Disease-free Survival Rates Research Articles

Expression of HECTD2 predicts peritoneal metastasis of gastric cancer and reconstructs immune microenvironment.

Peritoneal metastasis (PM) is a common metastasis site and death cause of gastric cancer, which is a complex biological process, but there is currently a lack of effective prediction and treatment targets. In this study, we first analyzed the differential gene expression of gastric cancer patients with or without peritoneal metastasis, and identified the HECT domain E3 ubiquitin protein ligase 2 (HECTD2) as the core gene of PM in gastric cancer. The current study shows that the role of HECTD2 in tumor is contradictory. In this study, our results show that the low expression of HECTD2 indicates that the survival rate of overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), and disease-free survival (DFS) are better, and can be used as an important component of prognostic indicators. In addition, through pathway enrichment analysis, we found that HECTD2 was mainly involved in metastasis related pathways such as extracellular matrix remodeling and cell adhesion in gastric cancer, and high expression of HECTD2 could activate epithelial-mesenchymal transition (EMT) metastasis related pathways in gastric cancer. In regulating the metastasis of gastric cancer cells, HECTD2 can also change the surrounding microenvironment, induce the enrichment of interstitial components and build an immune microenvironment conducive to tumor progression, while patients with low expression of HECTD2 may be more likely to benefit from immunotherapy. In conclusion, HECTD2 may be a novel biomarker for the diagnosis and prognosis of peritoneal metastasis of gastric cancer, providing basis for the mechanism of peritoneal metastasis of cancer and clinical medication.

Multidisciplinary tumor boards in oral cavity cancer: survival effect due to balancing guideline adherence and treatment delays

ObjectivesThe purpose of the study was to assess the impact of a pretherapeutic Multidisciplinary Tumor Board (MTB) presentation on the prognosis and treatment outcomes in patients with primary oral cavity carcinoma.Materials and methodsThis single-center study included 630 patients diagnosed with oral cavity carcinoma treated between 2010 and 2020. The study cohort was divided in a group with and without pretherapeutic MTB presentation. Data on patient demographics, tumor characteristics, treatment and the time to treatment initiation (TTI) were collected retrospectively.ResultsPrimary findings revealed no significant difference in 3-year survival rate (3-YSR) and 3-year disease-free survival rate (3-YDFSR) for the non-MTB and MTB group. The 3-YSR was 73.1% in the non-MTB group and 67.1% in the MTB group (p = 0.112). The 3-YDFSR was 73.8% in the non-MTB group and 76.5% in the MTB group (p = 0.447). Estimated mean 5-year survival (5-YS) and 5-year disease-free survival in (5-YDFS) did not differ significantly between both groups, across the UICC stages I-IV, as well as for the entire cohort. The TTI was significantly longer in the MTB group (33.5 days, CI: 31.3;35.7) compared to the non-MTB group (20.1 days, CI: 17.9;22.4, p < 0.001). The MTB group adhered more frequently to the national guidelines (68% vs. 79.6%, p < 0.01).ConclusionThe results demonstrate both positive and negative side effects of the MTB presentation in patients with oral cavity cancer. Further multicenter studies will be required to assess the impact of TTI and adherence to guidelines on the survival of oral cavity cancer patients.

Adjuvant chemoradiotherapy plus PD-1 inhibitor for pN3 gastric cancer: a randomized, multicenter, Phase III trial.

D2 surgery followed by adjuvant chemotherapy has been established as the standard of care for patients with locally advanced gastric cancer in Asian countries. However, its efficacy is still unsatisfactory, especially for pathological N3 disease. The RACING trial is a randomized, multicenter, Phase III trial designed to compare the efficacy and safety of chemotherapy alone versus chemotherapy in combination with PD-1 inhibitor and radiotherapy in patients with pN3 gastric or gastroesophageal junction adenocarcinoma. A total of 433 patients will be assigned at a 1:1 ratio to the two arms. The primary end point is the 3-year disease-free survival rate. The secondary end points include the 3-year overall survival rate, 3-year local recurrence-free survival rate, treatment-related adverse events and quality of life.Clinical Trial Registration: NCT04997837 (ClinicalTrials.gov).

Venetoclax plus low intensity chemotherapy for adults with acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL), the BCL2 inhibitor venetoclax may enhance the efficacy of chemotherapy allowing dose reductions that reduce toxicity. We designed a phase 1b study of venetoclax plus attenuated chemotherapy to determine the recommended phase 2 dose (RP2D) of venetoclax. The study enrolled 19 patients with ALL either newly diagnosed (≥60 years, n=11 [B-cell, n=8; T-cell, n=3]) or R/R (≥18 years, n=8 [B-cell, n=3; T-cell, n=5]). Venetoclax was given for 21 days with each cycle of mini-hyper-CVD (cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). There were no dose limiting toxicities at dose level (DL) 1 (n=3, 400 mg/day) or DL2 (n=6, 600 mg/day); DL2 was the RP2D and explored further (n=10). The most common non-hematologic adverse events were grade 3+ infections. There were no deaths within 60 days and no patients discontinued therapy for toxicity. There was no tumor lysis syndrome, hepatotoxicity, or prolonged cytopenias. Among patients with newly diagnosed ALL, 10/11 (90.9%) achieved a measurable residual disease-negative (<0.01% sensitivity) complete remission (CR) including 6 patients with hypodiploid TP53 mutated ALL. All patients in CR bridged to hematopoietic stem cell transplant (n=9) or completed protocol (n=1). With a median follow-up of 60.0 months, median disease-free survival (DFS) for patients with newly diagnosed ALL was 54.6 months (95% CI: 35.5 months - NA) with a 2-year DFS rate of 90% (95% CI, 71% - 100%). Among patients with R/R ALL, 3/8 (37.5%) achieved CR. In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well-tolerated with promising efficacy. NCT03319901.

Long-Term Disease-Free Survival and Health-Related Quality of Life Results of High-Dose-Rate Brachytherapy as Monotherapy for Low and Intermediate-Risk Prostate Cancer Treated in a Community Cancer Centre

To determine the long-term disease-free survival, long-term toxicity, and effect on health-related quality of life of a two-fraction regimen of high-dose-rate (HDR) prostate brachytherapy. Patients with low- or intermediate-risk prostate cancer were treated with CT-planned HDR brachytherapy as monotherapy in two implants of 13.5 Gy in one community cancer center. Prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC) questionnaires were evaluated at each follow-up visit. Biochemical recurrence (Phoenix definition) was evaluated to determine disease-free survival at 5 and 7 years. Proportion of patients in each IPSS category (mild = 0-7, moderate = 8-18, severe = 19+) was evaluated at each follow-up interval. Thirty patients were accrued to the study between 2014 and 2016. Median prostate-specific antigen was 8,7 (range 4.1-17.5). T stages were T1c = 65%, T2a = 21%, and T2b = 14%. Twenty-seven percent of patients had a Gleason score of 6 and 73% had a Gleason score of 7. 13% were in low risk category and 87% in intermediate risk category. Median follow-up was 84 months. There were no deaths at 84 months after brachytherapy. Disease-free survival was 90% at 5 years and 86% at 7 years. Two patients experienced late Grade 3 GU toxicity (6.6%). This study serves as proof of concept that HDR monotherapy can be performed successfully with excellent long-term outcomes in a community cancer center with adequate training and experience. The long-term disease-free survival rate and the health-related quality of life seem acceptable as compared to other treatment modalities. Further study is ongoing with regard to the optimal dosing regimen for HDR monotherapy.

Effectiveness of ultrasound-guided vacuum-assisted excision for treating benign breast lesions.

Ultrasound‑guided vacuum-assisted excision (UGVAE) and breast biopsy are widely used for the diagnosis and treatment of both benign and suspicious breast lesions. In this retrospective study, we aimed to determine the safety of UGVAE for benign breast lesions and provide guidance for clinical practice. We analyzed clinical and pathological data of female patients who had undergone UGVAE between January 2015 and December 2017 at our institution. All breast lesions were categorized according to the Breast Imaging Reporting and Data System (BI-RADS) before performing UGVAE. In our study cohort, UGVAE was used to resect 10,378 breast lesions from 5789 patients, and selected clinical and histopathological data were analyzed. The most common adverse events were postoperative bleeding (0.24%) and skin hypersensitivity (0.67%). The residual lesion rate was 2.27%. Fibroadenomas accounted for most of the benign lesions (7932 of 10,193; 77.82%). Breast cancer was diagnosed in 150 lesions from 128 patients. Multivariable binary logistic regression analyses showed that older age (odds ratio [OR] = 2.034, 95% confidence interval [CI]: 1.668-2.480, p < 0.001), higher BI-RADS category (OR = 9.514, 95% CI: 6.790-13.332, p < 0.001), and larger legion size (OR = 1.048, 95% CI: 1.019-1.077, p = 0.001) were associated with an increased likelihood of breast cancer. Ninety-six patients with breast cancer had undergone follow-up treatment, achieving a 3-year disease-free survival rate of 97.2% and a 3-year overall survival rate of 100%. UGVAE is a safe and effective means of removing benign breast lesions, causing minimal postoperative trauma and fewer complications compared with open surgery. Moreover, UGVAE had little impact on the follow-up treatment and survival of patients diagnosed with breast cancer.

Long term outcomes from the early days of minimally invasive thymoma surgery for Myasthenia Gravis patients: a follow-up of 19 years

BackgroundLong-term survival outcomes are crucial for accurately determining the effectiveness of treatment in an indolent disease like thymoma. We aimed to analyze the clinical findings in terms of survival and relapse patterns with a median follow up of 105 months (8.7 years) in patients with thymoma and myasthenia gravis who underwent minimally invasive surgery between 2002 and 2015.MethodsA total of 59 pathologically confirmed Masaoka Stage I and II thymoma patients with Myasthenia Gravis (MG) who underwent minimally invasive thymoma resection were included in this study. Primary aim of this study is to evaluate recurrences, overall and disease free survival in patients with a thymoma and MG in the long run. We also aimed to study the changes in Myasthenia Gravis medication during the follow-up.ResultsThe mean age of the patients was 47.6 +/13.5 years. Seventeen patients were at Masaoka Stage I and 42 were at Masaoka Stage II. The median follow-up time was 105 months. The mean size of the tumor was 3.6 cm +/16.2 cm. Twenty-one patients (35%) received adjuvant radiotherapy. There was no postoperative mortality and median length of hospital stay was 4 days. Two patients developed recurrences both presented with pleural metastases. Eight patients died because of non-oncologic pathologies. 10-year disease free survival and overall survival rates were calculated to 96.6% and 86.4% respectively.ConclusionThe 10-year survival analysis and current myasthenic status of stage I-II thymoma patients with myasthenia gravis who underwent minimally invasive surgery demonstrate that these procedures are both safe and effective.

Clinicopathological features and prognosis of mucinous breast carcinoma with a micropapillary structure.

To conduct a comparative analysis of clinicopathological data between mucinous micropapillary breast carcinoma (MUMPC) and pure mucinous carcinoma (PMC) without a micropapillary structure to elucidate the distinctive clinicopathological characteristics of MUMPC and their impact on prognosis. This retrospective analysis included 325 patients diagnosed with mammary mucinous carcinoma admitted to Tianjin Cancer Hospital between July 2014 and December 2019, including 197 patients with MUMPC and 128 patients with PMC without a micropapillary structure. Clinicopathological features were compared, and factors influencing the prognosis of MUMPC were analyzed. Survival analysis was conducted using the Kaplan-Meier method, and univariate and multivariate prognostic analyses for MUMPC were performed using the Cox proportional hazard regression model. The median follow-up period was 76 months. In the MUMPC and PMC groups, the disease-free survival (DFS) rates at 3, 5, and 7 years were 95.4%, 90.4%, 89.8%, and 100%, 98.4%, and 96.9%, respectively, with a statistically significant difference between the two groups (p = 0.009). Tumor, node, and metastasis (TNM) stage, lymph node metastasis, and endocrine treatment were significant factors influencing the prognosis of the MUMPC group (p < 0.001). Multivariate analysis revealed that lymph node metastasis and endocrine therapy were independent prognostic factors in patients with MUMPC (p < 0.001). Compared with PMC, the MUMPC group exhibited a higher prevalence of HER2 (11.2% vs. 3.1%, p = 0.009) and Ki-67 overexpression (79.7% vs. 60.2%, p < 0.001). The lymph node stage is the most crucial clinicopathological feature of MUMPC. Endocrine treatment strategy is an independent risk factor affecting the prognosis of MUMPC.

Improving treatment outcomes for patients with HER2‑positive breast cancer using neoadjuvant double HER2 blockade

Background. Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR.Aim. To improve recommendations regarding HER2-targeted agents and chemotherapy in the neoadjuvant treatment of BC.Materials and methods. N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia took participation in some clinical trials of neoadjuvant treatment of HER2-positive breast cancer, including NeoSphere and NeoALTTO. In multicenter, open-label, phase 2 randomised NeoSphere trial, patients with locally advanced, inflammatory, or early-stage HER2-positive BC were randomly assigned to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m2 from every 3 weeks, increasing to 100 mg/m2 from cycle 2 if tolerated) (group A), pertuzumab (420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC. Рatients in group C received four cycles of docetaxel prior to FEC, and trastuzumab 6 mg/kg every 3 weeks to complete 1 years treatment. In NeoALTTO trial from 455 patients 154 patients received lapatinib, 149 – trastuzumab, 152 – combination of lapatinib and trastuzumab.Results. Between 2007, and 2009, 417 patients were randomly assigned to group A (107 patients), group B (n = 107), group C (n = 107), or group D (n = 96). At clinical cutoff, 87 patients had disease progression or died. 5-year progressionfree survival rates were 81 % (95 % confidence interval (CI) 71–87) for group A, 86 % (95 % CI 72–91) for group B, 73 % for group C, and 73 % for group D (95 % CI 0.34–1.40). Disease-free survival rates were consistent with progressionfree survival rates and were 81 % (95 % CI 72–88) for group A, 84 % (95 % CI 72–91) for group B, 80 % (95 % CI 70–86) for group C, and 75 % (95 % CI 64–83) for group D. In NeoALTTO trial patients who achieved pCR had longer progressionfree survival (85 % (95 % CI 76–91)) compared with patients who did not achieve pCR (76 % (95 % CI 71–81)).Conclusion. High levels of progression-free survival and disease-free survival at 5–10-years follow-up show large and overlapping CI, but support the primary endpoint (pCR) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that pCR could be an early indicator of long-term outcome in early-stage HER2-positive BC.

Mismatched unrelated donors allogeneic hematopoietic stem cell transplantation with antithymocyte globulin for hematological malignancies: a multicenter retrospective study in China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) utilizing mismatched unrelated donors (MMUD) present a vital option for patients with hematologic malignancies without human leukocyte antigen (HLA)-matched donors. This multicenter retrospective study encompassed 211 adults with hematological malignancies receiving allo-HSCT with antithymocyte globulin (ATG) from ≥1 HLA locus MMUD. The findings revealed cumulative incidences of II-IV acute graft-versus-host disease (GVHD) at 180 days at 26.5%, and III-IV acute GVHD at 12.3%, with 3-year cumulative incidences for total and moderate-severe chronic GVHD at 37.0% and 21.0%. The 3-year non-relapse mortality (NRM) and relapse rates were 19.7% and 25.8%. The study reported a 3-year overall survival (OS) rate of 63.1%, a disease-free survival (DFS) rate of 54.5%, and a GVHD-free, relapse-free survival (GRFS) rate of 40.8%. Administration of a lower-dose ATG-Genzyme (ATG-G, ≤ 6 mg/kg) correlated with improved engraftment without significantly affecting survival, relapse, or viral reactivation rates. The quantity of HLA mismatches did not impact engraftment, GVHD, viral reactivation, OS, DFS, GRFS, relapse, or NRM. In conclusion, MMUD allo-HSCT with ATG demonstrates favorable outcomes for patients with hematological malignancies, with no evident correlation between the degree of mismatch and post-transplantation results. Utilizing a lower dose of ATG-G ( ≤ 6 mg/kg) proved efficacious, delivering comparable clinical advantage.

The Ongoing Development of Watch and Wait

AbstractThe nonoperative management of rectal cancer, known as watch and wait (W&amp;W), has gained increasing acceptance in recent years. This approach is based on using complete clinical response (cCR) as a marker for complete pathological response (pCR) following neoadjuvant chemoradiation (nCRT). Advances in nCRT regimens have resulted in higher tumor regression rates, making W&amp;W a viable option for selected patients. This study presents the historical evolution and efficacy of the W&amp;W strategy and offers modern recommendations based on recent clinical findings. Key findings include an 85 to 92% 5-year disease-free survival rate in patients achieving cCR, highlighting the potential for improved quality of life and reduced morbidity without compromising survival outcomes.

Phase II trial evaluating the long-term efficacy and peripheral sensory neuropathy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer

Adjuvant oxaliplatin plus capecitabine (XELOX) therapy is recommended for patients with curatively resected colon cancer. However, prospective data on its practical application in Japanese patients are limited. Therefore, we aimed to conduct a long-term clinical evaluation of the efficacy and safety of adjuvant XELOX in patients with curatively resected stage III colon cancer (MCSCO-1024). This prospective, multi-center, open-label, single-arm, phase II study enrolled patients with curatively resected stage III colon cancer. The treatment protocol consisted of a 120-minute intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and two divided doses oral capecitabine (2000 mg/m2/day) for 14 days in a 3-week cycle, totaling eight cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 5-year overall survival and long-term prognosis of peripheral sensory neuropathy. A total of 196 patients were enrolled between November 2011 and August 2014 (34 months). The 3-year DFS rate was 73%, and the 5-year overall survival rate was 87%. The overall incidence of peripheral sensory neuropathy was 17%, with a 1% rate of grade 3 neuropathy after 5 years. Adjuvant XELOX demonstrated utility and safety in the clinical management of Japanese patients with stage III colon cancer.

The Role of Radiotherapy in Indolent Ocular Adnexal and Orbital Lymphomas.

This study evaluates the oncological outcomes and toxicities of indolent ocular adnexal and orbital lymphomas (OOLs) treated with radiotherapy (RT) ± systemic therapy. A retrospective analysis of 44 patients with indolent OOLs treated with RT was conducted. Most patients (87%) had early-stage disease. Treatment involved RT alone (34%) or RT + systemic therapy (66%). The median RT dose was 30 Gy, with a median follow-up of 45 months. Local and systemic recurrence rates were 4% and 9%, respectively. Five-year overall and disease-free survival (DFS) rates were 96.2% and 83.6%. Early-stage patients showed similar DFS rates regardless of whether they received RT alone or RT plus systemic therapy. No grade 3 RT-related toxicity occurred, but systemic therapy led to grade 3 toxicity in 17% of patients. RT is essential for treating indolent OOLs, and combination with systemic therapies does not enhance outcomes for early-stage patients.

Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix: Comparison of Its Clinicopathological Characteristics and Programmed Death-ligand 1 Expression Status With Those of Other Endocervical Adenocarcinomas.

Invasive stratified mucin-producing carcinoma (ISMC) is a rare but aggressive variant of endocervical adenocarcinoma (EAC). The aim of this study was to investigate the differences in clinicopathological features, patient outcomes, and programmed death-ligand 1 (PD-L1) expression among ISMC, usual-type EAC (UEA), and gastric-type EAC (GEA). PD-L1 22C3 immunostaining was performed using 20 ISMCs, 20 UEAs, and 20 GEAs. Combined positive score (CPS) method was used to assess PD-L1 immunoreactivity. ISMC was diagnosed at a younger age and showed a more advanced stage and shorter survival than UEA. The disease-free survival (DFS) and overall survival (OS) rates of ISMC patients were lower than those of UEA but comparable to those of GEA. ISMC type was an independent prognostic factor for predicting short DFS [hazard ratio (HR)=2.790, 95% confidence interval (CI)=1.153-6.756] and OS (HR=6.071, 95%CI=1.257-29.327). All ISMCs showed PD-L1 over-expression with a mean CPS of 44.5 (range=10-100), which was higher than those of UEA (mean CPS=8.2) and GEA (mean CPS=6.5). PD-L1 positivity (CPS≥1) was also an independent prognostic factor for worse OS (HR=2.472, 95%CI=1.097-5.570). Despite PD-L1 over-expression, ISMC patients treated with pembrolizumab showed no clinical response. All examined ISMCs over-expressed PD-L1. ISMC showed higher PD-L1 expression than UEA and GEA and worse survival than UEA. PD-L1 over-expression was found to be a significant predictor for worse DFS and OS in patients with ISMC. Our data suggest that PD-L1 over-expression is associated with poor ISMC prognosis.

Laparoscopic pancreatoduodenectomy is safe for the treatment of pancreatic ductal adenocarcinoma treated by chemoradiotherapy compared with open pancreatoduodenectomy: A matched case-control study

BackgroundFew studies compared laparoscopic and open pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy. MethodsRetrospective cohort of patients who underwent laparoscopic or open pancreatoduodenectomy for resectable or borderline resectable pancreatic ductal adenocarcinoma after chemoradiotherapy between 2012 and 2023 was analyzed. Open pancreatoduodenectomy patients could theoretically benefit from the laparoscopic approach. We used a 1:2 (laparoscopic-to-open pancreatoduodenectomy) propensity score matching analysis stratified on age, gender, and body mass index. ResultsWe included 128 patients (33 laparoscopic and 95 open pancreatoduodenectomy), and after propensity score matching, 33 laparoscopic pancreatoduodenectomy and 66 open pancreatoduodenectomy were compared. There was no difference in demographic data except for lower tobacco use in laparoscopic pancreatoduodenectomy group (9% vs 30%, P = .023) with similar clinical presentation. Laparoscopic pancreatoduodenectomy compared to open pancreatoduodenectomy showed a longer median operative duration (380 vs 255 minutes, P < .001), shorter median length of resected vein (15 vs 23 mm, P = .01), longer median venous clamping time (29 vs 15 minutes, P = .005), similar median blood loss (300 vs 300 mL, P = .223), similar rate of hard pancreas (97% vs 85%, P = .094), and a larger median size of Wirsung duct (5 vs 4 mm, P = .02). Postoperative outcomes showed similar 90-day mortality rates (3% vs 3%, P > .99), Clavien-Dindo III-IV complications (6% vs 14%, P = .158), median lengths of hospital stay (12 vs 13 days, P = .409), and readmission rates (9% vs 18%, P = .366). Pathologic data showed similar R0 resection rates (88% vs 82%, P = .568). With a similar rate of adjuvant chemotherapy (P = .324) and shorter median follow-up with laparoscopic pancreatoduodenectomy (18 vs 34 months, P = .004), 3-year overall (P = .768) and disease-free (P = .839) survival rates were similar. ConclusionIn selected patients, laparoscopic pancreatoduodenectomy for pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy appears to be safe and feasible when performed in experienced centers.

Monitoring of Circulating Tumor DNA and Indication of De-Escalation Adjuvant Targeted Therapy for EGFR-Mutated NSCLC After Complete Resection

IntroductionEGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation. MethodsFrom January 2019 to December 2022, 71 patients with stages I to III NSCLC and EGFR (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD_Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group. ResultsOverall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post–EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0–35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission. ConclusionsOur initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring.

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.

Patients with gastroesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastroesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastroesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastroesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1:1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg IV every 2 weeks plus ipilimumab 1 mg/kg IV every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, loco-regional and distant failure rates and safety according to NCI-CTCAE v5.0. The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months (95% confidence interval [CI], 8.4-16.8 months) versus 20.8 months (95% CI, 15.0-29.9 months) for the chemotherapy group, HR 1.55 (95% CI, 1.07- 2.25, one-sided P=0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. Nivolumab/ipilimumab did not improve disease-free survival compared to chemotherapy in patients with ypN+ and/or R1 gastroesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.

Clinicopathological Characteristics and Perioperative Treatment of Epstein-Barr Virus-Associated Gastric Cancer: A Retrospective Study.

The clinicopathological characteristics and perioperative treatment outcomes of patients with EBVaGC who underwent radical gastrectomy in Tianjin Medical University Cancer Hospital from September 2016 to May 2022 were retrospectively reviewed. Disease-free survival (DFS) was analyzed and Cox regression analysis was performed to identify risk factors. The study cohort included 128 patients with EBVaGC. Histologically, 126 (98.4%) patients had adenocarcinoma and only 2 (1.6%) had adenosquamous carcinoma. In addition, 18 (14.1%) had nerve invasion and 29 (22.7%) had vascular invasion. Notably, 41 (32.0%) patients had tumors in the proximal stomach and 69 (53.9%) had no lymph node metastasis. Proficient mismatch repair was confirmed in all 104 patients with available results. Overall, 16 (12.5%) patients received neoadjuvant therapy, 81 (63.3%) received adjuvant therapy, and 10 (7.8%) received perioperative immunotherapy combined with chemotherapy. In total, 22 patients experienced disease progression or had died. The 3-year DFS rate was 75.0%. DFS was relatively poorer for patients with advanced tumor (T) stage, lymph node (N) stage, disease stage, and vascular invasion. EBVaGC had unique clinicopathological characteristics and prognosis. Advanced T, N, and disease stages, in addition to vascular invasion, were predictive of poorer DFS. However, the efficacy of perioperative treatment of EBVaGC remains uncertain.

Combined analysis of the MF18-02/MF18-03 NEOSENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in patients with breast cancer with a good response to neoadjuvant chemotherapy as long as radiotherapy is provided.

The omission of axillary lymph node dissection (ALND) remains controversial for patients with residual axillary disease after neoadjuvant chemotherapy (NAC), regardless of the residual burden. This study evaluated the oncologic safety and factors associated with outcomes in patients with residual axillary disease. These patients were treated solely with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), without ALND, after NAC. A joint analysis of two different multicenter cohorts-the retrospective cohort registry MF18-02 and the prospective observational cohort registry MF18-03 (NCT04250129)-was conducted between January 2004 and August 2022. All patients received regional nodal irradiation. Five hundred and one patients with cT1-4, N1-3M0 disease who achieved a complete clinical response to NAC underwent either SLNB alone (n=353) or TAD alone (n=148). At a median follow-up of 42 months, axillary and locoregional recurrence rates were 0.4% (n=2) and 0.8% (n=4). No significant difference was found in disease-free survival (DFS) and disease-specific survival (DSS) rates between patients undergoing TAD alone versus SLNB alone, those with breast positive versus negative pathologic complete response, SLN methodology, total metastatic LNof one versus ≥2, or metastasis types as isolated tumor cells with micrometastases versus macrometastases. In the multivariate analysis, patients with nonluminal pathology were more likely to have a worse DFS and DSS, respectively, without an increased axillary recurrence. The omission of ALND can be safely considered for patients who achieve a complete clinical response after NAC, even if residual disease is detected by pathologic examination. Provided that adjuvant radiotherapy is administered, neither the SLNB method nor the number of excised LNs significantly affects oncologic outcomes.

Invasive disease-free survival and brain metastasis rates in patients treated with neoadjuvant chemotherapy with trastuzumab and pertuzumab

Patients with HER2(+) early breast cancer (EBC) receiving neoadjuvant systemic therapy (NAST) have poorer outcomes if they have residual disease (RD). We analyzed IDFS and brain metastasis (BM) rates in patients with HER2(+) EBC treated with NAST and report the outcomes of patients with HER2(−) RD. Patients with HER2(+) EBC who received NAST between 1 Jan 2019 and 31 Jan 2022 were reviewed. IDFS was defined as the time from surgery until first occurrence of invasive breast cancer recurrence, distant recurrence, or death from any cause. The total cohort was 594 patients. pCR (ypT0/isN0) was achieved in 325(55%) and RD was seen in 269(45%) patients. In 269 patients with RD, 45(17%) did not have HER2 retesting and were excluded. In the remaining 224 patients, 143(64%) were HER2(+) and 81(36%) were HER2(−). With a median follow up of 24 months, 8 patients developed BM at initial recurrence, 4/325(1.2%) with pCR and 4/143(2.8%) with HER2(+) RD. IDFS events occurred in 22/594(3%) patients; 14/269(5%) in RD and 8/325(2%) in pCR (p = 0.04). There was no difference in IDFS between 9/143(6%) patients with HER2(+) RD or 5/81(6%) with HER2(−) RD (p = 0.10). Patients with RD had higher IDFS events than those with pCR. In those with RD, 36% lost HER2(+) status; IDFS events appeared similar in those with HER2(+) RD versus those with HER2(−) RD. The BM events seen in those with RD and pCR highlights the need for more effective therapy in NAST and adjuvant setting to minimize BM risk.