Tumor Shrinkage Rate Research Articles

Surufatinib plus toripalimab combined with etoposide and cisplatin as first-line treatment in advanced small-cell lung cancer patients: a phase Ib/II trial

There is still room for improvement in first-line treatment of advanced small cell lung cancer (SCLC). This trial firstly investigated efficacy and safety of antiangiogenic therapy (surufatinib) (200 mg, qd, po) plus anti-PD-1 treatment (toripalimab) (240 mg, d1, ivdrip) combined with etoposide (100 mg/m², d1-d3, iv, drip) and cisplatin (25 mg/m², d1-d3, ivdrip) for advanced SCLC as first-line treatment, which has been registered on ClinicalTrials.gov under the identifier NCT04996771. The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab. The primary endpoint was progression-free survival (PFS). The secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. All of the 38 patients were enrolled for safety analysis, while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment. After a median follow-up of 21.3 months, the ORR was 97.1% (34/35), and the DCR and the tumor shrinkage rate were both 100% (35/35). The median PFS was 6.9 months (95% CI: 4.6 m–9.2 m) and the median OS was 21.1 months (95% CI: 12.1 m–30.1 m). The 12-month, 18-month, and 24-month OS rates were 66.94%, 51.39% and 38.54%. The occurrence rate of grade ≥3 treatment-emergent adverse events (TEAEs) was 63.2% (24/38), including neutrophil count decreased (31.6%, 12/38), white blood cell count decreased (23.7%, 9/38) and platelet count decreased (10.5%, 4/38). No unexpected adverse events occurred. This novel four-drug regimen (surufatinib, toripalimab, etoposide plus cisplatin) revealed impressive therapeutic efficacy and tolerable toxicities.

Chemotherapy combined with lenvatinib and PD-1 may be a potential better alternative option for advanced unresectable intrahepatic cholangiocarcinoma: a retrospective real-world study.

Currently, the prognosis of advanced intrahepatic cholangiocarcinoma (ICC) is poor, and the current treatment methods are not effective. The aim of this study was to evaluate the anticancer efficacy of chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors (TKIs) in patients with ICC. We retrospectively screened patients with advanced intrahepatic cholangiocarcinoma (ICC) who received chemotherapy combined with lenvatinib and PD-1. We evaluated overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), the disease control rate (DCR), the tumor shrinkage rate, and safety. We enrolled 95 patients with ICC and divided them into three groups with a median follow-up duration of 15.1 months. The chemotherapy group (chemo-regimen group), chemotherapy combined with immune checkpoint inhibitors (dual-regimen group), and chemotherapy combined with lenvatinib (triple-regimen group) had median OS times of 13.1 months, 20.8 months, and 39.6 months, respectively. Notably, the triple-regimen group had a significantly longer OS than did the chemo-regimen and dual-regimen groups. The chemo-regimen group, dual-regimen group, and triple-regimen group reported median PFS durations of 4.8 months, 11.9 months, and 23.4 months, respectively. Both combination groups exhibited significantly longer PFS than the chemotherapy-only group (P<0.05). The ORRs of the chemo-regimen, dual-regimen, and triple-regimen groups were 18.2%, 55.5%, and 54.7%, respectively. The DCRs were 72.7%, 90%, and 96.2%, respectively, indicating significantly better outcomes in the combination therapy groups. The combination of chemotherapy with PD-1 inhibitors and lenvatinib demonstrates considerable efficacy and tolerability as a treatment strategy for patients with advanced ICC.

Evaluation of the prognosis in patients with small-cell lung cancer treated by chemotherapy using tumor shrinkage rate-based radiomics

BackgroundSmall-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown.MethodsWe performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan–Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC.ResultsThe TSR cutoff was identified to be − 6.6%. Median PFS and OS were longer in the group with a TSR < –6.6% than in the group with a TSR ≥ − 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < − 6.6% than when it was > − 6.6%. Brain metastasis-free survival was better in the group with a TSR < − 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS.ConclusionsThe TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis.

To compare the efficacy and safety of total neoadjuvant therapy (TNT) and neoadjuvant chemoradiotherapy (nCRT) in the treatment of middle and low locally advanced rectal cancer. Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates, surgical resection rates, tumor-free survival, and severe adverse events. To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options. A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese (CNKI, Wanfang, China Biomedical Literature Database) and English (PubMed, Embase) databases was performed. Two system assessors independently screened the studies according to the inclusion and exclusion criteria. Quality evaluation and data extraction were performed for the included literature. We used RevMan 5.3 software to perform a meta-analysis of the pathologic complete response (pCR) rate, T stage degradation rate, resection 0 (R0) rate, anal grade 3/4 acute toxicity rate, perioperative complications, overall survival (OS), and disease-free survival (DFS) in the TNT and nCRT groups. Finally, 14 studies were included, six of which were randomized controlled studies. A total of 3797 patients were included, including 1865 in the TNT group and 1932 in the nCRT group. The two sets of baseline data were comparable. The results of the meta-analysis showed that the pCR rate [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.30-1.90, P < 0.00001], T stage degradation rate (OR = 2.16, 95%CI: 1.63-2.57, P < 0.00001), and R0 resection rate (OR = 1.42, 95%CI: 1.09-1.85, P = 0.009) were significantly greater in the nCRT group than in the nCRT group. There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups. The 5-year OS [hazard ratio (HR) = 0.84, 95%CI: 0.69-1.02, P = 0.08] and DFS (HR = 0.94, 95%CI: 0.03-1.39, P = 0.74) of the TNT group were similar to those of the nCRT group. TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Predicting overall survival from tumor dynamics metrics using parametric statistical and machine learning models: application to patients with RET-altered solid tumors.

In oncology drug development, tumor dynamics modeling is widely applied to predict patients' overall survival (OS) via parametric models. However, the current modeling paradigm, which assumes a disease-specific link between tumor dynamics and survival, has its limitations. This is particularly evident in drug development scenarios where the clinical trial under consideration contains patients with tumor types for which there is little to no prior institutional data. In this work, we propose the use of a pan-indication solid tumor machine learning (ML) approach whereby all three tumor metrics (tumor shrinkage rate, tumor regrowth rate and time to tumor growth) are simultaneously used to predict patients' OS in a tumor type independent manner. We demonstrate the utility of this approach in a clinical trial of cancer patients treated with the tyrosine kinase inhibitor, pralsetinib. We compared the parametric and ML models and the results showed that the proposed ML approach is able to adequately predict patient OS across RET-altered solid tumors, including non-small cell lung cancer, medullary thyroid cancer as well as other solid tumors. While the findings of this study are promising, further research is needed for evaluating the generalizability of the ML model to other solid tumor types.

A proof-of-concept study of LXP5268 as an add-on neoadjuvant chemotherapy in patients with early-stage triple-negative breast cancer.

e12607 Background: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive subtype characterized by a high risk of mortality and a poor prognosis. The 2019 ASCO and St. Gallen International Consensus Guidelines strongly recommend neoadjuvant chemotherapy (NACT) for early-stage TNBC. Previous studies indicated that NACT improved overall and disease-free survival in early-stage TNBC. LXP5268, a drug in the 505(b)(2) category, has demonstrated efficacy in reducing tumor size in animal models. Our study aims to assess whether combining LXP5268 with NACT enhances anti-tumor efficacy and tumor shrinkage rates in early-stage TNBC patients. Methods: Enrolled patients had untreated stage II-III TNBC. NACT consisted of docetaxel every 3 weeks for four cycles, followed by epirubicin plus cyclophosphamide every 3 weeks for an additional four cycles (24 weeks total). In the LXP5268 add-on NACT (LXP5268+NACT) group, patients took LXP5268 orally once daily with NACT. After treatment, we analyzed tumor objective response rate (ORR), shrinkage rate by CT images, and adverse events (AEs) diagnosed by the principal investigator. Whole-exome sequencing (WES) was performed on 6 subjects in the LXP5268+NACT group, identifying potential germline variants and biomarkers, clinically interpreted following ACMG/AMP 2015 guidelines. Results: Both groups had similar baseline characteristics. LXP5268+NACT subjects (54.8 ± 7.2 years) and NACT subjects (59.3 ± 9.8 years) showed significant age differences ( p&lt;0.001). The ORR was 100% in both the LXP5268+NACT group (3 pathological complete response, pCR and 4 pathological partial response, pPR) and NACT group (6 pPR). The tumor shrinkage rate was significantly higher in the LXP5268+NACT group at 77.3% ± 21.8 compared to 43.4% ± 12.8 in the NACT group ( p&lt; 0.001). Moreover, subjects in the LXP5268+NACT group with a tumor reduction exceeding 50% surpassed those in the NACT group. AEs included neutropenia (85.7%), constipation (66.7%), and insomnia (66.7%), all grade 1. Interestingly, mutation in XIRP2 correlated with higher tumor shrinkage rate. Conclusions: LXP5268 combined with NACT was more effective than NACT alone for early-stage TNBC, without increasing AEs. These results highlight LXP5268's potential in TNBC therapy. Previous studies indicated XIRP2 mutations in metastatic breast cancer. LXP5268+NACT achieved pCR in XIRP2-mutated patients. Future clinical trials will expand to enhance result verification accuracy. Clinical trial information: CMUH106-REC3-145.

Early clues in the battle against advanced gastric cancer: How plasma ctDNA signals the effectiveness of PD-1 inhibitors with chemotherapy.

3042 Background: Combination therapy with Programmed Death 1 (PD-1) inhibitors and chemotherapy has shown efficacy in improving survival in advanced gastric cancer, but not all patients derive benefit. We aimed to explore whether early dynamic changes in circulating tumor DNA (ctDNA) can serve as predictors of treatment response and long-term survival in patients receiving first-line PD-1 inhibitors combined with chemotherapy. Methods: This is a prospective, single-center trial in which all patients are adults with advanced or metastatic GC/GEJC confirmed by pathology or imaging. 30 eligible patients will receive PD-1 mab (sintilimab/nivolumab (NIVO) Q3W) and chemotherapy (SOX/XELOX Q3W) regardless of programmed death ligand-1 status. Blood samples were collected before treatment and after two treatment cycles for ctDNA analysis. Plasma ctDNA was isolated for evaluating variant allele frequencies (VAF) of somatic mutations in 47 cancer-related genes using next-generation sequencing (NGS), ctDNA response was defined as clearance of maximum VAF (maxVAF) compared to baseline. CT scans were performed after every two cycles and will be categorized as responding (complete response plus partial response) or non-responding (progress disease plus stable disease) according to RECIST v1.1. Overall survival was calculated from the date of first PD-1 mab infusion to the time of death or censored at most recent follow-up; progression‐free survival was calculated from the date of first PD-1 mab infusion to the time of death or first documented progression, whichever came first, or censored at most recent follow-up. Results: In thirty advanced gastric cancer patients, the dynamic changes in maxVAF demonstrated a significant association with patients attaining either complete response (CR) or partial response (PR) to treatment (P=0.0021), but showed no correlation with stable disease (SD) or progress disease (PD). A substantial agreement was observed between ctDNA response and the best tumor shrinkage rate (Cohen's kappa=0.69). The objective response rate (ORR) among ctDNA responders was 85%, markedly higher compared to the 22% observed in non-responders (P=0.0073). Additionally, patients with ctDNA response had a significantly longer progression‐free survival (PFS) compared to patients without ctDNA response (median PFS 15.6 months vs 6.0 months; HR, 0.18; 95% CI, 0.06 to 0.61; p=0.003), overall survival (OS) was also significantly longer among ctDNA responders (median OS not reach[NR] vs 9.0 months; HR, 0.10; 95% CI, 0.01 to 0.88; p=0.011). Conclusions: ctDNA response serves as a potential biomarker for assessing treatment efficacy and long-term outcomes in advanced gastric cancer patients treated with first-line PD-1 inhibitors and chemotherapy. Clinical trial information: ChiCTR2200065366.

Preoperative Tyrosine Kinase Inhibitors Before Percutaneous Cryoablation for Clinical T1b Renal Tumors.

Purpose To treat renal cell carcinoma, local ablative therapy is a viable alternative treatment option. Traditionally, cryoablation has been used for the treatment of T1a renal tumors. However, recent technological developments have expanded its application to encompass select T1b renal tumors. Here, we present a retrospective study of the utilization of preoperative tyrosine kinase inhibitors(TKIs) to induce tumor shrinkage and achieve favorable outcomes in percutaneous cryoablation (PCA). Methods We retrospectively evaluated the data from nine patients with clinical T1b renal tumors who underwent PCA. Six patients with TKI pretreatment at our institution between 2016 and 2018 were included in the study. We evaluated the safety and efficacy of preoperative TKIs prior to PCA. Results All patients received axitinib with a median treatment duration of 80.5 days (IQR: 49-85). All patients experienced tumor shrinkage (median: 13.5 mm; IQR: 7-16); five experienced downstaging to T1a following tumor shrinkage. There were no severe adverse events (common terminology criteria for adverse events (CTCAE) grade ≥ 3) in TKIs. After the discontinuation of TKIs for two weeks, all PCA procedures were performed successfully without any severe complications. During a median follow-up of 46 months, no local recurrence was observed in any of these cases. Conclusion In cases with large renal tumors, TKI pretreatment prior to PCA had potential benefits in terms of tumor shrinkage and long-term local control rate. Further well-designed studies in larger populations are needed to validate our findings.

Abstract 4864: Epidemiological characteristics and treatment strategies of gastric cancer with neuroendocrine differentiation (NED)

Abstract Background: Gastric cancer with neuroendocrine differentiation (NED) occurs in 10% to 40% of cases, a significant proportion that is under-researched. The lack of clinical guidelines for this subgroup necessitates the development of effective treatment protocols. Methods: This study enrolled 149 gastric cancer patients, analyzing retained surgical wax blocks via immunohistochemistry for syn, CgA, and CD56 expressions. Patients were categorized into NED-positive and NED-negative groups for analysis, employing continuous variable analysis, categorical variable analysis, clustering, principal component analysis (PCA), feature importance analysis, heatmap analysis, and survival prognosis. Moreover, the clinical efficacy and safety of first-line (surufatinib + SOX + anti PD-1 antibody, n=3) and second-line (surufatinib + anti PD-1 antibody, n=3) treatments were observed in six advanced gastric cancer with NED patients, exploring the epidemiological characteristics, feasibility, and importance of clinical treatments for NED. Results: The study revealed a 10.1% incidence of NED positivity in gastric cancer patients. NED-positive patients exhibited a rapid decline in early survival probability, with a median relapse-free survival of 32.4 months compared to 41.5 months in NED-negative patients, indicating a poorer prognosis for NED-positive patients. In-depth analysis suggested significant correlations between NED status and factors such as gender, tumor location, pathological type, and AJCC staging, with the most significant associations observed in males, stage IIIA, and gastric angle location. In the six advanced gastric cancer with NED cases, effective tumor reduction was observed in both first-line (100% tumor shrinkage rate, ORR 66.7%, DCR 100%) and second-line treatments (66.7% tumor shrinkage rate, ORR 33.3%, DCR 100%), showing sustained partial responses (PR) exceeding 10 months in two patients and 7 months in one patient, respectively. The major grade 3 or higher TEAEs being neutropenia and thrombocytopenia in the first-line, and hypertension and proteinuria in the second-line therapy. Conclusion: This study provides pivotal epidemiological and clinical treatment evidence for gastric cancer with NED, underscoring the necessity of personalized treatment strategies for this subgroup. Future research should focus on refining treatment protocols to enhance the quality of life and overall prognosis for these patients. Citation Format: Zhen Huang, Jinlai Wei, Yifan Shen, Jun Zhang. Epidemiological characteristics and treatment strategies of gastric cancer with neuroendocrine differentiation (NED) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4864.

Molecular characterization of Chinese patients with small bowel adenocarcinoma.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.

Comprehensive evaluation of the relationship between biomarker profiles and neoadjuvant chemotherapy outcomes for breast cancer patients

BackgroundAccurately predicting the response to neoadjuvant chemotherapy (NAC) in breast cancer patients is crucial for guiding treatment strategies and enhancing clinical outcomes. Current studies have primarily focused on a limited set of biomarkers. More importantly, the results of many studies are in conflict. To address this, we conducted a comprehensive evaluation of the predictive value of a diverse range of clinically available molecular biomarkers in breast cancer, including HER2, ER, PR, TOPO II, EGFR, Ki67, CK5/6, AR, and p53. Additionally, we assessed changes in these biomarkers after NAC administration.MethodsOur study involved 189 patients with invasive breast cancer who underwent NAC at our institute. We examined biomarker profiles in core-needle biopsies taken before NAC and in surgical specimens obtained after NAC. We examined the association between these biomarkers and NAC outcomes, focusing on two main aspects: the rate of pathological complete response (pCR) and the reduction in tumor size. We used Chi-square and Mann-Whitney U tests to compare biomarker status changes between pCR and non-pCR patients. Linear regression analysis was employed to evaluate the relationship between biomarker status and tumor shrinkage rate. Additionally, we compared the expression status of these biomarkers before and after NAC using Chi-square and Wilcoxon signed-rank tests.Results and conclusionsOur results demonstrated significant differences in the expression levels of HER2, ER, PR, TOPO II, EGFR, and Ki67 between pCR and non-pCR patients, underscoring their potential as predictive markers for NAC outcomes. Importantly, our results have shed light on the contentious issue surrounding TOPO II in NAC outcome prediction. We have provided evidence that establishes a significantly positive association between TOPO II expression level and the pCR rate. Notably, tumor size was identified as a relevant predictive factor for achieving pCR. Regarding biomarker profiles, only Ki67 levels and TOPO II status exhibited changes following NAC, resolving previous controversies. While the ER and PR status remained unchanged, their expression values exhibited a slight but significant decrease post-NAC. Our results provide clarity and insights into the value and potential of using these biomarkers to predict NAC responses and prognosis in breast cancer patients.

The radiomics-clinical nomogram for predicting the response to initial superselective arterial embolization in renal angiomyolipoma, a preliminary study.

The aim of this study was to explore a radiomics-clinical model for predicting the response to initial superselective arterial embolization (SAE) in renal angiomyolipoma (RAML). A total of 78 patients with RAML were retrospectively enrolled. Clinical data were recorded and evaluated. Radiomic features were extracted from preoperative contrast-enhanced CT (CECT). Least absolute shrinkage and selection operator (LASSO) and intra- and inter-class correlation coefficients (ICCs) were used in feature selection. Logistic regression analysis was performed to develop the radiomics, clinical, and combined models where the fivefold cross-validation method was used. The predictive performance and calibration were evaluated by the receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) was used to measure clinical usefulness. The tumor shrinkage rate was 29.7% in total, and both fat and angiomyogenic components were significantly reduced. In the radiomics model, 12 significant features were selected. In the clinical model, maximum diameter (p = 0.001), angiomyogenic tissue ratio (p = 0.032), aneurysms (p = 0.048), and post-SAE time (p = 0.002) were significantly associated with greater volume reduction after SAE. Because of the severe linear dependence between radiomics signature and some clinical parameters, the combined model eventually included Rad-score, aneurysm, and post-SAE time. The radiomics-clinical model showed better discrimination (mean AUC = 0.83) than the radiomics model (mean AUC = 0.60) and the clinical model (mean AUC = 0.82). Calibration curve and DCA showed the goodness of fit and clinical usefulness of the radiomics-clinical model. The radiomics-clinical model incorporating radiomics features and clinical parameters can potentially predict the positive response to initial SAE in RAML and provide support for clinical treatment decisions.

Optimal Time-to-Surgery Recommendations Based on Primary Tumor Volume Regression for Patients with Resectable Esophageal Cancer after Neoadjuvant Chemoradiotherapy: A Retrospective Study.

Neoadjuvant chemoradiotherapy (NCRT) has shown promise in improving the prognosis of individuals with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the factors influencing tumor response and long-term survival in these patients remain unknown. The optimal timing for surgery after the completion of radiotherapy in LA-ESCC remains controversial. Therefore, this study was designed to identify biomarkers and to determine the optimal post-NCRT time-to-surgery (TTS) for patients with LA-ESCC. This retrospective study included patients with resectable LA-ESCC who underwent NCRT between May 2017 and June 2021. The tumor shrinkage rate was calculated as the difference between the pre- and post-primary gross tumor volume (GTVp) divided by the pre-GTVp. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival (PFS). We collected data from 248 patients with resectable LA-ESCC who underwent computed tomography (CT) scans before the initiation of treatment. The median follow-up time was 37.7 months. The optimal cutoff of tumor shrinkage was 45%. In the univariate and multivariate analyses, we found a significant association between the tumor shrinkage rate and PFS (p = 0.001). Among the subgroup of patients who responded to treatment, extending the TTS was associated with improved OS (p = 0.037) and PFS (p = 0.028). For patients with resectable LA-ESCC, the tumor shrinkage rate is an independent prognostic factor for PFS. Thus, for responders, prolonging TTS is recommended to obtain a better OS.

Recurrence and Survival Prediction Models for Receiving Preoperative Chemotherapy Pancreatic Ductal Adenocarcinoma Cancer: A Single-center Retrospective Research

Purpose: Regard preoperative chemotherapy as a holistic sequential treatment modality to identify predictive factors associated with recurrence and survival in pancreatic ductal adenocarcinoma (PDAC) and construct models to provide decision support and treatment selection for the candidate patients. Methods: Retrospect PDAC patients who received preoperative chemotherapy from January 2016 to June 2023 at the Second Affiliated Hospital of Zhejiang University School of Medicine. Run a univariate and multivariate analysis of factors associated with recurrence-free survival (RFS) and overall survival (OS). Scoring systems were developed based on the hazard ratios (HR) of all significant predictors. Kaplan–Meier analyses and log-rank tests were used to calculate RFS and OS. Results: A total of 72 PDAC patients with preoperative chemotherapy were analyzed. After preoperative chemotherapy, 21(29.17%) patients achieved any radiologic downstaging with 68(94.44%) patients achieving negative resection margin status (R0 margins). For carbohydrate antigen 19-9(CA19-9) non-secreting patients, shrinkage rate of length diameter of tumor≥20%(P=0.027), resection margin status(P=0.011) were independent predictors of OS. And for CA19-9 secreting patients, CA19-9 serum level at the end of chemotherapy≥1000(P=0.027) and resection margin status (P=0.012) were independent predictors of OS. Points according HR were allocated to these factors in the proposed scoring system, respectively. Recurrence curves and survival curves with statistically significant differences were also presented for patients grouped according to the scoring systems. For CA19-9 non-secreting patients, the OS of patients with a score from 2 to 2.97 was significantly shorter than that of patients with a score from 4.94 to 5.91 (P=0.009). And for CA19-9 secreting patients, the OS of patients with a score of 2 was significantly shorter than that of patients with a score from 3.75 to 4.99 (P&lt;0.001). Conclusion: Simple scoring models for RFS and OS incorporating CA19-9 serum levels or the tumor shrinkage rate and postoperative pathology may assist clinicians in evaluating prognosis of PDAC patients with preoperative chemotherapy.

Efficacy of bevacizumab combined with apatinib in the treatment of advanced metastatic gastric cancer.

To evaluate the clinical efficacy and safety of bevacizumab combined with apatinib in the treatment of advanced metastatic gastric cancer, providing insights for treatment decisions. We conducted a single-center retrospective study involving patients with metastatic gastric cancer treated with apatinib, with or without bevacizumab, between August 2018 and April 2021 at Nanchang Medical College. Data on efficacy, adverse events, response rates, and quality of life were collected and compared. No significant differences were observed in complete remission, partial response, stable disease, disease progression, objective response rate, or disease control rate between the groups (all P>0.05). The median progression-free survival was 9.23 months in the control group and 9.94 months in the observation group (P=0.587). Median overall survival (OS) was 19.64 months in the control group and 26.44 months in the observation group (P=0.187). Univariate and multivariate analyses identified combination therapy with apatinib and bevacizumab, primary lesion resection, and number of metastatic organs as independent prognostic factors for OS. Scores for role, emotional, somatic, cognitive, and social functions were significantly higher in the observation group post-intervention (all P<0.05). In patients with advanced metastatic gastric cancer, combined therapy with bevacizumab and apatinib significantly improved OS, enhanced response rates, and increased rates of early and maximal tumor shrinkage.

Tumor-Specific Activity of Precision Medicines in the NCI-MATCH Trial.

National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) is a precision medicine basket trial designed to test the effectiveness of treating cancers based on specific genetic changes in patients' tumors, regardless of cancer type. Multiple subprotocols have each tested different targeted therapies matched to specific genetic aberrations. Most subprotocols exhibited low rates of tumor shrinkage as evaluated across all tumor types enrolled. We hypothesized that these results may arise because these precision cancer therapies have tumor type-specific efficacy, as is common among other cancer therapies. To test the hypothesis that certain tumor types are more sensitive to specific therapies than other tumor types, we applied permutation testing to tumor volume change and progression-free survival data from 10 published NCI-MATCH subprotocols (together n = 435 patients). FDR was controlled by the Benjamini-Hochberg procedure. Six of ten subprotocols exhibited statistically significant evidence of tumor-specific drug sensitivity, four of which were previously considered negative based on response rate across all tumors. This signal-finding analysis highlights potential uses of FGFR tyrosine kinase inhibition in urothelial carcinomas with actionable FGFR aberrations and MEK inhibition in lung cancers with BRAF non-V600E mutations. In addition, it identifies low-grade serious ovarian carcinoma with BRAF v600E mutation as especially sensitive to BRAF and MEK co-inhibition (dabrafenib plus trametinib), a treatment that received accelerated FDA approval for advanced solid tumors with BRAF v600E mutation. These findings support the value of basket trials because even when precision medicines do not have tumor-agnostic activity, basket trials can identify tumor-specific activity for future study.

Endoscopic Ultrasonography-Derived Maximum Tumor Thickness and Tumor Shrinkage Rate as Independent Prognostic Factors in Locally Advanced Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy

Neoadjuvant chemoradiotherapy (NCRT) is increasingly used in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Endoscopic ultrasonography (EUS)-derived maximum tumor thickness (MTT) before and after standard NCRT for LA-ESCC indicates treatment response. However, the accuracy of predicting long-term survival remains uncertain. This study aimed to investigate the association between EUS-derived MTT pre- and post-NCRT and tumor shrinkage rate as well as long-term survival in patients with LA-ESCC receiving NCRT. We retrospectively enrolled patients with LA-ESCC who underwent EUS examination pre- and post-NCRT from 2017 to 2021. MTT was measured using EUS. Tumor shrinkage rate was the ratio of the difference between pre- and post-MTT to pre-MTT. The most fitted cut-off value defining the EUS response was determined by the receiver operating characteristic curve. Univariate and multivariate Cox regression analyses and Kaplan-Meier (KM) curves were used to calculate overall survival (OS) and progression-free survival (PFS). Data from another center were also used for external validation testing. The median follow-up period was 30.6 months.230 patients with LA-ESCC who underwent EUS pre- or post-NCRT were enrolled. Of the patients, 178 completed the first EUS pre-NCRT and obtained pre-MTT, 200 completed the re-examined EUS post-NCRT and obtained post-MTT, and 148 completed both EUS and achieved tumor shrinkage. In the whole group the 1-year and 3-year OS rates were 93.9% and 67.9%, and PFS rates were 77.7% and 54.1%, respectively. Thinner post-MTT (≤8.8 mm) and EUS-responders (tumor shrinkage rate≥52%) were independently associated with better OS. The result of EUS-respond was an independent prognostic factor could be confirmed in the external validation group. Among LA-ESCC patients with initial ultrasonic T2-3 staging and T4 staging, no statistically differences were observed between the responder and non-responder groups (P = 0.082; P = 0.190). EUS-derived MTT and tumor shrinkage post-NCRT are independent prognostic factors for long-term survival and may be an alternative method for evaluating tumor response in patients with LA-ESCC after NCRT. Initial tumor infiltration beyond esophageal adventitial layer on ultrasound effect could not, however, predict the long-term prognosis.

Stereotactic Radiosurgery (SRS) vs. Hypofractionated Stereotactic Radiotherapy (SRT) in Brain Metastases: Kinetic Responses

To evaluate the treatment responses of patients with brain metastases treated with SRS or SRT. Specifically, we intend to assess the differences in the kinetic response of SRS versus SRT. Brain metastasis patients who underwent SRS/SRT were collected consecutively between January 2014 and March 2021. The prescribed dose varied according to the tumor size. For SRS, the dose prescription followed the RTOG 90-05 protocol with 15 Gy, 18 Gy, and 24 Gy to the PTV for tumor diameters of 3.1-4 cm, 2.1-3 cm, and ≤ 2 cm, respectively. SRT was commonly used to treat larger lesions (3 cm in diameter) or those close to critical organs. The most common doses prescribed for SRT were 27 Gy in 3 fractions and 30 Gy in 5 fractions. All patients must have at least one imaging after treatment. If the tumor volume increased after the first imaging, which could be due to radiation necrosis or tumor progression, the following images would be excluded from the analysis. Multilevel linear regression was used to compare the kinetic response of SRS and SRT. The initial tumor volumes were adjusted in the model. Fifty-five patients with 128 brain metastases were treated with SRS (n = 85 lesions) or SRT (n = 42 lesions) between January 2014 and March 2021. At the time of analysis, 285 follow-up MRI scans were evaluated. Most patients had non-small cell lung cancer (75 lesions with SRS vs 20 lesions with SRT), followed by breast cancer (6 lesions with SRS vs 13 lesions with SRT). The median of the total dose (IQR) was 24 Gy (21-26 Gy) for SRS and 34 Gy (26-37 Gy) for SRT. For plan quality metrics in SRS/SRT, the median of Paddick's conformity index was 0.76 (IQR = 0.57-0.89) in SRS vs 0.84 (IQR = 0.69-9) in SRT with no statistically significant difference (p-value = 0.095). Likewise, the median homogeneity index in SRS was 1.34 (IQR = 1.22-1.43), compared to 1.36 (IQR = 1.21-1.57) in SRT, with no statistically significant difference (p-value = 0.21). The mean (range) of the initial tumor volume of SRS and SRT was 1 cc (0.01-13.7 cc) and 4 cc (0.02-17.70 cc), respectively. All tumors decreased in volume after treatment. The rate of tumor shrinkage in SRS was 0.13 cc per month (0.004 to 0.25, p-value 0.043). Compared to SRS, SRT made the tumors smaller at an additional rate of 0.45 cc per month (0.24 to 0.66, p-value < 0.001), even after adjusting for initial tumor volume. Most tumor progression or radiation necrosis appeared between 9 and 12 months after treatment. Following treatment, SRT exhibits better kinetic responses than SRS.

Ramucirumab plus FOLFIRI as second-line treatment for patients with RAS wild-type metastatic colorectal cancer previously treated with anti-EGFR antibody: JACCRO CC-16

Chemotherapy in combination with anti-epidermal growth factor receptor (EGFR) antibody is considered a first-line treatment regimen for RAS wild-type and left-sided metastatic colorectal cancer (mCRC), whereas second-line treatment regimens have not yet been established. Few studies have prospectively evaluated second-line treatment with anti-vascular endothelial growth factor antibody after first-line anti-EGFR antibody therapy for RAS wild-type mCRC. This non-randomized phase II trial investigated the clinical outcomes of second-line ramucirumab (RAM) plus fluorouracil, levofolinate, and irinotecan (FOLFIRI) after first-line anti-EGFR antibody in combination with doublet or triplet regimen in patients with RAS wild-type mCRC. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were PFS, overall survival (OS), objective response rate (ORR), rate of early tumor shrinkage (ETS), and safety. We hypothesized a threshold 6-month PFS rate of 30% and an expected 6-month PFS rate of 45%. Treatment was considered effective if the lower limit of the 90% confidence interval (CI) of the 6-month PFS rate was >0.30. Ninety-two patients were enrolled in the study. The primary tumor was located on the left side in 86 (95.6%) patients. Twenty (22.0%) patients had received triplet plus cetuximab as previous therapy. Six-month PFS rate was 58.2% (90% CI 49.3% to 66.2%) with a median PFS of 7.0 months (95% CI 5.7-7.6 months). Median OS was 23.6 months (95% CI 16.5-26.3 months). The ORR and ETS rate were 10.7% and 16.9%, respectively, in 83 patients with measurable lesions. The 6-month PFS rate was comparable between patients previously treated with doublet and triplet regimens; however, median PFS was longer for the doublet regimen (7.4 versus 6.4 months, P= 0.036). Our study demonstrated prospectively that RAM plus FOLFIRI is an effective second-line treatment after anti-EGFR antibody-containing first-line therapy in RAS wild-type and left-sided mCRC. Furthermore, the results were similar for patients who were previously treated with triplet regimen.

Comparison of the pathological response to 2 or 4 cycles of neoadjuvant CAPOX in II/III rectal cancer patients with low/intermediate risks: study protocol for a prospective, non-inferior, randomized control trial (COPEC trial)

BackgroundFor patients with low- and intermediate-risk stage II/III rectal cancer, current studies have reached a consensus that preoperative radiotherapy may be dispensed with, and neoadjuvant chemotherapy (NCT) alone might achieve an accepted local control. Our previous phase II study has evidenced that the morphological response of NCT could be better judged at a relatively early stage. Low- and intermediate-risk stage II/III rectal cancer patients could achieve a high rate of tumor shrinkage and downgrade after only 4 cycles of NCT and obvious tumor morphological changes could be observed after 2 cycles of NCT. However, there is still a lack of more detailed stratification and evidence for pathological criteria. The aim of the present study (comparison of the pathological response to 2 or 4 cycles of neoadjuvant CAPOX in II/III rectal cancer patients with low/intermediate risks, COPEC trial) is to determine the pathological tumor regression grade (pTRG) rate of 2 or 4 cycles of NCT in low- and intermediate-risk stage II/III rectal cancer and verify the feasibility of early identification of chemotherapy-insensitive population.Methods/designThis is a multicenter, prospective, non-inferior, randomized controlled trial (RCT) initiated by West China Hospital of Sichuan University and designed to be conducted in fourteen hospitals around China. Eligible patients will be centrally randomized into 2 or 4 cycles of CAPOX in a 1:1 ratio using the central automated randomization system offered by the O-trial online system (https://plus.o-trial.com/) and accept total mesorectal excision after 2 or 4 cycles of CAPOX (oxaliplatin 130 mg/m2, once daily on day 1, every 21 days and capecitabine 1000 mg/m2, twice daily on days 1 to 14, every 21 days). The primary endpoint is the proportion of patients with pathological no-tumor regression (pTRG 3), which is determined postoperatively by each sub-center and verified by the primary center.DiscussionCOPEC trial is designed to verify that the preoperative CAPOX chemotherapy for low- and intermediate-risk stage II/III rectal cancer could achieve a good response judgment after 2 cycles and obtain the tumor pathological response rate after 2 cycles of CAPOX. We hope the COPEC trial could help in establishing a consensus standard of low- and intermediate-risk rectal cancer and the early identification of stage II/III rectal patients with low- and intermediate-risk who are poorly responding to NCT.Trial registrationClinicaltrial.gov NCT04922853. Registered on June 4, 2021.