Higher Cancer-specific Survival Research Articles

Clinical, Prognosis, and Treatment Effect Features Analysis of Metachronous and Synchronous UTUC and BUC

ObjectiveTo provide a comprehensive understanding of the clinical features of patients with synchronous and metachronous upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) and inform surgical and postoperative adjuvant treatment planning. Patients and MethodA total of 292 consecutive patients with synchronous and metachronous UTUC-BUC were retrospectively enrolled and were categorized into three groups: (1) UTUC metachronous BUC (N = 185, UTUC-mBUC), (2) BUC-metachronous UTUC (N = 43, BUC-mUTUC), (3) synchronous UTUC-BUC (N = 64, sUTUC-BUC). We compared pathological characteristics and survival data among groups with Wilcoxon's rank sum tests, Pearson's chi-squared, and the Kaplan–Meier method. ResultsIn the sUTUC-BUC group, a higher proportion of patients exhibited UTUC tumors with grade G3 (56%, P = .001) and stage T4 (6%, P < .001) than group UTUC-mBUC (G3 = 16%, T4 = 0%). The proportion of patients with variant histology subtype in group sUTUC-BUC was higher than that of metachronous UTUC-BUC, involving squamous (P = .003), adenoid (P = .012), and sarcomatoid (P < .001) differentiation. It was also observed that the maximum diameter of the UTUC tumor of group sUTUC-BUC (median = 3.5) was significantly larger than group UTUC-mBUC (median = 2.5, P = .002) and group BUC-mUTUC (median = 2.2, P < .001). Notably, sUTUC-BUC has an increased risk of cancer-specific death compared with UTUC-mBUC (P < .001) and BUC-mUTUC (P < .001). On multivariable Cox regression, synchronous UTUC-BUC was an independent predictor of both RFS (P < .001; vs. UTUC-mBUC: HR 0.555, P = .004; vs. BUC-mUTUC: HR 0.279, P < .001) and CSS (P < .001, HR 29.737). Moreover, sUTUC-BUC showed a better response to intravesical therapy and chemotherapy with higher cancer-specific survival (P < .001) and recurrence-free survival (P = .034). ConclusionsThe prognosis and pathological characteristics among different metachronous and synchronous UTUC and BUC were diverse. The synchronous UTUC-BUC group showed variant histology subtype, high-grade tumors, advanced tumors, multifocal UTUC, worse cancer-specific survival, but better response to intravesical therapy and chemotherapy.

Variations in germ cell tumor histology by age and implications for cancer-specific survival among pediatric and adult males: A population-based study

PurposeFew studies have quantified differences in histology and implications for survival between male children and adults with germ cell tumors (GCT). We evaluated these differences and associations with cancer-specific survival (CSS) using Surveillance, Epidemiology, and End Results (SEER) cancer registries. MethodsSEER (1988–2016) was used to identify male patients 0 to 40 years of age diagnosed with seminoma and nonseminomatous GCT (NSGCT). Demographic and tumor characteristics were tabulated with histology distributions compared by age group (0–4, 12–18, 19–40 years old). CSS was evaluated in multivariable Cox proportional hazards regression models. ResultsAmong 27,204 patients identified, 1,538 (5.7%) were pediatric (0–18 years). Seminoma (54.3%) predominated in adult patients (ages 19–40). Among 0 to 4 years-old, yolk sac tumor (71.2%) and teratoma (21.5%) were most common. Mixed GCT (52.7%) was most prevalent among 12 to 18 years-old with seminoma, embryonal, and teratoma occurring in 12 to 15% each. Relative to pediatric patients, adult patients had similar CSS for seminoma but worse CSS for NSGCT on Kaplan–Meier curves with 9 years mean follow-up. Choriocarcinoma and yolk sac tumors carried the worst prognosis relative to seminoma for both children (HR 5.7 and HR 11.1, respectively, both P < 0.01) and adults (HR 4.6 and HR 4.6, respectively, both P < 0.01) adjusted for stage. ConclusionHistology of GCTs vary by age with yolk sac tumors and teratoma predominating for male patients 0 to 4 years, mixed GCT for 12 to 18 years, and seminoma for 19 to 40 years. Pediatric patients with NSGCT had higher CSS than their adult counterparts. Mixed GCT represented an increasing proportion of GCT over the study period. Age, stage, and histology impact CSS in both pediatric and adult populations.

Somatic Mutation of the Non-Muscle-Invasive Bladder Cancer Associated with Early Recurrence.

Next-generation sequencing (NGS) is widely used in muscle-invasive bladder cancer but has limited use in non-muscle-invasive bladder cancer (NMIBC) due to significant heterogeneity and high cancer-specific survival. Therefore, we evaluated the genomic information of NMIBC and identified molecular alterations associated with tumour recurrence. A total of 43 patients with NMIBC who underwent transurethral resection of the bladder were enrolled. We performed NGS using an Oncomine panel of tumour specimens and blood samples corresponding to each specimen. The somatic mutation results were analysed by pairwise comparison and logistic regression according to the recurrence of bladder tumours within 1 year. The median incidence of genetic variations in 43 tumour samples was 56 variations per sample, and a high tumour mutation burden (TMB) was associated with tumour recurrence (median variation 33 vs. 64, p = 0.023). The most mutated gene was adipose tissue macrophages (ATM) (79%), followed by neurofibromatosis-1 (NF1) (79%), and neurogenic locus notch homolog protein 1 (NOTCH1) (79%). In multivariable analysis, mutation of epidermal growth factor receptor (EGFR) (odds ratio [OR], 9.95; 95% confidence interval [CI], 1.40-70.96; p = 0.022) and telomerase reverse transcriptase (TERT) (OR, 7.92; 95% CI, 1.22-51.51; p = 0.030) were significant factors associated with the recurrence of bladder tumour within 1 year. Our results revealed that high TMB, EGFR mutation, and TERT mutation had a significant association with tumour recurrence in NMIBC. In addition, somatic mutations in EGFR and TERT could be useful prognostic biomarkers in NMIBC.

Surgery with adjuvant chemotherapy versus chemoradiation for early-stage large cell neuroendocrine cancer (LCNEC) of the lung: A SEER plus based analysis.

e20616 Background: LCNEC of the lung is a rare and highly aggressive tumor with neuroendocrine differentiation. Given its rare occurrence and lack of data from large randomized trials, treatment recommendations are based on the extrapolation of data, primarily from small-cell lung cancer studies. We conducted this study to evaluate the survival difference among patients with LCNEC with an N1 disease between those who received surgery and adjuvant chemotherapy versus definitive chemotherapy and radiotherapy. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER) plus 18 registries database to identify patients diagnosed with LCNEC with tumor stage of T1, T2, or T3 and nodal stage of N1. The study population included patients, 18 years and above, who underwent surgical resection followed by adjuvant chemotherapy and patients who received definitive chemo-radiotherapy for early stage LCNEC. Kaplan-Meier and log rank test were used to compare overall survival (OS) and Cancer specific survival (CSS). Multivariate survival analysis was done using the cox proportional hazards regression model. Results: A total of 178 patients were included, 57.3% (n = 102) were &lt; 65-year-old, 50.56% (n = 90) were male, mostly Caucasian 87.08% (n = 155) and identified as non-Hispanic 93.26% (n = 166). Out of them, 70.22% (n = 125) underwent surgery plus adjuvant chemotherapy and 29.78% (n = 53) underwent chemoradiation. Patients who underwent surgery with adjuvant chemotherapy had higher overall survival (OS) than chemoradiation (37 vs. 11 months respectively). 3-year (49.9% vs. 15.7%) and 5-year OS rates (36.7% vs. 10.4%) were also higher in the earlier group. On multivariate analysis after adjusting for age, gender, race and origin, patients who received chemoradiation had higher hazards as compared to those who received surgery and adjuvant chemotherapy (Hazard ratio: 2.91, 95% Confidence interval (CI):1.93,4.37, P value &lt; 0.001). When examining the cancer specific survival (CSS), similar results were observed with higher CSS in the surgery with adjuvant chemotherapy group (18 vs. 8 months) reaching a statistical significance of P &lt; 0.001 and higher hazards in chemoradiation group (Hazard ratio: 3.33, 95% Confidence interval (CI):2.09,5.28, P value &lt; 0.001). 3-year survival (26.47% vs. 2.7 %) and 5-year CSS rates (11.76% vs. not reached) were also pronounced in the patients treated with surgery with adjuvant chemotherapy. Conclusions: Our study demonstrates that patients with early stage LCNEC (T1-3 N1) disease treated with surgery and adjuvant chemotherapy had statistically significant overall and cancer specific survival rates compared to those treated with chemoradiation.

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma

(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment.

External Validation of a Novel Comprehensive Trifecta System in Predicting Oncologic and Functional Outcomes of Partial Nephrectomy: Results of a Multicentric Series.

Background: To validate a novel trifecta for evaluating outcomes of partial nephrectomy (PN) on a multicentric dataset. Methods: Between 2007 and 2020, three renal cancer databases were queried for patients with solitary renal masses who underwent PN (n = 649). Trifecta was estimated for overall cohort and contributing centers. Overall survival (OS), cancer-specific survival (CSS) and end-stage renal disease (ESRD) probabilities were assessed by Kaplan–Meier. Cox regression was used to identify predictors of OS, CSS, ESRD. For all analyses, a p < 0.05 was considered significant. Results: At a median follow-up of 22.7 months (IQR 12.5–76.5) overall trifecta was 76.7% [Centre A; (n = 230; 68.6%), B (n = 68; 77.3%), C (n = 200; 88.4%); p = 0.001). On Kaplan–Meier, patients achieving trifecta exhibited higher OS (p = 0.024), higher CSS (p = 0.015) and lower ESRD rates (p = 0.024). On multivariable analysis, age (HR 1.04; 95% CI 1.01–1.08) and trifecta (HR 0.34; 95% CI 0.15–0.76) were independent predictors of OS while pT stage (HR 1.95; 95% CI 0.45–8.43) and trifecta (HR 0.33; 95% CI 0.16–0.67) were predictors of CSS (each p < 0.01). Preoperative CKD stage ≥ 3a (HR 13.1; 95% CI 4.07–42.6) and trifecta (HR 0.41; 95% CI 0.19–0.87) were independent predictors of ESRD (each p < 0.05). Conclusions: On external validation, trifecta was an independent predictor of all PN endpoints, regardless of hilar control and ischemia duration.

Oncological Long-term Outcome After Whole-gland High-intensity Focused Ultrasound for Prostate Cancer—21-yr Follow-up

BackgroundOwing to the morbidity of established radical treatment options for prostate cancer, alternative whole-gland and focal treatment strategies have emerged. High-intensity focused ultrasound (HIFU) is one of the most studied sources for tissue ablation and has been used since the 1990s. ObjectiveTo provide 21-yr oncological long-term follow-up data of an unselected series of patients who underwent whole-gland HIFU for nonmetastatic prostate cancer. Design, setting, and participantsA total of 674 patients were treated between November 1997 and November 2012 in one university center. Outcome measurements and statistical analysisThe oncological outcome was assessed by biopsy failure–free survival (BFFS), salvage treatment–free survival (STFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Multivariable Cox proportional hazard regression analyses were performed to estimate the prognostic relevance of clinical variables. Results and limitationsIn total, 560 patients were included into the evaluation and the median follow-up was 15.1 yr, with a range up to 21.4 yr. At 15 yr, CSS rates for low-, intermediate-, and high-risk patients were 95%, 89%, and 65%, respectively; MFS, STFS-1 (salvage treatment other than HIFU), STFS-2 (salvage treatment including repeat HIFU), and BFFS rates were 91%, 85%, and 58%; 77%, 63%, and 29%; 67%, 52%, and 28%; and 82%, 73%, and 47%, respectively. Preoperative high-risk category was an independent predictor of inferior OS, CSS, MFS, STFS, and BFFS. ConclusionsAlthough whole-gland HIFU achieved good long-term cancer control in low- and intermediate-risk patients, high-risk patients should not be treated routinely by HIFU. Intermediate-risk patients achieve high CSS and MFS rates, but a relevant salvage treatment rate has to be reckoned with. Long-term data after whole-gland therapy might help derive implications for focal treatment sources and patient selection. Patient summaryLong-term data after whole-gland high-intensity focused ultrasound (HIFU) therapy are crucial to prove its oncological efficacy, and may help derive implications for focal treatment strategies and patient selection. In this context, whole-gland HIFU achieved good long-term cancer control up to 21 yr in low- and intermediate-risk prostate cancer (PCa) patients. Owing to considerably inferior long-term cancer control, it should not routinely be used in high-risk PCa patients.

Survival analysis of patients with prostate cancer and unfavorable risk factors treated with radical prostatectomy and salvage radiotherapy after biochemical recurrence and persistence

ObjectiveSurvival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). Materials and methodsRetrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥8, pathologic stage ≥pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4ng/ml.A survival analysis using Kaplan–Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. ResultsMean follow up: 72 (IQR 27–122) months, mean time to BR: 42 (IQR 20–112) months, mean PSA level at BR: 0.56 (IQR 0.42–0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients.Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10 years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15 years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15 years were 99.1%, 98.1% and 96.6%.Only time to BR <24 months (HR=2.55, p=.01) was identified as an independent risk factor for RFS after SRT. ConclusionsIn these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence >24 months responded better to rescue treatment.

Comparing the Oncological Outcomes of Cryoablation vs. Radical Prostatectomy in Low-Intermediate Risk Localized Prostate Cancer.

Purpose: To compare the oncologic outcomes of cryoablation (CA) and radical prostatectomy (RP) in patients with low- and intermediate-risk localized prostate cancer (PCa).Materials and Methods: PCa patients who received CA or RP between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Multivariable Cox proportional hazard analysis was used to compare the prostate cancer-specific survival (CSS) and overall survival (OS). We conducted 1:3 propensity score matching and adjusted standardized mortality ratio weighting (SMRW) to balance the clinicopathological characteristics.Results: Ninety-seven thousand seven hundred eighty-three patients were identified after preliminary screening. After matching, the CA and RP groups included 1,942 and 5,826 patients and had median follow-up periods of 85 and 72 months, respectively. CA had lower CSS and OS rates (hazard ratio [HR], 2.07; P = 0.007; HR, 2.09; P < 0.001, respectively) than did RP, which was consistent in the SMRW model (CSM: HR, 2.66; P < 0.001; OS: HR, 2.29; P < 0.001). The 10-years CSS and OS for CA vs. RP were 98.1 vs. 99.2% and 61.3 vs. 79.9%, respectively.Conclusions: In patients with low- to intermediate-risk localized PCa, CA had lower CSS rates than did RP. However, the high 10-years CSS rates indicated that CA could be an option for those who are not RP candidates. Further high-quality trials are needed to confirm and expand our findings.

Determining the prognostic significance of IKKα in prostate cancer.

As the survival of castration-resistant prostate cancer (CRPC) remains poor, and the nuclear factor-κB (NF-κB) pathways playkey roles in prostate cancer (PC) progression, several studies have focused on inhibiting the NF-κB pathway through generating inhibitory κB kinase subunitα (IKKα) small molecule inhibitors. However, the identification of prognostic markers able to discriminate which patients could benefit from IKKα inhibitors is urgently required. The present study investigated the prognostic value of IKKα, IKKα phosphorylated at serine 180 (p-IKKα S180) and threonine 23 (p-IKKα T23), and their relationship with the androgen receptor (AR) and Ki67 proliferation index to predict patient outcome. A cohort of 115 patients with hormone-naïve PC (HNPC) and CRPC specimens available were used to assess tumor cell expression of proteins within both the cytoplasm and the nucleus by immunohistochemistry. The expression levels were dichotomized (low vs high) to determine the associations between IKKα, AR, Ki67, and patients'Isurvival. In addition, an analysis was performed to assess potential IKKα associations with clinicopathological and inflammatory features, and potential IKKα correlations with other cancer pathways essential for CRPC growth. High levels of cytoplasmic IKKα were associated with a higher cancer-specific survival in HNPC patients with low AR expression (hazards ratio [HR], 0.33; 95% confidence interval [CI] log-rank, 0.11-0.98; P = .04). Furthermore, nuclear IKKα (HR, 2.60; 95% CI, 1.27-5.33; P = .01) and cytoplasmic p-IKKα S180 (HR, 2.10; 95% CI, 1.17-3.76; P = .01) were associated with a lower time to death from recurrence in patients with CRPC. In addition, high IKKα expression was associated with high levels of T-cells (CD3+ P = .01 and CD8+ P = .03) in HNPC; however, under castration conditions, high IKKα expression was associated with high levels of CD68+ macrophages (P = .04), higher Gleason score (P = .01) and more prostate-specific antigen concentration (P = .03). Finally, we identified crosstalk between IKKα and members of the canonical NF-κB pathway in the nucleus of HNPC. Otherwise, IKKα phosphorylated by noncanonical NF-κB and Akt pathways correlated with members of the canonical NF-κB pathway in CRPC. The present study reports that patients with CRPC expressing high levels of nuclear IKKα or cytoplasmic p-IKKα S180, which associated with a lower time to death from recurrence, may benefit from IKKα inhibitors.

Análisis de supervivencia de los pacientes con cáncer de próstata con factores patológicos desfavorables tratados con prostatectomía radical y radioterapia de rescate tras la recidiva y persistencia bioquímica

ObjectiveSurvival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). Materials and methodsRetrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥8, pathologic stage ≥pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4ng/ml.A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. ResultsMean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients.Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15years were 99.1%, 98.1% and 96.6%.Only time to BR <24months (HR=2.55, P=.01) was identified as an independent risk factor for RFS after SRT. ConclusionsIn these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence >24months responded better to rescue treatment.

Upfront radiotherapy with brachytherapy for medically inoperable and unresectable patients with high-risk endometrial cancer

ObjectivesComprehensive surgery with adjuvant therapy is standard of care for high-risk endometrial cancers, whereas upfront radiotherapy with brachytherapy is indicated for inoperable/unresectable patients, irrespective of risk. We evaluated outcomes for inoperable/unresectable patients with high-risk endometrial cancer (HREC: stage III and/or grade 3) and low-risk endometrial cancer (LREC: stage I/II and grade 1/2) treated with upfront radiotherapy. MethodsTwenty-nine patients with inoperable/unresectable endometrial cancer were treated with upfront radiotherapy at an academic medical center from 2012 to 2019. Cancer-specific survival (CSS), overall survival (OS), and recurrence rates between patients with HREC and LREC were compared. ResultsMedian follow-up was 17.0 months (range 3.7–54.0). Twenty cancers were stage I + II and nine were stage III. Twenty-one cancers were grade 1 + 2 and eight were grade 3. Thirteen patients (45%) had HREC. Twenty-five patients received radiotherapy/chemoradiotherapy for primary treatment, while 4 patients received chemoradiotherapy before surgery. All patients underwent high dose rate brachytherapy (HDR) with 7 receiving HDR alone and 22 receiving external beam radiation and HDR. Two-year CSS was 100% for both HREC and LREC patients (log-rank p = 0.32). There was no OS difference between HREC and LREC patients (2-year: 73% vs. 77%; log-rank p = 0.33). Four HREC and 1 LREC patients recurred with one local recurrence in each group. There were no acute grade ≥3 and two late grade ≥3 gastrointestinal/genitourinary toxicities. ConclusionsUpfront radiotherapy for inoperable/unresectable HREC patients was well tolerated with high local control and CSS rates. Upfront radiotherapy with brachytherapy remains important even for high-risk inoperable and unresectable endometrial cancer patients.

Metabolic syndrome is associated with improved cancer-specific survival in patients with localized clear cell renal cell carcinoma.

Metabolic syndrome (MetS) has been found to be prevalent in cancer and have implications in cancer outcomes. In this study, we attempted to evaluate the prognostic value of MetS in localized clear cell renal cell carcinoma (ccRCC) patients. We retrospectively collected clinicopathological data and pre-treatment laboratory test results of 480 patients with localized (T1-2N0M0) ccRCC undergoing radical or partial nephrectomy in Peking University First Hospital. MetS was diagnosed by criteria of the 2004 Chinese Medical Association Diabetes Society. Univariate and multivariate analyses were conducted to analyze the association between clinicopathological characteristics, MetS, and disease outcomes. In our cohort, 136 patients (28.3%) were diagnosed with MetS. Among them, 113 (83.1%) were men, suggesting that men were more likely to have MetS. This syndrome was also associated with increased pre-treatment creatinine levels. Median follow-up time was 70 months (range, 1-118 months) and 5-year overall survival (OS) rate was 92%. MetS was an independent favorable factor of cancer-specific survival (CSS) (P=0.017), and similar results were observed in Fuhrman nuclear grade 1-2 ccRCC patients by further analysis. Neither of the four components of the MetS (hypertension, diabetes mellitus, overweight/obesity and dyslipidemia) was an independent predictor of CSS. Patients who met more than 3 of the 4 criteria for MetS had higher CSS than those who met fewer than 2 criteria. MetS is an independent prognostic factor for better CSS in localized ccRCC patients.

Prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with non-small cell lung cancer: a meta-analysis.

The objective of this study is to explore the association between the pretreatment systemic immune-inflammation index (SII) and prognosis in non-small cell lung cancer (NSCLC) patients. A systemic literature search of PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP and SinoMed databases was performed from January 1, 1966 to April 15, 2019, to identify potential studies that assessed the prognostic role of the pretreatment SII in NSCLC. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the correlation of the pretreatment SII with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and cancer-specific survival (CSS) in NSCLC patients. A total of 9 studies involving 2,441 patients were eventually included. An elevated pretreatment SII indicated significantly poorer OS (HR =1.88, 95% CI: 1.50-2.36; P<0.001) with high heterogeneity (I2=60.6%, P=0.019), DFS/PFS (HR =2.50, 95% CI: 1.20-5.20; P=0.014) with high heterogeneity (I2=58.2%, P=0.092) and CSS (HR =1.852, 95% CI: 1.185-2.915; P=0.007). Subgroup analyses further verified the above results. In addition, compared with the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), the SII showed a much higher prognostic value in NSCLC. The pretreatment SII may serve as a useful prognostic indicator in NSCLC and contribute to prognosis evaluation and treatment strategy formulation. However, more well-designed studies are warranted to verify our findings.

The Prognosis of Papillary Thyroid Cancer with Initial Distant Metastasis is Strongly Associated with Extensive Extrathyroidal Extension: A Retrospective Cohort Study.

Extensive extrathyroidal extension (ETE) has a significant role in the prognosis of papillary thyroid cancer (PTC) without distant metastasis, but its role in PTC with initial distant metastasis has never been studied. This study aimed to evaluate the prognostic significance of extensive ETE regarding disease progression, survival, and remission in PTC patients with initial distant metastasis. This retrospective cohort study included PTC patients with initial distant metastasis who underwent total thyroidectomy with a median follow-up period of 6.7years. The prognostic significance of extensive ETE was assessed in terms of time to tumor progression (TTP), cancer-specific survival (CSS), and cumulative incidence of remission with all-cause death as the competing event. The study enrolled 64 patients. Of these patients, 21 (32.8%) had extensive ETE, which was associated with a shorter TTP (adjusted hazard ratio [HR], 4.10; p = 0.015) and a lower CSS rate (p = 0.002, log-rank), particularly for patients 55years of age or older with stage 4b disease (10-year CSS rate: 33.3% in those with and 92.3% in those without extensive ETE; p = 0.017). Additionally, remission was observed only in patients without extensive ETE (10-year cumulative incidence of remission: 0.0% in those with and 29.3% in those without extensive ETE; p = 0.013). Extensive ETE of the primary lesion results in poorer prognoses for PTC patients with initial distant metastasis. The high CSS rate for patients with stage 4b PTC but no extensive ETE indicates that the prognosis of this patient population should be distinguished from that of other stage 4 cases.

The who, when, and why of primary adrenal malignancies: Insights into the epidemiology of a rare clinical entity.

Primary malignancies of the adrenal glands are rare. Epidemiologic assessment of primary adrenal malignancies is lacking and has been limited to case reports and series. Population-level data can provide a better understanding of the incidence, distribution, and prognostic factors associated with these rare malignancies. The Surveillance, Epidemiology, and End Results database (1973-2013) was queried for all patients who were diagnosed with primary adrenal malignancies, categorized in 5 histologic groups: adrenocortical carcinoma (ACC), pheochromocytoma and paraganglioma (PH), neuroblastoma (NE), non-Hodgkin lymphoma (NHL), and sarcoma (SA). Age-adjusted incidence, distribution trends, and cancer-specific survival (CSS) for each group were analyzed. In total, 4695 patients with primary adrenal malignancies were identified, including 2057 with ACC, 512 with PH, 1863 with NE, 202 with NHL, and 61 with SA. The age-adjusted incidence of all 5 histologic subtypes was rising. Age at presentation differed substantially by histologic group: NE was the most prevalent during the first decade of life, whereas ACC predominated after age 30 years, and NHL outnumbered PH after age 70 years. Patient-specific factors were not associated with advanced disease at the time of presentation. The 5-year CSS rate for each histologic subtype was 38% for ACC, 69% for PH, 64% for NE, 38% for NHL, and 42% for SA. Survival outcomes for patients with ACC, NHL, PH and SA remained unchanged over the 40-year study period. Multimodal therapy was associated with higher CSS in patients with NE. This first population-level analysis of all primary adrenal malignancies provides important initial data regarding presentation and clinical outcomes. Notably, except for patients with NE, the survival of patients with these rare cancers has not improved over the past 40 years.

The effects of tumor size and postoperative radiotherapy for patients with adult low-grade (WHO grade II) infiltrative supratentorial astrocytoma/oligodendroglioma: A population-based and propensity score matched study.

BackgroundThe update of 2018 NCCN guidelines (central nervous system cancers) recommended the risk classification of postoperative patients diagnosed as adult low‐grade (WHO grade II) infiltrative supratentorial astrocytoma/oligodendroglioma (ALISA/O) should take tumor size into consideration. Moreover, the guidelines removed postoperative radiotherapy (PORT) for low risk patients. Our study aimed to explore the specific tumor size to divide postoperative patients into relatively low‐ or high risk subgroups and the effect of PORT for ALISA/O patients.MethodsWe conducted a retrospective study choosing 1277 postoperative ALISA/O patients from the Surveillance, Epidemiology, and End Results database. The X‐tile analysis provided the optimal cutoff point based on tumor size. The differences between surgery alone and surgery +RT groups were balanced by propensity score‐matched analysis. The multivariable analysis and the nomogram evaluated multiple prognostic factors based on cancer‐specific survival (CSS) and overall survival (OS).ResultsX‐tile plots defined 59 mm (P < 0.001) as the optimal cutoff tumor size value in terms of CSS, which was verified in multivariate analysis (P < 0.001). The Kaplan‐Meier analysis showed that the surgery alone had higher CSS and OS than surgery +RT, while the low risk group had no statistical significance after propensity score match. Multivariable analysis showed that surgery +RT was independently associated with diminished OS and CSS for high risk group, which had no statistical significance for low‐risk group.ConclusionsOur study suggested that tumor size of 59 mm was an optimal cutoff point to divide postoperative patients into relatively low‐ or high risk subgroups. PORT may not benefit patients, while the effects of PORT for low risk patients need further research.

Survival analysis of patients with spinal chordomas.

This study was aimed to analyze the survival of patients with spinal chordomas. Patients' data in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved and analyzed statistically. There were 765 patients with spinal chordomas between 1974 and 2013. The overall survival did not improve significantly over decades for patients receiving surgery and radiotherapy (SR) (P = 0.221). There were significant differences in overall survival among subgroups of patients receiving surgery (S), radiotherapy (R), and neither S nor R (NSR) (P = 0.031, 0.037, and 0.031, respectively). Cancer-specific survival did not change significantly among subgroups of patients receiving R (P = 0.411), while it increased steadily among subgroups of patients receiving S, SR, and NSR (P < 0.001, 0.001, and 0.049, respectively). In the multivariate Cox regression model, younger onset age (hazard ratio [HR] 1.052, P < 0.001), surgery (HR 0.291, P = 0.001), and tumor location of the sacrum (HR 0.401, P = 0.002) were associated with a better overall survival. Similarly, younger onset age (HR 1.036, P = 0.029), surgery (HR 0.221, P = 0.009), and tumor location of the sacrum (HR 0.287, P = 0.002) were also associated with a higher cancer-specific survival. The changes in overall and cancer-specific survival over time differ among different treatment groups. Younger onset age, surgical strategy, and tumor location of the sacrum may be correlated with a higher overall and cancer-specific survival.

Long-term Oncologic Outcome After Transanal Endoscopic Microsurgery for Rectal Carcinoma.

Transanal endoscopic microsurgery is superior to other methods of local excision of rectal cancer, but few studies report long-term follow-up data. This study investigated the use of transanal endoscopic microsurgery alone as curative and compromise therapy based on long-term disease recurrence and mortality. This was a retrospective review of prospectively collected data. The study was conducted at a tertiary care university medical center. The study included 133 patients treated between 1985 and 2007. There were 3 groups, including transanal endoscopic microsurgery in curative intent (low-risk rectal carcinoma, including pT1, G1/2, L0, and LX with clear margins and a minimal distance between tumor and resection margin of >1 mm (N = 64) or clear margins only (N = 18 ))) and as compromise therapy (high-risk or incompletely resected rectal carcinoma; N = 51). Log-rank tests were used to compare overall and cancer-specific survival. The median follow-up time was 8.6 years (range, 0.2-25.1 years), and a total of 131 of 133 patients (98.5%) were followed >5 years or until death. The preoperative diagnosis of carcinoma was not associated with belonging into 1 of the 3 categories. In patients with low-risk completely (>1 mm) resected carcinoma, the 5- and 10-year local recurrence rates were 6.6% and 11.6%. In patients with high-risk or incompletely resected carcinoma, the rates were 32.5% and 35.0% (p = 0.006). The 5- and 10-year cancer-specific survival rates for low-risk patients were 98.0% and 91.0% and 84.3% and 74.3% for high-risk patients (p = 0.05). The study was limited by its retrospective design and small subgroups. The high cancer-specific survival justifies transanal endoscopic microsurgery alone as curative treatment in low-risk rectal carcinoma. Complete resection is essential to lower the risk of local recurrence. The high local recurrence rate in patients with high-risk rectal carcinoma restricts the use of TEM alone as compromise therapy.

Prognostic value of stromal decorin expression in patients with breast cancer: a meta-analysis.

Numbers of studies have investigated the biological functions of decorin (DCN) in oncogenesis, tumor progression, angiogenesis and metastasis. Although many of them aim to highlight the prognostic value of stromal DCN expression in breast cancer, some controversial results still exist and a consensus has not been reached until now. Therefore, our meta-analysis aims to determine the prognostic significance of stromal DCN expression in breast cancer patients. PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literatures met out inclusion criteria. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I(2) statistic were employed to estimate the level of heterogeneity across the included studies. Sensitivity analysis was conducted to further identify the possible origins of heterogeneity. The publication bias was detected by Begg's test and Egger's test. There were three English literatures (involving 6 studies) included into our meta-analysis. On the one hand, both the summarized outcomes based on univariate analysis (HR: 0.513; 95% CI: 0.406-0.648; P<0.001) and multivariate analysis (HR: 0.544; 95% CI: 0.388-0.763; P<0.001) indicated that stromal DCN expression could promise the high cancer-specific survival (CSS) of breast cancer patients. On the other hand, both the summarized outcomes based on univariate analysis (HR: 0.504; 95% CI: 0.389-0.651; P<0.001) and multivariate analysis (HR: 0.568; 95% CI: 0.400-0.806; P=0.002) also indicated that stromal DCN expression was positively associated with high disease-free survival (DFS) of breast cancer patients. No significant heterogeneity or publication bias was observed within this meta-analysis. The present evidences indicate that high stromal DCN expression can significantly predict the good prognosis in patients with breast cancer. The discoveries from our meta-analysis have better be confirmed in the updated review pooling more relevant investigations in the future.