tbuckley/cabot-search huggingface dataset:
Exploration of neoadjuvant chemotherapy and post-tumor microenvironment for advanced gastric cancer (GC) or gastroesophageal junction cancer (EGJ).
Authors: Miaomiao Gou, Yunhe Gao, Zhi Qiao, Zhi-Kuan Wang, Yi Liu, Guanghai Dai
Journal: Journal of Clinical Oncology (2024)

e16099 Background: Neoadjuvant chemotherapy (NAC) is still the main strategy for operable local advanced gastric cancer (GC) or gastroesophageal junction cancer (EGJ). Keynote585 and Matterhorn studies had demonstrated the improvement of pathologic complete response rate (PCR), however, the overall survival benefit remains unclear. Little is known why patients’ response differently to NAC in terms of chemotherapy regiment and post neoadjuvant tumor microenvironment (TME). Methods: We retrospectively analyzed the resectable GC or EGJ patients who had been treated with neoadjuvant chemotherapy followed by surgery during 2019.11.26-2023.8.18 in the Chinese PLA general hospital. Patients with complete survival data were enrolled in the final evaluation. The association between clinical features or chemotherapy regiment and outcomes including TGR grade (NCCN criteria) and survival data were explored. Furthermore, tumor-microenvironment by means of multiplex fluorescence staining(mIHC) (CD8, CD68, CD56, PD1, PDL1, PANCK) after SOX neoadjuvant chemotherapy was analyzed. Results: 184 patients were offered neoadjuvant chemotherapy and underwent surgery. Due to follow-up lost, 141 patients with complete survival data were included in this analysis finally. Average age was 61, majority of patients were male. 85 patients received Sox and 33 received Xelox and 12 patients with docetaxel and S1(DS) and 11 patients were administered with triplets (FOLT and DOS). The median cycle of neoadjuvant treatment was 4(range from 1-7). Large proportion of patients were performed Laparoscopic. 31 patients suffered from post surgery complication. Above all, 1-year DFS and 2-year DFS, 3-year DFS rate were 72.6%, 54.8%, 49.0% respectively. 2-year OS and 3-year OS rate were 76.9%, 64.5%. PCR rate was 6.38% (n=9), which is consistent with other previous studies. 9 patients achieved TRG 0 and 26 had TRG 1. There is no statistical difference between triplets and double regiment of NEC for TRG0-1 group (45.5% vs 23.1%, p=0.099). The addition of docetaxel to oxaliplatin based therapy had not improved the TRG0-1 population compared with docetaxel-free regiment (30.4% VS 23.7%, p=0.496). YN0 is a predictor of longer survival in contrast YN+( 1-year DFS, 89.4% vs 62.8%, p=0.000).In the mIHC analyses, the density of CD8 positive and CD8+PD1- in the TGR0-1 group is higher than those cells in the TGR 2-3 group(P&lt;0.05). TGR0-1 group had lower density of PDL1+,CD68+PDL1+ and CD68+PDL1- cells in contrast to TGR 2-3 group(P&lt;0.05).Other multi-dimensional analyses were ongoing to be further disclosure. Conclusions: Neoadjuvant chemotherapy led to nearly 7% PCR rate for patients with local advanced GC. YN0 after NAC is a predictor of longer survival. CD8 positive and CD8+PD1- might be the determinant immune cells for better anticancer-response when exposed to chemotherapy.
Influence of neoadjuvant regimen on the prognosis of locally advanced gastric and gastroesophageal junction cancer with HER2 overexpression.
Authors: Lingdi Zhao, Xiao Liu, Guanglong Chen, Baozhen Ma, Jinxi Huang, Zhiqiang Jiang, Xinfang Hou, Ning Li, Peng Qin, Yong Zhang, Zibing Wang, Zhi Li, Quanli Gao
Journal: Journal of Clinical Oncology (2024)

e16082 Background: The relative high recurrence rate in locally advanced gastric or gastroesophageal junction (G/GEJ) cancer with Her2 overexpression after surgery, along with the absence of a standard neoadjuvant treatment protocol, necessitates exploration of novel approaches for this patient population. Methods: In this study, we conducted a retrospective analysis of clinical characteristics, postoperative pathological results, and survival data for patients who underwent neoadjuvant treatment and subsequent surgery at our center from September 2020 to December 31, 2022. The inclusion criteria were as follows: 1) pathologically confirmed adenocarcinoma of the G/GEJ; 2) diagnosed as cT3-4 or N+ by enhanced CT and endoscopic ultrasound; 3) Her2 immunohistochemistry 3+ or 2+ with Fish positive in biopsy specimens; 4) discussed in a multidisciplinary team for the need for neoadjuvant treatment; 5) received 2-4 cycles of neoadjuvant therapy; 6) underwent radical D2 surgery; 7) had complete follow-up data. Results: Seventy-three patients met the inclusion criteria, with 19 receiving chemotherapy + anti-PD-1, 10 receiving chemotherapy + anti-Her2, and 44 receiving chemotherapy alone. Their pCR rates were 31.6%, 10%, and 2.3%, respectively (P = 0.003); MPR rates were 42.1%, 30%, and 11.4% (P = 0.022). As of the last follow-up on December 31, 2023, the median DFS for the chemotherapy group was 18.1 months (95% confidence interval 14.9-21.3); median DFS for the other two groups had not been reached. DFS analysis revealed differences in median DFS among different neoadjuvant treatment regimens (P = 0.025); further pairwise comparisons indicated that this difference mainly stemmed from the chemotherapy + anti-Her2 group compared to the chemotherapy group. Conclusions: In locally advanced gastric and gastroesophageal junction cancer with Her2 overexpression, neoadjuvant chemotherapy combined with anti-Her2 treatment improves the pCR rate and prolongs DFS compared to neoadjuvant chemotherapy alone.
Multidisciplinary care for patients with gastroesophageal cancers (GEC): A quality improvement initiative in community cancer clinics.
Authors: Samuel Dooyema, Stephen Broderick, Janet Storey, Ilona Dewald, Jeffrey D. Carter, Cherilyn Heggen, Kelly E. McKinnon, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2024)

e16096 Background: Evidence-based guidelines for GEC management recommend multimodal care, which involves close coordination between medical, surgical, and radiation oncologists, together with specialists to manage symptoms and treatment-related adverse events (AEs). Optimizing the high level of multidisciplinary care required for effective GEC management poses substantial challenges for community oncology care teams. Methods: In August-October 2023, 57 healthcare providers (HCPs) from 4 US community oncology clinics completed surveys on challenges, barriers, and improvements needed in the multimodal care of patients with GEC. Based on findings from the baseline data, 70 HCPs participated in audit/feedback (AF) sessions to review site-specific gaps and challenges and develop action plans to address identified gaps. Follow-up surveys will evaluate the impact of changes in practice following action plan implementation. Results: Providers identified their 3 top challenges to providing care for patients with GEC: interdisciplinary care coordination, providing patient-centered supportive care, and managing AEs. They reported that care coordination was hampered by low frequency and poor-quality communication between medical oncology and surgical teams, by misalignment on methods of communication, and by a lack of relationship between the specialties. About one-third of HCPs reported recognizing and managing AEs as the most challenging aspect of caring for patients with GEC, including AEs that were immune-related (26%), dermatologic (19%), gastrointestinal (19%), neurologic (14%), immunosuppression-related (10%), and respiratory (5%). After the AF sessions, HCPs reported improving communication and coordination among care team members as an important means of improving and individualizing patient care plans and integrating new therapies into clinical workflows. Action plans included streamlining communication with surgical teams, increased use of patient navigation, and ensuring that every patient is reviewed through the multidisciplinary tumor board. With regard to AE management, action plans included improving patient education on AE identification, and better communication within the team on nutritional support. HCPs who participated showed improved confidence, knowledge, and competence in appropriately sequencing systemic therapy and surgical interventions. Conclusions: GEC care teams from community cancer clinics reported dissatisfaction with multidisciplinary care coordination, including poor communication between specialists involved in multimodal care of patients with GEC. Integration of sustainable changes in clinical workflows driven by this initiative improved oversight of multimodal care, improved workflows, and improved AE management.
Induction immunotherapy-based regimens followed by palliative CCRT may lead to conversion surgery in selected patients and boost survival for stage IV ESCC.
Authors: Jo-Pai Chen, Wei-Chen Lu, Fu-Jen Hsueh, Keng-Man Chiang, Hsing-wu Chen, Shang-Hsuan Peng, Chen-Han Chang, Ruey-Long Hong
Journal: Journal of Clinical Oncology (2024)

e16059 Background: ESCC is still a health burden in Taiwan; besides, double cancers easily occur in Taiwan, like HypoCa &amp; ESCC or OSCC and ESCC. ESCC is still an immunogenic cancer type. Nivolumab with chemotherapy or nivolumab with ipilimumab in CM648 study and pembrolizumab with chemotherapy in KN590 study have also won survival benefits compared with chemotherapy alone in frontline treatment for R/M ESCC, esp. for PDL1+ patients. In our previous study, EGFR TKI, such as afatinib, have multiple immuno-modulatory effects and may help to increase immunotherapy benefits in the 1 st line(67% ORR) of CT-unfit advanced ESCC. Following KN590 or chemotherapy failure, good rescue efficacy(70% ORR) was also seen in subsequent afatinib with anti-PD1.(ASCO-GI2022). Methods: We try to analyze the treatment options and final survivals of 72 patients with stage IV ESCC from 2010 to 2019 in my institution from National Taiwan University Hospital, Yun-lin Branch. Results: See Table. Conclusions: In this 10-year experience in one institution, we suggested induction Immuno-chemotherapy, Bio-immunochemotherapy, &amp; Bio-immunotherapy may lead to coversion chemoradiation, even to final surgery for stage IV ESCC with well systemic control in selected fit patients to boost further survival. Maintenance metronomic UFUR with anti-PD1 may also be beneficial. Afatinib with anti-PD1 could be a good option for (1)frontline treatment for double cancers or CT-unfit patients; (2)salvage treatment in later lines, even failing KN590 or CM648. [Table: see text]
Analysis of the value of chromosomal instability test for evaluating early efficacy assessment in advanced gastric cancer.
Authors: Xinpei Luo, Min Yuan, Zhuqing Liu, Rongjia Xie, Qing Xu
Journal: Journal of Clinical Oncology (2024)

e16060 Background: Gastric Cancer is featured by frequent somatic copy number alterations (SCNA) and high chromosomal instability (CIN). Circulating tumor DNA (ctDNA) is a minimally invasive approach, effective for the real-time follow-up of cancer. However, the clinical significance in gastric cancer is not yet determined.We performed this study to to evaluate whether ctDNA-based CIN analysis can predict treatment efficacy in advanced gastric cancer (AGC). Methods: The patients with surgery or cytopathology confirmed AGC and who received chemotherapy were enrolled. The blood sample (10ml) for ctDNA sequencing were obtained at baseline (BL) (before first-line chemotherapy) and at the time of efficacy assessment, respectively.The ctDNA of gastric cancer patients was isolated from plasma using QIAseq ctDNA extraction kit (Qiagen), and then repaired and amplified. The whole genome data were analyzed for DNA copy number abnormality, which was expressed as TFx value, and TFx ≥ 0.06% was taken as the positive value of chromosomal instability.Clinical responses (by RECIST 1.1 criteria) were estimated at the time points after 2 cycles of treatment. Results: A total of 18 patients were registered.There were 12 males and 6 females with a median age of 64 years (range 43-72 years).According to the RECIST1.1 criteria, there were 7cases of PR, 9 cases of SD, and 1 case of PD after treatment,1 case was under observation. Patients with CR+PR+SD were defined as the treatment-effective group, and with PD were defined as the treatment-ineffective group.The treatment-effective group mean value of CIN TFx value before treatment was 3.47±7.69, after treatment was 0.59±1.46(P&lt;0.05),14 (82.35%) of these patients experienced a decrease in TFx values after treatment.Patients in the treatment-naïve group showed elevated TFx values.We divided the patients into group A and group B,group A was defined as the TFx value did not fall into the normal range after treatment, and group B was defined as the TFx value fell into the normal range and was called the rapid clearance group.Comparing the efficacy to the CIN group, 71.4% of patients with PR showed rapid clearance of ctDNA, while no clearance of ctDNA was observed in patients with PD,50.0% of patients with SD showed rapid clearance of ctDNA. Rapid clearance of ctDNA was also associated with longer survival, with a median OS of 7.2 months in group A and 17.85 months in group B, with HR of 0.55 (95% CI: 0.081-3.775 P &gt; 0.05) However, there was no significant difference, probably due to too little data.In terms of PFS, Group B did not demonstrate benefit, with a median PFS of 5.9 months in Group A compared to only 3.9 months in Group B (P = 0.647). Conclusions: Dynamic ctDNA-based CIN assay can be used as a biomarker for efficacy assessment in metastatic gastric cancer. Rapid clearance of ctDNA is associated with longer survival, but this still needs to be validated with extensive data.
A single-arm, open-label phase II clinical trial of SHR-1210 (camrelizumab) in combination with nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma.
Authors: Feng Wang, Jin Xia, Xiangrui Meng, Yinghua Ji, Xiuli Yang, Yong-Gui Hong, Junsheng Wang, Donghai Cui, Zhiquan Luo
Journal: Journal of Clinical Oncology (2024)

e16007 Background: The prognosis of advanced esophageal cancer is bleak, and the current first-line regimen based on paclitaxel, cisplatin and fluorouracil (TPF) with an effective rate is about 30%. The second-line treatment regimen based on anti-PD-1/PD-L1 monoclonal antibodies obtained median overall survival (mOS) 10.8 months in phase I-II clinical trials, but a large proportion of patients (pts) still do not respond to this therapy. Additionally, nimotuzumab in the previous Cuba phase 2 study had a good disease control rate (DCR) combined with PF regimen. So, we conducted the study to evaluate the new combination modality efficacy and treatment-related adverse events (safety). The primary endpoints was ORR, and the secondary endpoints included overall survival (OS), DCR, progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the second-line treatment for ORR is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha=0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached CR/PR. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase 2 study, a total of 41 pts were administered. One case was lost to follow-up. The mean age was 45 years (range, 42-77). The results of the intention-to-treat analysis showed that the ORR was 36% (15/42). The mOS was 12.62 months with median follow-up 8.28 months. The 9-month and 12-month survival rates were 84% and 51%, respectively. The DCR was 81% (34/42). Median PFS was 9.89 months with median follow-up 9.17 months. In terms of safety, the incidence of TEAEs was 60% (25/42), of which 71% (30/42) had adverse events below grade 3 and 26% (11/42) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 10% (4/42), of which 0 case related to nimotuzumab and 4 cases related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma showed a trend benefit for ORR and OS with a controllable toxicity.
Early evidence of pancreatic enzyme insufficiency in patients with gastric neoplasia.
Authors: Raj N Shah, Joud Zakhour, Wissam Karam, Anas Alqam, Tanner Dean, Nassim H. Nabbout
Journal: Journal of Clinical Oncology (2024)

e16037 Background: The incidence and association of Exocrine Pancreatic Insufficiency (EPI) in patients with gastric neoplasms has not been well reported. Malnutrition and cachexia occur commonly in patients with advanced gastric cancer (AGC), significantly affecting the quality of life and prognosis in these patients. EPI is one of the factors associated with malnutrition and can cause increased morbidity and mortality. ( [1] ) While an association between pancreatic tumors and EPI has been well established, such an association has not been well studied with gastric tumors. Methods: We queried the HERON database for the number of patients diagnosed with Malignant neoplasms of the stomach using International Classification of Disease (ICD) code C16 who then developed EPI, represented by ICD codes K87, K86.6, and K89.9. We conducted a comparative analysis involving individuals diagnosed with gastric neoplasia but lacking a preceding diagnosis of EPI. Specifically, we examined two distinct groups within this cohort: those individuals who were subsequently diagnosed with EPI and those who were not. Additionally, our study incorporated a comparison with the broader general population, utilizing the same database. We used CHI squared testing, odds ratio, and Cramer’s V for statistical analysis. Results: We identified ICD codes in the whole database of 1566102 patients from the database inception to Jan 1, 2024. Out of these, 1609 patients had the diagnosis of gastric neoplasms in the database. 21 patients had the diagnosis of PEI occurring following the diagnosis of gastric neoplasm. 3148 patients developed EPI without gastric neoplasms. The association was statistically significant with a p-value of &lt; / = .001. The odds ratio reported was 6.58 (95% CI = 4.27-10.13). The Cramer’s V was 0.007. Conclusions: The findings reveal preliminary evidence within our cohort of a significant association between the diagnosis of gastric malignant neoplasm and subsequent development of EPI. However, the strength of this association, as indicated by Cramer’s V, is comparatively low. This could be attributed to various factors, including possible missed diagnosis related to limited physician awareness. To delve deeper into this early evidence, a prospective study should be initiated, and physician should pay special attention to this underreported condition. The study should also investigate subgroup variables such as the patient's age, gender, carcinoma stage at diagnosis, nutritional status before and after treatment, as well as the type and duration of treatment, including chemotherapy and radiotherapy. ( [2] ).
Envafolimab in combination with lenvatinib and albumin paclitaxel for previously treated advanced gastric/gastroesophageal junction adenocarcinoma: Preliminary analysis of a phase II, two-cohort study.
Authors: Xiaoying Zhao, Weijian Guo, Xiaodong Zhu, Wanjing Feng, Mingzhu Huang, Qirong Geng, Zhe Zhang, Xuedan Sheng
Journal: Journal of Clinical Oncology (2024)

e16039 Background: The combination of first-line chemotherapy and PD-1 has emerged as a standard treatment, enhancing the efficacy in advanced gastric/gastroesophageal junction (GEJ) cancer. The efficacy of the combination of second-line chemotherapy and PD-1/PD-L1 remains unclear. This study aims to observe the efficacy of Envafolimab plus tyrosine kinase inhibitors (TKIs) and second-line chemotherapy in the treatment of patients with advanced GEJ adenocarcinoma. Methods: This prospective, open-label, phaseⅡ, two cohort study was conducted to assess the efficacy and safety of Envafolimab-based therapy in patients experiencing progression after initial first-line treatment. Eligible patients with HER2-negative, microsatellite stable (MSS), advanced GEJ adenocarcinoma were consecutively enrolled and assigned into cohort A or cohort B, according to whether they received PD-1 inhibitors in the first-line treatment. Patients in both cohorts received Envafolimab (200mg, hypodermic injection, days 1 and 15, Q4W) combined with Lenvatinib (8mg/12mg, po, once a day) and albumin paclitaxel (100mg/m 2 , IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or patients refusal to continue treatment. The primary endpoint was objective response rate(ORR) per iRECIST v1.1, and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. The efficacy and safety data in this analysis were from patients in cohort A who previously failed in first-line chemotherapy and did not receive PD-1 or PD-L1 inhibitors ever. Results: From October 2022 to June 2023, cohort A enrolled 16 patients, and 15 of them were evaluable for efficacy analysis. The average age was 58.87 ±11.81 years, 80% patients were male. 6 patients had been tested for PD-L1 status, of which 1 (16.7%) was positive and 5 (83.3%) were negative. As of Jan29, 2024, the median follow-up was 10.6 months (95%CI = 8.67-12.53), the median number of treatment cycles was 7 cycles (IQR: 5, 8). Based on the iRECIST v1.1, the ORR was 60.00% (90% CI = 35.96%-80.91%), the DCR was 100.00% (90% CI = 81.90%-100.00%). The median PFS (mPFS) was 8.23 months (90% CI =6.27-8.61), and the median OS (mOS) was 10.6 months (90% CI =8.79-12.15). Overall incidences of adverse events (AEs) of any grade was 100%, and 75.00% (n = 12) had ≥ grade 3 AEs during treatment. Most treatment-related adverse events (TRAEs) of grade ≥3 included neutrophil count (56.25%), decreased leukocyte count (37.5%). Conclusions: In patients of advanced gastric cancer who have not previously received PD-1/PD-L1 inhibitors, this second-line combination therapy demonstrates promising preliminary effects. Clinical trial information: NCT06030934 .