Relapse-free Survival Rates Research Articles

Minimally invasive versus open multivisceral resection for rectal cancer clinically invading adjacent organs: a propensity score-matched analysis

BackgroundMinimally invasive surgery (MIS), such as laparoscopic and robotic surgery for rectal cancer, is performed worldwide. However, limited information is available on the advantages of MIS over open surgery for multivisceral resection for cases clinically invading adjacent organs.Patients and methodsThis was a retrospective propensity score-matching study of consecutive clinical T4b rectal cancer patients who underwent curative intent surgery between 2006 and 2021 at the University of Tokyo Hospital.ResultsSixty-nine patients who underwent multivisceral resection were analyzed. Thirty-three patients underwent MIS (the MIS group), while 36 underwent open surgery (the open group). Twenty-three patients were matched to each group. Conversion was required in 2 patients who underwent MIS (8.7%). R0 resection was achieved in 87.0% and 91.3% of patients in the MIS and open groups, respectively. The MIS group had significantly less blood loss (170 vs. 1130 mL; p < 0.0001), fewer Clavien–Dindo grade ≥ 2 postoperative complications (30.4% vs. 65.2%; p = 0.0170), and a shorter postoperative hospital stay (20 vs. 26 days; p = 0.0269) than the open group. The 3-year cancer-specific survival rate, relapse-free survival rate, and cumulative incidence of local recurrence were 75.7, 35.9, and 13.9%, respectively, in the MIS group and 84.5, 45.4, and 27.1%, respectively, in the open group, which were not significantly different (p = 0.8462, 0.4344, and 0.2976, respectively).ConclusionMIS had several short-term advantages over open surgery, such as lower complication rates, faster recovery, and a shorter hospital stay, in rectal cancer patients who underwent multivisceral resection.Graphical abstract

Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT

AbstractSelecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society for Blood and Marrow Transplantation database (2012-2021). For Haplo SCT, only those receiving posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis were included. Median age was 20 years, and the median time from diagnosis to transplantation 8.7 months. Compared with MUD, MMUD (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.52-5.6) and Haplo (HR, 5.15; 95% CI, 2.5-10.58) showed significantly higher risks of primary graft failure. MUD had lower rates of acute GVHD compared with MMUD and Haplo (grade 2-4: 13%, 22%, and 19%, respectively; P < .001; grade 3-4: 5%, 9%, and 7%, respectively; P = .028). The 3-year nonrelapse mortality rate was 14% for MUD, 19% for MMUD, and 27% for Haplo (P < .001), whereas overall survival and GVHD and relapse-free survival (GRFS) rates were 81% and 73% for MUD, 74% and 65% for MMUD, and 63% and 54% for Haplo, respectively (P < .001). In addition to donor type, multivariable analysis identified other factors associated with GRFS such as patient age, performance status, and interval between diagnosis and transplantation. For patients with SAA lacking an MSD, our findings support MUDs as the preferable alternative donor option. However, selecting between an MMUD and Haplo donor remains uncertain and requires further exploration.

Pathological Pleural Invasion is a Risk Factor for Late Recurrence in Long-Term Survivors of Non-small Cell Lung Cancer after Complete Resection.

Information regarding late recurrence after pulmonary resection for non-small cell lung cancer (NSCLC) is limited. This study aimed to analyze the risk factors for late recurrence after surgery for NSCLC in the current era. We conducted a retrospective study of patients who underwent complete resection for pathological I-III NSCLC between 2006 and 2015. Late recurrence was defined as a recurrence that met the following conditions: (1) the patient underwent chest computed tomography (CT) at or after 54 months after surgery and recurrence was not detected at that time, and (2) recurrence that occurred more than 5 years after surgery. The factors influencing late recurrence, relapse-free survival (RFS), and overall survival (OS) after surgery were analyzed. A total of 1275 with 5-year relapse-free survival after surgery were enrolled in this study. The mean age of the patients was 66.4 years and 54% of the patients were men. The median interval between surgery and the latest follow-up examination was 98 months. In total, 35 patients (2.7%) experienced late recurrence and 138 patients have died thus far. The cumulative recurrence, RFS, and OS rates at 10 years were 3.9%, 84.9%, and 86.3%, respectively. A multivariate analysis revealed that pleural invasion was an independent risk factor for late recurrence. Pleural invasion was a poor prognostic factor for both RFS and OS. Pleural invasion was a predictor of late recurrence. Age>67 years, preoperative serum carcinoembryonic antigen (CEA)>5 ng/ml, non-adenocarcinoma, and pleural invasion were poor prognostic factors for RFS.

Adalimumab Dose Reduction and Withdrawal in Stable Non-Infectious Pediatric Uveitis: An Open-Label, Prospective, Pilot Study

ABSTRACT Purposes This study investigated the feasibility of adalimumab (ADA) dose reduction and withdrawal strategy in children with stable pediatric non-infectious uveitis (PNIU). Methods This open-label prospective pilot trial recruited 18 stable PNIU patients (33 eyes) between two and eighteen years old who were treated with standard doses of ADA (20/40 mg every 2 weeks) plus oral methotrexate. The interval of ADA injection was extended to 4 weeks and followed up for 24 weeks. If the uveitis remained stable, ADA was discontinued and followed up for another 24 weeks. ADA was considered successfully stopped if no relapse occurred during this period. The relapse-free survival rate, best corrected visual acuity (BVCA), anterior chamber cell (ACC), vitritis, macular thickness (MT), and serum ADA levels were evaluated. Approval Number: 2021KYPJ201. ClinicalTrials.gov identifier: NCT05155592. Results The relapse-free survival rate was 22.2% (4/18) at 48 weeks. 33.3% (6/18) of patients relapsed when ADA was given every 4 weeks, while 44.5% of patients (8/18) relapsed after ADA was stopped. The four patients successfully withdrawn from ADA were all diagnosed with BD. No statistically significant differences (p > 0.05) were observed in BCVA and MT between baseline and final follow-up. The proportion of ACC and vitritis exhibited an upward trend (p < 0.05) during follow-up. Serum ADA gradually decreased to zero during follow-up in both non-recurrence and recurrence groups. Conclusions In PNIU children who reached remission for 6 months, ADA dose reduction and withdrawal were associated with a high risk of inflammation recurrence. Timely adjustment of ADA to the last effective dosage frequency can regain control of the inflammation. Detection of ADA serum levels in patients with recurrence may help find the appropriate interval of ADA use.

Long-term outcomes of robot-assisted laparoscopic surgery versus conventional laparoscopic surgery for rectal cancer: single-center, retrospective, propensity score analyses

Although the short-term outcomes of robot-assisted laparoscopic surgery (RALS) for rectal cancer are well known, the long-term oncologic outcomes of RALS compared with those of conventional laparoscopic surgery (CLS) are not clear. This study aimed to compare the long-term outcomes of RALS and CLS for rectal cancer using propensity score matching. This retrospective study included 185 patients with stage I–III rectal cancer who underwent radical surgery at our institute between 2010 and 2019. Propensity score analyses were performed with 3-year overall survival (OS) and relapse-free survival (RFS) as the primary endpoints. After case matching, the 3-year OS and 3-year RFS rates were 86.5% and 77.9% in the CLS group and 98.4% and 88.5% in the RALS group, respectively. Although there were no significant differences in OS (p = 0.195) or RFS (p = 0.518) between the groups, the RALS group had slightly better OS and RFS rates. 3-year cumulative (Cum) local recurrence (LR) and 3-year Cum distant metastasis (DM) were 9.7% and 8.7% in the CLS group and 4.5% and 10.8% in the RALS group, respectively. There were no significant differences in Cum-LR (p = 0.225) or Cum-DM (p = 0.318) between the groups. RALS is a reasonable surgical treatment option for patients with rectal cancer, with long-term outcomes similar to those of CLS in such patients.

Adjuvant Treatment with S-1 in Patients after R0-Resection of Adenocarcinoma of the Stomach and Esophagogastric Junction: A Multicenter Phase I/II Feasibility Study (GMBH-STO-0114)

Introduction: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients. Methods: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment. One treatment cycle consisted of oral S-1 (30 mg/m2 bid) for 14 days. Cycles were repeated every 3 weeks for 18 cycles (54 weeks). Primary endpoint was feasibility and tolerability. Safety was evaluated according to the Common Toxicity Criteria Adverse Events (CTCAE) version 4.0. Secondary endpoints were 1-year relapse-free survival (RFS) rate, RFS, and overall survival (OS). Results: Between October 2015 and February 2018, 32 patients were enrolled in 12 German centers, and 30 started adjuvant study treatment. Seventeen patients completed all 18 cycles. Two patients terminated study treatment early due to adverse events (AEs), 7 due to patient’s or investigator’s decision, and 4 due to recurrence or distant metastasis during adjuvant therapy. Dose levels were reduced to 25 mg/m2 in 9 patients and to 20 mg/m2 in 1 patient. Of patients completing all 18 cycles, 5 did so with reduced dosage of S-1. Documented grade ≥3 AEs were neutropenia, diarrhea, vomiting, polyneuropathy, palmar-plantar erythrodysaesthesia, and rash. Serious AEs were observed in 7 patients. Median RFS was 32.2 months. One-year RFS rate was 77%. Data on OS were still premature at the end of the study. Conclusion: Adjuvant treatment with S-1 for 1 year is a feasible and safe treatment option for Caucasian patients diagnosed with gastric adenocarcinoma or cancer of the EGJ after R0-resection.

Tale of two zones: investigating the clinical outcomes and research gaps in peripheral and transition zone prostate cancer through a systematic review and meta-analysis

ObjectiveTo assess pathological characteristics, clinical features and outcomes of patients diagnosed with peripheral zone (PZ) and transition zone (TZ) prostate cancer after prostatectomy.Methods and analysisWe systematically reviewed PubMed, EMBASE and...

Oncological and functional outcomes for transoral robotic surgery following previous radiation treatment for upper aerodigestive tract head and neck cancers. A French multicenter GETTEC group study.

Transoral robotic surgery (TORS) opens new perspectives. We evaluated the outcomes for patients having undergone TORS after previous radiotherapy. A retrospective multicenter study (n = 138) in a previously irradiated area between 2009 and 2020. Survival was assessed with the Kaplan-Meier method. Prognostic factors were evaluated using a chi-squared test, Fisher's test, or Wilcoxon's test. The median length of hospital stay was 12.5 days. Bleeding was the most frequent postoperative complication (15.2%, n = 22). Prophylactic vessel ligation did not significantly decrease bleeding. Complications were significantly lower for Tis, T1, and N0 tumors. 91.6% (n = 120) of the patients with a perioperative tracheotomy could be decannulated. Larynx was functional for 65.94% of the patients. The median length of follow-up was 26 months. The 5-year overall and relapse-free survival rates were respectively 59.9% and 43.4%. Oncological and functional results confirmed the value of TORS as a treatment in previously irradiated area.

Significance of Pulmonary Artery Dilatation in Lung Cancer Patients With Chronic Obstructive Pulmonary Disease Who Underwent Pulmonary Resection

BackgroundThe significance of pulmonary artery (PA) diameter in patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) who undergo pulmonary resection has not been elucidated. MethodsData of 357 patients with NSCLC and COPD who underwent pulmonary resection were retrospectively reviewed. The main PA diameter, determined by preoperative computed tomography, relative to the body surface area (PBR), was used as an index of PA dilatation, and patients were divided into 2 groups using median values. The relationship between the PBR and short- and long-term outcomes was also analyzed. ResultsThe mean age was 70.8 years, and 82% of the patients were men. The median main PA diameter was 24 mm (range, 17-43 mm), and the median PBR was 14.5 (range, 10.4-28.6). Lobectomy or more was performed in 276 patients (78%) and sublobar resection in 81 patients (22%). The postoperative complication rates did not differ between the low- and high-PBR groups (33% vs 32%, P = .91). The relapse-free survival (RFS) and overall survival (OS) rates of the low-PBR group were significantly better than those of the high-PBR group (5-year RFS: 76% vs 59%, P = .0003; 5-year OS: 88% vs 72%, P = .0010). A multivariable analysis identified high PBR as a poor prognostic factor for both RFS and OS. ConclusionsPA dilatation was associated with poor long-term outcomes and was an independent poor prognostic factor for both RFS and OS in NSCLC patients with COPD who underwent pulmonary resection.

Short- and Long-term Outcomes After Colonic Stent Insertion as a Bridge to Surgery in Elderly Colorectal Cancer Patients.

Colonic stents have been inserted as a bridge to surgery in patients with resectable colorectal cancer, allowing bowel decompression for systemic assessment and better preparation to avoid stoma construction. However, reports of short- and long-term prognoses for elderly patients remain limited. This retrospective study reviewed 175 consecutive patients who underwent colonic stent insertion for bowel obstruction followed by curative colectomy. Patients were divided into those >80 years old (Old, n=49) and those <80 years old (Young, n=126). After propensity score matching, 41 patients in each group matched. Before matching, performance status was poorer (p<0.001), postoperative complication rate was higher (p=0.009), adjuvant chemotherapy rate was lower (p<0.001), and hospital stay was longer (p<0.001) in the Old group. After matching, adjuvant chemotherapy rate was lower (9.8% vs. 39.0%; p=0.003) and hospital stay was longer (14 vs. 12 days; p=0.029) in the Old group. Five-year relapse-free survival (42.9% vs. 68.8%; p=0.200), overall survival (66.3% vs. 87.7%; p=0.081), and cancer-specific survival (68.2% vs. 87.7%; p=0.129) rates were comparable between groups. Colorectal resection after colonic stent insertion is useful for elderly patients, with potential to reduce postoperative complication rates and achieve good long-term results with appropriate case selection.

Clinical Impact of Preoperative Prognostic Nutritional Index in Surgical Patients With Pancreatic Cancer Treated With Perioperative Adjuvant Chemotherapy.

The prognostic nutritional index (PNI) is used as a marker to evaluate the nutritional and immunological status of patients with various cancers. This study aimed to investigate whether preoperative PNI is a prognostic factor in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. We retrospectively enrolled 232 pancreatic cancer patients who underwent surgical resection with perioperative adjuvant chemotherapy between January 2013 and December 2022. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression models. The optimal cutoff value for the preoperative PNI was 44.3 in the present study. PNI <44.3 was associated with older age (p<0.001) and affected the clinical course of postoperative adjuvant chemotherapy. The PNI <44.3 had an important influence on the decreased OS (25.1 vs. 39.0 months) and RFS (13.1 vs. 22.8 months). In univariate and multivariate analyses, the preoperative PNI was an independent prognostic factor for OS [hazard ratio (HR)=1.682, 95% confidence interval (CI)=1.059-2.673, p=0.028] and RFS (HR=1.559, 95% CI=1.037-2.344, p=0.033). Preoperative PNI is a prognostic factor for both OS and RFS in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. This study suggests that a low PNI may cause a lack of full-dose adjuvant chemotherapy, leading to recurrence and resulting in a poor prognosis for surgical pancreatic cancer patients treated with perioperative adjuvant chemotherapy.

Safety and Limitations of Laparoscopic Total Gastrectomy for Gastric Cancer: A Comparative Analysis of Short and Long-term Outcomes With Open Surgery.

Laparoscopic gastrectomy is a standard treatment strategy for gastric cancer (GC); however, the clinical impact of laparoscopic total gastrectomy (LTG) on survival outcomes remains unclear. We compared the short- and long-term results of LTG with those of open total gastrectomy (OTG). Patients undergoing total gastrectomy with lymph node dissection for Stage I/II/III GC between 2010 and 2020 were retrospectively analyzed. Patients were classified into those undergoing LTG (n=143, LTG group) and OTG (n=173, OTG group). The primary outcome was relapse-free survival (RFS). The LTG group exhibited a higher prevalence of early T and N factors, with pStage I/II/III distribution skewed toward early-stage in a ratio of 86/24/33 compared to 38/65/69 in the OTG group (p<0.001), respectively. Longer operation time (p<0.001), less blood loss (p<0.001), fewer grade 3-4 complications (p<0.001), and shorter hospital stay (p<0.001) were observed in the LTG than in the OTG group. LTG was associated with survival benefits for patients without indication for adjuvant chemotherapy [5-year RFS rate, 96.3% vs. 73.2%; hazard ratio (HR)=0.24; 95% confidence interval (CI)=0.10-0.56; p<0.001]. Among the eligibility criteria for adjuvant chemotherapy (Stage II/III excluding pT1 and pT3N0), while the LTG group received more frequently doublet-agent administration (56.5% vs. 11%, p<0.001), conversely, the OTG group exhibited slightly better long-term survival rates (5-year RFS rate, 33.9% vs. 50.2%; HR=1.31; 95%CI=0.82-2.10; p=0.251). LTG contributed to favorable short-term outcomes and demonstrated improved long-term outcomes in early-stage GC; however, careful consideration of indications is warranted for advanced GC cases.

Interaction of Vitamin D Supplements and Marine n-3 Fatty Acids on Digestive Tract Cancer Prognosis.

A meta-analysis suggested that marine n-3 polyunsaturated fatty acids (PUFAs), e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), might reduce cancer mortality. However, a randomized clinical trial of marine n-3 PUFA and vitamin D supplementation failed to verify this benefit. This study aimed to investigate the potential interaction between vitamin D supplementation and serum EPA and DHA levels. This post hoc analysis of the AMATERASU trial (UMIN000001977), a randomized controlled trial (RCT), included 302 patients with digestive tract cancers divided into two subgroups stratified by median serum levels of EPA + DHA into higher and lower halves. The 5-year relapse-free survival (RFS) rate was significantly higher in the higher half (80.9%) than the lower half (67.8%; hazard ratio (HR), 2.15; 95% CI, 1.29-3.59). In the patients in the lower EPA + DHA group, the 5-year RFS was significantly higher in the vitamin D (74.9%) than the placebo group (49.9%; HR, 0.43; 95% CI, 0.24-0.78). Conversely, vitamin D had no effect in the higher half, suggesting that vitamin D supplementation only had a significant interactive effect on RFS in the lower half (p for interaction = 0.03). These results suggest that vitamin D supplementation may reduce the risk of relapse or death by interacting with marine n-3 PUFAs.

Abstract 1410: An effect of Phenylalanine hydroxylase (PAH) deficiency on cancer development in kidney

Abstract Several studies have noted the importance of amino acid metabolism in cancer progression. Preliminary research using public cancer multi-omics data has revealed associations between heterozygous germline mutations in genes associated with amino acid metabolism and cancer development. In particular, the heterozygous status of the PAH gene enhances the risk of developing kidney cancer by more than three times. Phenylalanine hydroxylase (PAH) is an enzyme that converts phenylalanine to tyrosine. It is highly expressed in the liver and kidneys. Analysis of the blood metabolome in prospectively collected PAH heterozygous carriers indicates that heterozygous status causes metabolome fluctuations in the body. By the way, renal cell carcinoma (RCC) is an immunogenic tumor mainly infiltrated by T cells. Accordingly, we suggest that defects in the PAH gene change the metabolites in the body, leading to a reduction in immune function and an increased risk of developing kidney cancer. First, the expression of the PAH protein was confirmed through immunohistochemistry in a tissue microarray from RCC patients, and the results were then compared with clinical information. Next, we simulated the environment of PAH deficiency in vitro by treating the cells with phenylalanine (Phe) and its metabolite, phenylpyruvate (PRA), which accumulates during PAH dysfunction. The cytotoxicity of Phe and PPA was investigated using the WST assay. The Jurkat T cell line was cultured long-term in a medium containing Phe or PPA and then stimulated with PHA/PMA. Cytokine secretion was confirmed in these supernatants. In addition, purified primary human pan T cells were stimulated with Anti-CD3/CD28 in the medium containing either Phe or PPA. Proliferation was evaluated using CFSE staining. The IHC was performed on 467 tissues from RCC patients aged 29 to 101 years. We classified the cases into three scale scores based on the percentage of PAH intensity. Approximately 73% of cases were PAH-negative, and only 27% were positive (score 1+ or 2+). A comparison of IHC results with clinical information showed that lower PAH expression was associated with a lower relapse-free survival rate. Next, Phe and PPA exhibited minimal cytotoxicity. The secretion of representative proinflammatory cytokines IL-2 and TNF- α were dose-dependent and significantly decreased with Phe and PPA treatment. Additionally, cell proliferation, a critical step in acquiring effector functions of T cells, was inhibited by treatment with Phe and PPA, particularly in the CD8+ T cell population compared to CD4+ T cells. These results suggest that metabolite changes within the tissue microenvironment of the kidney, caused by Pah defects, may suppress anti-tumor immunity by impairing the function of immune cells. This novel discovery may contribute to the importance of the PAH gene as a new biomarker for diagnosing kidney cancer and to the development of kidney cancer therapy. Citation Format: Seojeong Kim, Jihyun Park, Jeongmin Park, Chaelin Kang, Kyung Chul Moon, Seung Seok Han, Youngil Koh, Sung-Soo Yoon. An effect of Phenylalanine hydroxylase (PAH) deficiency on cancer development in kidney [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1410.

Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study

Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P=0.09) and overall survival (OS) (log-rank P=0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n=17) than in the IDC group (n=10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Umberto VeronesiFoundation.

Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia.

In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KITmut ) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KITmut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KITmut (D816V/H/Y or N822K) were tested for KITmut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KITmut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KITmut -high (KIT_H) group and the KITmut -low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p=0.0040 and 0.021, respectively) and Course 2 consolidation (p=0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KITmut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.

Outcomes and prognostic factors of repeat pulmonary metastasectomy.

Information on prognostic factors after repeat pulmonary metastasectomy (PM) is limited, and outcomes after a third PM are not well documented. A single-institute retrospective study was conducted. Between 2000 and 2020, 68 patients underwent repeat PM for pulmonary metastases from various cancers. Outcomes and prognostic factors for the second PM and outcomes after the third PM were analysed. This study included 39 men and 29 women. The mean age at second PM was 53.2 years old. The primary tumours were soft tissue sarcoma in 24 patients, colorectal cancer in 19 and osteosarcoma in 10. The interval between the first PM procedure and detection of pulmonary metastasis after the first PM (months) was ≤12 in 37 patients and >12 in 31 patients. At the second PM, 20 patients underwent lobectomy or bilobectomy, and 48 underwent sublobar resection. Complete resection was achieved in 60 patients, and 52 patients experienced recurrence after the second PM. The 5-year relapse-free survival and overall survival rates after the second PM were 27% and 48%, respectively. Multivariable analysis revealed that the interval between the first PM and the subsequent detection of pulmonary metastasis (≤12 months) was a poor prognostic factor for both relapse-free survival and overall survival after the second PM. Seventeen patients underwent a third PM, 3 of whom achieved a 3-year disease-free survival. Patients with a period of >12 months between the first PM and the subsequent detection of pulmonary metastases showed favourable outcomes and are thus considered good candidates for second PM. A third PM may be beneficial for selected patients.

Optimal extent of lymph node dissection for high-risk gastric cancer stratified by a national clinical database risk calculator.

For patients with gastric cancer, a well-balanced treatment that considers both oncological aspects and surgical risk is demanded. This study aimed to explore the optimal extent of lymph node dissection (LND) for patients with gastric cancer according to surgical risk, stratified by the risk calculator system produced by the Japan National Clinical Database (NCD). We retrospectively evaluated 187 patients who underwent radical gastrectomy for gastric cancer. Using the median predicted anastomotic leak rate obtained by the NCD risk calculator as the cutoff value, we classified 97 and 90 patients as having high and low risks, respectively. In low-risk patients, although limited LND reduced the postoperative intraabdominal infectious complications (IAIC), multivariate analysis revealed standard LND as an independent prognostic factor that improved Relapse-free survival (RFS). In high-risk patients, the rates of postoperative IAIC and RFS were similar between standard and limited LND. Pancreatic fistula was not observed in the limited dissection group. Limited LND might be the optimal treatment strategy for patients with gastric cancer with high surgical risk.

A meta‑ and bioinformatics analysis of maspin expression levels influencing the prognosis of patients with breast cancer.

Maspin is a serine protease inhibitor that is encoded by the human SERPINB5 gene. As a tumor inhibitor, it can inhibit the growth of tumor cells, increase adhesion between tumor cells and inhibit tumor angiogenesis. In the present study, a meta- and bioinformatics analysis was performed through the PubMed and China National Knowledge Infrastructure databases including entries added until up to March 20, 2023. It was found that compared with normal breast tissue, maspin expression was downregulated in breast cancer tissue. Maspin expression was negatively associated with lymph node metastasis. According to Kaplan-Meier plotter, it was found that lower maspin expression was negatively associated with the overall and distant metastasis-free survival rate of patients with estrogen receptor-positive, luminal A and grade 2 breast cancer. High expression of maspin was also positively associated with the relapse-free survival rate of patients of the luminal A subtype. Low maspin expression was positively associated with the post-progression and distant metastasis-free survival rate of the progesterone receptor-negative subtype. According to the GEPIA database, SERPINB5 mRNA expression was higher in normal than breast cancer tissues and negatively correlated with the TNM stage. High expression of maspin was also positively associated with the overall survival rate. In the UALCAN database, it was found that the mRNA and promoter methylation levels of SERPINB5 were higher in normal than in breast cancer tissues. These findings suggest that the expression of maspin may serve as a potential marker to indicate the occurrence, subsequent progression and even prognosis of breast cancer.

Killer cell lectin-like receptor G2 facilitates aggressive phenotypes of gastric cancer cells via dual activation of the ERK1/2 and JAK/STAT pathways.

Advanced gastric cancer (GC) has a poor prognosis. This study aimed to identify novel GC-related genes as potential therapeutic targets. Killer cell lectin-like receptor G2 (KLRG2) was identified as a candidate gene by transcriptome analysis of metastatic GC tissues. Small interfering RNA-mediated KLRG2 knockdown in human GC cell lines was used to investigate KLRG2 involvement in signaling pathways and functional behaviors in vitro and in vivo. Clinicopathological data were analyzed in patients stratified according to tumor KLRG2 mRNA expression. KLRG2 knockdown in GC cells decreased cell proliferation, migration, and invasion; caused cell cycle arrest in G2/M phase; induced apoptosis via caspase activation; suppressed JAK/STAT and MAPK-ERK1/2 pathway activities; and upregulated p53 and p38 MAPK activities. In mouse xenograft models of peritoneal metastasis, the number and weight of disseminated GC nodules were decreased by KLRG2 knockdown. High tumor levels of KLRG2 mRNA were significantly associated with lower 5-year overall survival (OS) and relapse-free survival (RFS) rates in patients with Stage I-III GC (5-year OS rate: 64.4% vs. 80.0%, P = 0.009; 5-year RFS rate: 62.8% vs. 78.1%, P = 0.030). KLRG2 knockdown attenuated the malignant phenotypes of GC cells via downregulation of JAK/STAT and MAPK-ERK1/2 pathway activity and upregulation of p38 MAPK and p53. Targeted suppression of KLRG2 may serve as a new treatment approach for GC.