulose aerogel (HCA) as the top tribonegative layer, which allows the sensor to adapt dynamic thermal environments through both radiative cooling and heat insulation. The radiative cooling effect can cool down the temperatures of a sensor in summer, while the hollow microfibers in HCA provide ultralow thermal conductivity to reduce internal heat loss in winter. The prepared passive isothermal sensor is capable of maintaining the rated working temperature over an extensive temperature range of 0−100 °C, demonstrating for gripping hot and cold objects. While monitoring human movements under direct sunlight, the temperature of a conventional sensor rose by 12.3 °C, whereas the sensor experienced an increase of only 0.3 °C. Therefore, this work presents a promising strategy for adapting to environments, enabling wearable electronics to function effectively in dynamic thermal conditions.

Final analysis of modified (m)-FOLFOXIRI plus cetuximab versus bevacizumab for <i>RAS</i> wild-type and left-sided metastatic colorectal cancer: The DEEPER trial (JACCRO CC-13).

17 Background: The DEEPER trial (NCT02515734), which evaluated m-FOLFOXIRI (irinotecan 150 mg/m², oxaliplatin 85 mg/m², 5-FU 2400 mg/m²) plus cetuximab (cet) vs. bevacizumab (bev) as initial therapy in terms of depth of response (DpR) as the primary endpoint in RAS wild-type metastatic colorectal cancer (mCRC), has demonstrated a significantly better DpR in the cet arm (ASCO 2021). Moreover, favorable progression-free survival (PFS) was reported in the cet arm for patients (pts) with RAS / BRAF wild-type and left-sided tumors (ESMO 2023). Due to the small number of overall survival (OS) events, it was decided to extend the observation period, and the final survival analysis was performed at the cutoff date of August 2024. Methods: Survival analysis was pre-planned in the per-protocol set (PPS), which consisted of pts evaluable for the DpR by an external review board. The clinical outcomes were evaluated according to clinical factors including primary tumor sidedness, liver metastasis status, and BRAF status using a log-rank test. All statistical tests were two-sided, and P values ≤ 0.05 were considered significant. Results: 321 of 359 enrolled pts were defined as PPS (median age 65 years, 64% male, performance status [PS] 0/1: 91%/9%, left/right primary: 84%/16%). In RAS wild-type and left-sided tumors, median PFS and OS were 13.9 months vs. 12.1 months (HR 0.81, 95% CI 0.63-1.05) and 45.3 months vs. 41.9 months (HR 0.85, 95% CI 0.64-1.12) in the cet vs. bev arm, respectively. BRAF status was available in 234 (73%) of the 321 pts in the PPS. An exploratory analysis showed that PFS was significantly better in the cet arm compared to the bev arm (median 14.8 months vs. 11.9 months, HR 0.71, 95% CI 0.52-0.97) in 178 pts with RAS / BRAF wild-type and left-sided tumors. Additionally, OS was 50.2 months vs. 40.2 months (HR 0.74, 95% CI 0.53-1.05). Moreover, according to liver disease status, m-FOLFOXIRI plus cet was associated with longer PFS and OS in pts with RAS / BRAF wild-type and left-sided mCRC with extra-hepatic metastases (median 15.1 months vs. 11.4 months, HR 0.66, 95% CI 0.46-0.95 and 50.2 months vs. 38.6 months, HR 0.60, 95% CI 0.40-0.90), but not liver-limited disease (median 14.5 months vs. 15.5 months, HR 0.79, 95% CI 0.44-1.42 and 52.2 months vs. 49.9 months, HR 1.17, 95% CI 0.61-2.24). Conclusions: The final survival analysis of the DEEPER trial demonstrated favorable PFS and OS with m-FOLFOXIRI plus cet in pts with RAS / BRAF wild-type and left-sided mCRC. The m-FOLFOXIRI plus cet regimen may be a good option for initial therapy, offering longer survival times in pts with extra-hepatic metastases. Clinical trial information: jRCTs061180022 .

Prognostic factors for gastric cancer patients with positive peritoneal cytology who underwent upfront surgery.

400 Background: Positive peritoneal cytology (CY1) is classified as Stage IV disease, the standard treatment for which is systemic chemotherapy. However, CY1 is often diagnosed after surgery in patients for whom staging laparoscopy is not indicated. In addition, the treatment strategy for patients with CY1 diagnosed during surgery is controversial. The Japanese guidelines recommend upfront surgery followed by adjuvant chemotherapy for patients diagnosed with CY1 during surgery. To identify patients with CY1 who are most likely to benefit from upfront surgery, we investigated prognostic factors in patients with CY1 who underwent upfront surgery. Methods: A total of 169 gastric cancer patients diagnosed as P0CY1 during or after surgery who underwent R1 resection other than positive resection margins were included. The diagnosis of CY1 was obtained by staging laparoscopy or during laparotomy in 69 patients and after surgery in 87 patients. Fourteen patients were initially diagnosed as CY0 by staging laparoscopy but were rediagnosed as CY1 after surgery. The clinicopathological factors of overall survival (OS) and progression-free survival (PFS) were investigated. Prognostic factors were identified using Cox regression models. Results: The median patient age was 72 years, and there were 108 males. The histological type was undifferentiated type in all of 102 patients. The macroscopic types were 0 in 10) patients 1 in 3, 2 in 27 3 in 84 and 4 in 45). cT grades and cN grades were cT1 in 3, cT2 in 7, cT3 in 12, cT4 in 147, cN0 in 65cN1 in 30), cN2 in 46 and cN3 in 28. The median OS and PFS were 25.1 months and 14.6 months, with 5-year OS rate and PFS rate of 30% and 23%, respectively. A multivariate analysis for OS identified macroscopic type 0-2, Charlson Comorbidity Index&lt;3, and adjuvant chemotherapy as independent prognostic factors. Similarly, macroscopic type 0-2, tumor size &lt;80 mm, and adjuvant chemotherapy were identified as independent prognostic factors for PFS. In a subgroup analysis of patients who received adjuvant chemotherapy, macroscopic type 0-2 was the only independent prognostic factor for PFS. The 5-year PFS rate in patients with macroscopic type 0-2 was 42%. Conclusions: Patients with macroscopic type 0-2 who are suitable for adjuvant chemotherapy may have benefit from upfront surgery, even if peritoneal cytology is positive.

Trends in incidence and survival in anal adenocarcinoma: A SEER study of racial and age disparities.

1 Background: Anal adenocarcinoma, a rare but increasingly diagnosed malignancy, has demonstrated rising incidence rates, warranting a deeper analysis of its epidemiology and outcomes across demographic factors like race and age. Methods: A retrospective analysis of data from SEER database (2000-2020) was conducted. Incidence rates per 100,000 individuals and 5-year survival outcomes were compared across racial groups (White, Black, Asian, Hispanic) and age categories (≤50 years, 51-70 years, &gt;70 years). Additionally, trends were analyzed across two decades: 2000-2010 and 2010-2020. This study investigates epidemiological trends of anal adenocarcinoma, focusing on variations in incidence and survival outcomes by race and age, with specific comparisons between the periods 2000-2010 and 2010-2020. Results: Incidence of anal adenocarcinoma increased from 0.7 per 100,000 in 2000 to 1.6 per 100,000 in 2020. From 2000 to 2010, incidence increased rose 0.7 to 1.0 per 100,000, and from 2010 to 2020, it rose from 1.0 to 1.6 per 100,000. Rates were highest among Black individuals, increasing from 1.5 per 100,000 (2000-2010) to 2.3 (2010-2020), followed by White (1.2 to 1.5), Hispanic (0.8 to 1.0), and Asian populations (0.3 to 0.5). Age-related outcomes showed that in 2000-2010, patients aged ≤50 years had a 5-year survival rate of 75% versus 55% in age 51-70 versus 35% for &gt;70 years. In 2010-2020, these rates dropped to 70%, 50%, and 30% in respective age groups. Racial disparities in survival were evident: Black patients had a 5-year survival rate of 40% (2000-2010) and 35% (2010-2020), significantly lower than White patients, who had rates of 65% (2000-2010) and 60% (2010-2020). Conclusions: The incidence of anal adenocarcinoma has steadily increased from 2000 to 2020, particularly among the Black population, while survival rates have declined. Additionally, survival rates are lower in individuals older than 70 years. Highlighting disparities in incidence and outcomes, further research is essential to uncover the underlying causes and develop targeted interventions to mitigate risks and improve patient outcomes. Keywords: anal adenocarcinoma, epidemiology, race, age, survival rates, disparities. This table summarizes the key trends in anal adenocarcinoma incidence and survival by race and age over the two decades from 2000 to 2020. The increases in incidence, particularly among Black individuals, and the worsening survival rates, especially in older and Black populations, are notable findings from the study. Category 2000-2010 2010-2020 Change (2000-2020) Incidence per 100,000 (Overall) 0.7 → 1.0 1.0 → 1.6 +0.9 Incidence by Race - White 1.2 → 1.5 1.5 → 1.5 +0.3 - Black 1.5 → 2.3 2.3 → 2.3 +0.8 - Hispanic 0.8 → 1.0 1.0 → 1.0 +0.2 - Asian 0.3 → 0.5 0.5 → 0.5 +0.2 5-Year Survival by Age - ≤50 years 75% 70% -5% - 51-70 years 55% 50% -5% - &gt;70 years 35% 30% -5% 5-Year Survival by Race - White 65% 60% -5% - Black 40% 35% -5%

Tunable Electron Correlation in Epitaxial 1T‐TaS₂ Spirals (Adv. Mater. 6/2025)

Cancer Immunotherapy Trials Network 12: Pembrolizumab in HIV-Associated Kaposi Sarcoma

PURPOSE Cancer Immunotherapy Trials Network 12 demonstrated safety of pembrolizumab in treating advanced cancer in people with HIV. Here, we report results of the Kaposi sarcoma (KS) cohort. METHODS In this multicenter phase I trial, we enrolled participants with HIV-associated KS on antiretroviral therapy with CD4 + ≥50 cells/μL and HIV plasma RNA &lt;200 copies/mL. Pembrolizumab 200 mg intravenously was administered once every 3 weeks for up to 35 cycles. The primary end point was safety, and the secondary end point was KS response by modified AIDS Clinical Trials Group Criteria. RESULTS Thirty-two cisgender men enrolled with baseline median CD4 + T-cell count of 274 cells/µL. All but nine participants had received previous systemic KS therapy. Participants received a median of 11 cycles of pembrolizumab (range, 1-35). Sixty-six percent had grade ≥1 treatment-emergent adverse events, including one death from polyclonal KS herpesvirus–related B-cell lymphoproliferation. Thirty-one percent had ≥one immune-mediated AEs (imAEs) with 25% requiring systemic steroids. In 29 participants with evaluable KS, the overall response rate (ORR) was 62.1% (95% CI, 42.3 to 79.3) and did not differ by CD4 + T-cell count. ORR in the eight participants with evaluable disease without previous KS therapy was 87.5% (95% CI, 47.3 to 99.7). Median duration of response (DOR) was not reached, and the Kaplan-Meier estimate of DOR of ≥12 months was 92.3% (95% CI, 56.6 to 98.8). Median progression-free survival was 28.2 months (95% CI, 4.2 to noncalculable). CONCLUSION Pembrolizumab yielded a high rate of durable responses in HIV-associated KS. imAEs were successfully managed with standard guidelines.

Retrospective study of fluoropyrimidine chemotherapy dosing and toxicity in patients with screen-detected deleterious <i>DPYD</i> gene variants.

293 Background: Fluoropyrimidine chemotherapy agents are commonly used to treat solid tumors. Fluoropyrimidines are degraded by the enzyme dihydropyridine dehydrogenase (DPD), encoded by the DPYD gene. Deleterious variants in DPYD leads to functional DPD deficiency and increased toxicity risk. Methods: We conducted a retrospective study of patients with screen-detected deleterious DPYD variants who were treated with fluoropyrimidine chemotherapy between 01/01/15-04/15/23. Outcomes of interest were initial fluoropyrimidine dosing, dose adjustments (cycles 2-6), and early toxicities. Results: We identified 12 patients with heterozygous DPYD variants, including *2A (n=5), c.2846A&gt;T (3), c.1129-5923C&gt;G (2) and *13 (2). Initial chemotherapy regimens included FOLFOX (7), mFOLFIRINOX (3) and CAPEOX (1). Of 11 patients receiving FOLFOX/mFOLFIRINOX, nine began treatment with a 50-60% reduction of the 5-FU infusion dose, one received a 25% reduction, and one received a standard dose (due to treatment initiation prior to return of the genotype result). Seven patients tolerated the initial 5-FU infusion dose without further dose reductions, including three who tolerated limited dose-escalation. Four patients required further dose reduction from the cycle 1 dose, due to toxicity. The patient who received a standard 5-FU infusion dose in cycle 1 experienced grade 3 toxicity, but tolerated subsequent treatment after 50% dose reduction. The patient treated with CAPEOX tolerated 4 planned cycles with a 50% capecitabine dose reduction. Conclusions: Most patients who screened positive for deleterious DPYD gene variants tolerated fluoropyrimidine chemotherapy with a 50% dose reduction. However, 3 of 12 patients experienced toxicity requiring treatment discontinuation or dose reduction to less than 50% of the standard 5-FU dose.

A systematic literature review of studies assessing first-line (1L) treatments in patients with advanced, grade 2/3 (G2/G3) gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

663 Background: There is no universally accepted standard of care for newly diagnosed patients with G2/G3 advanced GEP-NETs. The phase 3 NETTER-2 trial showed that [ 177 Lu]Lu-DOTA-TATE plus long-acting octreotide demonstrated a significant improvement in progression-free survival (PFS) vs. high-dose long-acting octreotide alone in this patient population. We conducted a comprehensive review of the published literature to summarize the available evidence on other 1L treatments assessed in advanced, well-differentiated, G2/G3 GEP-NETs. Methods: Embase, MEDLINE, and CENTRAL were systematically searched (until Jan 2024) to identify relevant clinical trials and observational studies assessing 1L systemic therapies among adults with advanced, well-differentiated, G2/G3 GEP-NETs. Key conferences from the past three years were also reviewed. Comparators of interest included somatostatin analogues (SSAs; octreotide and lanreotide), targeted therapies (sunitinib and everolimus), and chemotherapies (CAPTEM, STZ+5-FU, FOLFIRI, and platinum-based therapies). Studies with mixed patient populations were also included if ≥80% of the study participants matched the eligibility criteria. The 2022 WHO classification system was applied in studies with available Ki-67 index data but lacking grade information. Results: A total of 31 studies met the review eligibility criteria (three randomized controlled trials, one open-label extension study, three single-arm trials, and 24 observational studies). None of the included studies entirely matched the NETTER-2 population but provided data only for specific sub-populations. The included studies were categorized either by overall GEP-NET (n=16) or pancreatic-NET only population (n=15) with no study exclusively assessing gastrointestinal-NET patients. Majority of the comparator studies assessed chemotherapies (n=14), followed by SSAs (n=10), targeted therapies (n=3), a combination of targeted therapy and chemotherapy (n=1), and mixed treatments (n=2). Heterogeneity was also observed in terms of patient characteristics (data reported only in 12 studies), sample size (&lt;50 patients in 20 studies), and disease grade (G2/G3: nine studies, G2 only: 12 studies, and G3 only: 10 studies). Grading was derived using Ki-67 index in two studies. Majority of the studies reported PFS data (n=22), with nine studies providing data for both PFS and overall survival (OS); Kaplan-Meier curves for PFS and OS were reported for only 13 and four studies, respectively. Conclusions: This systematic literature review highlights a substantial evidence gap and an unmet need in 1L treatment of G2/G3 GEP-NETs. Robust quantitative comparison of NETTER-2 data with published evidence on other 1L treatments was largely restricted by low sample sizes and the aforementioned heterogeneity.

Designing Silk Biomaterials toward Better Future Healthcare: The Development and Application of Silk‐Based Implantable Electronic Devices in Clinical Diagnosis and Therapy (Adv. Mater. 8/2025)

Designing Current Collectors to Stabilize Li Metal Anodes

Abstract Rechargeable batteries employing Li metal anodes have gained increasing attention due to their high energy density. Nevertheless, low stability and reversibility of Li metal anodes severely impeded their practical applications. Designing current collectors (CCs) with reasonable structure and composition is an efficient approach to stabilizing the Li metal anodes. However, an in‐depth comprehensive understanding about the design principles and modification strategies of CCs for realizing stable Li metal anodes is still lacking. Herein, a critical review focusing on the rational design of CCs for Li metal anodes is summarized. First, the requirements for CCs in Li metal anodes are elucidated to clarify the design objectives of CCs. Then, the modification strategies of CCs including lithiophilic site modification, 3D architecture construction, protective layer modification, and crystalline plane engineering, as well as the corresponding principles are highlighted. On this basis, the recent progress in the development of CCs for Li metal anodes is discussed. Finally, future directions are suggested to focus on developing operando monitoring technology, and designing the CCs and cells under practical conditions close to the requirements of commercial applications. This review will spur more insightful researches toward advanced CCs, and promote their commercialization.

Patterns of radiological progression in participants (pts) with embolization-eligible hepatocellular carcinoma (HCC) treated with durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) and placebos + TACE: EMERALD-1 post hoc analysis.

574 Background: EMERALD-1 (NCT03778957) met its primary endpoint, demonstrating improved progression-free survival (PFS) in pts with locoregional HCC treated with D + B + TACE versus placebos (PBO) + TACE (stratified Cox proportional hazards hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.98 [Lencioni R, et al. J Clin Oncol 2024;42(suppl 3). Abs LBA432]). This post hoc analysis assessed outcomes by radiological progression pattern in pts treated with D + B + TACE or PBO + TACE. Methods: Pts included in this analysis received D (1500 mg) or PBO for D (Q4W) in combination with conventional (c)- or drug-eluting bead (DEB)-TACE (investigator choice, 1–4 TACE procedures within 16 weeks). Subsequently, pts received D (1120 mg) + B (15 mg/kg), or PBO for D + B (Q3W). This study analyzed radiological progression patterns at the time of first progressive disease (PD) as assessed by the investigator per modified Response Evaluation Criteria in Solid Tumors. A new lesion was classified as a new intrahepatic lesion (NIH) or new extrahepatic lesion (NEH); tumor growth of existing intrahepatic lesions (increase of ≥20% of an existing target lesion with at least &gt;5 mm absolute increase or unequivocal PD with a non-target lesion) was classified as intrahepatic growth (IHG; categories were not mutually exclusive). Efficacy was assessed by time to progression (TTP). Results: In the D + B + TACE arm, 53.9% of pts had PD, and in the PBO + TACE arm 79.0% of pts had PD. The most common pattern of disease progression across both treatment arms was NIH, occurring in 73 (35.8%) and 107 (52.2%) pts in the D + B + TACE and PBO + TACE arms, respectively, with 31 (15.2%) and 34 (16.6%) pts exhibiting IHG, and 24 (11.8%) and 39 (19.0%) pts exhibiting NEH, respectively. Improved TTP was observed in pts treated with D + B + TACE versus PBO + TACE, regardless of progression pattern (Table). Conclusions: Overall, the rate of progression was lower with D + B + TACE compared with PBO + TACE. The pattern of disease progression observed with D + B + TACE and PBO + TACE was similar, with NIH the most common pattern of progression in both treatment arms. Consistent benefit in TTP was observed with D + B + TACE versus PBO + TACE, regardless of progression pattern. Clinical trial information: NCT03778957 . NIH IHG NEH D + B + TACE (n=73) PBO + TACE (n=107) D + B + TACE (n=31) PBO + TACE (n=34) D + B + TACE (n=24) PBO + TACE (n=39) Median (95% CI) TTP, months 13.7 (10.8–16.5) 8.8 (7.0–10.9) 5.1 (3.0–9.0) 4.3 (2.9–4.8) 6.7 (2.8–16.6) 4.6 (2.9–6.8) HR (95% CI)* 0.78 (0.57–1.07) 0.61 (0.36–1.03) 0.66 (0.36–1.15) *HR and CI were estimated using a Cox proportional hazards model, the CI was calculated using a profile likelihood approach.

Phase II study of neoadjuvant NALIRIFOX followed by chemoradiation with paclitaxel and carboplatin in locally advanced gastroesophageal cancer.

452 Background: We performed a single-arm phase II study of neoadjuvant NALIRIFOX and chemoradiation (CRT) with concurrent carboplatin/taxol (C/T) followed by surgery in patients with locally advanced gastroesophageal (GE) cancer. Methods: Patients were enrolled on an NCI sponsored, prospective, single arm study (NCT04656041). Key eligibility criteria included: histologically confirmed T3/4 or lymph node (LN) positive GE junction or esophageal cancer, ECOG PS ≤1, age 18+, and life expectancy &gt; 3 months. Exclusion criteria included: metastatic disease, prior chemotherapy or RT, or prior targeted therapy for diagnosis. Extensive LN disease beyond the surgical field (supraclavicular or para-aortic) was permitted if deemed feasible to be encompassed within a RT field. Laparoscopy was not required. Pts were treated with neoadjuvant NALIRIFOX x 4-8 cycles pending patient tolerance and physician discretion, restaging, CRT (50.4 Gy in 28 fractions) with concurrent C/T, restaging, followed by surgical resection. Dose reductions were at discretion of the treating physician. The primary study endpoint was the pathologic complete response rate following neoadjuvant treatment with NALIRIFOX and CRT with concurrent C/T. Major pathologic response (mPR) was defined as Tumor Regression Grade 0 and 1. Secondary endpoints included: 1) acute toxicity; 2) clinical response per RECIST criteria; 3) PFS and 4) OS. Results: From June 2021 to October 2023, 40 patients were enrolled. Median age was 64 (range: 47-82), and 31 patients were male (78%). All patients started NALIRIFOX, and the median number of NALIRIFOX received was 5 (range: 1-8). Reasons for discontinuation of NALIRIFOX were: physician discretion (n=29), subject withdrew from treatment (n=2), progressive disease (n=1), death (n=1). Rates of grade 3+ toxicity for overall, gastrointestinal, and hematologic attributed to NALIRIFOX were 55%, 35%, and 13% respectively. 35 patients started chemoRT (88%) and 33 patients completed chemoRT (83%). Rates of grade 3+ toxicity for overall, gastrointestinal, and hematologic attributed to chemoRT were 86%, 11%, and 9% respectively. Of 33 who completed chemoRT, two patients declined surgery (including 1 with clinical CR), and 31 (78%) patients went for surgical exploration. No patients were found with intraoperative metastases. Therefore, 31 (78%) patients underwent surgical resection. In total, 9 patients had pCR (29% in resected cohort, 23% in ITT cohort) and 15 had a major PR (48% in resected cohort, 38% in ITT cohort). In total, 10 (25% in ITT) patients had pCR or clinically CR at 1 year. Conclusions: Neoadjuvant NALIRIFOX followed by CRT is feasible with acceptable rates of treatment completion and grade 3+ toxicity. In our phase II trial, the rate of pCR is promising and further studies incorporating this regimen should be considered. Clinical trial information: NCT04656041 .

Assessing socioeconomic disparities and the likelihood of multimodal treatment utilization in patients with pancreatic cancer using SEER Medicare data.

677 Background: Optimal treatment for pancreatic cancer necessitates multimodal therapies combining surgery, chemotherapy, and radiation. Socioeconomic determinants of health may influence access to these treatments, leading to disparities in outcomes. This study examines the association between socioeconomic status (SES) and the likelihood of receiving multimodal treatment among pancreatic cancer patients using SEER Medicare data. Methods: Our study population consists of elderly persons diagnosed with pancreatic cancer from the 2008–2017 SEER-Medicare dataset. A multinomial logistic regression controlling for sociodemographic characteristics, cancer stage, comorbidities, geographic region, and ecological measures of urbanicity and SES was used to assess the likelihood of receiving one of three mutually exclusive treatment categories: no treatment, one modality (surgery, chemotherapy, or radiotherapy), or multiple modalities (different combinations of surgery, chemotherapy, and radiotherapy), with multiple modalities as the reference group. Survival analysis was conducted using Kaplan-Meier curves (KMC) and Cox proportional hazards (CPH) models. Results: Adjusted analyses showed that among stages 0–3 patients, living in areas with a high percentage of individuals without a high school education (non-HS) was associated with increased odds of receiving no treatment (OR = 1.26, p &lt; 0.01) and one modality (OR = 1.20, p &lt; 0.01) versus multiple modalities. Low median household income was linked to higher odds of no treatment (OR = 1.30, p &lt; 0.01) and one modality (OR = 1.16, p &lt; 0.05). This pattern persisted in stage 4 patients, where high non-HS percentage increased odds of no treatment (OR = 1.38, p &lt; 0.01), and low median income was associated with higher odds of no treatment (OR = 1.25, p &lt; 0.05). Non-Hispanic Black patients had higher odds of receiving no treatment in both stages 0–3 (OR = 1.26, p &lt; 0.05) and stage 4 (OR = 1.91, p &lt; 0.01) compared to Non-Hispanic Whites. Being married was associated with reduced odds of receiving no treatment for stages 0–3 (OR = 0.53, p &lt; 0.01) and stage 4 (OR = 0.55, p &lt; 0.01). Lower SES and being Non-Hispanic Black are associated with decreased likelihood of receiving multimodal treatment across all stages. Patients receiving multimodal therapies demonstrated improved survival on our KMC analysis, and CPH models indicated lower mortality for those receiving multiple modalities. Conclusions: Socioeconomic disparities significantly influence multimodal treatment utilization in pancreatic cancer. Lower SES indicators—high non-HS percentages, low median income—and being Non-Hispanic Black are associated with decreased use of multimodal therapies and poorer survival. Addressing these disparities is essential to ensure equitable access to optimal treatments and improve survival rates.

Highly Stretchable 3D Microelectrode Array for Noninvasive Functional Evaluation of Cardiac Spheroids and Midbrain Organoids (Adv. Mater. 6/2025)

High‐Throughput Screening and General Synthesis Strategy of Single‐Atom Nanozymes for Oral Squamous Cell Carcinoma Therapy

AbstractSingle‐atom nanozymes (SAzymes), with their superior enzyme‐like catalytic activity, have emerged as promising candidates for oncology therapeutics. The well‐defined structures of SAzymes make them well predictable by experiences and theoretical calculation. However, the effects of metal center species and coordination environments on enzyme‐like activity are variable, and screening catalytic activity by artificial experiments is challenging. High‐throughput screening can rapidly select the activity center structures of SAzymes with optimal enzyme‐like activity, thus their better application in tumor therapy is highly desirable. Herein, a “high‐throughput screening‐SAzymes structures” system is established for efficient oncology drug preparation by density functional theory for oxidase‐like processes and screened the differences brought about by different metals and coordination environments. Through this screening process, SAzymes with transition metals (Mn, Fe, Co, Ni) as active centers are synthesized and then tested the multi‐enzyme activities. It is found that the SAzyme with Co as the active metal center exhibited the best oxidase‐like activity, and the system further showed good anti‐oral squamous cell carcinoma properties both in vitro and in vivo. This study opens up a new avenue for the rational design of SAzymes in oral cancer therapy by combining computational screening and experimental validation.

Development and regulatory approval of a new systemic targeted therapy for advanced hepatocellular carcinoma.

613 Background: There are no commercially available devices for the treatment of patients with advanced hepatocellular carcinoma who have failed 1st line and 2nd line therapy. We have identified tumor-specific modulation frequencies in patients with advanced hepatocellular carcinoma. We exposed patients to radiofrequency electromagnetic fields, which are amplitude-modulated from 0.1 Hz to 100 kHz and measured changes in pulse pressure. Frequencies eliciting measurable changes in pulse pressure were selected as tumor-specific frequencies. Methods: Treatment is administered to patients with advanced hepatocellular carcinoma by means of a battery-operated portable device emitting 27 MHz radiofrequency electromagnetic fields, which are amplitude-modulated at hepatocellular carcinoma frequencies. The device is connected to a coaxial cable ending with a spoon-shaped antenna placed on the anterior part of the patient's tongue during treatment. Treatment is administered three times a day for one hour. Results: A total of 69 patients with advanced hepatocellular carcinoma received treatment with the TheraBionic device until progression or death. The median overall survival of patients who received treatment with the TheraBionic device after failing 1st line and 2nd line therapy was 9.15 (95% CI 1.6-34.8) months and the median overall survival of Child-Pugh A patients was 9.5 months, which are comparatively longer than the 7.8 months pooled estimated medians of the placebo arms of 11 randomized 1st line and 2nd line placebo-controlled studies assessing the safety and efficacy of new agents for the treatment of Child-Pugh A advanced HCC (Llovet, Montal et al., J Hepatol 2019). We also analyzed the survival of patients who had received two lines of systemic therapy and did not receive any additional cancer treatment while and after receiving treatment with the TheraBionic device. The median OS of these patients was 9.8 months and the median OS of the Child-Pugh A patients was 17.2 months, which are comparatively longer than the 7.74 months pooled estimated medians of the placebo arms of the above cited 11 randomized studies. To assess unknown device-related adverse events, we assessed patient reported symptoms using the same scale in the SHARP and Asian Pacific Sorafenib studies. The incidence of any grade adverse events among Child-Pugh A who received treatment with the TheraBionic device was not different from the Placebo group of the SHARP and Asian Pacific Sorafenib studies. There were no NCI Grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient developed grade 1 fatigue. Conclusions: The data presented here provide reasonable assurance of safety and probable benefit in patients with advanced hepatocellular carcinoma who have failed 1st line and 2nd line therapy: https://www.fda.gov/medical-devices/recently-approved-devices/therabionic-p1-h220001 .

Alteration of gut microbiota in patients with advanced hepatocellular carcinoma.

641 Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. Despite advancements in treatment, such as novel combinations of immunotherapy and targeted therapy or dual immunotherapy, the prognosis remains poor due to a lack of predictive biomarkers for treatment response. Gut microbiota alterations have been proposed as both potential diagnostic biomarker and predictive biomarker. However, data in this field are not well-established and are mostly derived from studies conducted in China and Western countries, which may not fully reflect the situation in Thailand. Methods: Fecal samples were collected from pre-treated advanced HCC patients who visited medical oncology outpatient clinic at Srinagarind hospital, Khon Kaen University (HCC group = 27) and analyzed using 16S rRNA sequencing of gut microbiota. Additional sequenced data from a healthy population (Control group = 31) who had no underlying disease and had normal liver ultrasonography were retrieved from a previous study conducted by Khon Kaen University (Cholangiocarcinoma Screening and Care Program, CASCAP). The datasets were compared using the Wilcoxon rank-sum test to analyze the alteration of gut microbiota between HCC group and control group. Results: The HCC group exhibited significantly lower biodiversity index (p&lt; 0.001) than control group in terms of richness, Shannon diversity index and Simpson’s index. The HCC group had significantly higher relative abundance of the phylum Proteobacteria (p&lt; 0.001), Firmicutes (p&lt; 0.001) and a lower abundance of the phylum Actinobacteria (p&lt; 0.001) compared to the control group. Additionally, the HCC group had significantly higher relative abundance of Stenotrophomonas, Granulicatella, Ruminococcus, Blautia, Phascolarctobacterium, Butyricoccus, Streptococcus, Escherichia-Shigella, Flavonifractor, Haemophilus and Lachnospira at the genus level. Further analysis of relative abundance of gut microbiota at the genus level and clinical prognostic parameters showed positive correlation between Streptococcus and 6-month survival status. Conclusions: Gut microbiota profile in patients with advanced HCC was significantly altered from healthy control group. This could be the evidence of microbial dysbiosis and may potentially be biomarker for prognosis.