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Improved spectral filtering of broadband diffractive neural network by loss function engineering
We engineer the loss function by removing the conventional physics-based energy constraint during the training of broadband diffractive neural networks (DNNs) to enhance their spectral filtering capabilities of supercontinuum light. Simulations show that compared to DNNs trained with conventional loss function, the suppression of out-of-band spectral intensities can be improved by three orders of magnitude, resulting in an extinction coefficient of 10−6. Additionally, the spectral resolution can be enhanced by over 50% with a 6.6% improvement of energy efficiency. These findings are corroborated by experiments conducted with a two-layer DNN. The proposed method holds promise for enhancing the performance of broadband DNNs across various applications, including spectral reconstruction, spectrum classification, and color image processing, among others.
A leucine responsive small RNA AbcR200 regulates expression of the lactate utilization (lut) operon in Acinetobacter baumannii DS002
End Point Surrogacy in First-Line Chronic Lymphocytic Leukemia
PURPOSE Surrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL. PATIENTS AND METHODS First, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials. Additionally, a joint-frailty copula model was fitted to validate correlation in the setting of targeted therapies (TT). Second, a meta-analysis of first-line phase III trials in CLL from 2008 to 2024 was performed. Treatment effect correlation was quantified from seven GCLLSG and nine published trials, using hazard ratios (HRs) for time-to-event and odds ratios for binary end points. RESULTS The GCLLSG analysis set comprised 4,237 patients. Patient-level correlation for PFS/OS was strong with Spearman Rho >0.9. The joint-frailty copula indicated a weak correlation for chemotherapy/chemoimmunotherapy (C/CIT) with a tau of 0.52 (95% CI, 0.49 to 0.55) while the correlation was strong for TT (tau, 0.91 [95% CI, 0.89 to 0.93). The meta-analysis set contained a total of 8,065 patients including 5,198 (64%) patients treated with C/CIT and 2,867 (36%) treated with TT. Treatment-effect correlation of the HRs for PFS and OS was R = 0.75 (95% CI, 0.74 to 0.76, R 2 = 0.56) while correlation of end-of-treatment MRD with PFS and OS was R = 0.88 (95% CI, –0.87 to 0.89; R 2 = 0.78) and 0.71 (95% CI, 0.69 to 0.73; R 2 = 0.5), respectively. CONCLUSION Patient-level correlation was confirmed in the setting of TTs while treatment-effect correlation between PFS and OS remains uncertain. MRD response status showed a high treatment-effect correlation with PFS but not OS, with the caveat of a limited number of randomized trials with available MRD data.
Germline pathogenic variants in a cohort of individuals with biliary tract cancer.
559 Background: Biliary tract cancers (BTC) are rare but have been implicated in hereditary cancer conditions such as Lynch syndrome (LS) and BRCA1 and BRCA2. Data from paired somatic and germline genetic testing on BTC have shown that ~5% may be related to germline pathogenic variants in BRCA1 and BRCA2. Identification of these germline pathogenic variants (PV) often provide patients with an opportunity for personalized treatment including platinum-based chemotherapies, PARP inhibitors and/or immunotherapy. Germline testing also provides crucial data to relatives regarding cancer risk and access to increased cancer surveillance and risk-reducing surgeries. Current guidelines recommend germline genetic testing when the likelihood of identifying a PV is >5%. The contribution of germline PV in BTC has not been described in a diverse patient population. Methods: In this prospective clinic-based study, individuals with BTC were referred by their oncologist for genetic counselling and testing. The majority of individuals were enrolled based on participation in the Legresley Biliary Registry, which recruits all individuals with BTC. Blood was sent for germline multi-gene panel testing. Results: Germline genetic testing was performed for 139 individuals. Average age of diagnosis was 57.8 years (range 28-84). The majority of individuals were diagnosed with intrahepatic cholangiocarcinoma (CCA) (54.7%), followed by extrahepatic CCA (20.9%) and gallbladder cancer (10.1%). The majority of individuals were male (56.1%). The population was ethnically diverse with 55% European, 24% Asian, 9% Middle Eastern/North African and 6% African. A minority of individuals had a previous cancer (18%) and 24.5% met current provincial eligibility criteria. Germline testing was complete on 136 individuals. 25/136 (14.7%) PV were identified in 20 individuals. 8/136 (5.9%) of the cohort carried PV in genes known to increase the risk for BTC ( BRCA1, BRCA2 and LS genes), 9/136 (6.6%) carried PV in other genes with clinically actionability (e.g. PALB2, ATM ), and 8/136 (5.9%) carried heterozygous PV in genes for recessive diseases. Variants of uncertain significance were identified in 42/136 (30.9%) and negative results were identified in 74/136 (54.4%). Personal and/or family history was not suggestive of the associated cancer condition in 9/16 (56%) of the PV cohort. Tumor profiling by whole genome sequencing on some individuals with PV found corresponding somatic mutational signatures, consistent with variant pathogenicity. Conclusions: Detection rates for PV in a diverse BTC cohort was up to 14.7%, including 5.9% among genes known to increase the risk for BTC. The majority of PV were found in individuals lacking personal and/or family history suggestive of the associated hereditary cancer condition. These results suggest that guidelines should be updated to recommend universal germline genetic testing for individuals with BTC.
Preliminary result of a phase Ib study: Efficacy and safety of FG-M108 plus gemcitabine/nab-paclitaxel as first-line (1L) treatment in patients with Claudin18.2-positive locally advanced unresectable or metastatic (LA/m) pancreatic cancer.
729 Background: FG-M108, an ADCC-enhanced anti-CLDN18.2 monoclonal antibody, showed significant efficacy in 1L treatment of gastric cancer. Herein, we report the safety and efficacy results of FG-M108 in 1L treatment of pancreatic cancer (cohort C2&D2). Methods: In this open-label, multicenter phase I/II study patients received FG-M108 (cohort C2: 300mg/m 2 or cohort D2: 600mg/m 2 Q3W) plus gemcitabine (1000mg/m 2 , d1, d8, Q3W) and nab-paclitaxel (125mg/m 2 , d1, d8, Q3W). Eligible patients were those with CLDN18.2 positive (IHC 1+/2+/3+≥10%) previously untreated LA/m pancreatic cancer. The primary endpoint were the incidence of adverse events (AEs) and preliminary clinical efficacy (ORR, DCR, DOR, PFS, and OS). Results: As of Sep 5 2024, 50 patients were enrolled and received FG-M108+gemcitabine/nab-paclitaxel treatment (39 patients in cohort C2, 11 patients in cohort D2). The median age was 61 (range 30-72). 47 (94%) patients were with CLDN18.2 moderate-high expression (IHC 2+/3+≥40%). Out of 50 patients, 44 patients had at least one tumor assessment after baseline and included in the efficacy analysis set. The results of ORR and DCR in cohort C2 were 32.4% and 100.0%, while that in cohort D2 were 30.0% and 90.0%, respectively. In cohort C2, the median PFS and median DOR were 6.8 months and 9.8 months, respectively. In the subgroup patients with CLDN18.2 moderate-high expression, the median PFS and median DOR were 7.6 months and 9.8 months, respectively. The median OS has not been reached. FG-M108 related AEs were observed in all patients, with 39 patients (78%) having Grade 3/4 AEs and no FG-M108 related fatal AE was observed. The most common FG-M108 related AEs in cohort C2 & D2 were anemia (56.2% vs 63.6%), nausea (56.4% vs 36.4%), vomiting (48.7% vs 45.5%), and hypoalbuminemia (46.2% vs 54.5%). Conclusions: The combined therapy of FG-M108 plus chemotherapy as 1L treatment for patients with CLDN18.2 positive pancreatic cancer was well tolerated with encouraging survival especially in patients with CLDN18.2 moderate-high expression, deserving further investigation. Clinical trial information: NCT04894825 .
Outcome of radiation related esophageal stricture from endoscopic dilation.
387 Background: Esophageal strictures present a significant challenge, particularly in cases of radiation-induced strictures. Esophageal dilation is a commonly used intervention aimed at improving swallowing function and nutritional status. However, radiation-induced strictures are amongst the most refractory to dilation. Understanding the success and limitations of this procedure is crucial for optimizing patient outcomes in the cancer population. Methods: This was a single-center retrospective chart review of 736 patients who received radiation as well as an EGD between 2014 and 2024. Patients without a radiation-induced stricture that was dilated were excluded. All continuous data are summarized as medians with interquartile ranges (IQR). Independent t-test was used for comparison among different groups. Results: 192 were eligible for this study. Our population was mostly male (58%) with a median age of 66 (IQR 67-74). The leading cancer diagnosis were esophageal (37%), head and neck (30.2%), and lung (17.1%). Radiation targets were head and neck (50.5%), lung (45.3%), both (1.6%), or other (1.6%). Patients were receiving active chemotherapy in 9.9% of cases. Mortality by the end of the study period was 51%. The median radiation dose was 5040 cGy (IQR 5040-6600) in a median of 28 fractions (IQR 26-33). Common indications for dilation were dysphagia (91.1%), weight loss (21.9%), and tube feed dependency (17.2%). Strictures were most often dilated 2 to 4 times (39.6%) to a median dilation size of 14 mm (IQR 12-15). Of note, 18.2% of patients needed 8 or more dilations. Dilation was associated with weight gain in 46.4% of patients, PEG tube removal in 3.1%, both forms of improvement in 9.9%, and no change in 40.6%. Complications included perforation (3.6%), aspiration pneumonia (3.6%), chest pain (0.5%), and hospitalization (0.5%). No significant differences were found in maximum dilation size, number of dilations, initial luminal diameter of the stricture, and initial length of the stricture between those who had clinical improvement as compared to those who did not. Conclusions: Our study reported 59.4% clinical improvement from esophageal dilation for radiation-induced strictures with nearly 20% of patients needing 8 or more dilations. The stricture dilation parameters did not appear to affect the success rate. This is the largest known single study of esophageal dilation for radiation-induced strictures.
Electric field-induced depolarization of direct current and alternating current poled PMN-PT single crystals
Understanding the depolarization of ferroelectric materials caused by external stimuli is critical for maintaining the aligned polarization states. Although thermal depolarization in poled materials is well established, the mechanisms of electric field-induced depolarization remain largely unexplored. In this study, we investigate the electrical depoling behavior of [001]-oriented rhombohedral Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) single crystals poled using direct current poling (DCP) and alternating current poling (ACP). We reveal that the ACP sample exhibits a lower reverse coercive field than the DCP specimen. We compare the effects of bipolar and unipolar electric fields applied in the reverse poling direction, analyzing the changes in permittivity and piezoelectric resonance. Piezoresponse force microscopy is employed to characterize domain configurations in poled and electrically depoled samples. Our findings suggest that property degradation may arise from the nucleation and growth of domains oriented opposite to the initial arrangement.
A fucose-binding superlectin from Enterobacter cloacae with high Lewis and ABO blood group antigen specificity
A phase II double window of opportunity trial evaluating the oral TGF-beta receptor I inhibitor vactosertib in patients undergoing standard of care preoperative therapy for locally advanced esophageal adenocarcinoma.
TPS516 Background: Esophageal adenocarcinoma (EAC) is the seventh most common cancer globally and ranks sixth in overall mortality. Despite improvements in pre-operative therapy, EAC has a high recurrence rate, especially among patients whose tumors do not achieve pathologic complete response (pCR), thus there is a critical need to enhance pCR rate and improve long-term outcomes. We recently discovered that a subset of EACs are driven by tumor-intrinsic oncogenic TGFβ signaling and have identified two potential biomarkers to predict response to anti-TGFβ therapy. One of these biomarkers is enriched in poorly differentiated EAC. We hypothesize that TGFβ signaling blockade will exert a tumor-inhibitory effect in patients with EAC and propose a double window-of-opportunity trial to test if TGFβ receptor I inhibitor vactosertib can improve pCR and induce tumor metabolic response in patients undergoing neoadjuvant therapy for localized EAC. Methods: This phase II double window of opportunity study assesses the efficacy and pharmacodynamics of the oral TGFβ Receptor I inhibitor vactosertib in patients with locally advanced esophageal adenocarcinoma (EAC). Patients will be treated with single-agent vactosertib in two windows of opportunity: the first will be prior to initiation of standard of care neoadjuvant therapy and the second after completion of neoadjuvant therapy prior to surgery. Patients will be eligible if they have poorly differentiated EAC and are appropriate for neoadjuvant therapy followed by resection as per standard of care. The primary objectives are improvement in pCR compared to historical controls and metabolic response (decrease in fluorodeoxyglucose uptake by PET CT) in the primary tumor after the first window. Secondary objectives will evaluate biomarkers of response identified in preclinical studies. Pre- and post-first window of opportunity treatment biopsies will be obtained for correlative and exploratory analyses. Clinical trial information: NCT06044311 .
Impact of pancreatic tumour biomechanics on diagnosis and post-operative complications.
756 Background: Around 600 people are diagnosed with pancreatic cancer in Ireland each year, with 90% of these having pancreatic ductal adenocarcinoma (PDAC). Five-year survival for PDAC is around 10%. PDAC upregulates stromal collagen formation which contributes to tissue stiffness. Stiffer pancreatic tumours have worse oncological outcomes due to faster progression and increased chemoresistance. Softer pancreata, conversely, are more likely to develop post-operative pancreatic fistulae (POPF), a significant post-pancreatectomy complication. While incorporated in risk scores, softness is currently determined by subjective intra-operative observation. Methods: Atomic force microscopy (AFM) is the gold standard technique used to measure biomechanics at a cellular length scale. We obtained fine needle biopsies (FNBs) of pancreatic tumours during diagnostic endoscopic ultrasound. This is the first time tissue biomechanics have been measured from pancreatic biopsies. Separately, we applied this technique to pancreatic tumours and adjacent normal tissue following resection. We also assessed collagen organisation in these pancreatic tumours to understand its contribution to the observed mechanical properties. Results: Of the patients with PDAC who underwent FNB, those presenting with metastatic disease had significantly stiffer tumours than those without, 1,490 Pa (SD 2,048.03 Pa) vs 250 Pa (SD 555.06 Pa) (p<0.0001). Neuroendocrine tumours exhibited larger variance compared to PDAC (p < 0.0001), SD 5,885.97 Pa vs SD 1,797.23 Pa. Regarding tumours which have undergone curative resection, tumour stroma is significantly stiffer than both cancer and benign epithelium. The collagen strands in this stroma are straighter, more numerous, and more packed than epithelial tissues. Pancreata which develop post-operative pancreatic fistulae (POPF) are softer than those which do not 96.42 Pa (SD 691.14 Pa) vs 343.99 Pa (SD 1,678.37 Pa). Conclusions: We describe a novel technique to measure the biomechanical properties of pancreatic biopsies. Using this technique, we now have the opportunity to measure these properties for the first time on all pancreatic tumours, including those presenting with unresectable disease. It is possible to distinguish between different types of tumour based on the biomechanical profile of biopsies. Previous ex vivo studies have linked stiffer tumours to a higher metastatic potential, and our results are the first to suggest that this may be true in a human population. In resected tumours, we confirm the anecdotal belief that softer pancreata are associated with POPF. Overall, this research demonstrates that tissue biomechanics has potential diagnostic and prognostic applications in pancreatic cancer.
Circulating tumor DNA for predicting complete response to total neoadjuvant therapy in locally advanced rectal cancer: ENSEMBLE-2.
284 Background: Total neoadjuvant therapy (TNT) has dramatically shifted the paradigm in the treatment of locally advanced rectal cancer (LARC), prolonging survival with high rates of pathologic complete response (pCR) and introducing non-operative management (NOM). However, no predictive biomarkers of TNT efficacy, the regrowth of NOM, or prognosis have been developed. Circulating tumor DNA (ctDNA) is a minimally invasive biomarker used to detect molecular residual disease (MRD) and predict recurrence in colon cancer after curative resection. The effectiveness of ctDNA MRD status as a predictive biomarker for TNT was evaluated in the Phase II TNT study, ENSEMBLE-2 (jRCTs071210143), conducted in Japan. Methods: Patients with LARC undergoing TNT were enrolled in ENSEMBLE-2. Protocol treatment was defined as total mesorectal excision (TME) following long course chemoradiotherapy (LCCRT: 50.4Gy, capecitabine) plus four cycles of CAPOX. NOM was allowed if a clinical complete response (cCR) was achieved in the evaluation after TNT. ctDNA MRD was measured by Signatera (Natera, Inc.) at the following time points: baseline, after LCCRT, after TNT, post operative 4w, 12w, 24, 36 and 48w in the GALAXY trial (UMIN000039205). Results: A total of 28 patients were enrolled in the study. Treatment was discontinued at the patient's request in one case. After completing TNT, TME and NOM were performed in 21 (77.8%) and 6 (21.4%) patients, respectively. ctDNA positivity rates were 96.4. % (27/28) at baseline, 14.8% (4/27) after LCCRT, and 34.6 % (9/26) after TNT. Post-LCCRT ctDNA status was not significantly associated with cCR + near CR (nCR) vs. incomplete clinical response (iCR), pCR vs. non-pCR (p=0.065 and p=0.539, respectively). In contrast, ctDNA status after TNT was significantly associated with cCR + nCR vs. iCR (p=0.028), as well as pCR vs. non-pCR (p=0.038). Conclusions: Our study indicates that post TNT ctDNA status may be a predictive biomarker for TNT response in LARC patients. ctDNA negativity upon completion of neoadjuvant treatment may indicate a favorable response. Clinical trial information: jRCTs071210143 . Correlation with ctDNA, clinical response, treatment after TNT and pathological response. After LCCRT p value After TNT p value Clinical ResponsecCR + nCR vs. iCR (ctDNA -/+) cCR + nCR 18 / 1 0.065 cCR + nCR 15 / 4 0.028 iCR 5 / 3 iCR 2 / 5 Treatment after TNTNOM vs. TME (ctDNA -/+) TME 17 / 3 0.438 TME 11 / 9 0.063 NOM 6 / 0 NOM 6 / 0 Pathological response after TMEpCR vs. non pCR (ctDNA -/+) pCR 5 / 0 0.539 pCR 5 / 0 0.038 non pCR 12 / 3 non pCR 6 / 9 Fisher's exact test was used to statistically examine the correlation between ctDNA MRD status and the factors at each timing.
Disparities in stage of diagnosis of colon cancer: Differences by Hispanic background, race, and ethnicity.
24 Background: Given noted heterogeneity in Hispanic adults, cancer outcomes reported in aggregate may not detect disparities within specific Hispanic subgroups. The objective was to assess whether any potential differences in colon cancer (CC) stage at diagnosis among patients with Hispanic background (HBackground) could be explained by differences in socio-economic determinants of health (SDOH) including income, education and insurance status. Methods: The National Cancer Database was queried for patients diagnosed with CC from 2004 to 2021. Two logistic regression models generated adjusted odds ratios of late-stage (III-IV) vs early-stage (I-II) CC at diagnosis, disaggregated either by HBackground or R&E, compared to non-Hispanic White (NHW) patients. Model 1 controlled for patient/facility characteristics; Model 2 controlled for additional SDOH. Results: Of the 442,742 CC patients identified, 6% were Hispanics. Compared to NH adults, Hispanic patients were more likely (6% higher odds, p<0.0001) to present with late-stage CC. When Hispanic patients were disaggregated by HBackground, some were more likely (Mexicans 16%; Cubans 20% and South/Central Americans 12%) than NHW adults to present with late-stage CC while others (Puerto Ricans and Dominicans) were not. Disaggregation by R&E indicated that only Hispanic-White patients were more likely (12%) to present with late-stage disease than NHW patients. Controlling for SDOH, R&E differences in stage at diagnosis persisted but HBackground differences became insignificant (Table). Conclusions: Disaggregation of Hispanic adults by HBackground identifies specific subgroups at increased risk for late-stage CC at diagnosis. Understanding modifiable SDOH may identify opportunities for improving early detection of CC and outcomes in specific Hispanic subgroups. Odds of presenting with late-stage colon cancer of “Hispanic” patients disaggregated by race and ethnicity or Hispanic background compared to non-Hispanic Whites. Disaggregation based on: Model 1: Adjusted for age, facility type, year of diagnosis, and Charlson-Deyo comorbidity Model 2: Adjusted for age, facility type, year of diagnosis, Charlson-Deyo comorbidity, neighborhood income, neighborhood education, and insurance status aOR (95% CI) p-value aOR (95% CI) p-value Non-Hispanic White (n=418,046) (ref) (ref) Hispanic White (n=24,058) 1.12 (1.09, 1.15) <.0001 1.04 (1.01, 1.07) 0.01 Hispanic Background Mexican (n=3,612) 1.16 (1.08, 1.24) <.0001 1.05 (0.97, 1.13) 0.25 South/Central American (n= 1,734) 1.12 (1.02, 1.24) 0.02 1.01 (0.91, 1.12) 0.83 Cuban (n=937) 1.20 (1.05, 1.36) 0.001 1.11 (0.97, 1.27) 0.13 Puerto Rican (n=1,280) 1.07 (0.95, 1.19) 0.28 1.01 (0.90, 1.14) 0.88 Dominican (n=465) 1.14 (0.94, 1.39) 0.18 1.02 (0.83, 1.25) 0.85 aOR, Adjusted odds ratio; CI, confidence Interval.
Toward flexible intensity control of resonantly scattered <b> <i>γ</i> </b>-rays using multi-frequency vibrating resonant absorber
We report a method for coherent control of γ-photons, enabling the shaping of γ-ray intensity in nearly arbitrary waveforms. Different intensity waveforms are created by adjusting the motion profile of a resonant absorber (an ensemble of Mössbauer nuclei) and tuning the energy of the incident radiation. A crucial aspect of this method is the use of a low fundamental frequency of vibrations, which broadens the possibilities for γ-ray control. The results of numerical simulations are experimentally validated by generating single and double γ-pulses and inducing short-term absorption. For this, a resonant absorber containing 57Fe nuclei was vibrated with different motion profiles composed of 12 harmonics with a fundamental frequency of 1 MHz. The proposed technique represents an advancement in the manipulation of γ-rays, and potentially x rays, paving the way for the performance of unique types of γ-ray or x-ray quantum experiments and the development of tools such as adjustable table-top γ-pulse sources or γ-ray or x-ray delays and gates. Moreover, inverse application of the method enables investigation of motion at the picometer scale.
ECM stiffness regulates lung fibroblast survival through RasGRF1-dependent signaling
HERIZON-BTC-302: A phase 3 study of zanidatamab with standard-of-care (SOC) therapy vs SOC alone for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced/metastatic biliary tract cancer (BTC).
TPS648 Background: Zanidatamab is a humanized, IgG1-like, HER2-targeted bispecific antibody that simultaneously binds to 2 non-overlapping domains on HER2. Zanidatamab is being investigated for the treatment of HER2-expressing solid tumors, including BTC. In the phase 2 HERIZON-BTC-01 trial, zanidatamab monotherapy demonstrated promising antitumor activity in 80 patients with previously treated HER2-positive BTC. Confirmed objective response rate (cORR) was 41.3% with rapid and durable responses and a manageable safety profile. This phase 3 trial is assessing zanidatamab + SOC therapy vs SOC alone for first-line treatment of HER2-positive advanced/metastatic BTC. Methods: This ongoing, global, phase 3, randomized, open-label trial (NCT06282575) is investigating the efficacy and safety of zanidatamab with cisplatin and gemcitabine (CisGem) vs CisGem alone ± a programmed cell death protein-1/ligand 1 (PD-1/L1) inhibitor (pembrolizumab or durvalumab at physician’s discretion if locally approved) as first-line treatment for patients with advanced HER2-positive BTC. Eligibility criteria include ≥18 years of age; locally advanced, unresectable, or metastatic HER2-positive BTC by immunohistochemistry and in situ hybridization assay (IHC 3+ or IHC 2+/ISH+); and Eastern Cooperative Oncology Group performance status ≤1. Patients may have received ≤2 cycles of a gemcitabine-based regimen ± pembrolizumab or durvalumab. Prior HER2-targeted therapy is not allowed except for patients who completed it for breast cancer >5 years prior to BTC diagnosis. Eligible patients will be randomized to receive zanidatamab (flat 2-tiered dosing: 1800 mg intravenous [IV; body weight <70 kg] or 2400 mg IV [body weight ≥70 kg] every 3 weeks) + a standard dose of CisGem ± a PD1/L1 inhibitor or CisGem alone ± a PD1/L1 inhibitor (≤8 cycles). The primary endpoint is progression-free survival (PFS) in patients with IHC 3+ tumors. Secondary/exploratory endpoints include overall survival (IHC 3+ subgroup; overall population), PFS (overall population), cORR, incidence and severity of adverse events, and patient-reported outcomes. The study is currently recruiting patients. Clinical trial information: NCT06282575 .
Impact of Lauren’s subtype in locally-advanced gastric cancer (LAGC) prognosis: A call for change.
497 Background: Patients with LAGC should undergo perioperative chemotherapy and surgery. Lauren’s diffuse subtype and signet-ring cell carcinoma have been linked to worse outcomes and chemoresistance in this setting. This study aimed to assess the impact of Lauren’s classification on response to neoadjuvant chemotherapy and prognosis in LAGC. Methods: This analysis involved adult patients from a prospectively collected gastric cancer database who had histologically confirmed LAGC and received curative-intent perioperative chemotherapy and surgery. Patients were classified into two groups according to Lauren’s classification: intestinal and non-intestinal subtypes (including diffuse, signet-ring cell carcinoma and mixed histologies). Clinicopathological and treatment characteristics (age, gender, primary site, HER-2 status, staging laparoscopy, neoadjuvant chemotherapy, surgery and pathological complete response) of the two groups were compared using chi-square tests. Survival curves were obtained using Kaplan-Meier, and log-rank and Cox proportional models used to compare survival between groups. Results: Between 2015 and 2022, 174 patients met the inclusion criteria, with a median follow-up of 62.2 months (95% CI: 57.9-66.9). The intestinal subtype comprised 72 patients (41.4%) and the non-intestinal subtype included 102 (58.6%). The median age of diagnosis was significantly higher for the intestinal subtype (63 years) compared to the non-intestinal subtype (56 years; p<0.001). Female patients represented 26.4% of the intestinal subtype and 46.1% of the non-intestinal subtype (p=0.013). The primary gastric site was more prevalent in the non-intestinal subtype (78.4%) compared to the intestinal subtype (51.4%; p<0.001). HER-2 positivity was observed in 12.5% of intestinal and 4.5% of non-intestinal subtypes (p=0.14). Staging laparoscopy was conducted in 67 out of 72 (93%) patients with the intestinal subtype and in 96 out of 102 (94.1%) patients with the non-intestinal subtype, p=1. FLOT and FOLFOX/CAPOX protocols were administered in 50% and 40.2% of intestinal subtype cases, and in 53.9% and 36.2% of non-intestinal subtype cases, respectively (p=0.14). Pathological complete response rates were 8.5% for intestinal and 11.5% for non-intestinal subtypes (p=0.46). Three-year recurrence-free survival rates were 67.1% for intestinal and 64.6% for non-intestinal subtypes (HR=0.99, 95% CI: 0.61-1.61, p=0.96), while five-year overall survival rates were 73.3% and 67.2%, respectively (HR=1.12, 95% CI: 0.63-1.97, p=0.70). Conclusions: Our findings demonstrate that the non-intestinal subtype is more common in younger, female patients with primary gastric sites. However, Lauren’s subtype did not significantly correlate with pathological staging post-neoadjuvant chemotherapy or prognosis in LAGC. Lauren’s subtype should not influence treatment decisions in LAGC.
Intraperitoneal and intravenous paclitaxel plus S-1 versus intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis: Results from the multicenter, randomized, phase 3 DRAGON-01 trial.
327 Background: The optimal chemotherapeutic regimen for gastric cancer with peritoneal metastasis remains undefined. We evaluated the efficacy and safety of intraperitoneal and intravenous paclitaxel plus S-1 (NIPS Group) versus paclitaxel plus S-1 (PS Group) in gastric cancer patients with peritoneal metastasis. Methods: In this multicenter, randomized, controlled, phase 3 trial, patients were recruited from 9 cancer centers in China. Eligible patients were aged 18~75 years with an Eastern Cooperative Oncology Group performance status of 0~1, histologically confirmed gastric adenocarcinoma, peritoneal metastases from gastric cancer requiring definitive diagnosis by laparoscopy, without gastric outflow tract obstruction and intestinal obstruction, no prior treatment with chemotherapy, radiation therapy, targeted therapy or immunotherapy. Eligible patients were randomly assigned (2:1) to receive either intravenous paclitaxel at 50 mg/m² and intraperitoneal paclitaxel at 20 mg/m² on days 1 and 8, along with oral S-1 at a dose of 80 mg/m² on days 1~14, or intravenous paclitaxel at 70 mg/m² on days 1 and 8, along with oral S-1 at 80 mg/m² on days 1~14. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all participants. A sample size of 238 patients was calculated to provide 80% power with a one-sided alpha of 0.1, accounting for a 10% dropout rate. Survival was analyzed using Kaplan-Meier curves and compared with the log-rank test. Cox regression was used for multivariate analysis. A P -value < 0.05 was considered statistically significant. Results: From May 10, 2017, to March 9, 2022, 246 patients were screened and 222 were included in the modified intention-to-treat population, of whom 148 patients were assigned to the NIPS Group and 74 to the PS group. As of data cutoff (March 9, 2024), the median survival time was 19.4 months (95% CI, 17.1~22.9), in the NIPS group and 13.9 months (95% CI, 10.3~16.1) in the PS group (HR = 0.66; 95% CI 0.49 - 0.88; P = 0.005). The 1-year and 2-year overall survival rates were 69.6% and 37.2% in the NIPS group, compared to 54.1% and 20.3% in the PS group. The most common grade 3~4 adverse events were leukopenia (21.7% in the NIPS group, and 24.7% in the PS group) and neutropenia (19.9% in the NIPS group, and 23.4% in the PS group). No treatment-related deaths were reported. Conclusions: Intraperitoneal and intravenous paclitaxel plus S-1 significantly improved the overall survival compared to intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis, with manageable toxicity. Clinical trial information: ChiCTR-IIR-16009802.
Racial disparities in cancer stage at diagnosis among older adults with gastrointestinal cancers in the southeastern United States.
806 Background: Prior studies have documented racial disparities in survival among older adults with various gastrointestinal (GI) cancers, but mechanisms remain poorly understood. We hypothesized that delayed diagnosis leading to advanced cancer stage at presentation could be a contributing factor to these disparities. Methods: We included adults ≥ 60 years with newly diagnosed GI cancers presenting for initial consultation at University of Alabama at Birmingham from October 2017 to April 2024. Using self-reported race and ethnicity, we stratified patients into Non-Hispanic Whites, Non-Hispanic Black, Hispanics and other category. For this analysis, we limited our cohort to the first two categories. Cancer stage was abstracted from the Electronic Health Record and followed American Joint Commission on Staging (AJCC) 7 th manual. We performed two-sided Pearson’s chi square test to test the association between stage at diagnosis and race. We performed this analysis for the overall cohort as well as for specific GI cancer types. The level of significance was set at p < 0.05. Results: A total of 1714 patients were included; Out of which 74% were non non-Hispanic white and 26% were African American. The median age at presentation was 68 years (interquartile range: 64 - 74), and 42% were females. The most common cancer type was colorectal (28%) followed by pancreatic (26%), hepatobiliary (22%), other GI cancers (14%) and gastroesophageal (10%). Overall, around 45% patients had Stage IV at diagnosis, followed by Stage III (26%), Stage II (17%) and Stage I (11%). We found that as compared to non-Hispanic Whites, non-Hispanic Blacks were more likely to have advanced stage disease, stage III (29% vs 25%) and stage IV (47% vs 45%), this association was statistically significant (Table). Furthermore, this association was most prominent for pancreatic cancers, where non-Hispanic Blacks were more likely to have advanced stage disease, stage III (21% vs 16%), and stage IV (50% vs 47%; p < 0.05). Conclusions: We report that among older adults with GI cancers, African Americans were more likely to have advanced stage at diagnosis compared to non-Hispanic whites, specifically in patients with pancreatic cancer. This finding may contribute to some of the racial disparities observed in survival outcomes in this population. Contingency table showing frequencies (%) of cancer stages for non-Hispanic Whites and African Americans. GI Cancer Stage Non-Hispanic White African American p value Stage I 138 (11%) 51 (11%) <0.05 Stage II 236 (19%) 57 (13%) Stage III 321 (25%) 129 (29%) Stage IV 572 (45%) 210 (47%)
Effect of electronic state for in-materio physical reservoir computing performance with a porphyrin-polyoxometalate/single-walled carbon nanotube network
Semiconducting single-walled carbon nanotube (SWNT)/porphyrin-polyoxometalate (por-POM) networks were fabricated using [H4tBuTPP]2[SV2W10O40] (tBu H4TPP-POM) and [H4TPP]2[SV2W10O40] (H4TPP-POM) to compare their reservoir computing (RC) performances. Nonlinear electrical properties, phase shifts, and higher harmonics, which are required for superior RC performances, were generated in SWNT/por-POM networks. Lissajous plots show various phase shifts as the input frequency decreases, reflecting the relaxation time of the dynamics in the por-POMs. The SWNT/H4TPP-POM network exhibits the best performance of the RC benchmark task, indicating that H4TPP-POM generates rich chemical dynamics based on different charge accumulation with different electronic state in por-POM.