Novel MEN1-associated retroperitoneal pleomorphic liposarcoma.

Soft tissue sarcomas are rarely associated with mutations of the MEN1 gene. We report a patient with a large retroperitoneal pleomorphic liposarcoma harboring a rare mutation of the MEN1 gene not previously reported to be associated with soft tissue sarcomas. This report expands the known spectrum of MEN1-associated cancers.

High expression of PAX8-AS1 correlates with poor prognosis and response to fluorouracil-based chemotherapy in stage II colon cancer.

Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.

Determining the optimal timing of adjuvant chemotherapy initiation after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Studies on several malignancies have suggested that the time to commencement of adjuvant chemotherapy (AC) is associated with survival outcomes. There have, however, been no relevant reports of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: This clinical study examined newly diagnosed patients between April 2017 and December 2020. The primary endpoint was progression-free survival (PFS). Inverse probability of treatment weighting was used to control for confounding factors. Cox models with restricted cubic splines, Kaplan-Meier method and log-rank tests were used to evaluate the relationship between AC timing and survival. RESULTS: A total of 551 patients were identified [median age, 45 years (interquartile range 36-52 years); 383 (69.5%) male]. Restricted cubic splines demonstrated that the timing of AC initiation had a U-shaped association with PFS. The risk of disease progression decreased within 37 days and subsequently increased. From 37 to 90 days, each additional 7-day delay conferred worse PFS of 1.32 months {hazard ratio (HR): 1.14 [95% confidence interval (CI) 1.01-1.28], P = 0.04}. The cut-off value of the receiver operating characteristic curve for initiation was 69.5 days. At a median follow-up of 48 months, the PFS was significantly better in patients initiated within 69.5 days [HR: 2.18 (95% CI 1.17-4.06), log-rank P = 0.009], with a higher 3-year rate [78.8% (95% CI 75.1% to 82.7%) versus 59.0% (95% CI 42.2% to 82.5%)] than beyond 69.5 days. Positive results were also observed in secondary endpoints. The initiation group was an independent prognostic factor [HR: 2.28 (95% CI 1.42-3.66), P < 0.001]. CONCLUSIONS: The optimal timing of AC initiation is ∼37 days after concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. A delay beyond 69.5 days is associated with compromised survival. Efforts should be made to address the reasons for delays and ensure the timely initiation of AC.

How to Tackle Discordance in Adjuvant Chemotherapy Recommendations by Using Oncotype DX Results, in Early-Stage Breast Cancer.

BACKGROUND: The use of the Oncotype DX test reduces the rate of adjuvant chemotherapy recommendations. Few in-depth analyses have been performed on this decision-making process. METHODS: We retrospectively analyzed patient data based on available Oncotype DX test results (RS) irrespective of nodal status at a single center. We collected recommendations from six oncologists, first without RS (pre-RS) and then with RS results (post-RS). We investigated changes in recommendations, agreement between oncologist decisions, and the effect of different National Comprehensive Cancer Network (NCCN) recommendation categories (for, against, and considering chemotherapy). RESULTS: Data from 201 patients were included in the analysis. Recommendation of chemotherapy decreased by an average of 39.5%. Agreement improved substantially with RS, with a kappa value pre-RS of 0.37 (fair agreement) and post-RS of 0.75 (substantial agreement). Discordance remained substantial in cases where the NCCN recommendations considered chemotherapy only (32%). Pre-RS consensus against chemotherapy predicted low RS results (50 out of 51 patients). Post-RS consensus was highest in the NCCN chemotherapy recommendation group. CONCLUSIONS: The Oncotype DX test substantially improves decision accuracy in recommending adjuvant chemotherapy. It may be further improved with a consensus decision. In the case of pre-RS consensus against chemotherapy, the test can be spared.

The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (> 2 cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study.

BACKGROUND: The use of adjuvant osimertinib for epidermal growth factor receptor (EGFR) mutants is expected to expand to earlier stage I in the future, potentially competing with the current standard of care, oral tegafur/uracil (UFT), in Japan. However, the effect of EGFR mutation status on the therapeutic effect of UFT remains unclear. This study was conducted as an exploratory analysis of a retrospective observational study that investigated the real-world data of postoperative adjuvant chemotherapy in Japan (CSPOR-LC03). METHODS: Between 2008 and 2013, 1812 patients with completely resected adenocarcinoma diagnosed as pathologic stage I (T1 > 2 cm, TNM classification, sixth edition) who have maintained organ function, and no history of other cancers were included. The primary endpoint was the 5-year disease-free survival (DFS) rate, and we compared this rate between four groups classified based on the administration of adjuvant UFT and EGFR mutation status. RESULTS: Of the 933 (51%) patients with EGFR mutations, 394 underwent adjuvant UFT therapy. Of the 879 (49%) patients without EGFR mutations, 393 underwent adjuvant UFT therapy. The 5-year DFS of UFT+/EGFR+ and UFT-/EGFR+ patients were 82.0 and 87.1%, respectively, and those of UFT+/EGFR- and UFT-/EGFR- patients were 80.0 and 86.9%, respectively. DFS was significantly worse in the UFT+ group than in the UFT- group (P = 0.015). Adjuvant UFT therapy was not an independent prognostic factor for DFS, regardless of the EGFR mutation status. CONCLUSION: In pathologic stage I (>2 cm) lung adenocarcinomas with EGFR mutation, the survival benefit of adjuvant UFT was not observed.

Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: subgroup analysis from CIRCULATE-Japan GALAXY.

BACKGROUND: The prognostic role of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection and its utility for postsurgical risk stratification has been reported in colorectal cancer. In this study, we explored the use of ctDNA-based MRD detection in patients with colorectal liver metastases (CLM), for whom the survival benefit of adjuvant chemotherapy (ACT) after surgical resection remains unclear. METHODS: Patients with CLM without extrahepatic disease from the GALAXY study (UMIN000039205) were included. The disease-free survival (DFS) benefit of ACT was evaluated in MRD-positive and -negative groups after adjusting for age, gender, number, and size of liver metastases, RAS status, and previous history of oxaliplatin for primary cancer. ctDNA was detected using a personalized, tumor-informed 16-plex polymerase chain reaction-next-generation sequencing (mPCR-NGS) assay. ctDNA-based MRD status was evaluated 2-10 weeks after curative surgery, before the start of ACT. RESULTS: Among 6061 patients registered in GALAXY, 190 surgically resected CLM patients without any preoperative chemotherapy were included with a median follow-up of 24 months (1-48 months). ctDNA positivity in the MRD window was 32.1% (61/190). ACT was administered to 25.1% (48/190) of patients. In the MRD-positive group, 24-month DFS was higher for patients treated with ACT [33.3% versus not reached, adjusted hazard ratio (HR): 0.07, P < 0.0001]; whereas no benefit of ACT was seen in the MRD-negative group (24-month DFS: 72.3% versus 62.2%, adjusted HR: 0.68, P = 0.371). Multivariate analysis showed that the size of liver metastases (HR: 3.94, P = 0.031) was prognostic of DFS in the MRD-positive group. In the MRD-negative group, however, none of the clinicopathological factors were prognostic of DFS. CONCLUSIONS: Our data suggest that ACT may offer notable clinical benefits in MRD-positive patients with CLM. MRD status-based risk stratification could be potentially incorporated in future clinical trials for CLM.

Successful outcome achieved with adjuvant chemotherapy with irinotecan plus cisplatin in rectal neuroendocrine carcinoma: a case report.

BACKGROUND: Rectal neuroendocrine carcinomas (NECs) are rare and associated with poorer prognoses compared to conventional adenocarcinomas. The efficacy of adjuvant chemotherapy for resectable rectal NECs remains uncertain. Herein, we present a case of rectal NEC successfully treated with postoperative chemotherapy using irinotecan plus cisplatin. CASE PRESENTATION: A 48-year-old woman with a history of endometrial cancer presented with an intramural rectal tumour detected on follow-up imaging. Colonoscopy revealed a 30 mm submucosal tumour, and laparoscopic low anterior resection was performed. Histopathological examination showed poorly differentiated atypical cells with solid growth patterns. Metastasis from the uterine cancer was ruled out due to histological differences between the primary uterine tumour and the rectal lesion, as well as the absence of hormone receptor immunohistochemical expression. Further immunohistochemical analysis revealed diffuse CD56 positivity, a high mitotic rate (> 20/10 high power fields) and a Ki-67 labelling index exceeding 70%. Based on these findings, a diagnosis of rectal NEC, T3N0M0, Stage IIB (UICC 8th edition), was established. Given the aggressive nature of the tumour evidenced by a high Ki-67 labelling index, adjuvant chemotherapy comprising six cycles of irinotecan plus cisplatin was administered to mitigate the risk of recurrence. At the 3-year follow-up, the patient was free of disease recurrence. CONCLUSION: This case highlights the importance of multidisciplinary surgical interventions followed by adjuvant chemotherapy in managing rectal NECs.

Patient-Reported Outcomes of Postoperative NSCLC Patients with or without Staged Chinese Herb Medicine Therapy during Adjuvant Chemotherapy (NALLC 2): A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION: The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).

Clinical, pathological, and adjuvant chemotherapy use differences among microsatellite unstable and microsatellite stable colon cancers.

Background: Colon cancers are categorized into mismatch repair deficient/microsatellite unstable (MSI-H) and mismatch repair proficient/microsatellite stable (MSS) cancers. This study aims to compare the disease characteristics and trends in the utilization of cancer therapies across different age groups and stages in these two groups. Methods: MSI-H and MSS colon adenocarcinomas from 2010 to 2016 were identified using the National Cancer Database. We compared patient and disease characteristics between the two groups and evaluated the use of adjuvant chemotherapy across age groups and cancer stages. Within MSI-H and MSS groups, we conducted a landmark analysis after propensity score matching for adjuvant chemotherapy versus no chemotherapy to determine its effect on survival. Results: Of the 542,368 patients that met inclusion criteria, 120,751 (22%) had mismatch repair results available-out of these 96,928 (80%) had MSS colon cancers while 23,823 (19.7%) had MSI-H cancers. MSI-H disease had a bimodal age distribution (<40 years = 22%; ≥75 years = 26%) and was frequent among females (22%) and non-Hispanic Whites (20%). Among those < 65 years, 15% of low-risk stage 2 MSI-H patients and 40% of high-risk stage 2 MSI-H patients received adjuvant chemotherapy. More than two-thirds of stage 3 patients <65 years received adjuvant chemotherapy in both groups. After conducting propensity-score matching for age, gender, and co-morbidities, we found that adjuvant chemotherapy use had a trend towards lower overall survival (OS) in low-risk stage 2 MSI-H (HR = 1.8 [95% CI, 0.8-4.02]) and high-risk stage 2 MSI-H (HR = 1.42 [95% CI, 0.96-2.12]) groups. Adjuvant chemotherapy significantly improved OS in stage 3 colon cancer patients irrespective of microsatellite status or risk category of disease. Conclusions: MSI-H colon cancer had bimodal age distribution. Among stage 2 MSI-H patients <65 years, a notable proportion received adjuvant chemotherapy. Among MSI-H stage 2 patients, adjuvant chemotherapy use was associated with lower survival while it significantly improved survival for stage 3 patients, irrespective of MSI status.

Comparison of the effectiveness of neoadjuvant chemotherapy and adjuvant chemotherapy for improving prognosis in triple-negative breast cancer patients.

OBJECTIVE: To compare the effectiveness of surgery combined with neoadjuvant chemotherapy and radiotherapy (SNCR) versus surgery combined with adjuvant chemotherapy and radiotherapy (SACR) in improving the prognosis of triple-negative breast cancer (TNBC) patients. METHODS: Clinical data from 112 TNBC patients treated between January 2014 and February 2019 were retrospectively collected. Data included clinical characteristics and 5-year disease-free survival (DFS). Kaplan-Meier (K-M) survival curves were used to analyze the associations of various factors with DFS. Lasso-Cox regression was used to screen significant variables identified by K-M survival analysis. Multivariate Cox regression was used to determine independent prognostic factors affecting DFS. RESULTS: K-M survival analysis showed that treatment regimen (P=0.012), TNM (tumor, node, metastasis) staging (P=0.049), N staging (P=0.015), P53 (P=0.015), KI-67 (P=0.002), neutrophil-to-lymphocyte ratio (NLR) (P<0.001), platelet-to-lymphocyte ratio (PLR) (P<0.001), and cancer antigen 153 (CA153) (P<0.001) were associated with DFS in TNBC patients. Lasso-Cox regression analysis identified treatment regimen, TNM stage, P53, KI-67, NLR, PLR, and CA153 as features related to DFS when λ=0.053741 (1se). Multivariate Cox regression analysis revealed that treatment regimen (P<0.001, 95% CI: 2.309-14.396, HR=5.765), P53 (P=0.010, 95% CI: 1.315-7.864, HR=3.216), and NLR (P=0.001, 95% CI: 2.098-14.553, HR=5.525) were independent prognostic factors affecting DFS. A nomogram model was constructed, and time-dependent receiver operating characteristic (ROC) curve analysis showed that the model's areas under the curve (AUC) for predicting 1-, 3-, and 5-year DFS were 0.928, 0.816, and 0.665, respectively. CONCLUSION: The SNCR regimen significantly improves DFS in patients with stage IIb to IIIa TNBC compared to the traditional SACR regimen.

Systemic immunoinflammatory index and prognostic nutrition index for predicting pathologic responses of patients with advanced gastric cancer after neoadjuvant therapy for advanced gastric cancer.

To investigate the value of prognostic nutrition index (PNI) and systemic immunoinflammatory index (SII) for predicting pathological responses of patients with advanced gastric cancer (GC) after neo-adjuvant chemotherapy (NACT). The clinicopathological data of 326 patients with advanced GC who received NACT in Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) from January 2017 to December 2021 were retrospectively collected. The SII and PNI of patients were calculated. The receiver operating characteristics (ROC) curve was leveraged for getting the optimal cutoff values of SII and PNI. The pathological response of patients after NACT, as obtained from their postoperative pathological examinations, was evaluated based on the tumor regression grade (TRG) criteria. Multivariate regression analysis was employed for identifying factors that led to various pathological responses after NACT in advanced GC patients. The log-rank test was utilized for between-group comparison of patients' survival curves. The SII and PNI were 507.45 and 48.48 respectively, and their levels were divided into high and low groups. Pathological response (TRG 0-1) was observed in 66 cases (20.25%), while non-pathological response (TRG 2-3) was observed in 260 cases (79.75%). The results of multivariate logistic regression analysis showed that tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX (capecitabine combined with oxaliplatin), SII < 507.45 (P=0.002), PNI > 48.48 were all independent factors affecting the pathological responses of advanced GC patients after NACT (all P < 0.05). With SII and PNI being included, the AUC was 0.821 (95% CI: 0.765-0.876), and the specificity was 87.90% and the sensitivity was 64.20%. The Kaplan-Meier survival curve analysis showed that NACT patients with tumor diameter < 5 cm, ypT T0-T2, ypN N0, XELOX chemotherapy regimen, SII < 507.45 and SII ≥ 507.45 had a higher survival rate. (P < 0.001). Before treatment, tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX, SII < 507.45, PNI > 48.48 were all independent factors affecting the pathological response of advanced GC patients after NACT. Moreover, the inclusion of SII and PNI increased the accuracy of predicting the pathological response of patients after NACT.

Efficacy and safety of nanoparticle albumin­bound paclitaxel compared with solvent­based paclitaxel in adjuvant therapy for breast cancer: A retrospective study.

The current evidence for the use of nanoparticle albumin-bound paclitaxel (nab-PTX) for adjuvant breast cancer chemotherapy is insufficient. The present study aimed to assess the efficacy and toxicity of nab-PTX in comparison with solvent-based paclitaxel (sb-PTX) in postoperative adjuvant breast cancer treatment. A total of 345 patients were included in the study and separated into nab-PTX (n=289) and sb-PTX (n=56) groups based on the type of taxane used in the adjuvant chemotherapy regimen. The study evaluated the baseline characteristics in both groups and the risk factors for postoperative recurrence of mammary cancer. Furthermore, data concerning disease-free survival (DFS) and adverse effects were obtained and analyzed, and group confounding variables were addressed using 1:2 propensity score matching (PSM). Comparisons before PSM revealed significant differences in baseline characteristics including age, underlying disease, lymph node involvement, vascular invasion, human epidermal growth factor receptor 2 and axillary surgery (P<0.05). Following PSM, there were 90 patients in the nab-PTX group and 56 in the sb-PTX group, with no significant differences in the baseline differences (P>0.05). Before PSM, the 73-month DFS rate was 97.9% in the nab-PTX group compared with 91.1% in the sb-PTX group. However, there were no significant differences between the groups before or after PSM (P=0.15 and P=0.49, respectively). Additionally, Cox regression analysis demonstrated a significantly lower chance of recurrence in patients aged >45 years [hazard ratio (HR), 0.197; 95% confidence interval (CI), 0.052-0.753; P=0.018], whereas underlying disease (HR, 5.352; 95% CI, 1.310-21.854; P=0.019) and lymph node infiltration (HR, 8.930; 95% CI, 1.121-71.161; P=0.039) significantly increased the risk of recurrence. Regarding safety, the sb-PTX group had a significantly greater incidence of anaphylaxis, whereas the nab-PTX group had significantly increased rates of anemia and peripheral neuropathy (P<0.05). In summary, the 73-month DFS rate of the nab-PTX cohort exceeded that of the sb-PTX cohort, but no significant difference was detected between them. Underlying disease, lymph node metastasis and an age of ≤45 years are significant predictors of postoperative recurrence of breast cancer.

Evaluating the Efficacy of Different Treatment Intensities in Nasopharyngeal Carcinoma Patients: A Nationwide Cancer Registry-Based Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy of different treatment intensities (TIs) in patients with nasopharyngeal carcinoma (NPC). METHODS: The study assessed newly diagnosed, non-metastatic NPC patients from the Taiwan Cancer Registry between 2010 and 2017. TIs were divided into four groups: TI1 [radiotherapy (RT) alone or induction chemotherapy (IC) followed by RT); TI2 (concurrent chemoradiotherapy (CRT) alone); TI3 (IC followed by CRT or CRT followed by adjuvant chemotherapy (AC)]; and TI4 (IC followed by CRT followed by AC). The primary outcome was cancer-specific survival (CSS). RESULTS: The study included 9863 patients. For stage I-II NPC patients, there was no significant difference in CSS among the different TI groups. For stage III patients, those receiving TI3 had better CSS (hazard ratio [HR] 0.69) compared with those receiving TI1. No significant differences in CSS were noted among those receiving TI2, TI3, and TI4. For stage IVA-B patients, those receiving TI2 (HR 0.70), TI3 (HR 0.49), and TI4 (HR 0.43) had better CSS compared with those receiving TI1. Compared with stage IVA-B patients receiving TI2, those receiving TI3 (HR 0.70) and TI4 (HR 0.61) had significantly better CSS. No differences in CSS were noted between those receiving TI3 and TI4. CONCLUSIONS: For stage I-II NPC patients, RT alone is appropriate. For stage III and IVA-B patients, IC + CRT or CRT + AC may be needed to achieve optimal outcomes. No advantage of IC + CRT + AC over IC + CRT or CRT + AC was observed.

Multitask machine learning-based tumor-associated collagen signatures predict peritoneal recurrence and disease-free survival in gastric cancer.

BACKGROUND: Accurate prediction of peritoneal recurrence for gastric cancer (GC) is crucial in clinic. The collagen alterations in tumor microenvironment affect the migration and treatment response of cancer cells. Herein, we proposed multitask machine learning-based tumor-associated collagen signatures (TACS), which are composed of quantitative collagen features derived from multiphoton imaging, to simultaneously predict peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS). METHODS: Among 713 consecutive patients, with 275 in training cohort, 222 patients in internal validation cohort, and 216 patients in external validation cohort, we developed and validated a multitask machine learning model for simultaneously predicting peritoneal recurrence (TACSPR) and disease-free survival (TACSDFS). The accuracy of the model for prediction of peritoneal recurrence and prognosis as well as its association with adjuvant chemotherapy were evaluated. RESULTS: The TACSPR and TACSDFS were independently associated with peritoneal recurrence and disease-free survival in three cohorts, respectively (all P < 0.001). The TACSPR demonstrated a favorable performance for peritoneal recurrence in all three cohorts. In addition, the TACSDFS also showed a satisfactory accuracy for disease-free survival among included patients. For stage II and III diseases, adjuvant chemotherapy improved the survival of patients with low TACSPR and low TACSDFS, or high TACSPR and low TACSDFS, or low TACSPR and high TACSDFS, but had no impact on patients with high TACSPR and high TACSDFS. CONCLUSIONS: The multitask machine learning model allows accurate prediction of peritoneal recurrence and survival for GC and could distinguish patients who might benefit from adjuvant chemotherapy.

Differential effect of tumor budding on the benefit of adjuvant chemotherapy in stage II colorectal cancer: a retrospective observational study.

Background: Tumor budding (TB) has been shown to be a poor prognostic indicator after colorectal cancer (CRC) surgery. The aim of the present study is to evaluate the predictive role of morphological features (e.g., the number, structure, and location of tumor buds, and their reaction with the extracellular mesenchyme) in postoperative adjuvant chemotherapy in surgically resectable stage II CRC. Methods: Between 2016 and 2019, 336 patients with stage II CRC who underwent radical surgery were enrolled in this study. TB status was determined according to the criteria adopted at the 2016 International Tumor Budding Consensus Conference (ITBCC). We retrospectively recorded all the clinical and pathological data and assessed the effect of different types of TB status on patients' recurrence-free survival (RFS) and overall survival (OS). Results: Of the 336 patients, 173, 88, and 75 were budding grade 1 (BD1), BD2, and BD3, respectively. The 5-year RFS rates were 84.6%, 81.2%, and 68.0% (P=0.01), and the 5-year OS rates were 91.0%, 83.3%, and 76.2% (P=0.007) in BD1, BD2, and BD3, respectively. TB grade was strongly associated with vascular invasion status and mucinous adenocarcinoma, and BD3 was detected in 51.7% of patients with positive vascular invasion. The multivariate analysis showed that only age, perineural invasion, and TB grade [BD2 vs. BD1, hazard ratio (HR) =1.468, 95% confidence interval (CI): 0.703-3.063, P=0.30; BD3 vs. BD1, HR =2.310, 95% CI: 1.154-4.625, P=0.01] had an independent effect on RFS. In addition, the Kaplan-Meier curve analysis showed that BD3 patients had the worst RFS (P=0.01). The OS of the adjuvant chemotherapy group was significantly improved compared to that of the surgery-only group in the BD1/2 patients (HR =0.278, 95% CI: 0.114-0.676, P=0.005) but not in the BD3 patients with significant interaction (Pinteraction=0.03). Conclusions: Our results indicate that TB could play a subsidiary role in selecting stage II CRC patients who could achieve a favorable prognosis with chemotherapy.

The benefit of adjuvant chemotherapy in pathological T1-3N0M0 rectal mucinous adenocarcinoma: no improvement survival outcomes based on long-term survival analysis of large population data.

Background: Currently, the benefits of the administration of adjuvant chemotherapy (AT) in pathological low-risk rectal mucinous adenocarcinoma (RM) with T1-3N0M0 are unclear. The objective of this study is to retrospectively investigate the clinical significance of AT in terms of survival outcomes for patients with pathological T1-3N0M0 RM using data from a large population. Methods: The patient data were collected from the Surveillance, Epidemiology, and End Results (SEER) Program. The Chi-squared test was used to analyze categorical variables. The survival curves were compared using the log-rank test and the Kaplan-Meier method. A multivariate proportional hazards regression (Cox) model was applied to identify the independent prognostic factors of survival outcomes. Propensity score matching (PSM) was utilized to eliminate the differences between groups and estimate AT's effect. Results: The median follow-up duration for the rectal cancer (RC) cohort was 116 months. Multivariate analyses revealed that RM was a significant adverse prognostic factor, correlating with poorer overall survival (OS) and cancer-specific survival (CSS) for RC [hazard ratio (HR): 1.226, 95% confidence interval (CI): 1.094-1.375, P<0.001; HR: 1.446, 95% CI: 1.242-1.683, P<0.001]. Among patients with RM, the rates of 5-year OS and CSS were 68.6% and 79.3% in the AT (-) group, respectively. Additionally, the AT (+) group exhibited similar rates of 65.6% for 5-year OS and 74% for CSS (P=0.80, P=0.26). Subtype analysis according to preoperative therapy status showed that AT also did not significantly affect survival outcomes (P=0.65, P=0.34; P=0.90, P=0.76). Conclusions: Our study found that RM is a poor prognostic factor in pathological T1-3N0M0 RC. However, AT does not appear necessary to improve survival outcomes of pathological T1-3N0M0 RM.

Developing Patient-Derived 3D-Bioprinting models of pancreatic cancer.

INTRODUCTION: Pancreatic cancer (PC) remains a challenging malignancy, and adjuvant chemotherapy is critical in improving patient survival post-surgery. However, the intrinsic heterogeneity of PC necessitates personalized treatment strategies, highlighting the need for reliable preclinical models. OBJECTIVES: This study aimed to develop novel patient-derived preclinical PC models using three-dimensional bioprinting (3DP) technology. METHODS: Patient-derived PC models were established using 3DP technology. Genomic and histological analyses were performed to characterize these models and compare them with corresponding patient tissues. Chemotherapeutic drug sensitivity tests were conducted on the PC 3DP models, and correlations with clinical outcomes were analyzed. RESULTS: The study successfully established PC 3DP models with a modeling success rate of 86.96%. These models preserved genomic and histological features consistent with patient tissues. Drug sensitivity testing revealed significant heterogeneity among PC 3DP models, mirroring clinical variability, and potential correlations with clinical outcomes. CONCLUSION: The PC 3DP models demonstrated their utility as reliable preclinical tools, retaining key genomic and histological characteristics. Importantly, drug sensitivity profiles in these models showed potential correlations with clinical outcomes, indicating their promise in customizing treatment strategies and predicting patient prognoses. Further validation with larger patient cohorts is warranted to confirm their potential clinical utility.

Effect of postsurgical adjuvant chemotherapy timing on outcomes in patients with pancreatic cancer - a systematic review and meta-analysis.

To assess the association between the timing of postsurgical adjuvant chemotherapy and overall survival (OS) and disease-free survival (DFS) in patients with pancreatic cancer (PC). Literature search of PubMed, EMBASE, and Scopus databases was done for randomized controlled trials (RCTs) or observational studies (cohort studies, case-control studies), reporting outcomes of adult PC patients (aged 18 and above) who underwent surgery and received adjuvant chemotherapy at different time points after the operation. Pooled effect sizes were quantified and reported as hazard ratio (HR). The primary outcomes were OS and DFS. A random effects model to was used account for potential variability across studies. Sixteen studies were included. There was no significant difference between early and delayed initiation of adjuvant chemotherapy in terms of OS (HR 1.03, 95% CI: 0.98, 1.08) and DFS (HR 1.09, 95% CI: 0.91, 1.31). Subgroup analyses based on tumour stage, sample size, and the number of chemotherapeutic agents used did not reveal significant associations. Delayed initiation was associated with reduced OS in patients with well- to moderately differentiated tumours, with the confidence intervals approaching statistical significance (HR 1.12, 95% CI: 1.00,1.25). There was no significant association between the timing of postoperative adjuvant chemotherapy initiation and OS and DFS in patients with pancreatic cancer. These findings underscore the importance of optimizing treatment strategies and suggest that clinicians need to focus on other critical aspects such as drug selection, dosage, and patient-specific factors that might substantially impact treatment efficacy.

ENGOT-en11/GOG-3053/KEYNOTE-B21: A Randomised, Double-Blind, Phase 3 Study of Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy in Patients With Newly Diagnosed, High-Risk Endometrial Cancer.

BACKGROUND: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent pMMR and dMMR endometrial cancer (EC), with greater magnitude of benefit in the dMMR phenotype. We evaluated addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly-diagnosed, high-risk EC without any residual macroscopic disease following curative-intent surgery. METHODS: Patients with histologically confirmed high-risk (FIGO stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology) EC following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200mg or placebo Q3W for 6 cycles added to carboplatin-paclitaxel followed by pembrolizumab 400mg or placebo Q6W for 6 cycles per treatment assignment. Radiotherapy was at the investigator's discretion. Primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. RESULTS: 1095 patients were randomised (pembrolizumab, n=545; placebo, n=550). At this interim analysis (data cutoff, 4-March2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group (hazard ratio, 1.02 [95% CI, 0.79‒1.32]; P=0.570). Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI, 0.14‒0.69) in the dMMR population (n=281) and 1.20 (95% CI, 0.91‒1.57) in the pMMR population (n=814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. CONCLUSION: Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly-diagnosed, high-risk, all-comer EC. Preplanned subgroup analyses for stratification factors suggests pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable.

A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage II-III gastric cancer patients.

Objective: Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions. In this study, we evaluated the clinical feasibility of the single patient classifier (SPC) test, a new clinical-grade prognostic assay, in stage II-III gastric cancer patients. Methods: A prospective multicenter study was conducted, involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals. The SPC test was employed to stratify patients into risk groups, and its feasibility and performance were evaluated. The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment. Furthermore, 3-year disease-free survivals of risk groups were analyzed. Results: The SPC test met the primary endpoint criteria. The 99.5% of SPC tests were timely delivered to hospitals before the postoperative treatment started. In a clinical setting, the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d. Furthermore, 3-year disease-free survivals were significantly different between risk groups classified with SPC tests. Conclusions: This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies. It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.