Worse Recurrence-free Survival Research Articles

Intertumoral Heterogeneity Based on MRI Radiomic Features Estimates Recurrence in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) heterogeneity impacts prognosis, and imaging is a potential indicator. To characterize HCC image subtypes in MRI and correlate subtypes with recurrence. Retrospective. A total of 440 patients (training cohort = 213, internal test cohort = 140, external test cohort = 87) from three centers. 1.5-T/3.0-T, fast/turbo spin-echo T2-weighted, spin-echo echo-planar diffusion-weighted, contrast-enhanced three-dimensional gradient-recalled-echo T1-weighted with extracellular agents (Gd-DTPA, Gd-DTPA-BMA, and Gd-BOPTA). Three-dimensional volume-of-interest of HCC was contoured on portal venous phase, then coregistered with precontrast and late arterial phases. Subtypes were identified using non-negative matrix factorization by analyzing radiomics features from volume-of-interests, and correlated with recurrence. Clinical (demographic and laboratory data), pathological, and radiologic features were compared across subtypes. Among clinical, radiologic features and subtypes, variables with variance inflation factor above 10 were excluded. Variables (P < 0.10) in univariate Cox regression were included in stepwise multivariate analysis. Three recurrence estimation models were built: clinical-radiologic model, subtype model, hybrid model integrating clinical-radiologic characteristics, and subtypes. Mann-Whitney U test, Kruskal-Wallis H test, chi-square test, Fisher's exact test, Kaplan-Meier curves, log-rank test, concordance index (C-index). Significance level: P < 0.05. Two subtypes were identified across three cohorts (subtype 1:subtype 2 of 86:127, 60:80, and 36:51, respectively). Subtype 1 showed higher microvascular invasion (MVI)-positive rates (53%-57% vs. 26%-31%), and worse recurrence-free survival. Hazard ratio (HR) for the subtype is 6.10 in subtype model. Clinical-radiologic model included alpha-fetoprotein (HR: 3.01), macrovascular invasion (HR: 2.32), nonsmooth tumor margin (HR: 1.81), rim enhancement (HR: 3.13), and intratumoral artery (HR: 2.21). Hybrid model included alpha-fetoprotein (HR: 2.70), nonsmooth tumor margin (HR: 1.51), rim enhancement (HR: 3.25), and subtypes (HR: 5.34). Subtype model was comparable to clinical-radiologic model (C-index: 0.71-0.73 vs. 0.71-0.73), but hybrid model outperformed both (C-index: 0.77-0.79). MRI radiomics-based clustering identified two HCC subtypes with distinct MVI status and recurrence-free survival. Hybrid model showed superior capability to estimate recurrence. 3 TECHNICAL EFFICACY STAGE: 2.

Association of the TRIM family protein with survival outcomes and clinicopathological features in colorectal cancer: a systematic review and meta-analysis

BackgroundThe tripartite motif (TRIM) proteins have been reported to play crucial roles in various malignancies. However, the clinical significance of TRIM proteins in colorectal cancer (CRC) remains controversial. This study aimed to evaluate the association between TRIM proteins and the clinicopathological features and survival outcomes in patients with CRC.MethodsWe performed a meta-analysis to investigate whether TRIM is a prognostic factor in CRC. PubMed, Embase, Web of Science, CNKI and Weipu databases were searched to identify eligible studies that evaluated the association between TRIM proteins and overall survival (OS), as well as the clinicopathological features of patients with CRC. Hazard ratios (HR) or odds ratios (OR) with 95% confidence interval (CI) were derived and pooled using a fixed-effects model.ResultsFrom inception to March 2023, we extracted study characteristics and prognostic data for each identified study. Twelve studies enrolling 1608 patients were eligible for inclusion. Data on OS and recurrence-free survival (RFS) were available for 12 and 2 studies, respectively. The pooled analysis results showed a significant correlation between the elevated TRIM proteins and shorter OS (HR = 2.42, 95% CI: 1.96–2.99) and worse RFS (HR = 2.51, 95% CI: 1.78–3.54) in patients with CRC. The combined ORs indicated that TRIM protein over-expression was significantly associated with advanced TNM stage (OR = 2.26, 95% CI: 1.25–4.10), deep tumor invasion (OR = 2.01, 95% CI: 1.04–3.88), lymph node metastasis (OR = 2.99, 95% CI: 2.19–4.09) and perineural invasion (OR = 1.95, 95% CI: 1.18–3.23).ConclusionsOur findings suggest that TRIM proteins can predict tumor progression and poor prognosis in CRC. Therefore, TRIM proteins may be promising therapeutic targets for patients with CRC.Graphical

The role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer.

Breast cancer is a common malignancy with the highest mortality rate among women worldwide. Its incidence is on the rise year after year, accounting for more than one-tenth of new cancers worldwide. Increasing evidence suggests that forkhead box (FOX) transcription factors play an important role in the occurrence and development of breast cancer. However, little is known about the relationship between the expression, prognostic value, function, and immune infiltration of FOX transcription factors in tumor microenvironment. We used bioinformatics to investigate expression and function of FOX factor in breast cancer. Our results revealed the expression levels of FOXA1 and FOXM1 were significantly higher in breast cancer tissues than in normal tissues. The high expression of mRNA in FOXA1 (P < .05), FOXM1 (P < .01), and FOXP1 (P < .05) groups was related to tumor stage. Survival analysis results showed that increased FOXP1 mRNA levels were significantly associated with overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) in all patients with breast cancer (P < .05). Patients with the FOXA1 high-expression group had better RFS and DMFS than the low-expression group (P < .05), while patients with FOXM1 high-expression group had worse RFS, OS, and DMFS than the low-expression group (P < .05). Meanwhile, mutation analysis showed that genetic alterations in FOX transcription factors were significantly associated with shorter OS and progression-free survival (P < .05), but not with disease-free survival (P = .710) in patients with breast cancer. FOXP1, FOXA1, and FOXM1 may be used as potential biomarkers to predict the prognosis of patients with breast cancer. Functional enrichment indicated that FOX was mainly involved in cell division, cell senescence, cell cycle, and prolactin signaling pathway. In patients with breast cancer, FOXC2 expression was negatively correlated with the infiltration of B cells and positively correlated with the infiltration of neutrophils and dendritic cells. However, FOXM1 was negatively correlated with the infiltration of CD8 + T cells and macrophages and positively correlated with the infiltration of neutrophils and dendritic cells. These findings provided novel insights into the screening of prognostic biomarkers of the FOX family in breast cancer and laid a foundation for further research on the immune infiltration of the FOX transcription factor family members in tumors.

Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

Prognostic significance of postoperative complications for patients with hepatocellular carcinoma relative to alpha-feto protein and tumor burden score

INTRODUCTIONWe sought to elucidate the impact of postoperative complications on patient outcomes relative to differences in alpha-fetoprotein-tumor burden score (ATS) among patients with hepatocellular carcinoma (HCC). METHODSPatients who underwent resection of HCC between 2000-2020 were identified from an international database. Moderate/severe complication was defined using the optimal cut-off value of the comprehensive complication index (CCI) based on data splits observed on the log-rank test. RESULTSA total of 1,124 patients was included. CCI cut-off value of 16.6 was identified as the optimal prognostic threshold. Moderate/severe complication group was more likely to have worse recurrence free survival [RFS] compared to no/ mild complication group (2-year RFS; no/ mild complication: 55.9% vs. moderate/severe complication: 38.1% p<0.001). Of note, low and medium ATS patients who experienced moderate/severe complications had a higher risk of recurrence (2-year RFS; no/mild complication: postoperative complications 70.0% vs. moderate/severe complication: 51.1%, p=0.006; medium: no/mild complication: 50.8% vs moderate/severe complication: 56.7%, p=0.01); however, postoperative complications were not associated with worse outcomes among patients with ATS (no/mild complication: 39.1% vs. moderate/severe complication: 29.2%, p=0.20). CONCLUSIONSThese data serve to emphasize how reduction in postoperative complications may be crucial to improve prognosis, particularly among patients with favorable HCC characteristics.

ASO Visual Abstract: High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival Following Resection of Extremity and Truncal Soft-Tissue Sarcoma.

ASO Visual Abstract: High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival Following Resection of Extremity and Truncal Soft-Tissue Sarcoma.

The radiological characteristics, tertiary lymphoid structures, and survival status associated with EGFR mutation in patients with subsolid nodules like stage I-II LUAD.

BackgroundEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules.Materials and methodsThe inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis.ResultsFinally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037).ConclusionsIn early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation.

High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival (RFS) After Resection of Extremity and Truncal Soft Tissue Sarcoma.

Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes. The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and recurrence-free survival (RFS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. The study identified 577 patients. The median SVI was 44 (interquartile range [IQR], 19-67), with 195 patients categorized as high SVI and 265 patients as low SVI. The median age, tumor size, histologic subtype, grade, comorbidities, stage, follow-up time, and perioperative chemotherapy and radiation utilization were similar between the high and low SVI cohorts. The patients with high SVI had worse OS (p = 0.07) and RFS (p = 0.016) than the patients with low SVI. High SVI was independently associated with shorter RFS in the multivariate analysis (hazard ratio, 1.64; 95% confidence interval, 1.06-2.54) but not with OS (HR, 1.47; 95% CI 0.84-2.56). High community-level social vulnerability appears to be independently associated with worse RFS for patients undergoing resection of extremity and truncal soft tissue sarcoma. The effect of patient and community-level social risk factors should be considered in the treatment of patients with extremity sarcoma.

Is there a prognostic difference among stage I lung adenocarcinoma patients with different BRAF-mutation status?

The data of the prognostic role of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early-stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan-Meier method and compared by log-rank test. Cox proportional hazard models, propensity-score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence-free survival (RFS). The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E-mutant patients were detected to have concurrent EGFR mutations, one for 19-del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild-type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.

Prognostic impact of HER2 biomarker levels in trastuzumab-treated early HER2-positive breast cancer

BackgroundOverexpression of human epidermal growth factor receptor 2 (HER2) caused by HER2 gene amplification is a driver in breast cancer tumorigenesis. We aimed to investigate the prognostic significance of manual scoring and digital image analysis (DIA) algorithm assessment of HER2 copy numbers and HER2/CEP17 ratios, along with ERBB2 mRNA levels among early-stage HER2-positive breast cancer patients treated with trastuzumab.MethodsThis retrospective study comprised 371 early HER2-positive breast cancer patients treated with adjuvant trastuzumab, with HER2 re-testing performed on whole tumor sections. Digitized tumor tissue slides were manually scored and assessed with uPath HER2 Dual ISH image analysis, breast algorithm. Targeted ERBB2 mRNA levels were assessed by the Xpert® Breast Cancer STRAT4 Assay. HER2 copy number and HER2/CEP17 ratio from in situ hybridization assessment, along with ERBB2 mRNA levels, were explored in relation to recurrence-free survival (RFS).ResultsThe analysis showed that patients with tumors with the highest and lowest manually counted HER2 copy number levels had worse RFS than those with intermediate levels (HR = 2.7, CI 1.4–5.3, p = 0.003 and HR = 2.1, CI 1.1–3.9, p = 0.03, respectively). A similar trend was observed for HER2/CEP17 ratio, and the DIA algorithm confirmed the results. Moreover, patients with tumors with the highest and the lowest values of ERBB2 mRNA had a significantly worse prognosis (HR = 2.7, CI 1.4–5.1, p = 0.003 and HR = 2.8, CI 1.4–5.5, p = 0.004, respectively) compared to those with intermediate levels.ConclusionsOur findings suggest that the association between any of the three HER2 biomarkers and RFS was nonlinear. Patients with tumors with the highest levels of HER2 gene amplification or ERBB2 mRNA were associated with a worse prognosis than those with intermediate levels, which is of importance to investigate in future clinical trials studying HER2-targeted therapy.

Preoperative low plasma creatine kinase levels predict worse survival outcomes in bladder cancer after radical cystectomy.

To evaluate the prognostic significance of preoperative creatine kinase (CK) levels in bladder cancer (BCa) patients who underwent radical cystectomy (RC). 570 BCa patients with RC were identified between 2010 and 2020. 108.5U/L of CK levels were defined as the cutoff value. Logistic regression analysis and Cox regression models were performed to evaluate the association between CK levels and oncologic outcomes. Subgroup analyses were performed to address cofounding factors. Preoperative low CK levels were associated with worse recurrence-free survival (RFS, log-rank P = 0.001) and overall survival (OS, log-rank P = 0.002). Multivariate analysis revealed that preoperative low CK levels were an independent predictor for worse RFS (hazard ratio [HR]: 1.683; P < 0.001) and OS (HR: 1.567; P = 0.002). The preoperative low CK level independently predicts worse survival outcomes in BCa after RC. Incorporating it into prediction models might be valuable to assist risk stratification.

Effect of time interval between surgery and the initiation of adjuvant therapy on the oncologic outcomes of early-stage endometrial cancer.

To identify the impact of time interval between surgery and initial adjuvant radiotherapy on oncologic outcomes in early-stage endometrial cancer. This retrospective cohort study included patients with stage I/II endometrial cancer who underwent surgical staging and adjuvant therapy at Songklanagarind Hospital from January 1, 2007, to December 31, 2017. Patients were categorized into two groups: TI <6 weeks and TI ≥6 weeks. The effects of TI and clinicopathological factors on recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox proportional-hazards regression. In total, 177 patients were enrolled, with 52% receiving adjuvant radiotherapy at <6 weeks (overall median TI 5.7 weeks). The recurrence and death rates were 13% and 10.2%, respectively. The median follow-up time was 46.6 months. The overall 3-year RFS and OS rates were 88.2% and 85.2%, respectively. The TI significantly affected the 3-year RFS (94.4% vs 81.2%; P = 0.008) and 3-year OS (95.5% vs 83.2%; P = 0.012) in patients with TI <6 and ≥6 weeks, respectively. In multivariate analysis, the depth of myometrial invasion (MI), presence of lymphovascular space invasion, and TI were independent prognostic factors for both RFS and OS. Delaying the TI (≥6 weeks) was significantly associated with a worse RFS (hazard ratio [HR] 3.70; 95% confidence interval [CI]: 1.34-10.22; P = 0.012) and an inferior OS (HR 3.80; 95% CI: 1.23-11.69; P = 0.02). A delay in the TI between surgery and the initiation of adjuvant radiotherapy of ≥6 weeks negatively affected the oncologic outcomes in early-stage endometrial cancer.

Impact of adjuvant treatment on survival in patients with 2023 FIGO stage IIC endometrial cancer: a retrospective analysis from two tertiary centers in Korea and Taiwan.

In early-stage endometrial cancer, aggressive histologic types (grade 3 endometrioid, serous, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types) are associated with an increased risk of distant metastases and worse survival. However, the optimal adjuvant treatment for these patients remains controversial. The present study investigated the outcomes of different adjuvant treatments in patients with 2023 FIGO stage IIC endometrial cancer. We retrospectively identified patients with 2023 FIGO stage IIC endometrial cancer who underwent surgery followed by either adjuvant treatment or observation from 2000 to 2020 at two tertiary centers in Korea and Taiwan. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and Cox proportional-hazards models. We also analyzed recurrence patterns after different adjuvant treatments. A total of 272 patients were identified; 204 received adjuvant treatment postoperatively, whereas 68 only underwent observation. Adjuvant treatment was not associated with improved RFS or OS. Non-endometrioid histologic types (p=0.003) and presence of lymphovascular space invasion (LVSI, p=0.002) were associated with worse RFS, whereas only non-endometrioid histologic types impacted OS (p=0.004). In subgroup analyses, adjuvant treatment improved OS in patients with LVSI (p=0.020) and in patients with both LVSI and grade 3 endometrioid histologic type (p=0.007). We found no difference in locoregional and distant recurrence between patients undergoing adjuvant treatment or observation. In this study, the addition of adjuvant treatment was associated with an OS benefit for patients with LVSI, especially those with grade 3 endometrioid tumors.

Prognostic Effect of Mismatch Repair Status in Early-Stage Endometrial Cancer Treated With Adjuvant Radiation: A Multi-institutional Analysis

The aim of this work was to report the effect of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial adenocarcinoma (EEC) who receive adjuvant radiation therapy. This is a multi-institutional retrospective cohort study across 11 institutions in North America. Patients with known MMR status and stage I-II EEC status postsurgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated via the Kaplan-Meier method. Univariable and multivariable analyses were performed via Cox proportional hazard models for RFS and OS. Statistical analyses were conducted using SPSS version 27. In total, 744 patients with a median age at diagnosis of 65 years (IQR, 58-71) were included. Most patients were White (69.4%) and had Federation of Obstetrics and Gynecology 2009 stage I (84%) and Federation of Obstetrics and Gynecology grade 1 to 2 (73%). MMR deficiency was reported in 234 patients (31.5%), whereas 510 patients (68.5%) had preserved MMR. External beam radiation therapy with or without vaginal brachytherapy was delivered to 186 patients (25%), whereas 558 patients (75%) received vaginal brachytherapy alone. At a median follow-up of 43.5 months, the estimated crude OS and RFS rates for the entire cohort were 92.5% and 84%, respectively. MMR status was significantly correlated with RFS. RFS was inferior for MMR deficiency compared with preserved MMR (74.3% vs 88.6%, P < .001). However, no difference in OS was seen (90.8% vs 93.2%, P = .5). On multivariable analysis, MMR deficiency status was associated with worse RFS (hazard ratio, 1.86; P = .001) but not OS. MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiation therapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted.

Exploratory analysis of the cervix tumoral HPV antigen-specific T-cell repertoire during chemoradiation and after brachytherapy

Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020-1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-β/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2-50.2 fold-increase from baseline), frequency (1.2-1.7), rearrangements (1.2-40.2), and clonality (1.2-15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy.

Prognostic significance of HALP score and combination of peripheral blood multiple indicators in patients with early breast cancer.

To assess the prognostic significance of preoperative hemoglobin, albumin, lymphocyte, and platelet (HALP) score combined with multiple peripheral blood indicators in patients with early breast cancer (EBC). A total of 411 patients with early invasive breast cancer underwent breast-conserving surgery or radical surgery at Changzhou No.2 People's Hospital from January 2015 to December 2020. The cut-off values of HALP, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) were calculated using the software X-tile. The primary outcomes were recurrence-free survival (RFS), which was analyzed using the Kaplan Meier (K-M) method, while log-rank was used to test the differences between high and low curves. Cox regression analysis was used to analyze the prognostic significance of HALP. Furthermore, the prognostic predictive value of independent prognostic factors was determined using the receiver operating characteristic (ROC) curve. Low HALP score (P<0.0001), high PLR (P<0.0001), and low LMR (P = 0.0345) were significantly associated with worse RFS. Body mass index (BMI)<24 (P = 0.0036), no diabetes (P = 0.0205), earlier TNM stage (P = 0.0005), and no lymph node metastasis (P = 0.0022) were positively correlated with longer survival HALP scores (hazard ratio [HR] 95% confidence interval [CI]: 0.08 (0.024-0.265), P<0.0001), BMI (HR 95%CI: 0.254 (0.109-0.589), P = 0.001), TNM stage (HR 95%CI: 0.153 (0.041-0.571), P = 0.005), and diabetes (HR 95%CI: 0.259 (0.085-0.785), P = 0.017) were demonstrated as independent prognostic factors by Cox regression analysis. The ROC curves depicted that the two most valuable factors were TNM stage and HALP, and combined independent factors were more accurate in prognostic prediction than any single factor. This further indicated that the TNM stage combined HALP or BMI were more valuable combinations. The HALP score was an independent prognostic factor for EBC and was significantly associated with worse RFS. This score may predict the probability of postoperative tumor recurrence or metastasis before surgery.

Recurrence-Free Survival in Patients With Surgically Resected Non-Small Cell Lung Cancer: A Systematic Literature Review and Meta-Analysis

BackgroundStandard treatment for early-stage or locoregionally-advanced non-small cell lung cancer (NSCLC) includes surgical resection. Recurrence after surgery is commonly reported, but a summary estimate for post-surgical recurrence-free survival (RFS) in NSCLC patients is lacking. Research QuestionWhat is the RFS following surgery in stage I-III NSCLC patients at different timepoints and what factors are associated with RFS? Study Design and MethodsA systematic search was performed in MEDLINE, EMBASE and Cochrane databases between January 2011-June 2021. The primary outcome was RFS at 1-, 2-, 3-, and 5-years post-resection. Single-arm, random-effects meta-analyses calculated effect estimates and 95% confidence intervals (CI). Analyses were stratified by stage/sub-stage per the American Joint Committee on Cancer Staging Manual, and RFS was estimated 1) after pooling studies using 7th or 8th edition staging criteria and 2) among studies using only 8th edition. Meta-regressions were performed to assess associations between RFS and patient demographic/clinical characteristics of interest. ResultsData from 471 studies comprising 1,060 surgical study arms were extracted. RFS estimates from 60,695 patients staged with 7th or 8th edition were analyzed. RFS ranged from 96% at 1-year post-resection to 82% at 5 years for stage I, and from 68% at 1-year to 34% at 5 years for stage III. Estimates for patients staged using only 8th edition criteria were slightly higher. Older age, higher percentage of males, advancing stage, larger tumor size, and geographical region (North America/Europe vs. Asia) were significantly associated with worse RFS. InterpretationThis study presents a comprehensive assessment of reported RFS from published clinical literature, offering estimates at multiple post-surgical time points and by geographical region. Findings can inform treatment decisions, clinical trial design, and future research to improve outcomes among NSCLC patients. RegistrationProtocol was not registered, but study was conducted based on a pre-specified protocol.

Clinicopathological Significances of Peritumoral Budding in Colorectal Cancer: A Detailed Analysis Based on Mucinous and Micropapillary Pattern

The present study aimed to evaluate the correlations between peritumoral tumor budding (PTB) and the clinicopathological characteristics of colorectal cancer (CRC) according to histological components. The PTBs were investigated and divided into high and low groups. The clinicopathological significance and prognostic implications of PTB in CRC were evaluated. High PTB was found in 104 of 266 CRCs (39.1%). High PTB was significantly correlated with left-sided tumors, lymphatic invasion, lymph node metastasis, distant metastasis, and high pTNM stage. However, there was no significant correlation between PTB and the other clinicopathological characteristics. PTB was significantly higher in CRCs without the mucinous component than those with the mucinous component (p = 0.008). However, there was no significant difference between CRCs with and without the micropapillary pattern (p = 0.123). Patients with high PTB had worse recurrence-free survival than those with low PTB (p = 0.031). In the subgroup analysis based on histological components, a significant correlation between PTB and recurrence-free survival was found in CRC with a micropapillary pattern but not in those without a micropapillary pattern (p = 0.010 and p = 0.178, respectively). These findings indicate that high PTB is significantly correlated with aggressive tumor behaviors and worse survival in patients with CRC. However, the prognostic implications of PTB can differ according to histological components.

Large cribriform glands (> 0.25 mm diameter) as a predictor of adverse pathology in men with Grade Group 2 prostate cancer.

A recent outcome-based, radical prostatectomy study defined > 0.25 mm diameter to distinguish large versus small cribriform glands, with > 0.25 mm associated with worse recurrence-free survival. This study evaluates whether identification of > 0.25 mm cribriform glands in Grade Group 2 patients at biopsy is associated with adverse pathology at radical prostatectomy. Tumours containing biopsy slides for 133 patients with Grade Group 2 prostate cancer with subsequent radical prostatectomy were re-reviewed for large cribriform glands (diameter > 0.25 mm). The primary outcome was adverse pathology (Grade Groups 3-5; stage pT3a or greater, or pN1). The secondary outcome was recurrence-free survival. Cribriform pattern was present in 52 of 133 (39%) patients; of these, 16 of 52 (31%) had large cribriform glands and 36 of 52 (69%) had only small cribriform glands. Patients with large cribriform glands had significantly more adverse pathology at radical prostatectomy compared to patients with small cribriform glands and no cribriform glands (large = 11 of 16, 69%; small = 12 of 36, 33%; no cribriform = 25 of 81, 31%; χ2 P-value 0.01). On multivariate analysis, large cribriform glands were also associated with adverse pathology, independent of age, prostate-specific antigen (PSA)/PSA density at diagnosis, year of diagnosis and biopsy cores percentage positive (global P-value 0.02). Large cribriform glands were also associated with increased CAPRA-S surgical risk score (Kruskal-Wallis P-value 0.02). Large cribriform glands using a diameter > 0.25 mm definition in Grade Group 2 patients on biopsy are associated with increased risk of adverse pathology at radical prostatectomy. The presence of large cribriform histology should be considered when offering active surveillance for those with Grade Group 2 disease.

Is FAST FORWARD the Way Forward in Radiotherapy for Locally Advanced Breast Cancer – Learnings From the COVID Pandemic

IntroductionLow middle-income countries (LMICs), including India, have paucity of external beam radiotherapy (RT) machines leading to prolonged wait times for RT. Delay in delivery of RT has been shown to adversely affect outcomes in locally advanced breast cancer (LABC). With the availability of results of multiple randomized controlled trials, hypofractionated RT delivered over 3 to 4 weeks became the standard of care in breast cancer RT. MethodsWe conducted a retrospective audit of 172 LABC patients treated with ultrahypofractionated adjuvant RT (radiotherapy completed in 1 week) during the COVID pandemic. Log rank and Cox-regression model used for univariate and multi-variate analyses. ResultsNo patient developed grade 3 esophagitis. Grade 2 esophagitis requiring short term narcotic analgesics was seen in 12 (6.9%) patients. Grade 2 or higher toxicity peaked between 2 and 3 weeks after RT. The estimated 2 and 3- year recurrence free survival (RFS) for the cohort is 87.1 % and 81.4 %, respectively. The estimated 2 and 3-year overall survival for the cohort is 95% and 91.3%. On multivariate analysis, presence of extra-nodal extension was found to be an independent factor associated with worse RFS (P = .028). ConclusionsFAST FORWARD protocol RT in LABC appears well tolerated.