Chemotherapy Group Research Articles

Prognostic significance of adjuvant chemotherapy in stage I-II endometrial carcinoma patients who underwent lymphadenectomy.

Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Epidemiological trends and factors associated with survival in patients with medulloblastoma: A 45-year population-based retrospective study

Medulloblastoma (MB) is a primary brain malignancy. However, updated epidemiological data and long-term outcomes are lacking.The clinical and epidemiological datasets of patients with MB in the current study were obtained from the Surveillance, Epidemiology, and End Results (SEER) databases. Joinpoint regression models were used to assess the rate of changes in the incidence, prevalence, and treatment trends in patients with MB. Cox hazard and competition risk model analyses were used to assess overall survival (OS) and cancer-specific survival (CSS).The age-adjusted incidence of MB remained relatively stable at 0.15 per 100,000 individuals in 2019. The annual percentage change (APC) of females remained stable, whereas that of males increased over time. The 20-year limited-duration prevalence of patients with MB increased significantly from 0.00016 % in 1999 to 0.00203 % in 2018. Patients aged 5–19 years accounted for 46.7 % of all age groups, and the trend for the three treatments was increased. Average annual percentage change (AAPC) for the chemotherapy group was increased in patients aged 20 + years MB [AAPC = 2.66 (95 % CI 0.93–6.31)]. Multivariate analysis revealed that OS and CSS varied significantly according to age, year of diagnosis, histology, stage, surgery, and radiotherapy. Subgroup analysis showed that chemotherapy was associated with a favorable prognosis in high-risk groups.The incidence of MB remained relatively stable, and its prevalence increased significantly. This current population-based study further identified the prognostic factors in patients with MB. Moreover, the use of chemotherapy was associated with better survival in high-risk groups.

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease

BackgroundResection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy.MethodsPatients with a diagnosis of pCCA between 1997–2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS.ResultsOverall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55–1.07).ConclusionsPalliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial

In Asia, adjuvant chemotherapy after gastrectomy with D2 or more extensive lymph-node dissection is standard treatment for people with pathological stage III gastric or gastro-oesophageal junction (GEJ) cancer. We aimed to assess the efficacy and safety of adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy administered in this setting. ATTRACTION-5 was a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial conducted at 96 hospitals in Japan, South Korea, Taiwan, and China. Eligible patients were aged between 20 years and 80 years with histologically confirmed pathological stage IIIA-C gastric or GEJ adenocarcinoma after gastrectomy with D2 or more extensive lymph-node dissection, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and available tumour tissue for PD-L1 expression analysis. Patients were randomly assigned (1:1) to receive either nivolumab plus chemotherapy or placebo plus chemotherapy via an interactive web-response system with block sizes of four. Investigational treatment, either nivolumab 360 mg or placebo, was administered intravenously for 30 min once every 3 weeks. Adjuvant chemotherapy was administered as either tegafur-gimeracil-oteracil (S-1) at an initial dose of 40 mg/m2 per dose orally twice per day for 28 consecutive days, followed by 14 days off per cycle, or capecitabine plus oxaliplatin consisting of an initial dose of intravenous oxaliplatin 130 mg/m2 for 2 h every 21 days and capecitabine 1000 mg/m2 per dose orally twice per day for 14 consecutive days, followed by 7 days off treatment. The primary endpoint was relapse-free survival by central assessment. The intention-to-treat population, consisting of all randomly assigned patients, was used for analysis of efficacy endpoints. The safety population, defined as patients who received at least one dose of trial drug, was used for analysis of safety endpoints. This trial is registered with ClinicalTrials.gov (NCT03006705) and is closed. Between Feb 1, 2017, and Aug 15, 2019, 755 patients were randomly assigned to receive either adjuvant nivolumab plus chemotherapy (n=377) or adjuvant placebo plus chemotherapy (n=378). 267 (71%) of 377 patients in the nivolumab group and 263 (70%) of 378 patients in the placebo group were male; 110 (29%) of 377 patients in the nivolumab group and 115 (31%) of 378 patients in the placebo group were female. 745 patients received assigned treatment (371 in the nivolumab plus chemotherapy group; 374 in the placebo plus chemotherapy group), which was the safety population. Median time from first dose to data cutoff was 49·1 months (IQR 43·1-56·7). 3-year relapse-free survival was 68·4% (95% CI 63·0-73·2) in the nivolumab plus chemotherapy group and 65·3% (59·9-70·2) in the placebo plus chemotherapy group; the hazard ratio for relapse-free survival was 0·90 (95·72% CI 0·69-1·18; p=0·44). Treatment-related adverse events occurred in 366 (99%) of 371 patients in the nivolumab plus chemotherapy group and 364 (98%) of 374 patients in the placebo plus chemotherapy group. Discontinuation due to adverse events was more frequent in the nivolumab plus chemotherapy group (34 [9%] of 371 patients) than the placebo plus chemotherapy group (13 [4%] of 374 patients). The most common treatment-related adverse events were decreased appetite, nausea, diarrhoea, neutrophil count decreased, and peripheral sensory neuropathy. The results of this trial do not support the addition of nivolumab to postoperative adjuvant therapy for patients with untreated, locally advanced, resectable gastric or GEJ cancer. Ono Pharmaceutical and Bristol Myers Squibb.

Real-world TRAE association between niraparib and platinum-based chemotherapy.

Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated. Patients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher's exact test were used for correlation analysis. 1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p<0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p<0.001), red blood cell count decreased (57.5% vs 92.5%, p<0.001), anemia (55% vs 87.5%, p<0.001) and neutrophil count decreased (35% vs 85%, p<0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified. 1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.

Efficacy and Safety of Shen Fu Injection Alleviating Chemotherapy-Induced Peripheral Neurotoxicity: A Randomized Controlled Trial

Objective: To analyze the effect of Shenfu injection on Chemotherapy-Induced Peripheral Neuropathy (CIPN) at different stages of tumor chemotherapy. Method: An analysis of 153 patients who were divided into chemotherapy group and combined group was performed chemotherapy within two to six cycles with oxaliplatin or paclitaxel, and combined with or without Shenfu injection. Efficacy evaluation was divided into two phases, including the short-term incidence of CIPN and the long-term incidence of CIPN. Subgroup analysis was performed on the combined group to compare the incidence of CIPN in different usage time of Shenfu injection. Preliminary comparison of the incidence of common side effects. Results: The short-term incidence rates of CIPN in the combined group and chemotherapy group were 27.85% and 66.22%, respectively (P&lt;0.01), and the long-term incidence rates were 17.72% and 45.95%, respectively (P&lt;0.01). In the combined group of 5-6 cycles chemotherapy, divided into two groups according to the time used of Shenfu injection, greater than 3 weeks and less than 3 weeks, and the short-term incidence rates of CIPN were 28.57% and 69.23%, respectively, and the longterm incidence rates of CIPN was 14.29% and 46.15%, respectively. Adverse reactions evaluation showed that the occurrence of bone marrow suppression were 35.44% and 60.81% (P&lt;0.05) in the combined group and chemotherapy group, and there was no significant difference in digestive tract reaction, liver and kidney toxicity. Conclusion: Shenfu injection significantly reduced the incidence of CIPN and had a good security.

Clinical diagnosis and treatment of 37 cases of gallbladder neuroendocrine carcinoma

ObjectiveThis study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC).MethodsRetrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis.ResultsTwelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89–30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61–7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67–43.33 months) for Group 3 (n = 4), and 19 months (range 7.89–30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004).ConclusionSurgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging.

Efficacy and side effects of pembrolizumab plus chemotherapy vs. chemotherapy alone in patients with advanced gastric or gastroesophageal junction adenocarcinoma: A meta‑analysis.

Recently, the treatment plan of pembrolizumab plus chemotherapy was regarded as a promising treatment for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJC). However, the efficacy and side effects of pembrolizumab plus chemotherapy still lack evidence-based medical evidence to support. Therefore, a meta-analysis was conducted to evaluate the hot issue. By searching PubMed, EMBASE, Cochrane Library, Web of Science, any randomized clinical studies of pembrolizumab plus chemotherapy versus chemotherapy in patients with advanced GC/GEJC met the inclusion criteria were included. The quality of the literature was evaluated and the data was extracted. A correlative software was also used to analyze the data and to draw a conclusion. After screening 14,015 studies, four studies were eligible for the meta-analysis. Compared with chemotherapy alone group, the overall survival (OS) rate was significantly longer. In programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 subgroup and PD-L1 CPS ≥10 subgroup analyses, the results showed that the response rate (RR) and complete response rate (CR) were both higher in pembrolizumab plus chemotherapy group compared with chemotherapy alone group. There were not significant differences in the CR, the treatment-related adverse events, succumbed to drug-related events and succumbed to immune-mediated events between the two groups. However, the effect events such as the treatment-related adverse events led to discontinuation, the 3-5 treatment-related adverse events and the immune-mediated adverse events and infusion reactions were more common in pembrolizumab plus chemotherapy group. In conclusion, the current meta-analysis revealed that, in treating advanced GC/GEJC, pembrolizumab plus chemotherapy had improved therapeutic efficacies than chemotherapy alone, as evidenced by the significantly longer OS. Furthermore, the patients in PD-L1 CPS ≥1 subgroup and PD-L1 CPS ≥10 subgroup appeared to benefit from pembrolizumab plus chemotherapy treatment because of higher RR and CR. However, side effects such as the treatment-related adverse events leading to discontinuation, the 3-5 treatment-related adverse events, and immune-mediated adverse events and infusion reactions deserved more attention.

Prognosis and predictive factors of conversion surgery for initially unresectable advanced colorectal cancer

PurposeThe aim of this study was to report the outcomes of conversion surgery for initially unresectable advanced colorectal cancer and to identify factors that enable successful conversion surgery.MethodsWe compared the outcomes of patients with colorectal cancer with distant metastases, including extrahepatic metastases, who underwent upfront surgery, neoadjuvant chemotherapy, conversion surgery, and chemotherapy only at our department from 2007 to 2020. In addition, factors influencing the achievement of conversion surgery in patients who were initially unresectable were examined in univariate and multivariate analyses.ResultsOf 342 colorectal cancer patients with distant metastases treated during the study period, 239 were judged to be initially unresectable, and 17 (conversion rate: 7.1%) underwent conversion surgery. The prognosis for the conversion surgery group was better than that of the chemotherapy only group but worse than that of the upfront surgery group. In the conversion surgery group, the recurrence-free survival after resection was significantly shorter than that upfront surgery group and neoadjuvant chemotherapy group, and no patients have been cured. Among patients who were initially unresectable, left-sided primary cancer and normal CA19-9 level were identified as independent factors contributing to the achievement of conversion surgery in a multivariate analysis.ConclusionsAlthough relapse after conversion surgery is common, and no patients have been cured thus far, overall survival was better in comparison to patients who received chemotherapy only. Among unresectable cases, patients with left-sided primary cancer and normal CA19-9 levels are likely to be candidates for conversion surgery.

Diagnostic accuracy and clinical value of [68Ga]Ga-FAPI-46 PET/CT for staging patients with ovarian cancer: study protocol for a prospective clinical trial

Background[18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [18F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [18F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT and [18F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management.Methods and designFifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [18F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [68Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [18F]FDG PET/CT). Study subjects in Group B will undergo an additional [68Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [68Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting.DiscussionTo our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [68Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [68Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response.Trial registrationclinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.

Comparative efficacy of immune checkpoint inhibitors versus chemotherapy alone in diffuse pleural mesothelioma.

This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real-world diffuse pleural mesothelioma patients in China. Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs-treated group (n = 46) and the chemotherapy-only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. The median progression-free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs-treated group and the chemotherapy group, respectively. The ICIs-treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan-Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38-0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26-0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first- and second-/third-line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

Final analysis of the randomized phase 3 ESCORT-1st trial: Camrelizumab plus chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma.

4055 Background: The ESCORT-1st trial (NCT03691090) was a randomized, double-blind, placebo-controlled, phase 3 trial that aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy compared to placebo plus chemotherapy in previously untreated patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). Interim analysis of this trial showed significantly longer overall survival (OS) and progression-free survival (PFS) with camrelizumab plus chemotherapy compared to placebo plus chemotherapy (Luo et al., JAMA, 2021). In this report, we present the final analysis of the efficacy and safety outcomes from the ESCORT-1st study, with an additional 1.5-year follow-up. Methods: A total of 596 eligible patients with previously untreated advanced or metastatic ESCC were randomly assigned in a 1:1 ratio to receive either camrelizumab 200 mg or placebo for up to 2 years, in combination with up to 6 cycles of paclitaxel and cisplatin. All treatments were administered intravenously every 3 weeks. Randomization was stratified based on the presence of liver metastases and previous definitive chemoradiotherapy. The primary endpoints of the study were OS and PFS as assessed by an independent review committee. The data cutoff for this final analysis was April 30, 2022. Results: At the data cutoff, the minimum follow-up period was 24 months, and no patients remained on the study treatment. Among the patients, 214 (71.8%) in the camrelizumab plus chemotherapy group and 250 (83.9%) in the placebo plus chemotherapy group had died. The camrelizumab plus chemotherapy group demonstrated a longer median OS compared to the placebo plus chemotherapy group (15.6 months [95% CI 14.0–18.4] vs 12.6 months [95% CI 11.2–13.8], HR 0.70 [95% CI 0.58–0.84]; one-sided P&lt;0.0001). The 1-year, 2-year, and 3-year OS rates were 62.4% vs 51.7%, 35.9% vs 23.8%, and 25.6% vs 12.8% in the camrelizumab plus chemotherapy group and the placebo plus chemotherapy group, respectively. The median investigator-assessed PFS was also longer with camrelizumab plus chemotherapy compared to placebo plus chemotherapy (7.6 months [95% CI 6.9–8.3] vs 5.8 months [95% CI 5.6–6.6]; HR 0.54 [95% CI 0.45–0.65]; one-sided P&lt;0.0001). No new safety signals were identified during the extended follow-up period. Conclusions: The extended follow-up of the ESCORT-1st trial reaffirms that camrelizumab plus chemotherapy provides significant and clinically meaningful improvements in OS and PFS compared to placebo plus chemotherapy, with a manageable safety profile for patients with untreated advanced or metastatic ESCC. These findings further support the use of first-line camrelizumab plus chemotherapy as the standard of care for these patients. Clinical trial information: NCT03691090 .

Immunotherapy-based therapy versus chemotherapy for the neoadjuvant treatment of locally advanced dMMR/MSI-H gastric cancer.

e16121 Background: Growing evidences have suggested that immunotherapy represents a promising treatment for the neoadjuvant treatment of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer. The study aimed to compare the efficacy of neoadjuvant chemotherapy and immune checkpoint inhibitor (ICI)-based therapy in locally advanced, dMMR/MSI-H gastric cancer. Methods: Patients with MSI-H/dMMR locally advanced gastric cancer who received neoadjuvant chemotherapy, or ICI-based therapy between December 2018 and June 2023 at West China Hospital, Sichuan University were included. Patient data were collected from the prospectively database program of gastric cancer at our Hospital. Demographic and clinicopathologic data of patients were collected, including age, sex, ECOG performance status, primary tumor site, tumor staging, Lauren’s classification, tumor response, tumor regression grade (TRG), R0 resection, disease-free survival (DFS) and overall survival (OS). Results: A total of 21 patients treated with ICIs-based regimens and 18 patients treated with chemotherapy were included. In the ICI-based therapy group, 10 patients (47.6%) received dual PD-1 and CTLA-4 blockade, 1 patient (4.8%) received PD-1 blockade, and 10 patients (47.6%) received PD-1 blockade combined with chemotherapy. The median age of chemotherapy group and ICI-based group were 63 years (range, 36-76 years) and 59 years (range, 34-74 years), respectively. The rates of T4b and limited metastases were significantly higher in the ICI-based therapy group compared to chemotherapy group (T4b: 11.1% vs. 23.8%; limited metastases: 0% vs. 19.0%). 17 patients (94.4%) in the chemotherapy group and 20 patients (95.2%) in the ICI-based therapy group underwent R0 radical gastrectomy. One patient in the chemotherapy group did not undergo surgery due to disease progression. One patient in the ICI-based therapy group refused radical gastrectomy. For patients undergoing surgery, TRG 0-1 rate was obviously lower in patients receiving chemotherapy compared to those treated with ICI-based regimen (0.0% vs. 78.9%). The pCR rates in the chemotherapy group and ICI-based group were 0.0% and 57.9%, respectively. The pCR rates in patients treated with dual PD-1/CTLA-4 blockade and PD-1 blockade with chemotherapy were 66.6% and 50.0% (P = 0.65). Median DFS and OS have not yet been achieved due to the short follow-up time. Conclusions: Improvements in TRG 0-1 rate and pCR rate suggested that ICI-based treatments are favorable in the neoadjuvant setting of locally advanced, dMMR/MSI-H gastric cancer compared to chemotherapy. However, within the overall favorable group, there was no differences between dual PD-1/CTLA-4 blockade and PD-1 blockade with chemotherapy in term of pCR rate. Whether high pCR rates can translate into long-term survival benefits requires longer follow-up time.

Efficacy and safety of the vebreltinib in patients with previously treated, secondary glioblastoma/IDH mutant glioblastoma with PTPRZ1-METFUsion GENe (FUGEN): A randomised, multicentre, open-label, phase II/III trial.

2003 Background: Although gliomas with mutated IDH have an improved prognosis compared to gliomas with wild-type IDH, IDH-mutant gliomas carry a high risk of malignant transformation from low-grade gliomas into high-grade gliomas within 10 years, resulting in poor prognosis. However, effective targeted drugs for high-grade gliomas are still lacking. Here, we report data from the FUGEN study of Vebreltinib, the first completed phase II/III trial of sGBM / IDH mutant glioblastoma patients with previously treated, PTPRZ1-MET Fusion gene positive. Methods: In this open-label, phase II/III trial, we randomly assigned, in a 1:1 ratio, 84 patients with Histologically confirmed secondary GBM or IDH-mutant GBM to receive twice-daily oral vebreltinib in 300 mg dose or the investigator's choice of chemotherapy (temozolomide [100-150 mg/m2/day, 7days on followed by 7 days off ] or cis-platinum [80-100 mg/m2 for 3 days] combined with etoposide [100mg/m2/day for 3 days]) every 28 days. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). Results: 42 patients of the vebreltinib group and 39 patients of the chemotherapy group were included in the full analysis set. After a median follow-up of 4.44 months, the median OS in the vebreltinib group and chemotherapy group was 6.31 months (95% CI, 4.44-8.77) and 3.38 months (95% CI, 2.37-4.27), respectively. The HR for OS was 0.52 (90% CI, 0.32-0.85; P = 0.009). The median PFS in the vebreltinib group and chemotherapy group was 1.87 months (95% CI, 1.41-2.76) and 1.05 months (95% CI, 0.95-1.77), respectively. The HR for PFS was 0.54 (95% CI, 0.33-0.88; P = 0.014). No significant differences were observed in ORR (9.5% vs. 2.6%) for the vebreltinib group and chemotherapy group. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the vebreltinib group, as compared with 12.2% of those in the chemotherapy group. No treatment-related deaths were observed. Conclusions: These results of the FUGEN trail support the use of vebreltinib as the first target therapy in patients with previously treated, PTPRZ1-MET fusion gene positive, secondary glioblastoma / IDH-mutant glioblastoma, and shed light on a novel therapeutic pathway in the landscape of IDH-mutant high-grade gliomas. Clinical Trials Information: NCT06105619 and ChiCTR2300077783 Research Funding:Beijing Pearl Biotechnology Co., Ltd. and Avistone Biotechnology Limited. Clinical trial information: NCT06105619 .

Effect of endoscopic surgery combined with chemotherapy and radiotherapy on prognosis of early nasopharyngeal carcinoma patients in high incidence area

Objective:To investigate the differences in the therapeutic effects of endoscopic surgery combined with chemotherapy and endoscopic surgery combined with radiotherapy in the treatment of early nasopharyngeal carcinoma, and to select individualized treatment strategy for early nasopharyngeal carcinoma. Methods:The clinical data of 68 patients with early nasopharyngeal carcinoma（T1-2N₀M₀） who received surgical treatment in a high-incidence area were retrospectively analyzed. According to different treatment methods, they were divided into the surgery + chemotherapy group（n=34, treated with endoscopic surgery combined with chemotherapy） and the surgery + radiotherapy group（n=34, treated with endoscopic surgery combined with radiotherapy）. Propensity score matching was used to match the patient data between the two groups at a 1∶1 ratio. Patients were followed up, and the survival rates and hematological toxicities were compared between the two groups. Results:Twenty-four cases in the surgery + chemotherapy group and 24 cases in the surgery + radiotherapy group were successfully matched. After matching, there was no statistically significant difference in T stage, and clinical stage between the two groups（all P>0.05）. The 3-year OS and DFS in the surgery + chemotherapy group were 100.0% and 95.8%, respectively, while the 3-year OS and DFS in the surgery + radiotherapy group were 100.0% and 100.0%, respectively, with no significant difference in survival rates between the two groups（both P>0.05）. After treatment, there was no statistically significant difference in bone marrow suppression between the surgery + chemotherapy group and the surgery + radiotherapy group （all P> 0.05） Conclusion:Endoscopic surgery combined with chemotherapy and surgery combined with radiotherapy have comparable clinical efficacy in the treatment of early nasopharyngeal carcinoma, but without radiotherapy-related complications, which is worth further investigation.

CT-guided Percutaneous Microwave Ablation Combined with Local Radiotherapy or Chemotherapy of Malignant Pulmonary Tumors.

The study aimed to investigate the clinical efficacy of CT-guided microwave ablation (MWA) combined with 125I seed implantation or bronchial arterial infusion (BAI) chemotherapy in the treatment of malignant pulmonary tumors. A total of 56 patients who underwent MWA, MWA combined with 125I particle implantation, or MWA combined with BAI chemotherapy for advanced lung cancer or metastatic lung cancer from January 2015 to June 2021 in Guangdong Provincial People's Hospital were enrolled. Among them, 21 patients were treated with MWA (MWA), 18 with MWA combined with 125I seed implantation (MWA+125I), and 17 with MWA combined with BAI chemotherapy (MWA+BAI). The short-term outcomes, complications, Eastern Cooperative Oncology Group (ECOG) performance score (Zubrod-ECOG-WHO, ZPS), survival, and factors related to survival were compared between the three groups. The response rate of the MWA group (9.52%) was significantly lower than that of the MWA+125I group (50.00%) and MWA+BAI chemotherapy group (47.06%), and the differences were statistically significant (p < 0.05). The incidence of complications in the MWA, MWA+125I, and MWA+BAI chemotherapy groups was 47.62%, 55.56%, and 52.94%, respectively, with no significant difference (p > 0.05). Three months after the treatment, the ZPS of the MWA+125I and MWA+BAI chemotherapy groups was significantly lower than before treatment and significantly lower than that of the MWA group in the same period; the differences were statistically significant (p < 0.05). The median survival time of the MWA+125I group was 18 (9.983, 26.017) months and that of the MWA+BAI chemotherapy group was 21 (0.465, 41.535) months, both of which were higher than that of the MWA group [11 (6.686, 15.314) months]; the differences were statistically significant (p < 0.05). Cox regression analysis was performed on the factors related to survival and revealed treatment mode as a protective factor [HR = 0.433, 95% CI = (0.191, 0.984), p = 0.046]. Other factors, such as gender, age, and tumor size, did not independently affect survival. CT-guided MWA combined with 125I seed implantation and MWA combined with BAI chemotherapy are safe and effective for the treatment of advanced lung cancer and metastatic lung cancer, and can control tumor progression and prolong survival time.

Benefit of perioperative chemotherapy in the patients with loco-regional recurrence of HR-positive HER2-negative breast cancer: A multi-institutional retrospective cohort study.

526 Background: Loco-regional recurrence (LRR) in breast cancer (BC) is addressed with multimodal treatment, yet the prognosis remains unfavorable. The benefit of adjuvant chemotherapy for the hormone receptor-positive, HER2-negative (HR+HER2-) subtype of BC is controversial. Methods: We performed a multi-institutional retrospective cohort study under the Japan Clinical Oncology Group. This study focused on patients without distant metastasis who developed HR+HER2- ipsilateral breast tumor recurrence (IBTR) or other LRR (oLRR) including recurrence in skin, chest wall, or regional lymph nodes. The patients received curative surgery for LRR between 2014 and 2018. Patients were divided into two groups: the chemotherapy group and no chemotherapy group before/after LRR. We performed a Cox proportional hazards model to evaluate invasive disease-free survival (iDFS) between the two groups. Sensitivity analysis was conducted using propensity score (PS) matching and IPTW. Results: A total of 967 patients were registered from 41 institutions, and 958 patients concordant with inclusion criteria were analyzed. There were 509 patients (53%) of only IBTR and 449 patients (47%) of oLRR. Neoadjuvant/Adjuvant chemotherapy was administered to 235 patients (25%), while 722 (75%) did not receive it. Compared to the no-chemotherapy group, the chemotherapy group included a higher number of patients aged 41-60, oLRR, and recurrences during adjuvant endocrine therapy. At a median follow-up of 5.2 years (Interquartile range: 4.1-6.5), the 5-year iDFS rate was 75.4% (95% CI: 72.4-78.2). Multivariate analysis showed an improvement in iDFS for the chemotherapy group (HR: 0.70, 95% CI: 0.49-0.99, p = 0.045). Sensitivity analysis also consistently suggested the effectiveness of chemotherapy (PS matching HR 0.76, IPTW HR 0.75). In the subgroup analysis, the chemotherapy group showed more significant iDFS improvement in cases with oLRR, recurrences during adjuvant endocrine therapy for primary BC, and those without perioperative chemotherapy for primary BC. Conclusions: Our study showed improvement in iDFS in patients who received perioperative chemotherapy for HR+HER2- LRR. This improvement was particularly notable in patients with oLRR, recurrences during adjuvant endocrine therapy, and those without perioperative chemotherapy for primary BC. [Table: see text]

Efficacy and safety of immunotherapy in patients with liver metastases in patients with esophageal cancer: A retrospective, real-world study.

e16033 Background: Advanced or metastatic esophageal cancer patients tend to have a poor prognosis. The liver is the most common organ of distant metastasis in esophageal cancer. The liver metastases associated with a higher risk of survival. Developing the optimal treatment modalities is especially important for those patients. The efficacy of programmed cell death protein 1 (PD-1) or its ligand (PD-L1) inhibitors have not been clearly clarified in liver metastasis of esophageal cancer. Methods: This is a single-center, retrospective, real-world study. We collected general information and clinical data from patients with liver metastasis of esophageal cancer who admitted to Luoyang Central Hospital between April 2020 and October 2023. All patients were first diagnosed esophageal cancer with liver metastasis and received PD-1 or PD-L1 inhibitor regimen or chemotherapy regimen for the first time. Patients treated with interventional therapy or who had received PD-1 or PD-L1 inhibitors were excluded. The efficacy and safety of patients receiving immunotherapy were evaluated, including overall survival (OS), objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), grade 3-5 treatment-related adverse events (TRAE), and immune-related adverse events (irAE). We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses. Results: We enrolled 61 patients with a median age of 61 (44-88) years, 63.9% males; 37 in the immunotherapy group (23 in the first-line group, 62.2%) and 24 in the chemotherapy group (19 in the first-line group, 79.2%). Median OS was 14.1 (95% CI 11.4-16.8) months in the immunotherapy group and 9.2 (95% CI 8.5-9.9, p &lt; 0.01) months in the chemotherapy group; In first-line treatment, the median OS in the two groups was 19.4 (95%CI 15.0-22.2) months and 9.6 (95%CI 8.9-10.3, p &lt; 0.01) months. In all patients, Median PFS was 7.2 (95% CI 6.4 – 8.0) months in the immunotherapy group and 4.6 (95% CI 3.8 – 5.4) months in the chemotherapy group, p = 0.174. The ORR of immunotherapy and chemotherapy was 56.8% and 33.3%; DCR was 78.4% and 62.5%. Univariate and multivariate analysis showed that N stage and treatment regimen were significant factors related with OS. Grade 3 TRAE in immunotherapy group and chemotherapy group were 29.7% and 29.2%, respectively. The incidence of irAEs was 10.8%. No treatment-related deaths occurred. Conclusions: This real-world data showed PD-1 or PD-L1 inhibitors might have good efficacy and manageable safety in EC patients with liver metastases, especially in first-line patients. [Table: see text]

The results of adding immunotherapy to chemotherapy in patients with small cell lung cancer: Registurk-Lung study—Real-world data.

e20006 Background: Evaluation of real-world data together with data in clinical studies is very important in the evaluation of treatment algorithms. In real life, treatments are applied to the elderly, patients with poor performance and unusual groups with comorbidities. Determining these treatment results is important in the creation of treatment algorithms. The studies on the addition of immunotherapeutic agents to the standard chemotherapy regimen in patients with small cell lung cancer have found a significant survival advantage. In this study, we evaluated the real-life reflections of the results of these clinical trials. Methods: In our country, within the scope of the Registurk-Lung observational study (NCT05254119), a total of 1008 patients with extensive stage small cell lung cancer were evaluated between December 2021 and December 2023 in 42 centers representing the whole country. The demographic, histopathological, molecular and clinical data of the patients were recorded. The relationship between progression-free survival (PFS) time and overall survival (OS) time with these characteristics was investigated. Results: The median age was 64 (31-88) years and 17.6% of the patients were female. The proportion of patients who never smoked was only 4.7 %. Histopathologically, 36.4% of the patients were diagnosed with squamous cell carcinoma. At the time of diagnosis, brain metastases were present in 13.9 % of the patients and liver metastases were present in 12.1% of the patients. Only 19.4 percent of patients received chemoimmunotherapy. Eighty-three percent of the patients received atezolizumab as immunotherapy in combination with chemotherapy and as maintenance treatment. The other patients received durvalumab and pembrolizumab.Patients who did not receive immunotherapy received platinum plus etoposide chemotherapy regimen as a medyan 4 cycle. The overall response rate was 49.0 % in the chemotherapy group and 52.8 % in the combination group. The PFS was 7.6 (95% CI: 6.9-8.3) months in chemoimmunotherapy group and 7.3 (95% CI: 6.5-8.1) months in chemotherapy group. Also, the OS was 15.5 months (95% CI: 11.1-19.9) in chemoimmunotherapy group and 11.8 (95% CI: 10.5-13.2) months in chemotherapy group. When the two groups were compared, there was a positive trend in terms of PFS in the immunochemotherapy group, but this difference was not statistically significant (p:0,802). In terms of overall survival, there was a statistically significant improvement in the chemoimmunotherapy group (p:0,049). Conclusions: The addition of immunotherapy to the treatment of patients with small cell lung cancer, which we have been treating with dual combination chemotherapy for many years, has provided a survival benefit. This situation brings with it new hopes for future studies.

Outcomes of patients with peritoneal carcinomatosis treated with HIPEC and chemotherapy or HIPEC alone: A single center community experience.

e15578 Background: Peritoneal carcinomatosis is a common presentation of intraperitoneal malignancies. The optimal management of peritoneal carcinomatosis is currently unknown but can contain a combination of HIPEC and chemotherapy. Optimal timing and order of these interventions is controversial. HIPEC surgery alone can provide a cure rate of approximately 16% with macroscopically complete resection. The PRODIGE 7 trial demonstrated no difference in overall survival between HIPEC plus cytoreduction versus cytoreduction alone with six months of systemic chemotherapy. Which patients should receive HIPEC, chemotherapy and HIPEC or chemotherapy alone remains unknown. Methods: This is a single center, retrospective chart review assessing all patients age 18 and above who received HIPEC surgery with and without the administration of chemotherapy at Ascension Saint John Hospital. Results: We found that there was no significant difference in overall survival and progression free survival between the HIPEC and HIPEC with chemotherapy group with a OS of 57.2 months and 52.5 months; and PFS of 33.6 and 34.4 months respectively. We found that patients with a PCI score between 0 and 13, overall survival favored the HIPEC alone group versus the HIPEC with chemotherapy with a p value of 0.043. There was no difference in progression free survival and overall survival in all other groups when stratified by PCI. When stratified by disease subtype, we no differences between PFS and OS for both appendiceal and colon cancer. Conclusions: The primary objective of this study was to investigate the difference in overall survival and progression free survival among patients with peritoneal carcinomatosis when treated with either HIPEC with systemic chemotherapy versus HIPEC alone. This analysis among 100 patients showed no statistically significant differences in OS or PFS for patients receiving a combination of HIPEC with systemic chemotherapy versus HIPEC alone. The only exception to this was with respect to OS in patients with a PCI score between 0-13. In this group, 0 patients in the HIPEC along group experienced disease progression where 5 progressed in the HIPEC and chemotherapy group. Our data suggests that HIPEC alone may be a reasonable treatment approach for patients with a low PCI score. Important conclusions can be drawn from the data when compared to historical trials. The PROTEGE 7 study found that the median overall survival was approximately 41.7 months for the HIPEC and cytoreductive surgery group and 41.2 months versus cytoreductive surgery alone. The overall survival for the HIPEC alone group was 57.2 months and 52.5 months for the HIPEC plus chemotherapy group. This data suggests that the combination of HIPEC and chemotherapy is a reasonable approach to patients with peritoneal carcinomatosis.