Subgroup Analysis For Overall Survival Research Articles

Oncological long-term outcomes of laparoscopic versus open gastrectomy for cT3-4 gastric cancer at surgical staging: a propensity-score matched cohort study.

The oncological efficacy of laparoscopic surgery for advanced gastric cancer (AGC) has been evaluated by several randomized trials. However, the inclusion of earlier-stage disease was a limitation in previous studies. Patients with cT3-4 gastric cancer, determined by surgical staging to minimize migration of earlier stages, treated at a tertiary cancer center from 2009 to 2018 were included. Based on the surgical approach, the patients were divided into two groups: the laparoscopic gastrectomy (LG) and the open gastrectomy (OG) and matched for age, sex, macroscopic appearance (type 4 or non-type 4), body mass index, estimated tumor size, clinical stage T3'T4, clinical N stage, pathologic T stage (T3 or T4), and type of surgery (total or distal gastrectomy). 588 patients (221 LG, 367 OG) were included in the analysis. After 1:1 propensity-score matching, 386 patients (193 LG, 193 OG) were assigned for analysis. In the LG group, operation time was longer with lower blood loss. The incidence of postoperative complications (≥ grade III) did not differ significantly between the groups (OG: 8.3%, vs. LG: 9.3%). Overall survival (OS) was longer in the LG group (5-year OS: 79.3 vs. 73% HR 0.66, 95% CI 0.44-0.99, P = 0.0497). Relapse-free survival (RFS) did not show a statistical difference (5-year RFS: 69.5 vs. 68.7 HR 0.88, 95% CI 0.62-1.26, P = 0.487). Subgroup analysis for OS also demonstrated equivalent outcomes. LG demonstrates comparable safety and efficacy to OG for advanced gastric cancer at surgical staging, with similar rates of severe complications and long-term oncological outcomes. Further research is needed to validate these findings, particularly for total gastrectomy and for patients from Western populations.

Nanoliposomal irinotecan with fluorouracil and folinic acid, FOLFIRINOX, and S-1 as second-line treatment for unresectable pancreatic cancer after gemcitabine/nab-paclitaxel

This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab–paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.

The subgroup analysis by age and geriatric assessment in a phase III study comparison of trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in older patients with advanced stage HER2-positive breast cancer (JCOG1607 HERB TEA study).

1031 Background: The JCOG1607, HERB TEA Study, is a phase III trial that compared trastuzumab emtansine (T-DM1) with the HPD regimen (trastuzumab, pertuzumab, docetaxel) in older patients with advanced HER2-positive breast cancer. The primary objective was to confirm the non-inferiority of T-DM1 to HPD in overall survival (OS), with a margin of 1.35 for hazard ratio (HR). The trial was terminated early due to futility at the planned first interim analysis. T-DM1 didn't show non-inferiority to HPD in OS (HR 1.263; 95% confidence interval [CI], 0.677-2.357). Median progression-free survival (PFS) was 11.3 months for T-DM1 and 15.6 months for HPD (HR 1.373; 95% CI, 0.917-2.056). However, the condition of older patients varies widely, and we conducted a subgroup analysis to investigate the subgroup that could benefit from T-DM1 with fewer side effects as a first-line treatment. Methods: Subgroup analysis for OS and PFS involved 148 patients enrolled in JCOG1607, considering age and PS (&lt;75 years old and PS 0,1 or &lt;75 years old and PS 2 or ≥75 years old), Geriatric 8 (G8) score (≥15 or &lt;15), Instrumental Activity of Daily Living (IADL) score (8 or &lt;8), visceral/brain metastasis presence (with or without), and other factors. Results: Subgroup of &lt;75 and PS 2 was not evaluable. For OS, HR of T-DM1 arm to HPD arm was 0.749 (95% CI: 0.310-1.808) in the group aged &lt;75 years, while 2.867 (95%CI: 1.018-8.069) in the group aged ≥75 years (Table). G8 score and the IADL score did not show significant differences in HR for OS, although low G8 score group and low IADL score group tended to have higher OS in HPD arm than T-DM1 arm: HR of T-DM1 arm to HPD arm of 1.541 (95% CI: 0.755-3.142) in low G8 score group and 2.147 (95% CI: 0.656-7.025) in low IADL score group. For PFS, patients with visceral/brain metastasis had HR of T-DM1 arm to HPD arm of 1.794 (95% CI: 1.092-2.948). No other subgroup showed a significant difference in HR for PFS. Conclusions: No subgroups benefiting from T-DM1 as first-line treatment were identified. HPD remains the standard for advanced HER2-positive breast cancer, regardless of age (even in ≥75 years) G8 score, or IADL. Clinical trial information: UMIN000030783. [Table: see text]

Percutaneous cryoablation of breast cancer metastases: Analysis of long-term single center experience, efficacy and outcomes.

e13105 Background: Percutaneous image-guided cryoablation is a minimally invasive loco-regional treatment modality with wide availability and advantages of minimal sedation, short recovery, and ability to continue concurrent systemic therapy. However, there is a paucity of data about its long-term effects in the treatment of metastatic breast cancer despite evidence suggesting a potential survival advantage with loco-regional therapy for oligo-metastatic disease. Methods: We conducted retrospective analysis of patients who underwent CT-guided percutaneous cryoablation for metastatic breast cancer and had at least 1 follow up post cryoablation. Patient data including demographics, cancer treatment history and outcomes were extracted by chart review after IRB approval. Descriptive analyses of overall survival (OS), progression-free survival (PFS), and time to next-line treatment (TTNL) was performed. Results: The study encompassed 37 metastatic breast cancer patients who underwent cryotherapy between 2004-2021. These ablation procedures targeted various metastatic sites, which included the liver, lung, renal, lymph nodes, subcutaneous nodules, and bone. Their median age at the time of cryoablation was 58 years (range: 34-90). Among them, 46% had triple-negative breast cancer (TNBC), 41% were HR+/HER2-, and 8% were HER2+. Prior to first cryoablation procedure, 59% of patients had received more than one line of systemic therapy, and 73% were actively undergoing systemic treatment. The median size of the metastatic lesions treated with cryoablation was 1.8 cm (range: 0.4-6.5 cm). The most frequent site for cryotherapy was the liver (38%), followed by lymph nodes (30%). For the entire cohort, median PFS, TTNL, and OS were 7.1, 14, and 65.7 months, respectively. Subgroup analysis revealed mPFS of 3.1, 7.4 and 14.2 months for TNBC, Her2+ and HR+/Her2- cohorts respectively. Subgroup analysis for OS was not reported due to the small number of events and premature follow up time. Among the 27 patients who experienced disease progression, the majority (74%) had distant progression, with 22% occurring within the same organ but outside the ablation zone. Local recurrence within the ablation zone was rare, observed in only 4% of cases. Conclusions: Percutaneous image-guided cryoablation of metastatic breast cancer lesions demonstrated durable local response, prolonged PFS, TTNL and OS. Future studies investigating cryoablation as part of a multidisciplinary treatment approach for patients with metastatic breast cancer are worthwhile to confirm disease control rate and improvement in survival.

Prognostic Value of the Gustave Roussy Immune Score in Lung Cancer: A Meta-Analysis

Purpose To clarify the prognostic role of the Gustave Roussy immune (GRIm) score in lung cancer. Methods The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched up to March 30, 2024. The primary outcomes included overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the associations between the GRIm score and survival, and subgroup analyses were performed based on pathological type (non-small cell lung cancer vs. small cell lung cancer), tumor stage (advanced vs. limited stage) and treatment approach (immune checkpoint inhibitor vs. surgery vs. chemotherapy). Results Eight studies with 1,333 participants were included. The pooled results showed that a higher GRIm score predicted worse OS (HR = 1.96, 95% CI: 1.54–2.49, P < 0.001) and PFS (HR = 1.64, 95% CI: 1.22–2.21, P = 0.001). Subgroup analyses for OS and PFS showed similar results. However, subgroup analyses for PFS indicated that the association between the GRIm score and PFS was nonsignificant among patients with small cell lung cancer (P = 0.114) and among patients treated with chemotherapy (P = 0.276). Conclusion The GRIm score might serve as a novel prognostic factor for lung cancer. Additional studies are still needed to verify these findings.

Comparative efficacy of immune checkpoint inhibitors combined with chemotherapy in patients with advanced driver-gene negative non-small cell lung cancer: A systematic review and network meta-analysis

ObjectiveTo evaluate the efficacy of different combinations of immune checkpoint inhibitors (ICIs) and chemotherapy (CT) in the treatment of advanced non-small cell lung cancer (NSCLC). MethodsWe obtained relevant randomized controlled trials (RCTs) from databases such as PubMed, Embase, Web of Science, and The Cochrane Library up to May 31, 2023. The analysis of clinical prognostic factors was performed using R 4.2.3 and STATA 15.0. The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events of grade 3–5 severity (Grade ≥3 TRAE). ResultsA total of 17 randomized controlled trials (RCTs) were conducted between 2012 and 2023, involving 7792 patients. These trials evaluated 11 different treatment methods. The results of these trials showed that in terms of overall survival (OS) and progression-free survival (PFS), the combination of tislelizumab with chemotherapy and the combination of camrelizumab with chemotherapy were particularly effective. Moreover, when compared with other combination therapies, pembrolizumab combined with chemotherapy showed superiority in terms of disease control rate (DCR) and objective response rate (ORR). Subgroup analyses further demonstrated that the addition of immune checkpoint inhibitors (ICIs) to chemotherapy significantly improved PFS and OS in patients without liver metastasis and in those with brain metastasis. Additionally, carboplatin-based combination therapy was found to confer favorable survival benefits in terms of PFS, while cisplatin-based combination therapy showed the most favorable outcomes in terms of OS. The results of subgroup analyses for overall survival (OS) showed that the combination of immunotherapy and chemotherapy yielded positive outcomes in specific subgroups. These subgroups were characterized by PD-L1 Tumor Proportion Score (TPS) of 50 % or higher, usage of anti-PD-1 medications, age below 65, male gender, smoking history, and non-squamous cell carcinoma histology. Superior effectiveness was demonstrated only in extending the progression-free survival (PFS) of female patients and patients with squamous carcinoma. Meanwhile, other patient cohorts did not show the same level of improvement. ConclusionsTislelizumab, camrelizumab or pembrolizumab combined with chemotherapy may be the optimal first-line treatment strategies for NSCLC.

Optimal surgical management of unifocal vs. multifocal NF-PNETs: a respective cohort study

BackgroundPancreatic neuroendocrine tumors (PNETs) represent 1–2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched.MethodsThis retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test.ResultsOf 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence.ConclusionThis study’s findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious “wait-and-see” approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance.

Efficacy of S-1 Adjuvant Chemotherapy for Resected Biliary Tract Cancer: A Retrospective Propensity-Matched Analysis.

Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P = .04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR: .57, 95% CI: .33-.97, P = .03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection.

Association between preoperative neutrophil-to-lymphocyte ratio and the survival outcomes of esophageal cancer patients underwent esophagectomy: a systematic review and meta-analysis.

The purpose of this study was to assess the association between preoperative neutrophil-to-lymphocyte ratio (NLR) and the survival outcomes of esophageal cancer patients who underwent esophagectomy, the latest and comprehensive systematic review performed. Related literature retrieved from PubMed, Web of Science, Embase, and Cochrane before January 2024, according to the inclusion criteria. Outcomes measured were overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and cancer-specific survival (CSS). Eighteen studies with 6,119 esophageal cancer patients were retained for analysis. Meta-analysis demonstrated that OS (HR: 1.47; 95% CI: 1.29, 1.67; P < 0.00001), DFS (HR: 1.62; 95% CI: 1.29, 2.05; P < 0.0001), and CSS (HR: 1.62; 95% CI: 1.29, 2.05; P < 0.0001) were significantly shorter in the high NLR group compared with the low NLR group. In addition, meta-analysis revealed a similar RFS (HR: 1.47; 95% CI: 0.92, 2.35; P = 0.10) among the two groups. Subgroup analysis of OS and DFS based on mean/median age, NLR cutoff, and region found that all subgroups remained significant difference between two groups. Among esophageal cancer patients who underwent esophagectomy, preoperative NLR can be used as prognostic factor independently. High-preoperative NLR is associated with poor prognosis. More large-scale, multicenter prospective clinical studies are needed to further validate the relationship between preoperative NLR and prognosis of esophageal cancer.

The prognostic role of lymphocyte-to-monocyte ratio in patients with resectable pancreatic cancer: a systematic review and meta-analysis.

This systematic review and meta-analysis examined whether the lymphocyte-to-monocyte ratio (LMR) can serve as an indicator for predicting the prognosis of patients with resectable pancreatic cancer. This meta-analysis was registered with PROSPERO: CRD42023461260. A systematic literature search was conducted in the PubMed, Embase, Cochrane, and Web of Science databases up to September 2023 to assess whether LMR can predict the prognosis of patients with resectable pancreatic cancer. The outcomes measured included subgroup analyses of overall survival (OS) with hazard ratios (HR) and confidence intervals of geographical region, patient population, and LMR threshold. A sensitivity analysis was also performed for OS and HR and confidence intervals were calculated for recurrence-free survival (RFS). A total of 14 eligible articles, comprising 4,019 patients, were included in the comprehensive analysis. The results of this comprehensive analysis indicate that LMR is a robust predictor of OS, demonstrating strong prognostic significance (HR = 0.55, 95% CI [0.44-0.69], I2 = 79%, P < 0.00001). This predictive significance extended to various types of pancreatic cancer, such as pancreatic ductal adenocarcinoma (HR = 0.73, 95% CI [0.57-0.93], I2 = 46%, P = 0.01), pancreatic neuroendocrine neoplasms (HR = 0.81, 95% CI [0.66-0.99], P = 0.04) and other subtypes (HR = 0.40, 95% CI [0.22-0.72], I2 = 89%, P < 0.00001), but not to pancreatic head cancer (HR = 0.46, 95% CI [0.16-1.13], I2 = 59%, P = 0.12). LMR retained its predictive value across different regions, including Asia (HR = 0.62, 95% CI [0.47-0.76], I2 = 68%, P < 0.0001), Europe (HR = 0.78, 95% CI [0.67-0.91], I2 = 0%, P = 0.002), and the Americas (HR = 0.14, 95% CI [0.08-0.24], I2 = 0%, P < 0.00001). Notably, both LMR cut-off values greater than or equal to three (HR = 0.62, 95% CI [0.47-0.82], I2 = 67%, P = 0.0009) and less than three (HR = 0.47, 95% CI [0.32-0.69], I2 = 85%, P = 0.0001) exhibited prognostic significance. The sensitivity analysis for OS confirmed the strong predictive value of LMR, whereas LMR did not exhibit predictive significance for RFS (HR = 0.35, 95% CI [0.09-1.32], I2 = 95%, P = 0.12). In both subgroups categorized by Newcastle-Ottawa Scale (NOS) scores of ≥7 (HR = 0.66, 95% CI [0.54-0.80], I2 = 53%, P = 0.04) and <7 (HR = 0.41, CI [0.23-0.72], I2 = 89%, P < 0.00001), LMR was demonstrated to have predictive value. Despite the observed heterogeneity and potential biases in the included studies, the findings of this study suggest that LMR may serve as a valuable predictor of OS in patients with resectable pancreatic cancer.

Improved Survival with Venetoclax in Patients with Acute Myeloid Leukemia: A Retrospective Single-Center Cohort Study

Background: Venetoclax in combination with azacitidine or low-dose cytarabine has become standard treatment for newly diagnosed elderly or unfit patients with acute myeloid leukemia (AML). Since approval of venetoclax in 2020 in Japan, venetoclax combination therapy have been also used for relapsed or refractory patients although its role in relapsed or refractory disease is not well defined. The survival impact of chemotherapy with venetoclax combination therapy compared with that without venetoclax combination therapy on AML patients in a real-life setting is scarcely reported. Objective: The aim of this retrospective study was to evaluate chemotherapy with or without venetoclax combination therapy in patients with newly diagnosed AML in our institution. Patients and Methods: This study included 234 non-M3 newly diagnosed AML patients who were treated with or without venetoclax combination therapy between February 2008 and July 2023 in our hospital. We evaluated overall survival and composite complete remission (complete remission or complete remission with incomplete hematologic recovery). Overall survival was compared with the use of a cox proportional-hazards regression model adjusted for age (1-year increase) and cytogenetic risk (favorable or intermediate vs. adverse). Composite complete remission was compared between the treatment groups with the use of a logistic regression model adjusted for the same prognostic factors. Subgroup analyses of overall survival was performed according to variables based on disease characteristics at baseline to assess whether the beneficial effect of venetoclax combination therapy varied among specific patient subgroups. Results: We identified 41 patients who were treated with venetoclax as first-line or later treatment and 193 patients who were treated without venetoclax. In the venetoclax group, 26 (63.4%) received venetoclax combination therapy as first-line and 15 (36.6%) as second- or later-line treatement. Twenty (48.8%) were treated with venetoclax combined with azacitidine, 12 (29.3%) with low-dose cytarabine and 9 (22.0%) with both in their course of treatment. Patients in the venetoclax group was older than those in the non-venetoclax group (median age, 76 years vs. 67 years, respectively; P&amp;lt;0.001). FLT3, NPM1, TP53 and IDH1/2 mutational status was comparable between groups. The percentage of patients classified as poor cytogenetic risk category according to the NCCN guidelines for AML, 2021 was higher in the venetoclax group than that in the non-venetoclax group (51.2% vs. 28.0%, respectively; P=0.005). The percentage of patients who umderwent allogeneic hematopoietic stem cell transplantation was lower in the venetoclax group than that in the non-venetoclax group (2.4% vs. 16.6%, respectively; P=0.014). Composite complete remission was achieved in 46.3% (95% CI, 30.7 to 62.6) of the patients in the venetoclax group and 54.4% (95% CI, 47.1 to 61.6) of the patients in the non-venetoclax group (P=0.199). In a Cox model adjusting for age and cytogenetic risk, the 1-year overall survival rate was 79.4% (95% confidence interval [CI], 66.5 to 87.8) in the venetoclax group, as compared with 68.0% (95% CI, 59.6 to 75.0) in the non-venetoclax group (adjusted hazard ratio, 0.64; 95% CI, 0.41 to 1.00; P=0.049). Subgroup analysis of overall survival showed a greater survival benefit in the venetoclax group than in the non-venetoclax group in patients who were 70 years of age or older (P=0.003 for interaction) and in patients with de novo AML (P=0.022 for interaction) after adjustment for age and cytogenetic risk. Conclusions: These real-world data suggested that incorporation of venetoclax combination therapy into existing therapies improved survival in patients with AML. The survival benefit of venetoclax combination therapy was greater in elderly patient and in de novo AML patients than secondary AML patients. Interpretation of the results must be careful because the sample size in the venetoclax group was small. To confirm our findings, further investigation in a larger patient population is required.

Effect of different surgical approaches on the survival and safety of Siewert type II esophagogastric junction adenocarcinoma: a systematic review and meta-analysis

BackgroundWhether a transthoracic (TT) procedure by a thoracic surgeon or a transabdominal (TA) by a gastrointestinal surgeon is best for Siewert type II esophagogastric junction adenocarcinoma (EGJA) remains unknown. Survival and perioperative outcomes were compared between the two groups in this meta-analysis to clarify this argument.MethodsWe searched 7 databases for eligible studies comparing TT and TA procedures for Siewert type II EGJA. The final analyzed endpoints included intraoperative and hospitalization outcomes, recurrence, complication, and survival.ResultsSeventeen studies involving 10,756 patients met the inclusion criteria. The TA group had higher rates of overall survival (OS) (HR: 1.31 [1.20 ~ 1.44], p < 0.00001) and disease-free survival (DFS) (HR: 1.49 [1.24 ~ 1.79], p < 0.0001). The survival advantage of OSR and DFSR increased with time. Subgroup analysis of OS and DFS suggested that TA remained the preferred approach among all subgroups. More total/positive lymph nodes were retrieved, and fewer lymph node recurrences were found in the TA group. The analysis of perioperative outcomes revealed that the TA procedure was longer, had more intraoperative blood loss, and prolonged hospital stay. Similar R0 resection rates, as well as total recurrence, local recurrence, liver recurrence, peritoneal recurrence, lung recurrence, anastomosis recurrence and multiple recurrence rates, were found between the two groups. The safety analysis showed that the TT procedure led to more total complications, anastomotic leakages, cases of pneumonia, and cases of pleural effusion.ConclusionsThe TA procedure appeared to be a suitable choice for patients with Siewert type II EGJA because of its association with longer survival, fewer recurrences, and better safety.

First-line treatment options for advanced gastric/gastroesophageal junction cancer patients with PD-L1-positive: a systematic review and meta-analysis.

Literature search through major databases in English and Chinese: PubMed, Embase, Cochrane library, web of Science and CNKI updated on 10 March 2023. Randomized controlled trials were selected to investigate chemotherapy plus programmed death 1 inhibitor versus chemotherapy. A total of 7 randomised controlled trials including 5788 participants were included. The overall survival (hazard ratio=0.79;95% CI: 0.74-0.85, P<0.01), progression-free survival (hazard ratio=0.72; 95% CI: 0.67-0.77, P<0.01) and objective response rate (risk ratio=1.24,95% CI: 1.18-1.31, P<0.05) were longer than chemotherapy alone in the pooled analysis. For subgroup analyses of overall survival, programmed death 1 inhibitors plus chemotherapy had a significant advantage in patients with combined positive score greater than or equal to 5, in Asia, in men and in those younger than 65 years (P<0.01), as were immune-mediated adverse events (odds ratio=8.86;95% CI: 1.26-62.47,P<0.05) and treatment-related grade 3-5 adverse events (odds ratio=1.40,95% CI:1.20-1.62, P<0.01). Programmed death 1 inhibitors plus chemotherapy have significant antitumour activity compared to chemotherapy alone. However, it is riskier in terms of toxicity than chemotherapy. The authors recommend programmed death 1 inhibitors plus chemotherapy as the optimal treatment regimen for patients with positive programmed death ligand 1 expression, in Asia, male and less than 65 years of age. More well-designed studies are needed to investigate the efficacy and safety of different immune plus chemotherapy drug doses and regimens.

Real-world outcomes of patients (pts) with malignant solid tumors treated with immune checkpoint inhibitors (ICI) in relation to smoking status: The SAKK 80/19 SMOKER study.

6619 Background: ICIs are the standard of care for the treatment of different advanced solid organ tumors. Especially in advanced non-small-cell lung cancer, never-smokers were shown to have an inferior outcome when compared to ex-smokers/smokers, suggesting that the smoking status could be a predictive marker for survival benefits under ICI treatment. Methods: Pts within the Swiss Alpine Tumor Immunology Registry (AlpineTIR) treated with an ICI were differentiated by their smoking status (ex-smokers/smokers versus never-smokers). Overall survival (OS) and progression-free survival (PFS) from the start of the first ICI treatment were analyzed by smoking status. Further, subgroup analyses for OS and PFS were done for the most common disease entities. Results: A total of 702 pts were included, from which 455 pts (65%) were ex-smokers/smokers, 213 pts (30%) were never smokers, and 34 pts (5%) had an unknown smoking status. The median follow-up time from the administration of the first ICI to the statistical analysis was 2.7 years (95% CI: 2.3 to 3.2 years). The most frequent tumors were lung cancer (50%), melanoma (13%), renal cell cancer (7%), bladder cancer (6%), and others (24%). Across all indications, the median OS was 1.7 years (95% CI: 1.4 to 2.6 years) for never-smokers (n = 213) and 1.5 years (95% CI: 1.2 to 1.8 years) for smokers (n = 455) (HR: 1.10, 95% CI: 0.89 - 1.37). The median PFS was 6.3 months (95% CI: 4.4 to 8.3 months) for non-smokers and 6.2 months (95% CI: 5.2 to 7.0 months) for smokers (HR: 1.05, 95% CI: 0.87 - 1.27). In lung cancer pts, the median OS was 1.4 years (95% CI: 0.8 to 2.8 years) for never-smokers (n = 43) and 1.4 years (95% CI: 1.2 to 1.7 years) for smokers (n = 302) (HR: 1.02, 95% CI: 0.68 - 1.51). In melanoma pts, the median OS was 3.4 years (95% CI: 1.8 to not reached (NR) years) for never-smokers (n = 54) and 1.7 years (95% CI: 0.8 to NR years) for smokers (n = 34) (HR: 1.35, 95% CI: 0.72 - 2.53). In renal cell cancer pts, the median OS was 1.5 years (95% CI: 1.0 to 3.6 years) for never-smokers (n = 28) and 3.5 years (95% CI: 0.6 to NR years) for smokers (n= 17) (HR: 0.74, 95% CI: 0.31 - 1.78). In bladder cancer pts, the median OS was 1.8 years (95% CI: 0.6 to NR years) for never-smokers (n = 17) and 1.4 years (95% CI: 0.5 to NR years) for smokers (n = 26) (HR: 0.88, 95% CI: 0.39 - 1.99). Conclusions: No survival difference between smokers and non-smokers with metastatic solid organ tumors treated with ICIs could be detected. Interestingly, even in the subgroup of lung cancer pts, no difference was seen. Based on these data, the smoking status should not guide ICI treatment decisions.

The Geriatric Nutritional Risk Index is a prognostic marker in patients with metastatic colorectal cancer.

The Geriatric Nutritional Risk Index (GNRI) is a nutritional index for elderly patients that is associated with prognosis in cancer patients. We investigated using the GNRI in patients with metastatic colorectal cancer to predict prognosis. This study included 419 metastatic colorectal cancer patients who received first-line chemotherapy between February 2005 and December 2020. First, we calculated pre-treatment GNRI and divided the patients into four groups according to the values (G1-G4). We evaluated patient characteristics and overall survival in the four groups. Overall, 419 patients were included. The median follow-up was 34.4months. Lower GNRI was positively associated with a lower grade Eastern Cooperative Oncology Group Performance Status (p = 0.009), synchronous metastases (p < 0.001), primary tumor resection prior to chemotherapy (p = 0.006), and did not undergo resection after chemotherapy (p < 0.001). Patients with low GNRI had significantly shorter overall survival than the group with high GNRI (median OS: G1 = 19.3months [M], G2 = 30.8M, G3 = 38M, G4 = 39.7M; log-rank test, p < 0.001). Multivariate Cox regression analysis showed that GNRI was an independent prognostic factor (G3: HR = 0.49, 95% CI = 0.35-0.69; G4: HR = 0.67, 95% CI = 0.48-0.93). In the subgroup analysis of overall survival, we found no interaction between clinicopathological factors and the prognostic value of GNRI. Interestingly, younger patients (< 70years) but not older patients showed a significant difference in overall survival according to GNRI, despite being the metric being designed for elderly patients. Pretreatment GNRI can be a prognostic marker for patients with mCRC who received systemic chemotherapy.

Subgroup Analysis of Overall Survival among Smoking and Non-Smoking Elderly Patients with HNSCC.

Smoking is a leading cause of head and neck squamous cell carcinoma (HNSCC). However, non-smokers are also affected by HNSCC, and the prognostic factors applicable to older non-smokers with HNSCC are largely unknown. The aim of this study was to determine predictors of overall survival (OS) in patients both with and without a smoking history aged 70 and over at initial diagnosis. Retrospective data of patients aged ≥70 (initial diagnoses 2004-2018) were examined. Evaluated predictors included tumour stage, biological age, health and therapy. A total of 688 patients (520 smokers, 168 non-smokers) were included with a median age of 74. The 5-year OS was 39.6%. Non-smokers had significantly improved OS compared to smokers (52.0% versus 36.0%, p < 0.001). Disease-free survival (DFS) differed significantly between both groups (hazard ratio = 1.3; 95%CI 1.04-1.626). TNM stage and the recommended therapies (curative versus palliative) were comparable. The proportion of p16-positive oropharyngeal carcinomas was significantly higher in non-smokers (76.7% versus 43.8%, p < 0.001). Smokers were significantly more likely to be men (p < 0.001), drinkers (p < 0.001), and have poorer health status (Karnofsky performance status, KPS, p = 0.023). They were also more likely to have additional tumours (p = 0.012) and lower treatment adherence (p = 0.038). Important predictors of OS identified in both groups, were, among others, alcohol abuse, KPS, Charlson comorbidity index, site of primary tumour, UICC stage and treatment received. Elderly non-smokers are also affected by HNSCC, however, both OS and DFS are increased compared to smokers.

Abstract P2-02-03: Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis

Abstract Background: Adjuvant regional nodal irradiation together with whole breast or chest wall irradiation is considered standard of care in most node positive early breast cancer. Existing data on adding internal mammary irradiation (IMNI) to the regional nodal fields are inconsistent. The objective of this study was to conduct a meta-analysis to explore the efficacy and safety of adding IMNI to adjuvant radiotherapy in early-stage, high risk breast cancer. Methods: A search of PubMed and EMBASE identified randomized trials that investigated the addition of IMNI to standard adjuvant radiation in early-stage breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall survival (OS), breast cancer specific survival (BCSS), disease-free survival (DFS) and distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer and cardiovascular morbidity and mortality were also extracted. These data where pooled in a meta-analysis using RevMan 5.4. Results: Analysis included 5 trials comprising 10,994 patients. Compared to the control group, IMNI was associated with a small, but statistically significant improvement in OS (HR=0.91, 95% 0.85-0.97, p=0.004), BCSS (HR=0.84, 95%0.77-0.92, p&amp;lt; 0.001), DFS (HR=0.89, 95% CI 0.82-0.98, p= 0.01) and DMFS (HR=0.89, 95% 0.81-0.98, p=0.02). IMNI was also associated with reduced odds for regional (OR=0.58, 95% 0.44-0.75, p&amp;lt; 0.001) and loco-regional recurrence (OR=0.85, 95% CI 0.72-1.00, p=0.04). Subgroup analyses for OS by tumor location (medial/central vs. lateral) and by nodal burden showed similar benefit is all subgroups. The odds for cardiotoxicity were higher, but did not reach statistical significance (OR=1.23, 95% 0.99-1.53, p=0.07). There was no association with cardiovascular mortality (OR=1.00, 95% 0.69-1.46, p=1.00). There were also comparable odds for non-breast cancer mortality (OR=1.05, 95% 0.79-1.41, p=0.74), secondary cancer (OR=0.95, 95% 0.82-1.10, p=0.51) and contra-lateral breast cancer (OR=1.07, 95% 0.77-1.51, p=0.68). Conclusions: Compared to the control group the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness. Non-significant association with increased cardiovascular toxicity requires further study in longer-term studies. Citation Format: Yasmin Korzets, Dina Levitas, Ahuva Grubstein, Ben W Corn, Eitan Amir, Hadar Goldvaser. Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-03.

Final overall survival (OS) analysis of atezolizumab (atezo) monotherapy vs chemotherapy (chemo) in untreated locally advanced or metastatic urothelial carcinoma (mUC) from the Phase 3 IMvigor130 study.

LBA441 Background: Two interim OS analyses from IMvigor130 demonstrated non-statistically significant OS benefit with atezo monotherapy (Arm B) vs placebo + platinum (investigator [INV] choice of carboplatin or cisplatin [carbo or cis])/gemcitabine (plt/gem; Arm C) in patients (pts) with PD-L1–high (IC2/3) mUC, as well as a favorable safety profile vs chemo (Galsky Lancet 2020, Davis AACR 2021). Exploratory data showed clinical benefit with atezo monotherapy in cis-ineligible pts with IC2/3 tumors. Here, we report the final OS analysis from IMvigor130 Arms B and C. Methods: Pts were randomly assigned 1:1:1 to Arm A (atezo + plt/gem; not reported here), B or C. Due to the statistical testing hierarchy, no formal comparison of OS (co-primary endpoint) in Arm B vs C was performed in ITT and IC2/3 pts. ORR and DOR, both per INV-assessed RECIST 1.1 (secondary endpoints), and safety were assessed. Subgroup analyses of OS in cis-ineligible pts and disease control rate (DCR, confirmed CR, PR or [SD ≥6 mo]) were exploratory. Results: As of data cutoff Aug 31, 2022, time since last pt randomly assigned was 49 mo. OS data (Table) did not show benefit for ITT pts, while an HR of 0.56 (0.34, 0.91) was seen in the cis-ineligible IC2/3 subgroup. In the ITT population, the 24-mo OS rates were 34% in Arm B and 32% in Arm C. ORR was 24% (87/359; 38% DCR) in Arm B and 44% (158/356; 59% DCR) in Arm C; median DOR was 29.6 and 8.1 mo, respectively. In cis-ineligible IC2/3 pts, ORR was 40% (20/50) in Arm B and 33% (14/43) in Arm C. Median DOR was not evaluable in Arm B and 6.2 mo in Arm C. Of safety-evaluable pts, 57 of 354 in Arm B (16%) and 312 of 389 in Arm C (80%) had a Gr 3/4 treatment-related AE (TRAE); 3 (1%) and 4 (1%), respectively, had a Gr 5 TRAE. Gr 3/4 AEs of special interest occurred in 36 pts (10%) in Arm B and 17 (4%) in Arm C. Conclusions: The final OS analysis was consistent with previous data. Atezo monotherapy continued to show better tolerability vs chemo with no new safety concerns. These exploratory data support the benefit-risk ratio of atezo monotherapy vs chemo for first-line cis-ineligible IC2/3 mUC. Clinical trial information: NCT02807636 . [Table: see text]

Investigation of the clinicopathological and prognostic role of circMTO1 in multiple cancers

ABSTRACT Objective To observe the prognostic value of circular RNA mitochondrial tRNA translation optimization 1 (circMTO1) in human tumors. Methods We searched multiple databases for related reports published before November 01, 2021. The OR/HR and 95% CI were extracted to explore the correlation between circMTO1 expression and clinicopathological features in various cancers. The stability of the results from meta-analysis was estimated via sensitivity analysis. We adopted Begg’s funnel plots and Egger’s test to appraise the potential bias of publication. Subgroup analysis for overall survival (OS) were also performed. Results 11 studies containing 1383 patients and 4 articles including 536 patients were enrolled. We found that low expression status of circMTO1 was significantly related to big tumor size (OR=2.11, 95% CI: 1.26-3.56, P<0.05), poor differentiation tumors (OR=2.09, 95% CI: 1.46-2.98, P<0.05), OS (HR=2.02, 95% CI: 1.63-2.50, P<0.05), disease-free survival (DFS) (HR=1.83, 95% CI: 1.27-2.56, P<0.05) of cancers. Subgroup analysis indicated that low expression status of circMTO1 was correlated with OS, regardless of analysis method, cut-off value, case number and NOS score. Conclusions The low expression of circMTO1 may predict big tumor size, poor differentiation and worse outcome of cancer, presenting that circMTO1 may be a useful biomarker for prognosis of tumors.

Differential Impact on Survival in Myeloid Neoplasm Patients with U2AF1 Mutations

Introduction:U2AF1 mutations (m) are associated with abnormal splicing of genes involved in functionally important pathways, such as cell cycle progression and RNA processing. The U2AF1 gene has specific hotspots for mutations primarily involving the S34F and Q157P residues within the ZnF1 and ZnF2 causing mis-splicing of genes critical for hematopoiesis. Most recently in European Leukemia Net 2022 guidelines, U2AF1m is categorized as high-risk disease with inferior survival. We analyze outcome of U2AF1m in myeloid neoplasms and co-mutation patterns in large cohort of patients treated at Mayo Clinic. Methods: We reviewed our myeloid neoplasms patients (pts) database who underwent NGS (MC OncoHeme 42 genes panel) testing between October 2015 and August 2021. We identified 121 myeloid neoplasm pts with U2AF1m, and these were analyzed for clinical characteristics, co-mutational patterns, and outcomes using SPSS statistical software. An appropriate IRB approved was obtained. Results: The median age at diagnosis was 71 years (range [R], 19-92) (Table 1). Sixty-one (51%) pts were diagnosed with MDS, 29 (24%) pts with myeloproliferative neoplasms (MPN), 23 (19%) pts with acute myeloid leukemia (AML), 12 (10%) pts with MDS/MPN overlap and 3 (2.5%) pts with clonal cytopenia of unknown significance (CCUS). Out of 61 pts diagnosed with MDS, 59 pts had risk stratification information based on the revised international prognostic scoring system (IPSS-R): 20 (33.9%), 18 (30.5%), 17 (28.8%) and 4 (6.8%) patients were stratified into low, intermediate, high, and very high risk, respectively. Thirty-one out of 102 (30%) pts with MDS/MPN/MDS-MPN overlap progressed to AML with median time to AML progression 14.6 months (R, 1-118). Forty-four percent and 32% of pts had mutations involving the S34F and Q157P hotspots respectively, while the remaining had Q157R (12%), S34Y (6%), R156H (5%) and R35L (1%). The median variable allele frequency (VAF) was 38% (R, 2-49). Isolated U2AF1m was seen in 15 (12.4%) patients, 9 of these patients were diagnosed as MDS. The rest of the patients (87.6%) had at least 1 co-mutation, the most common ones being ASLX1 (46%), JAK2 (19%), TET2 (17.5%), RUNX1 (14%), DNMT3A (14%) and BCOR (14%). We did sub-group analysis for overall survival (OS) in advanced MDS and AML patients harboring most frequent U2AF1 mutations (S34F, Q157P and Q157R). The mOS was 31.3, 20.5 and 8.8 months (mo) in MDS/AML pts with S34F, Q157P and Q157R mutations, respectively (p= 0.005, Figure 1A). While VAF <40% (OS 21.5 mo) vs VAF >40% (OS 24.5 mo) had no differential impact on OS (p= 0.98, Figure 1B). Conclusion: In this study, we have demonstrated that U2AF1 gene with S34F hotspot have better OS, while Q157R had significantly inferior OS in pts with MDS/AML. Contrary to earlier reports we did not observe significant survival difference in MDS/AML patients with VAF cutoff of 40%. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal