tbuckley/cabot-search huggingface dataset:
Treatment modalities for advanced solid pseudopapillary tumor of the pancreas.
Authors: Mengli Yue, Yize Mao, Qiuxia Yang, Fang Wang, Honggui Tang, Xiaofang Yu, Shengping Li, Fenghua Wang
Journal: Journal of Clinical Oncology (2024)

e16327 Background: Solid pseudopapillary tumor (SPT) of the pancreas is a rare low-grade malignant tumor. However, a minority of SPT patients present aggressive behavior and develop recurrent or metastatic diseases. The treatment strategies of advanced SPTs remain unclear. Our study aimed to explore the treatment modalities of aggressive SPTs and the role of endocrine therapy. Methods: The data on clinicopathologic characteristics and treatment of advanced SPT patients from Sun Yat-Sen University Cancer Center and Shen Zhen People's Hospital were collected. The treatment modalities were explored by co-analyzing our local cohort and published literatures. Single sample gene set enrichment analysis (ssGSEA) was used to explore the functional enrichment pathway (GSE43795). Fresh surgical specimens from 10 SPT patients were collected for endocrine drugs sensitive test in vitro by performing tumor histoculture end-point staining computer image analysis (TECIA). Results: A total of 77 advanced SPT patients including 14 cases in our local cohort and 63 cases from published literatures were enrolled. 60 patients received local treatment including cytoreductive surgery, interventional therapy or radiation therapy. 55 patients who had undergone cytoreductive surgery have better outcome compared with others (P = 0.046, HR = 4.12). 31 patients received systemic chemotherapy and 6 patients received targeted therapy. There were 2 patients achieved partial response after chemotherapy. In our local cohort, 5 patients received endocrine therapy with tamoxifen plus megestrol. One patient achieved partial response with duration of response (DOR) of 89 months. 4 patients showed stable disease. ssGSEA for GSE43795 showed that Wnt signaling pathway and its inhibitory pathway-progesterone receptor signaling pathway were simultaneously enriched in SPTs. The results of endocrine drug sensitive test in vitro by TECIA showed response rate of 50% (5/10) in megestrol group, 40% (4/10) in tamoxifen group, and 30% (3/10) in testosterone propionate group. Conclusions: Advanced SPTs did not appear chemosensitive. Cytoreductive surgery may improve survival. Simultaneously enriching Wnt and progesterone receptor signaling pathway may partially explain the low aggressive ability of SPT and their unbalance may lead to the aggressive behavior of SPT. Endocrine therapy with tamoxifen plus megestrol, by enhancing the progesterone signaling pathway, seems to be a promising regimen for advanced SPTs, which is worth to be noted and further studied.
Safety and clinical activity of cadonilimab, an anti PD-1/CTLA-4 bispecific antibody, for patients with persistent, recurrent, or metastatic cervical cancer (R/M CC): A retrospective, real-world study.
Authors: Shi Fan, Tao Wang, Qiying Zhang, Juan Wang, Jin Su, Zi Liu
Journal: Journal of Clinical Oncology (2024)

e17522 Background: Recurrent, metastatic or persistent cervical cancer (R/M cc) patients have limited treatment options. Immune chechpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies, cadonilimab monotherapy has shown promising efficacy and tolerable toxicity in pre-treated R/M CC (NCT04380805).We aimed to assess the safety and clinical activity of Cadonilimab combination therapy(including chemotherapy, radiotherapy, targeted therapy, or immunotherapy) in patients with advanced r/m CC. Methods: Pts (FIGO stage IIIc2r-IVb CC) previously treated with or not candidates for standard therapy, aged ≥ 18 years, with ECOG PS ≤ 2, and measurable (RECIST 1.1) or evaluable disease, were enrolled.All patients received at least one dose of Cadonilimab (10mg/kg, Q3W or 6mg/kg Q2W), 32 patients received concurrent radiotherapy, 66 patients received concurrent chemotherapy, 57patients received targeted therapy, and 4 patients received local injections of oncolytic virus.Immune-related adverse events (irAEs), objective response rate (ORR) and disease control rate (DCR) were evaluated. Results: 82 pts were enrolled from Jul 13, 2022, to Dec 20, 2023. As of Jan 10, 2024, we assessed safety in all pts and efficacy in pts with at least one tumor assessment result. IrAEs of any grade occurred in 46 (56.1%) pts. Grade ≥ 3 irAE occurred in 15 (18.3%) pts. The most frequent were irAEs hypothyroidism (28,34%), Rash (5,6%), infusion reaction (3,3.7%), hepatitis (2,2.4%), there were no toxic deaths reported. The ORR was 70.4% (57/81,95% CI:60.2%-80.5%) with 23 (28.4%) CR,34 PR, 5 SD, and the DCR was 76.5% (62/81,95% CI:67.1%-86.0%). Especially, 6 Pts had previously received immunotherapy, and 2 of them achieved PR. mPFS and mOS data are not mature by cut-off date. Conclusions: Cadonilimab combined with standard therapy (including radiotherapy, chemotherapy and targeted therapy) was well tolerated, with encouraging antitumor activity in pts with R/M CC. Pts who had failed checkpoint inhibitor therapy may still benefit from cardonilimab. Meanwhile, long-term safety and activity evaluation still needs following up.
A retrospective study of PD-1/PD-L1 combination therapy versus TKI monotherapy in elderly patients with uHCC.
Authors: Nanya Wang, Yu Li, Ying Wang, Bo Liu, Shibo Wang
Journal: Journal of Clinical Oncology (2024)

e16191 Background: The rising elderly population worldwide has led to an increase in cases of liver cancer among individuals aged ≥65 years. With the advancement of medical treatments, the management of unresectable hepatocellular carcinoma (uHCC) now predominantly involves immunotherapy combination therapy. However, existing data in elderly patients are limited. Therefore, we conducted a retrospective analysis on the efficacy and safety of immune combination therapy compared with TKI monotherapy in elderly uHCC patients. Methods: A retrospective analysis was conducted on uHCC patients aged ≥65 years at the First Hospital of Jilin University between March 2019 and July 2023. The targeted therapy used in this study included, but not limited to, sorafenib, lenvatinib. PD-1/PD-L1 inhibitors such as pembrolizumab and atezolizumab were also utilized. Follow-up was conducted until death, loss to follow-up, or December 2023. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs) and immune-related AEs (irAEs). Results: A total of 70 patients were included in this study, with 33 patients receiving monotherapy, and 37 patients receiving immune combination therapy. The median age was 68 years old, with 78.8% being male. The combination therapy group had a higher ORR (10.8% vs. 3.0%) DCR (48.5% vs. 45.9%) compared to the monotherapy group. However, there were no statistically significant differences in median PFS (7.0 vs. 12.0 months) and median OS (9.8 vs. 17.5 months) between the two groups. Among the subgroups, combination therapy showed better results except for patients with ascites. Immune combination therapy appeared to be superior to monotherapy in terms of both PFS (6.2 vs. 6.8 months, P = 0.888) and OS (6.8 vs. 10.2 months, P = 0.888). Multivariate analysis showed that elevated total bilirubin may be a risk factor for OS in patients ≥65 years old. Regarding safety, the adverse event (AE) rate was 39.3% in the monotherapy group. The most common AEs reported were abdominal distension (18.2%), fatigue (15.2%), and proteinuria (6.1%). In the combination therapy group, the AE rate was higher at 59.4%, with the most common AEs being thyroid function abnormalities (24.3%), fatigue(24.3%), decreased appetite(18.9%), and hypertension(18.9%). The rate of drug withdrawal due to adverse reactions was significantly higher in patients receiving combination therapy compared to those receiving monotherapy (40.5% vs. 12.1%, P = 0.008). Conclusions: In elderly uHCC patients (≥65 years old), immune combination therapy shows a higher ORR and potentially longer PFS and OS except patients with ascites. AEs and drug withdrawal rates are higher in the combination therapy group. Further discussions are needed to determine the optimal treatment strategy for elderly uHCC patients.
Clinical and analytical validation for HRD status using targeted panel sequencing.
Authors: Hua Bao, Rui Liu, Haimeng Tang, Xuxiaochen Wu, Xiaoxi Chen, Yong Wu, Xue Wu, Yang Shao
Journal: Journal of Clinical Oncology (2024)

e17501 Background: In cancer therapy, understanding homologous recombination deficiency (HRD) is paramount, particularly due to its positive association with sensitivity to PARP inhibitor (PARPi) therapy. We propose using a targeted sequencing approach as a cost-effective and efficient alternative to the current standard of whole genome sequencing (WGS). In this study, we determine the sensitivity and clinical applications of a panel of 437 genes and over 12000 heterozygous SNP loci for evaluating HRD. Methods: HRD positivity for this assay was set at an HRD score of ≥38. To determine the limit of detection (LOD), we diluted 19 samples (4 tiers, 20 repeats each) with known HRD status. Accuracy of the assay was determined by comparing HRD status calls of 40 samples with those obtained through whole genome sequencing. Reproducibility of the assay was tested by measuring variance of HRD status for 30 samples between experimental conditions (2 operators* 3 repeats). Samples were obtained from 85 ovarian cancer (OC) patients undergoing platinum-based (Pt) chemotherapy and were profiled using our targeted sequencing assay. Results: The LOD for BRAC1/2 copy number deletions was established at a tumor purity (TP) of 30%. On the level of individual mutations, LODs range between 1.74% to 5.85% AF with a median of 2.26% AF. Repeatability analysis yields high concordance (APA= 97.83%, 95%CI= 95.34% - 99.00%; ANA= 97.73%, 95%CI= 95.13% - 98.95%), which emphasizes the precision of the assay. Comparisons against WGS based HRD scores reveal strong correlations, with Pearson coefficients of 0.975 for single sample (tumor sample only) and 0.987 for paired sample (tumor + normal sample) HRD score analysis. Through tumor profiling, we identified novel gene mutations associated with resistance to PARPi therapy in the HRD-positive population of our cohort. In the clinical setting, HRD-positive OC patients were found to experience longer progression free survival than their HRD-negative counterparts (median PFS = 18.3 vs 11.4 months, p&lt;0.05). Upon further investigation, we observed that HRD-positive patients who did not carry pathogenic alterations on BRCA1/2 gene showed significantly longer PFS than HRD-negative patients without pathogenic BRCA1/2 alterations (median PFS = 18.5 vs 11.6 months, p&lt;0.05). Conclusions: In summary, this targeted panel offers enhanced sensitivity, reliability, and precision in the assessment of HRD status for informed cancer therapy decisions. In practice, we showed that the targeted sequencing approach is a viable solution for determining HRD status of OC patients and can potentially serve as a predictive biomarker for treatment response. We believe that out assay emerges as a cornerstone in the advancement of personalized cancer care, and offers a sensitive, reliable, and precise approach to HRD assessment for improving patient outcomes.
Immunotherapy-based neoadjuvant therapy followed by concurrent chemoradiotherapy in locally advanced and advanced cervical cancer: A real-world study.
Authors: Qianxue Wei, Hui Qu, Tingting Gong, Song Gao, Nan Tian, Xiuqin Li
Journal: Journal of Clinical Oncology (2024)

e17509 Background: Locally advanced and advanced cervical cancer (CC), characterized by extensive local invasion and potential distant metastasis, present substantial clinical challenges. Although concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced CC, a considerable proportion (23%-34%) of treated pts experienced recurrence or subsequent metastasis. Recently, neoadjuvant therapy (NAT) has been proposed to increase the radiosensitivity and decreases the fraction of hypoxic cells. Particularly, immunotherapy (IO)-based NAT has shown high activity in treating CC. Moreover, IO plus CRT has shown promise in enhancing both local control and systemic response. Hence, we analyzed the efficacy and safety of IO-based NAT followed by CCRT for locally advanced and advanced CC in a real-world setting. Methods: This study retrospectively analyzed data from pts with locally advanced and advanced CC who underwent IO-based NAT followed by CCRT at Shengjing Hospital of China Medical University from January 2022 to January 2024. Outcome measures included complete response (CR), partial response (PR), objective response rate (ORR), progression free survival (PFS), and safety. Tumor responses after neoadjuvant or CCRT therapy were evaluated using RECIST v1.1 and PFS was analyzed with the Kaplan-Meir method. Safety was assessed by adverse events (AEs) referring to CTCAEs v 5.0. Results: A total of 20 pts (median age 57 years, range, 39-72) were included in this analysis, with 15% at stage IIIB, 60% at IIIC, 10% at IVA, and 15% at IVB. Eight (40%) pts received 1 cycle of neoadjuvant IO, 8 (40%) received 1-4 cycles of neoadjuvant IO + chemotherapy, and 4 (20%) received 2 cycles of neoadjuvant IO + bevacizumab (Bev) + chemotherapy. After NAT, all 20 pts received CCRT. In the overall population, ORR after NAT was 55% (11/20), with 5% CR and 50% PR. Regarding different IO-based NAT regimens, objective responses were achieved in 1 of 8 (12.5%) pts receiving neoadjuvant IO, 6 of 8 (75%) pts receiving neoadjuvant IO + chemotherapy, and 4 of 4 (100%) pts receiving neoadjuvant IO + Bev + chemotherapy. After CCRT, 6 (30%) pts had a CR and 7 (35%) pts had a PR, resulting in an ORR of 65.0%. At a median follow-up of 14.9 months, the median PFS was not reached, with a 12-month and 24-month PFS rates of 68% and 56%, respectively. The most common treatment-related AEs during NAT were white blood cell count decreased (50%) and neutrophil count decreased. Conclusions: IO-based NAT followed by CCRT were effective and well-tolerated for pts with locally advanced and advanced CC. This treatment modalities may provide a potential therapeutic strategy for locally advanced and advanced CC.
Laparoscopic versus open pancreatoduodenectomy for periampullary tumors: An updated systematic review and meta-analysis.
Authors: Vinicius Bittar, Pedro Cotta Abrahão Reis, Giulia Almirón, Ana Júlia Schramm, João Pedro Oliveira, Renato Cagnacci, Marcos Pedro Guedes Camandaroba
Journal: Journal of Clinical Oncology (2024)

e16362 Background: Laparoscopic pancreatoduodenectomy (LPD) has emerged as an alternative to open technique in treating periampullary tumors, particularly pancreatic ductal adenocarcinoma (PDAC). However, the evidence regarding safety and efficacy of LPD compared to open pancreatoduodenectomy (OPD) remains unclear. Methods: According to PRISMA guidelines, we searched PubMed, Embase, and Cochrane Library in December 2023 for randomized controlled trials (RCTs) that directly compare LPD versus OPD in patients with periampullary tumors. Outcomes were stratified as intraoperative outcomes, postoperative complications, in-hospital and short-term, and prespecified subanalysis was performed in patients with PDAC. All statistical analysis was performed using R software version 4.3.1 with a random-effects model. Results: Five RCTs yielding 1,018 patients with periampullary tumors were included, of whom 511 (50.2%) were randomized to LPD group. The total follow-up time was 90 days. LPD was associated with a longer operation time (MD 66.75; 95% CI 26.59 to 106.92; p = 0.001; I2= 87%; Figure 1A), lower intraoperative blood loss (MD -124.05; 95% CI -178.56 to -69.53; p &lt; 0.001; I2= 86%; Figure 1B), and shorter length of stay (MD -1.37; 95% IC -2.31 to -0.43; p = 0.004; I2= 14%; Figure 1C) as compared to OPD. In terms of 90-day mortality rates and number of lymph nodes yield, no significant differences were found between both groups. Subgroup analysis for PDAC consistently aligned with the overall results and provided relatively lower heterogeneity compared to the primary analysis. Conclusions: Our meta-analysis of RCTs suggests that LPD is an effective and safe alternative for patients with periampullary tumors, with lower intraoperative blood loss and shorter length of stay.
Early prediction of pancreatic cancer through detection of methylated circulating DNA in blood.
Authors: Ruo-Kai Lin
Journal: Journal of Clinical Oncology (2024)

e16353 Background: Pancreatic cancer represents a significant oncological challenge, contributing markedly to cancer-associated mortalities. This is attributed to the asymptomatic nature of early-stage disease, its inherently aggressive phenotype, and a notably suboptimal response to existing systemic therapies. Hence, the formulation of efficacious early diagnostic modalities for pancreatic cancer amenable to surgical resection is imperative to augment patient prognoses and enhance survival outcomes. Methods: The Infinium MethylationEPIC v2.0 BeadChip platform facilitated the examination of methylation profiles within plasma samples, while the HumanMethylation450 BeadChip array was employed for analogous analyses in corresponding tissue specimens from Taiwanese pancreatic cancer cohorts, aiding in gene selection. Subsequent methylation status verification was conducted via quantitative Methylation-Specific PCR (qMSP) on both genomic DNA and circulating cell-free DNA samples. For external methylation confirmation within a Western demographic, data from The Cancer Genome Atlas (TCGA) Portal were utilized, with further validation conducted using plasma samples from U.S. pancreatic cancer patients. Total 105 plasma from pancreatic cancer patients and healthy subjects were analyzed to calculate the candidate the accuracy, sensitivity, specificity of biomarkers for predict the pancreatic cancer. Results: The test exhibited an accuracy of 90.4%, sensitivity of 92.3%, and specificity of 90.1% in the detection of pancreatic cancer. Detection levels increased from 0% in healthy individuals to 87.5% in Stage I and 100% in Stages II, III, and IV. The CA19-9 marker displayed limited specificity with a high rate of false positives. Moreover, the test dynamically evaluated tumor burden by monitoring circulating methylated ZFP30 and FBXL7 in the plasma of breast cancer patients post-treatment. Conclusions: The analysis of plasma for methylated ZFP30 and FBXL7 provides an innovative and accurate noninvasive method that outperforms the existing blood biomarker CA19-9 for the prediction and ongoing assessment of tumor burden following treatment in pancreatic cancer.
Integrating pathomics and radiomics for predicting survival among patients with intrahepatic cholangiocarcinoma undergoing surgical resection.
Authors: Mingyu Wan, Yifei Shen, Nong Xu, Jian Ruan
Journal: Journal of Clinical Oncology (2024)

e16255 Background: Intrahepatic cholangiocarcinoma (ICC) is characterized by a high degree of malignancy and poor prognosis. Surgical resection remains the primary curative approach for this type of cancer. However, there is a lack of effective predictive tools for patients undergoing such treatments. Methods: In this study, we employed a random forest algorithm to develop our predictive model, which was rigorously validated through a ten-fold cross-validation method. The model leveraged the five most pertinent features extracted from the radiomics dataset to generate predictions. Subsequently, these predictive outcomes were utilized to discern and analyze the distinctions among features within the proteomics dataset to uncover the intricate associations between radiomic signatures and proteomic profiles. Results: In this study, a radiomics prognostic model based on MRI data (n = 150) was developed using a random forest algorithm, and validated using ten-fold cross-validation, achieving an AUC of 0.709. Subsequently, a similar approach was applied to construct a pathology-based model (n = 150), which resulted in an AUC of 0.815. The integration of proteomic and radiomic models reveals that the upregulation of VNN1 and the downregulation of SCGN are significantly associated with prognosis, suggesting a group of highly interactive proteins that may play key roles in the biological process under study. Conclusions: The integration of these omics models is beneficial for predicting the prognosis of ICC patients post-surgery.
Chemotherapy with or without surgery for locally advanced or borderline resectable pancreatic ductal adenocarcinoma: A retrospective multicenter international study.
Authors: Marino Venerito, Danmei Zhang, Selina Becht, Juliane Schütz, ChristophDaniel Steup, Ulli Simone Bankstahl, Timorshah Habibzada, Farsaneh Sadeghlar, Marco De Scordilli, Elena Ongaro, Sebastian Krug, Maria A Gonzalez-Carmona, Thorsten Goetze, Fabian Finkelmeier, Thomas Jens Ettrich, Renato Cannizzaro, Klara Dorman, Caspar Franck
Journal: Journal of Clinical Oncology (2024)

e16352 Background: Current clinical guidelines recommend surgery for patients with locally advanced (LA)/borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) who achieve disease control after induction therapy. However, the additional survival benefit of surgery in these patients is unknown. Methods: In this multicenter international retrospective cohort study, consecutive patients with BR/LA PDAC who achieved disease control after three to six months of induction therapy (combination chemotherapy or chemoradiotherapy) between January 2014 and July 2021 were retrospectively identified at 8 centers in Germany and Italy. Resectability status was determined by consensus in a multidisciplinary tumor board based on imaging findings, serum CA19-9, performance status and clinical response. Patient characteristics, progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression analysis was used to compare survival data. Results: A total of 138 patients who achieved disease control with induction therapy were analyzed. The median age at diagnosis was 66 years (range 45-82) and 43% of patients were female. 73 patients underwent surgery and 65 patients did not (median age 64 and 69 years, respectively, p = 0.02). Median OS was 20.0 months (95%CI 16.1-23.8) in the surgery group and 18.0 months (95%CI 13.6-22.4) in the nonsurgery group (hazard ratio for death, 0.90; 95%CI, 0.63 to 1.29, p = 0.57). Median PFS was 14.0 months (95%CI 8.9-19.1) in the surgery group and 15.0 months (95%CI 11.7-18.3) in the nonsurgery group (hazard ratio for disease progression, 1.04; 95%CI, 73 to 1,47, p = 0.83). The 2-year survival rates in the surgery and nonsurgery groups were 32.9% and 40.0%, respectively, with an overall odds ratio of 0.74 (95% CI: 0.37-1.47). Conclusions: In our multicenter international retrospective analysis, additional surgery did not confer a survival advantage to patients with BR/LA PDAC who achieved disease control with induction therapy.
Alternative Payment Models and Performance in Federally Qualified Health Centers
Authors: Justin Markowski, Jacob Wallace, Mark Schlesinger, Chima D. Ndumele
Journal: JAMA Internal Medicine (2024)

Several state Medicaid agencies have transitioned from traditional fee-for-service to a value-centric alternative payment model (APM) to reimburse federally qualified health centers (FQHCs). Little is known about the effects of this shift on FQHC performance.