Significant Difference In Recurrence-free Survival Research Articles

Gastrointestinal Stromal Tumors: 10-Year Experience in Cancer Center-The Ottawa Hospital (TOH).

(1) Background: The management of gastrointestinal stromal tumors (GIST) has significantly evolved over the last two decades, with the introduction of tyrosine kinase inhibitors (TKI). We aim to report 10 years of experience of GIST management at a regional cancer center in Canada. (2) Methods: We retrospectively analyzed the records of 248 consecutive patients diagnosed with GIST between 2011 and 2021. We describe the clinical and pathological data, management, and outcome, including survival. (3) Results: The most common GIST sites were the stomach 63% (156), followed by the small bowel 29% (73). At diagnosis, 83% (206) of patients had localized disease (stage I–III). According to the modified National Institutes of Health consensus criteria (NIH) for GIST, around 45% (90) had intermediate or high-risk disease. Most patients, 86% (213), underwent curative surgical resection. Forty-nine patients received adjuvant imatinib, while forty-three patients had advanced disease and received at least one line of TKI. With a median follow-up of 47 months, the 5-year recurrence-free survival (RFS) rates for very low and low risk were 100% and 94%, respectively, while those for intermediate and high risk were 84% and 51%, respectively. The 5-year overall survival (OS) rates for very low and low risk were 100% and 94%, while intermediate, high risk, and advanced were 91%, 88%, and 65%, respectively. Using the Kaplan–Meier method, there were statistically significant differences in RFS and OS between NIH risk groups, p < 0.0005. In univariate analysis, ECOG, site, mitosis, secondary malignancy, and size were predictors for OS. High mitosis and large size (>5 cm) were associated with worse RFS. (4) Conclusions: Curative surgical resection remains the gold standard management of GIST. Our results are comparable to the reported literature. Further research is needed to explore histology’s role in risk stratification and initiating adjuvant TKI.

Histone lysine methylation patterns in prostate cancer microenvironment infiltration: Integrated bioinformatic analysis and histological validation.

BackgroundEpigenetic reprogramming through dysregulated histone lysine methylation (HLM) plays a crucial role in prostate cancer (PCa) progression. This study aimed to comprehensively evaluate HLM modification patterns in PCa microenvironment infiltration.Materials and methodsNinety-one HLM regulators in The Cancer Genome Atlas (TCGA) dataset were analyzed using bioinformatics. Differentially expressed genes (DEGs) and survival analyses were performed using TCGA-PRAD clinicopathologic and follow-up information. Consensus clustering analysis divided patients into subgroups. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. Tumor mutation burden (TMB) and tumor microenvironment (TME) cell infiltration were evaluated in different HLM clusters. Quantitative real-time PCR (qPCR) analysis assessed HLM regulators in clinical PCa tissues.ResultsThe tumor vs. normal (TN), Gleason score (GS) > 7 vs. GS < 7, pathological T stage (pT) = 2 vs. pT = 3, and TP53 mutation vs. wild-type comparisons using TCGA-PRAD dataset revealed 3 intersecting HLM regulators (EZH2, NSD2, and KMT5C) that were consistently upregulated in advanced PCa (GS > 7, pT3, HR > 1, and TP53 mutation) (P < 0.05) and verified in clinical PCa tissues. Consensus clustering analysis revealed three distinct HLM modification patterns (HLMclusters). However, no significant differences in recurrence-free survival (RFS) rates were found among the groups (P > 0.05). We screened 189 HLM phenotype-related genes that overlapped in the pairwise comparisons of HLMclusters and P < 0.01 in the Cox regression analysis. Three distinct subgroups (geneClusters) were revealed based on the 189 genes, in which cluster A involved the most advanced PCa (PSA > 10, T3-4, GS8-10, and biochemical recurrence) and the poorest RFS. The HLM score (HLMscore) was calculated by principal component analysis (PCA) of HLM phenotype-related genes that have positive predictive value for RFS (P < 0.001) and immune therapy responses (in the CTLA4-positive and -negative responses accompanied by a PD1-negative response).ConclusionWe comprehensively evaluated HLM regulators in the PCa microenvironment using TCGA-PRAD, revealing a nonnegligible role of HLM patterns in PCa complexity and heterogeneity. Elucidating the effects of HLM regulators in PCa may enhance prognostics, aggressiveness assessments, and immunotherapy strategies.

Hepatic Arterial Infusion Chemotherapy as a Timing Strategy for Conversion Surgery to Treat Hepatocellular Carcinoma: A Single-Center Real-World Study.

ObjectiveTo evaluate whether surgery-related complications are increased after hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin plus fluorouracil/leucovorin for conversion compared with primary hepatocellular carcinoma (HCC) resection and the optimal timing of conversion surgery (CS).BackgroundHAIC has been widely used for advanced HCC, especially initially unresectable HCC, to facilitate conversion to curative-intent resection in approximately 23.8% of cases. However, the optimal timing of surgery to reduce surgical complications must be clarified.MethodsData from 320 HCC patients, including 107 initially unresectable patients in the HAIC-Surgery group and 213 patients in the Surgery group, were retrospectively collected and analyzed. Survival outcomes and the incidence of surgery-related complications were compared.ResultsThere was no significant difference in recurrence-free survival (RFS) between the HAIC-Surgery group and the Surgery group (HR: 1.140, 95% CI: 0.8027–1.618, p=0.444). The HAIC-Surgery group had a higher incidence of surgery-related complications than the Surgery group [biliary leakage (10.3% vs 4.2%, p=0.035), abdominal bleeding (10.3% vs 3.8%, p=0.020), pleural effusion (56.1% vs 23.0%, p<0.0001) and ascites effusion (17.8% vs 5.2%, p<0.0001)]. In the HAIC-Surgery group, postoperative liver function decreased and abdominal bleeding increased with more preoperative HAIC cycles (Spearman=0.229, p=0.042, Spearman=0.198, p=0.041, respectively). The pathological complete remission (pCR) rate after 3–5 HAIC cycles was significantly higher than that after 1–2 cycles (29.4% vs 13.2%, p=0.043).ConclusionThe prognosis of advanced HCC after conversion surgery is comparable to that after direct surgery. Rather than increasing pCR, more HAIC cycles can exacerbate liver dysfunction and surgery-related complications.

Does para-aortic lymphadenectomy improve survival in pathologically diagnosed early-stage grade 3 endometrioid and non-endometrioid endometrial cancers? A retrospective cohort study in Korea and Taiwan

PurposeThe therapeutic effect of para-aortic lymphadenectomy in early-stage high-grade endometrial cancer remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared to pelvic lymphadenectomy alone in patients with pathologically diagnosed FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers. MethodsWe retrospectively reviewed the medical records of 281 patients with histologically confirmed FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers who underwent pelvic lymphadenectomy alone or combined pelvic and para-aortic lymphadenectomy in staging surgery at two tertiary centers in Korea and Taiwan. Prognostic factors to predict outcomes in these cases were also analyzed. ResultsAmong 281 patients, 144 underwent pelvic lymphadenectomy alone and 137 underwent combined pelvic and para-aortic lymphadenectomy. Within a median follow-up of 45 months, there was no significant difference in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In multivariable analysis, age at diagnosis ≥60 years (HR = 2.20, 95% CI 1.25–3.87, p = 0.006) and positive lymph-vascular space invasion (LVSI) (HR = 2.79, 95% CI 1.60–4.85, p < 0.001) were associated with worse RFS, and only non-endometrioid histology was associated with worse OS (HR = 3.18, 95% CI 1.42–7.12, p = 0.005). In further subgroup analysis, beneficial effects of combined pelvic and para-aortic lymphadenectomy on RFS and OS were not observed. ConclusionsIn this study, combined pelvic and para-aortic lymphadenectomy could not improve survival compared to pelvic lymphadenectomy alone in patients with FIGO stage I-II grade 3 endometrioid and non-endometrioid endometrial cancers. Therefore, para-aortic lymphadenectomy may be omitted for these cases.

Adjuvant nivolumab versus ipilimumab (CheckMate 238 trial): Reassessment of 4-year efficacy outcomes in patients with stage III melanoma per AJCC-8 staging criteria

PurposeNivolumab was approved as adjuvant therapy for melanoma based on data from CheckMate 238, which enrolled patients per American Joint Committee on Cancer version 7 (AJCC-7) criteria. Here, we analyse long-term outcomes per AJCC-8 staging criteria compared with AJCC-7 results to inform clinical decisions for patients diagnosed per AJCC-8. Patients and methodsIn a double-blind, phase 3 trial (NCT02388906), patients aged ≥15 years with resected, histologically confirmed AJCC-7 stage IIIB, IIIC, or IV melanoma were randomised to receive nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses and then every 12 weeks, both intravenously ≤1 year. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were assessed in patients with stage III disease, per AJCC-7 and AJCC-8. ResultsPer AJCC-7 staging, 42.4% and 57.3% of patients were in substage IIIB and IIIC, respectively; per AJCC-8, 1.1%, 30.4%, 62.8%, and 5.0% were in IIIA, IIIB, IIIC, and IIID. After 4 years' minimum follow-up, the AJCC-7 superior efficacy of nivolumab over ipilimumab in patients with resected stage III melanoma was preserved per AJCC-8 analysis. No statistically significant difference in RFS between stage III substage hazard ratios was observed per AJCC-7 or -8 staging criteria (interaction test: AJCC-7, P = 0.8115; AJCC-8, P = 0.1051; P = 0.8392 ((AJCC-7) and P = 0.8678 (AJCC-8) for DMFS). ConclusionsCheckMate 238 4-year RFS and DMFS outcomes are consistent per AJCC-7 and AJCC-8 staging criteria. Outcome benefits can therefore be translated for patients diagnosed per AJCC-8.

Prognosis of Patients with 1-4cm Papillary Thyroid Cancer Who Underwent Lobectomy: Focus on Gross Extrathyroidal Extension Invading Only the Strap Muscles.

This study was designed to evaluate the prognostic implication of gross extrathyroidal extension (ETE) invading the strap muscles after thyroid lobectomy in patients with 1-4cm papillary thyroid cancer (PTC). This retrospective cohort study included patients with 1-4cm PTC who underwent thyroid lobectomy from 2005 to 2012. Overall, 595 patients were enrolled after excluding patients with aggressive variants of PTC, gross ETE into a major neck structure, and lateral cervical lymph node (LN) metastasis. We evaluated the risk factors for structural recurrence after lobectomy in 1-4cm PTC. Seventy-eight patients (13.1%) had gross ETE invading only the strap muscles. During the median follow-up period of 7.7 years, structural recurrence was confirmed in 35 patients (5.9%). The presence of gross ETE was an independent risk factor for structural recurrence (hazard ratio 2.54, 95% confidence interval 1.19-5.44; p = 0.016). Subgroup analysis of patients with gross ETE showed that 11 and 47 patients had low- and intermediate-risk LN metastasis, respectively. A significant difference in recurrence-free survival was observed according to the degree of cervical LN metastasis (p = 0.03). Those without LN metastasis or low-risk LNs had a 75% lower risk of recurrence when compared with those with both gross ETE and intermediate-risk LNs. Gross ETE and intermediate-risk cervical LN metastasis were associated with a significantly high risk of recurrence after lobectomy in patients with 1-4cm PTC. Completion thyroidectomy would be considered in this subgroup of patients but not in all patients with gross ETE invading only the strap muscles.

Hypofractionated or Conventionally Fractionated Adjuvant Radiotherapy After Regional Lymph Node Dissection for High-Risk Stage III Melanoma

AimsAdjuvant radiotherapy can be beneficial after regional lymph node dissection for high-risk stage III melanoma, as it has been shown to reduce the risk of recurrence in the node field. However, the optimal fractionation schedule is unknown and both hypofractionated and conventionally fractionated adjuvant radiotherapy are used. The present study examined the oncological outcomes of these two approaches in patients treated in an era before effective systemic immunotherapy became available. Materials and methodsThis retrospective cohort study involved 335 patients with stage III melanoma who received adjuvant radiotherapy after therapeutic regional lymph node dissection for metastatic melanoma between 1990 and 2011. Information on tumour characteristics, radiotherapy doses and fractionation schedules and patient outcomes was retrieved from the institution's database and patients' medical records. ResultsHypofractionated radiotherapy (median dose 33 Gy in six fractions over 3 weeks) was given to 95 patients (28%) and conventionally fractionated radiotherapy (median dose 48 Gy in 20 fractions over 4 weeks) to 240 patients (72%). Five-year lymph node field control rates were 86.0% (95% confidence interval 78.4–94.4%) for the hypofractionated group and 85.5% (95% confidence interval 80.5–90.7%) for the conventional fractionation group (P = 0.87). There were no significant differences in recurrence-free survival (RFS) (41.7%, 95% confidence interval 32.5–53.5 versus 31.9%, 95% confidence interval 26.1–38.9; P = 0.18) or overall survival (41.2%, 95% confidence interval 32.1–52.8 versus 45.0%, 95% confidence interval 38.7–52.4; P = 0.77). On multivariate analysis, extranodal spread was associated with decreased RFS (P = 0.04) and the number of resected lymph nodes containing metastatic melanoma was associated with decreased RFS (P = 0.0006) and overall survival (P = 0.01). ConclusionLymph node field control rates, RFS and overall survival were similar after hypofractionated and conventionally fractionated adjuvant radiotherapy. The presence of extranodal spread and an increasing number of positive lymph nodes were predictive of an unfavourable outcome.

Optimal value of lymph node ratio and metastatic lymph node size to predict risk of recurrence in pediatric thyroid cancer with lateral neck metastasis

BackgroundNo specific guideline exists for risk stratification based on lymph node (LN) status in pediatric thyroid cancer. The purpose of our study is to identify optimal values of lymph node ratio (LNR) and largest metastatic LN size for predicting recurrent/persistent disease, especially in children with lateral neck metastasis (N1b). MethodsWe conducted a retrospective study from January 1997 to June 2018 at Samsung Medical Center. A total of 50 papillary thyroid carcinoma (PTC) patients who underwent total thyroidectomy + both central neck dissection (CND) + modified radical neck dissection (MRND) (unilateral or bilateral) was enrolled. ResultsThe median follow-up duration was 60.8 months (range, 6.2–247 months). The mean age was 14.6 years, and the mean tumor size was 2.9 cm. Mean size of the largest metastatic LN was 1.5 cm. Mean value of central LNR was 0.6, and mean value of lateral LNR was 0.3. Largest metastatic LN size [HR = 2.0 (95% CI 1.0–4.0), p = 0.040] and lateral LNR [HR = 43.6 (95% CI 2.2–871.0), p = 0.014] were significant prognostic factors for recurrence. The optimal combination of lateral LNR and largest metastatic LN size to predict recurrence were 0.3 and 2.5 cm, respectively, with the largest AUC (AUC at 60 months = 77.4) and significant p-value (p = 0.009 and p = 0.021) (Table 3). Kaplan-Meier curves showed significant differences in recurrence-free survival (RFS) rates among four groups (Fig. 2A,2B). ConclusionsIn pediatric PTC patients with N1b, lateral LNR and largest metastatic LN size are significant predictors for recurrence. Children with lateral LNR > 0.3 or any metastatic lymph node > 2.5 cm in the largest dimension have higher risk for recurrence. Children are classified as extensive N1b if lateral LNR > 0.3 or pathologic N1 with largest LN size > 2.5 cm, and vice versa.

Impact of Renal Cell Carcinoma Histological Variants on Recurrence After Partial Nephrectomy: A Multi-Institutional, Prospective Study (UROCCR Study 82).

The prognostic impact of renal cell carcinoma (RCC) morphotype remains unclear in patients who undergo partial nephrectomy (PN). Our objective was to determine the risk factors for recurrence after PN, including RCC morphotype. Patients with RCC who had undergone PN were extracted from the prospective, national French database, UroCCR. Patients with genetic predisposition, bilateral or multiple tumours, and those who had undergone secondary totalization were excluded. Primary endpoint was 5-year, recurrence-free survival (RFS), and secondary endpoint was overall survival (OS). Risk factors for recurrence were assessed by multivariable Cox regression analysis. Overall, 2,767 patients were included (70% male; median age: 61 years [interquartile range (IQR) 51-69]). Most (71.5%) of the PN procedures were robot-assisted. Overall, 2,573 (93.0%) patients were recurrence free, and 74 died (2.7%). Five-year RFS was 84.9% (IQR 82.4-87.4). A significant difference in RFS was observed between RCC morphotypes (p < 0.001). Surgical margins (hazard ratio [HR] = 2.0 [95% confidence interval (CI): 1.3-3.2], p < 0.01), pT stage >1 (HR = 2.6 [95% CI: 1.8-3.7], p < 0.01]) and Fuhrmann grade >2 (HR = 1.9 [95% CI: 1.4-2.6], p < 0.001) were risk factors for recurrence, whereas chromophobe subtype was a protective factor (HR = 0.08 [95% CI: 0.01-0.6], p = 0.02). Five-year OS was 94.0% [92.4-95.7], and there were no significant differences between RCC subgroups (p = 0.06). The main study limitation was its design (multicentre national database), which may be responsible for declarative bias. Chromophobe morphotype was significantly associated with better RFS in RCC patients who underwent PN. Conversely, pT stage, Fuhrman group and positive surgical margins were risk factors for recurrence.

Effect of Different General Anesthesia Methods on the Prognosis of Patients with Breast Cancer after Resection: A Systematic Review and Meta-analysis.

Background The effect of total intravenous anesthesia (TIVA) and inhalation anesthesia (IA) on the prognosis of breast cancer patients has been controversial. The study is aimed at exploring the effects of different anesthesia methods on the postoperative prognosis of breast cancer patients. Methods Literature retrieval was conducted in PubMed, EMBASE, MEDLINE, Embase, CENTRAL, and CNKI databases. The literature topic was to compare the effects of TIVA and IA on the prognosis of patients undergoing breast cancer resection. Two researchers extracted data from the literature independently. This study included randomized controlled trials that evaluated for risk of bias according to the “Risk assessment Tool for Bias in Randomized Trials” in the Cochrane Manual. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in observational studies. The chi-square test was used for the heterogeneity test. Publication bias was assessed using funnel plots and Egger's test. If heterogeneity existed between literature, subgroup analysis and sensitivity analysis were used to explore the source of heterogeneity. Sensitivity analysis was performed by excluding low-quality and different-effect models. Data were statistically analyzed using the Cochrane software RevMan 5.3. Hazard ratio (HR) and 95% confidence interval (CI) were used for statistical description. Results Seven literatures were selected for meta-analysis. There were 9781 patients, 3736 (38.20%) receiving TIVA and 6045 (61.80%) receiving inhalation anesthesia. There was no significant difference in overall survival (OS) between TIVA and IA breast cancer patients (HR = 1.05, 95% CI (0.91, 1.22), Z = 0.70, P = 0.49). There was no difference in the literature (χ2 = 6.82, P = 0.34, I2 = 12%), and there was no obvious publication bias. There was no significant difference in recurrence-free survival (RFS) between TIVA and IA patients (HR = 0.95, 95% CI (0.79, 1.13), Z = 0.61, P = 0.54). There was no heterogeneity in the literature (χ2 = 5.23, P = 0.52, I2 = 0%), and there was no significant publication bias. Conclusion There is no significant difference in OS and RFS between TIVA and IA patients during breast cancer resection. The prognostic effects of TIVA and IA were similar.

Abstract 5785: Tumors with higher heterogeneity were associated with poorer survival outcome in early stage lung adenocarcinoma cancer patients with low tumor mutational burden

Abstract Background: Response to immune checkpoint inhibitors is associated with tumor mutational burden (TMB). Pembrolizumab has recently been approved by the FDA for use in patients with high TMB. However low TMB patients are not considered good responders and could benefit from stratification. The predictive value of other biomarkers such as intratumor heterogeneity (ITH) has been studied across a range of cancer indications. The utility of ITH in Lung Adenocarcinoma (LUAD) has not been established. Here we evaluate the relationship between ITH and outcome in early stage low TMB patients and explore differences in immune cell enrichment and predicted driver genes. Stratifying early stage patients may yield an opportunity to improve Recurrence Free Survival (RFS) and lower the risk of progression to late stage disease. Methods: All molecular data was obtained from the Tumor Cancer Genome Atlas via the GDC Data Portal. Clinical data was from the PanCancer Atlas dataset through cBioPortal. We estimated ITH using PyClone, an algorithm that estimates the number of tumor clones. We generated our ITH values in triplicate across 3 separate days, yielding an average PyClone clone number. Clones with &amp;gt;2 mutations were counted. We used p-value minimization to choose 1.4 for the TMB cutoff and 2.6 for the PyClone cutoff. We generated 4 groups: HTHI, HTLI, LTHI, and LTLI, where H - high, L- low, T-TMB, and I-ITH. Immune cell enrichment analysis was obtained from the xCell webtool. Driver gene prediction was performed with OncoDriveClust via the R package maftools. Results: We found a statistically significant difference in RFS between early stage (Stage I and Stage II) LTHI (N = 18) and LTLI (N = 40) patients (16.69 months vs. 33.27 months, p-value = 0.0056). Interestingly the predicted driver genes did not significantly differ between these two groups. One driver (EGFR) and two drivers (EGFR and TP53) genes were predicted for LTHI and LTLI, respectively. Gene set enrichment analysis showed statistically significant differences in key immune subtypes. B-cells were depressed and Th1 cells were elevated in LTHI, both of which are associated with poorer survival outcomes. Conclusion: We found an association between high ITH and poor survival in low TMB early stage LUAD patients. Early stage patients can be stratified using heterogeneity metrics like PyClone. Given the presence of immune subtypes known to associate with poorer outcomes, early stage LTHI patients may benefit from additional adjuvant therapies. Citation Format: Stanislav Fridland, Young Kwang Chae. Tumors with higher heterogeneity were associated with poorer survival outcome in early stage lung adenocarcinoma cancer patients with low tumor mutational burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5785.

Analysis of the effect of spread through air spaces on postoperative recurrence-free survival in patients with stage pT1N0M0 lung adenocarcinoma of different tumor size

Objective: To investigate the effect of spread through air spaces (STAS) on the postoperative prognosis of patients with stage pT1N0M0 lung adenocarcinoma according to different tumor sizes. Methods: The clinicopathological and follow-up data of 511 patients with pT1N0M0 lung adenocarcinoma treated surgically in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to June 2018 were retrospectively analyzed. There were 285 males and 226 females, aged 60 (53, 66) years. Those patients were divided into two groups according to STAS status, including STAS (-) group (342 cases) and STAS (+) group (169 cases). And the stratified analysis was performed according to the American Cancer Consortium (AJCC) 8th edition postoperative pathological tumor size T-stage (pT) of lung cancer, which was divided into pT1a (pT≤1 cm, 93 cases), pT1b (1 cm<pT≤2 cm, 280 cases), pT1c group (2 cm<pT≤3 cm, 138 cases) and pT1b/c (1 cm<pT≤3 cm, 418 cases). Univariate and multivariate Cox regression analyses and inverse probability weighted (IPTW) adjusted Kaplan-Meier (K-M) curves were used to analyze the effect of STAS on recurrence-free survival (RFS) in patients included in this study. Results: The recurrence rate was significantly higher in the STAS (+) group compared to the STAS (-) group (22.5% vs 3.2%, P<0.001). Multifactorial Cox regression analysis based on pT stratification showed that the risks of recurrence were 4.56-fold (95%CI:1.56-13.33; P=0.006) and 3.16-fold (95%CI:1.07-9.33; P=0.038) higher in pT1b and pT1c staged patients with STAS (+) than in STAS (-) patients, respectively. There was no significant difference in RFS between the STAS (-) group of pT1b/c, pT1b and pT1c and all pT1a patients [(84.97±0.72) vs (84.05±1.11) months, (85.60±0.74) vs (84.05±1.11) months, (81.49±1.63) vs (84.05±1.11) months; all P>0.05]. Before and after IPTW adjustment, statistically significant differences were found in RFS between STAS (+) group and STAS (-) group [(72.50±2.23) vs (85.12±0.72) months, (77.74±1.12) vs (84.59±0.64) months, all P<0.001]. In addition, the risks of both local and distant recurrence were higher in STAS (+) group compared to STAS (-) group (6.7% vs 1.2% and 8.2% vs 3.6%, respectively; both P<0.05). Conclusion: For lung adenocarcinoma patients with pT1bN0M0 and pT1cN0M0, those patients with STAS (+) had a higher incidence of both local and distant recurrence and with poor RFS.

Prognostic Value of Platelet-to-Lymphocyte Ratio in Non-Muscle Invasive Bladder Cancer Patients: Intravesical Bacillus Calmette-Guerin Treatment After Transurethral Resection of Bladder Tumor

The objective of this study was to investigate the platelet-to-lymphocyte ratio (PLR) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 197 patients who underwent intravesical Bacillus Calmette-Guerin treatment after transurethral resection of bladder (TURB) were included. We divided the patients into different groups according to the treatment stage before and during induction treatment as Group 1 and Group 2, and set the change value of PLR as the Group 3. The cutoff values of PLR were determined through receiver operation characteristics curves analysis. we found a significant difference in recurrence-free survival (RFS) and progression-free survival (PFS) between patients with high serum PLR and those with low serum PLR in Group 1, as well as Group 2. Cox multivariate analysis revealed that tumor number ≥3, high grade, and history of carcinoma in situ (CIS) were significant factors predicting RFS and PFS. The PLR values before and during induction therapy could be used as predictors for the progression and recurrence of NMIBC patients receiving BCG immunotherapy. the PLR values after induction therapy have a stronger predictive power.

Dose of intra-operative opioids has no impact on recurrence or survival in primary liver cancer.

Intra-operative use of opioid analgesics might have an impact on cancer recurrence and survival after surgery. The objective of this study was to investigate the association between the intra-operative fentanyl equivalents and survival outcomes in patients with primary liver cancer after receiving hepatectomy. This was a retrospective single-center cohort study, and clinical data of 700 patients with primary liver cancer who underwent hepatectomy in Harbin Medical University Cancer Hospital from September 2013 to August 2018 were reviewed. After propensity matching, 376 patients were included. Patients were divided into high-dose and low-dose groups according to the median intra-operative fentanyl equivalents (1.500 mg). Kaplan Meier curve and Cox proportional hazards regression model were used. Results of univariable analysis showed there were no significant differences in recurrence-free survival (RFS) (p=0.136) and overall survival (OS) (p=0.444) between high-dose fentanyl equivalents and low-dose fentanyl equivalents group. The multivariable Cox regression analysis found that the dose of intra-operative fentanyl equivalents was not associated with RFS (HR: 1.119, 95%CI: 0.851-1.472, p=0.422) or OS (HR: 0.939, 95%CI: 0.668-1.319, p=0.715). The amounts of intra-operative fentanyl equivalents had no impact on recurrence-free or overall survival in patients with primary liver cancer after curative hepatectomy.

The efficacy of anatomic resection for hepatocellular carcinoma within Milan criteria: A retrospective single-institution case-matched study

IntroductionStill now, the efficacy of anatomic resection (AR) for hepatocellular carcinoma (HCC) is controversial. The aim of this study is to examine it in our cohort and detect an optimal indicator for AR. MethodsThe present study included 656 patients with primary HCC within Milan criteria who underwent hepatectomy from 2000 to 2019. Our cohort was divided into AR (n = 378) and non-anatomic resection (NAR) (n = 278) groups, and 1:1 propensity score matching (PSM) was performed to minimize the effect of potential confounders. Recurrence-free survival (RFS), overall survival (OS), and a preoperative indicator for AR were examined. Results210 patients from each group were well-matched, and preoperative confounding factors were balanced between the two groups. There was no significant difference in RFS and OS between the two groups before (RFS; HR = 0.89 P = 0.25, OS; HR = 1.08 P = 0.64) and after PSM (RFS; HR = 0.93 P = 0.60, OS; HR = 1.07 P = 0.75). Subgroup analysis showed that the survival improvement effect of AR was observed in cases with a fucosylated fraction of alfa-fetoprotein (AFP-L3) > 10% and poorly differentiation (P for interaction <0.05). Moreover, the logistic regression analysis showed that preoperative AFP-L3 > 10% was an independent predictor for poorly differentiation (OR = 2.58, P = 0.03). ConclusionThe efficacy of AR for patients with primary HCC within Milan criteria was not shown. But it was suggested that AFP-L3 > 10% might be a preoperative indicator of AR for HCC within Milan criteria.

Selection of an impedance- or magnetic field-based electro-anatomical mapping platform does not affect outcomes of outflow tract premature ventricular complex manual ablation

Comparative data are virtually missing about the performance of different electro-anatomical mapping (EAM) system platforms on outflow tract (OT) premature ventricular complex (PVC) ablation outcomes with manual ablation catheters. We aimed to compare the acute success-, complication-, and long-term recurrence rates of impedance-based (IMP) and magnetic field-based (MAG) EAM platforms in manual OT PVC ablation. Single-centre, propensity score matched data of 39–39 patients ablated for OT PVCs in 2015–17 with IMP or MAG platforms were analysed. Acute success rate, peri-procedural complications, post-ablation daily PVC burden, and long-term recurrence rates were compared on intention-to-treat basis. Acute success rate was similar in the IMP and MAG group (77 vs. 82%, p = 0.78). There was a single case of femoral pseudo-aneurysm and no cardiac tamponade occurred. PVC burden fell significantly from baseline 24.0% [15.0–30.0%] to 3.3% [0.25–10.5%] (p < 0.001) post-ablation, with no difference between EAM platforms (IMP: 2.6% [0.5–12.0%] vs. MAG: 4.0% [2.0–6.5%]; p = 0.60). There was no significant difference in recurrence-free survival of the intention-to-treat cohort of the IMP and MAG groups (54 vs. 60%, p = 0.82, respectively) during 12 months of follow-up. Ablation with the aid of both impedance- and magnetic field-based EAM platforms can considerably reduce OT PVC burden and give similar acute- and long-term freedom from arrhythmia.

Does Lymph Node Dissection Impact Adjuvant Treatment or Survival Outcomes in High-Risk Endometrial Cancers?

ObjectivesLymphadenectomy does not improve overall survival outcomes in patients with low-risk endometrial cancers. Sentinel node mapping has a high detection rate and accuracy; however, its prognostic implications have not been well explored. We evaluated the overall survival and therapies received by patients undergoing varied lymph node dissection approaches for high-risk endometrial cancers.MethodsRetrospective review of grade 3 endometrioid and high-grade non-endometrioid cancers at one institution over ten years. Patients who received neoadjuvant therapy and/or debulking of only grossly abnormal lymph nodes were excluded. Data was abstracted from electronic medical records. Chi-squared tests and survival analyses were used to compare groups.ResultsOne hundred and fifty-three patients with grade 3 endometrioid, serous, clear cell, carcinosarcoma, or mixed high-grade on final pathology were identified; 16 had no lymph node dissection, 26 had sentinel lymph nodes, and 111 had complete lymph node dissection. Patients with open surgery were more likely to have complete nodes than sentinel nodes when compared to a minimally invasive approach (p<0.001). Sentinel nodal dissection significantly impacted the utilization of, or modality choice, in adjuvant therapy (p=0.051). Recurrence-free survival and cancer-specific overall survival were not significantly different across the three nodal-assessment groups.Conclusions Sentinel lymph node dissection in high-risk endometrial cancers led to no significant differences in recurrence-free survival or cancer-specific overall survival. While limited by sample size and its retrospective nature, results from this single-institution study are hypothesis-generating and prompt consideration of non-inferiority trials. Performing the least invasive surgery possibly can lead to fewer complications while maintaining overall survival outcomes.

Radical prostatectomy findings and oncologic outcomes in patients with prostate cancer detected on systematic sextant biopsy only, MRI-targeted biopsy only, or both.

Magnetic resonance imaging-targeted biopsy (T-Bx) has been shown to more accurately detect clinically significant prostate cancer. However, the clinical significance of cancer detection on T-Bx, followed by definitive treatment, needs to be further investigated. We herein investigated unique cohorts of patients with prostate cancer detected on systematic sextant biopsy (S-Bx) and/or T-Bx. We assessed consecutive patients who had undergone T-Bx with concurrent S-Bx (6 sites, ≥12 cores), followed by radical prostatectomy from 2015 to 2019. Within our Surgical Pathology database, we identified a total of 222 men who met the inclusion criteria for prostatic adenocarcinoma on either S-Bx or T-Bx, or both (B-Bx). Radical prostatectomy findings and oncologic outcomes were then compared among groups. Prostate cancer was detected on S-Bx only (n = 32; 14%), T-Bx only (n = 40; 18%), or B-Bx (n = 150; 68%). Compared to cases with cancer detected on S-Bx only, those on T-Bx only or B-Bx showed significantly higher tumor grade (highest Grade Group in each patient) on biopsy and significantly larger estimated tumor volume on prostatectomy. There were no significant differences in tumor volume on biopsy, tumor grade on prostatectomy (except S-Bx vs. B-Bx), pT or pN stage category, surgical margin status, or preoperative prostate-specific antigen level between cases where cancer was detected on S-Bx only vs. T-Bx only or B-Bx. There were also no significant differences in any of these clinicopathologic features between cancers detected on T-Bx only vs. B-Bx. Kaplan-Meier analysis revealed a significantly higher risk of biochemical recurrence after prostatectomy in patients whose cancer was detected on T-Bx only (P = 0.020) or B-Bx (P = 0.032) than in those on S-Bx only. No significant difference in recurrence-free survival between T-Bx only vs. B-Bx cases (P = 0.601) was seen. In multivariate analysis, cancer detection on T-Bx only (vs. S-Bx only) showed significance for recurrence (hazard ratio = 8.482, P = 0.045). Detection of prostate cancer on T-Bx, in addition to or instead of S-Bx, was found to be associated with larger tumor volume as well as worse prognosis. However, no significant clinicopathologic impact of simultaneous tumor detection on S-Bx was indicated in patients with prostate cancer present on T-Bx.

Subclassifying triple-negative breast cancers and its potential clinical utility.

The molecular subtyping of triple-negative breast cancer (TNBC) is critical to guiding individualized patient treatment. In this study, we sought to characterize the clinicopathologic features of TNBC subtypes and to identify correlates of patient survival in an effort to provide a robust foundation for treatment planning. We additionally assessed PD-L1 expression in Chinese TNBC patients and evaluated the relationship between such expression and immunotherapeutic treatment outcomes. Based on analyses of histologic characteristics including apocrine differentiation, tumor-infiltrating lymphocytes, and metaplastic features, we selected immunohistochemical (IHC) markers including CD8, FOXC1, and AR for use in classifying TNBC cases. Associations between these subtypes and a range of clinicopathologic characteristics were evaluated. We classified a cohort of 93 TNBC patients into individuals with luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immune-suppressed (BLIS), and mesenchymal (MES) tumor subtypes (23, 24, 39, and 7 cases, respectively). PD-L1 positivity was observed in 49.6% of cases and was more common in individuals with IM subtype disease. Mismatch repair deficiency (dMMR) was observed in just one patient. Significant differences in histologic grade, pT stage, lymphocyte distribution patterns, large scarring areas without cells in tumor of central (central scar), and PD-L1, P53, and Rb status were observed among these TNBC subtypes, whereas no such differences were observed with respect to age, invasion pattern, or pN stage. Rates of disease progression were higher at the 40-50month follow-up time point, but there were no significant differences in recurrence-free survival or breast cancer-specific survival among these subtypes. IHC markers associated with clinicopathologic characteristics represent a powerful approach to TNBC molecular typing, providing a foundation for precision patient treatment. PD-L1 expression may represent a relevant factor in TNBC patient immunotherapeutic treatment planning, whereas dMMR is not likely to be of substantial value when evaluating immunotherapeutic efficacy in these patients.

A nomogram based on multi-modal ultrasound for prediction of microvascular invasion and recurrence of hepatocellular carcinoma

ObjectiveTo establish and validate a nomogram based on multi-modal ultrasound for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC), and to assess the ability thereof to stratify recurrence-free survival (RFS). MethodsA total of 287 HCC patients undergoing surgical resection were prospectively enrolled, including 210 patients in the training cohort and 77 patients in the test cohort. All patients underwent conventional ultrasound, contrast-enhanced ultrasonography, and shear wave elastography examinations within one week before surgery. Taking histopathological examination result as the reference standard, independent factors associated with MVI in HCC were determined by logistic regression and a nomogram was established and further evaluated. The Kaplan-Meier method was used to analyze the prognostic value of histologic MVI status and nomogram-predicted MVI status. ResultsMultivariate analysis showed that tumor diameter, echogenicity, tumor shape, arterial phase peritumoral enhancement and enhancement level in portal venous phase were independent predictors of MVI (all p < 0.05). The nomogram based on these variables showed good discrimination and calibration with the areas under the receiver operating characteristic curve (AUC) of 0.821 (0.762–0.870) and 0.789 (0.681–0.874) in the training and test cohorts. There was a significant difference in RFS between the nomogram-predicted MVI positive and the nomogram-predicted MVI negative groups in training and test cohorts (p < 0.001 and p = 0.004 respectively). ConclusionsThe multimodal ultrasound features were effective imaging markers for preoperative prediction of MVI of HCC and the nomogram might be an effective tool to stratify the risk of recurrence and guide the individualized treatment of HCC.