Independent Predictor Of Worse Overall Survival Research Articles

When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database

BackgroundRectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy particularly in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy.MethodsA retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004–2019) was performed. First, univariate and multivariate Cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterward, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group.ResultsA total of 1837 patients (49.8% female; mean age 56.6 ± 12.3 years) underwent radical resection of a rNET. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high-risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared with 15.9 months when neoadjuvant therapy was not given (p = 0.006).ConclusionsNeoadjuvant chemotherapy improved the OS of patients with high-grade rNET by 15 months and may be indicated for this group.

A national database analysis of the evolution of outcomes of surgery for anal melanoma.

This study assessed trends in treatment and outcomes of anal melanomas over a 17-year period. NCDB was searched for patients with anal melanoma (2004-2020). Receiver-operating characteristic curve analysis was used to determine cutoff year marking increased overall survival (OS) of anal melanoma. Characteristics, treatments, and outcomes in consecutive time periods were compared. A total of 815 patients (mean age: 67.2 years; 59.4% female) were included: 354 in Period 1 (2004-2012) and 461 in Period 2 (2013-2020). Period 2 included fewer abdominoperineal resections (18% vs. 28%, p = 0.002), more local tumor excisions (61.1% vs. 55%, p = 0.002), more often immunotherapy (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 2.22-5.22, p < 0.001) and less often chemotherapy (OR: 0.516, 95% CI: 0.352-0.755, p < 0.001) administered and longer median OS (25.2 vs. 19.8 months, p = 0.006). Independent predictors of worse OS were older age (hazard ratio [HR]: 1.02, p = 0.012), higher Charlson score (HR: 2.32, p = 0.02), and greater number of positive lymph nodes (HR: 1.15, p < 0.001); conversely private insurance (HR: 0.385, p = 0.008) was predictive of increased OS. Anal melanoma patients diagnosed between 2013 and 2020 underwent fewer abdominoperineal resections and more local excisions than patients diagnosed between 2004 and 2013. Increased immunotherapy and longer median OS were noted in period two. Age and private insurance were significant predictors of OS, remaining constant across time periods.

Perineural invasion score system and clinical outcomes in resected pancreatic cancer patients

Background/objectivesPerineural invasion (PNI), classified according to its presence or absence in tumor specimens, is recognized as a poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC) patients. Herein, we identified five histological features of PNI and investigated their impact on survival outcomes of PDAC resected patients. MethodsFive histopathological features of PNI (diameter, number, site, sheath involvement, and mitotic figures within perineural invasion) were combined in an additional final score (ranging from 0 to 8), and clinical data of PDAC patients were retrospectively analyzed. PNI + patients were stratified in two categories according to the median score value (<6 and ≥ 6, respectively). Impact of PNI on disease-free survival (DFS) and overall survival (OS) were analyzed. ResultsForty-five patients were enrolled, of whom 34 with PNI (PNI+) and 11 without PNI (PNI-). The DFS was 11 months vs. not reached (NR) (p = 0.258), while the OS was 19 months vs. NR (p = 0.040) in PNI+ and PNI- patients, respectively. A ≥6 PNI was identified as an independent predictor of worse OS vs. <6 PNI + patients (29 vs. 11 months, p < 0.001) and <6 PNI+ and PNI- patients (43 vs. 11 months, p < 0.001). PNI ≥6 was an independent negative prognostic factor of DFS vs. <6 PNI+ and PNI- patients (13 vs. 6 months, p = 0.022). ConclusionsWe report a PNI scoring system that stratifies surgically-treated PDAC patients in a graded manner that correlates with patient prognosis better than the current dichotomous (presence/absence) definition. However, further and larger studies are needed to support this PNI scoring system.

Surgical Outcomes in Non-Small Cell Lung Cancer with Distant Metastasis: The Prognostic Significance of Delayed Metastasis Diagnosis.

The diagnosis of distant metastasis on preoperative examinations for non-small cell lung cancer (NSCLC) can be challenging, leading to surgery for some patients with uncertain metastasis. This study evaluated the prognostic impact of delayed diagnosis of metastasis on patients who underwent upfront surgery. The study enrolled patients who underwent lobectomy or pneumonectomy for NSCLC between June 2010 and December 2017 and evaluated the presence of distant metastasis before surgery. Overall survival (OS) for patients with stage IV cancer was compared with that for patients without metastasis, and the prognostic factors were analyzed. Of 3046 patients (mean age, 63 years; 1770 men), 100 (3.3 %) had distant metastasis, diagnosed preoperatively in 1.4 % (42/3046) and postoperatively in 1.9 % (58/3046) of the patients. The two most common metastasis sites diagnosed after surgery were contralateral lung (22/58, 37.9 %) and ipsilateral pleura (16/58, 27.6 %). The OS (median, 42.7 months) for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer (P = 0.865), whereas the OS (median OS, 91.7 months) for the patients with stage IV cancer diagnosed preoperatively was better than for the patients with stage IIIB cancer (P = 0.001). Among the patients with distant metastasis, squamous cell type (hazard ratio [HR], 3.15; P = 0.002) and systemic treatment for metastasis (HR, 2.42; P = 0.002) were independent predictors of worse OS. Among NSCLC patients undergoing upfront surgery, the OS for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer. For patients with stage IV disease, squamous cell type and systemic treatment for metastasis were prognostic factors for poorer OS.

Survival Analysis and Prognostic Factors for Peri-ocular Malignancies in Malaysia

Introduction: This study aims to determine the prognostic factors and survival outcomes of patients that underwent this surgery. Method: A retrospective review of 43 patients who underwent exenteration for periocular malignancies over a 14-year period was carried out. Patient demographics, tumour histology, treatment details, surgical margins’ status and post-operative survival were recorded. The survival outcome examined was the overall survival (OS) rate. Cox regression and Kaplan-Meier analysis were used to evaluate post-exenteration survival. Results: In total, 20 females and 23 males with a median age of 62 ± 17.3 years were identified. The most common indication for exenteration was basal cell carcinoma (20.9%), followed by squamous cell carcinoma (18.6%), adenocystic carcinoma (14%), malignant melanoma (14%) and sebaceous gland carcinoma (11.6%). The independent predictors for worse OS on multivariate analysis were Chinese ethnicity (adjusted hazard ratio [aHR] 4.95, p =0.017), sebaceous gland carcinoma (aHR 57.61 p=0.006), adenocystic carcinoma (aHR 45.87, p=0.008), clear surgical margins (aHR 5.41, p=0.025), receiving only chemotherapy (aHR 169.13, p=0.004), and receiving both adjuvant chemotherapy and radiotherapy (aHR 41.51, p=0.010). Conclusion: We recommend targeted public health initiatives for Chinese patients due to their increased mortality risk from peri-ocular malignancies. In addition, we advise comprehensive adjuvant therapy for all patients regardless of whether a clear surgical margin is achieved. Basal cell carcinoma and adenocystic carcinoma may also benefit from genetic research. We advocate more training for ophthalmologists to identify periocular malignancies earlier for better treatment options and increased chances of survival.

Development and validation of web-based dynamic nomograms predictive of disease-free and overall survival in patients who underwent pneumonectomy for primary lung cancer.

The tumour-node-metastasis (TNM) staging system is insufficient to precisely distinguish the long-term survival of patients who underwent pneumonectomy for primary lung cancer. Therefore, this study sought to identify determinants of disease-free (DFS) and overall survival (OS) for incorporation into web-based dynamic nomograms. The clinicopathological variables, surgical methods and follow-up information of 1,261 consecutive patients who underwent pneumonectomy for primary lung cancer between January 2008 and December 2018 at Sun Yat-sen University Cancer Center were collected. Nomograms for predicting DFS and OS were built based on the significantly independent predictors identified in the training cohort (n = 1,009) and then were tested on the validation cohort (n = 252). The concordance index (C-index) and time-independent area under the receiver-operator characteristic curve (AUC) assessed the nomogram's discrimination accuracy. Decision curve analysis (DCA) was applied to evaluate the clinical utility. During a median follow-up time of 40.5 months, disease recurrence and death were observed in 446 (35.4%) and 665 (52.7%) patients in the whole cohort, respectively. In the training cohort, a higher C-reactive protein to albumin ratio, intrapericardial pulmonary artery ligation, lymph node metastasis, and adjuvant therapy were significantly correlated with a higher risk for disease recurrence; similarly, the independent predictors for worse OS were intrapericardial pulmonary artery and vein ligation, higher T stage, lymph node metastasis, and no adjuvant therapy. In the validation cohort, the integrated DFS and OS nomograms showed well-fitted calibration curves and yielded good discrimination powers with C-index of 0.667 (95% confidence intervals CIs [0.610-0.724]) and 0.697 (95% CIs [0.649-0.745]), respectively. Moreover, the AUCs for 1-year, 3-year, and 5-year DFS were 0.655, 0.726, and 0.735, respectively, and those for 3-year, 5-year, and 10-year OS were 0.741, 0.765, and 0.709, respectively. DCA demonstrated that our nomograms could bring more net benefit than the TNM staging system. Although pneumonectomy for primary lung cancer has brought encouraging long-term outcomes, the constructed prediction models could assist in precisely identifying patients at high risk and developing personalized treatment strategies to further improve survival.

Radiologic Extranodal Extension of Metastatic Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Prognostic Utility and Diagnostic Performance.

BACKGROUND. Pathologic extranodal extension (ENE) in metastatic lymph nodes (LNs) has been associated with unfavorable prognosis in patients with non-small cell lung cancer (NSCLC). OBJECTIVE. The purpose of this article was to evaluate the prognostic utility of radiologic ENE and its diagnostic performance in predicting pathologic ENE in patients with NSCLC. METHODS. This retrospective study included 382 patients (mean age, 67 ± 10 [SD] years; 297 men, 85 women) diagnosed with NSCLC and clinical N1 or N2 disease between January 2010 and December 2016. Two thoracic radiologists reviewed staging chest CT examinations to record subjective overall impression for radiologic ENE (no ENE, possible/probable ENE, or unambiguous ENE), reviewing 30 examinations in consensus and the remaining examinations independently. Kaplan-Meier survival analysis and multivariable Cox proportional hazards model were used to evaluate the utility of radiologic ENE in predicting overall survival (OS). Prognostic utility of radiologic ENE was also assessed in patients with clinical N2a disease. In patients who underwent surgery, sensitivity and specificity were determined of radiologic unambiguous ENE in predicting pathologic ENE. RESULTS. The 5-year OS rates for no ENE, possible/probable ENE, and unambiguous ENE were 44.4%, 39.1%, and 20.9% for reader 1 and 45.7%, 36.6%, and 25.6% for reader 2, respectively. Unambiguous ENE was an independent prognostic factor for worse OS (reader 1: adjusted HR, 1.72, p = .008; reader 2: adjusted HR, 1.56, p = .03), whereas possible/probable ENE was not (reader 1: adjusted HR, 1.18, p = .33; reader 2: adjusted HR, 1.21, p = .25). In patients with clinical N2a disease, 5-year OS rate in patients with versus without unambiguous ENE for reader 1 was 22.2% versus 40.6% (p = .59) and for reader 2 was 27.6% versus 41.0% (p = .49). In 203 patients who underwent surgery (66 with pathologic ENE), sensitivity and specificity of radiologic unambiguous ENE for predicting pathologic ENE were 11% and 93% for reader 1 and 23% and 87% for reader 2. CONCLUSION. Radiologic unambiguous ENE was an independent predictor of worse OS in patients with NSCLC. The finding had low sensitivity but high specificity for pathologic ENE. CLINICAL IMPACT. Radiologic ENE may have a role in NSCLC staging workup and treatment selection.

Metabolic bulk volume predicts survival in a homogeneous cohort of stage II/III diffuse large B-cell lymphoma patients undergoing R-CHOP treatment.

Accurate risk stratification can improve lymphoma management, but current volumetric 18F-fluorodeoxyglucose (FDG) indicators require time-consuming segmentation of all lesions in the body. Herein, we investigated the prognostic values of readily obtainable metabolic bulk volume (MBV) and bulky lesion glycolysis (BLG) that measure the single largest lesion. The study subjects were a homogeneous cohort of 242 newly diagnosed stage II or III diffuse large B-cell lymphoma (DLBCL) patients who underwent first-line R-CHOP treatment. Baseline PET/CT was retrospectively analyzed for maximum transverse diameter (MTD), total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), MBV, and BLG. Volumes were drawn using 30% SUVmax as threshold. Kaplan-Meier survival analysis and the Cox proportional hazards model assessed the ability to predict overall survival (OS) and progression-free survival (PFS). During a median follow-up period of 5.4 years (maximum of 12.7 years), events occurred in 85 patients, including progression, relapse, and death (65 deaths occurred at a median of 17.6 months). Receiver operating characteristic (ROC) analysis identified an optimal TMTV of 112 cm3, MBV of 88 cm3, TLG of 950, and BLG of 750 for discerning events. Patients with high MBV were more likely to have stage III disease; worse ECOG performance; higher IPI risk score; increased LDH; and high SUVmax, MTD, TMTV, TLG, and BLG. Kaplan-Meier survival analysis showed that high TMTV (p = 0.005 and < 0.001), MBV (both p < 0.001), TLG (p < 0.001 and 0.008), and BLG (p = 0.018 and 0.049) were associated with significantly worse OS and PFS. On Cox multivariate analysis, older age (> 60 years; HR, 2.74; 95% CI, 1.58-4.75; p < 0.001) and high MBV (HR, 2.74; 95% CI, 1.05-6.54; p = 0.023) were independent predictors of worse OS. Older age (hazard ratio [HR], 2.90; 95% CI, 1.74-4.82; p < 0.001) and high MBV (HR, 2.36; 95% CI, 1.15-6.54; p = 0.032) were also independent predictors of worse PFS. Furthermore, among subjects ≤60 years, high MBV remained the only significant independent predictor of worse OS (HR, 4.269; 95% CI, 1.03-17.76; p = 0.046) and PFS (HR, 6.047; 95% CI, 1.73-21.11; p = 0.005). Among subjects with stage III disease, only greater age (HR, 2.540; 95% CI, 1.22-5.30; p = 0.013) and high MBV (HR, 6.476; 95% CI, 1.20-31.9; p = 0.030) were significantly associated with worse OS, while greater age was the only independent predictor of worse PFS (HR, 6.145; 95% CI, 1.10-4.17; p = 0.024). MBV easily obtained from the single largest lesion may provide a clinically useful FDG volumetric prognostic indicator in stage II/III DLBCL patients treated with R-CHOP.

Neoadjuvant chemotherapy versus upfront surgery as the initial treatment for patients with resectable, synchronous colorectal cancer liver metastases.

Although perioperative chemotherapy has been the standard treatment for colorectal cancer with resectable liver metastases (CRLM), studies that have compared neoadjuvant chemotherapy (NAC) and upfront surgery, especially in the setting of synchronous metastases are rare. We compared perioperative outcomes, overall survival (OS) and overall survival after recurrence (rOS) in a retrospective study of 281 total and 104 propensity score-matched (PSM) patients who underwent curative resection, with or without NAC, for synchronous CRLM, from 2006 to 2017. A Cox regression model was developed forOS. After PSM, 52 NAC and 52 upfront surgery patients with similar baseline characteristics were compared. Postoperative morbidity, mortality, and 5-year OS rate (NAC: 78.9%, surgery: 64.0%; p = 0.102) were similar between groups; however, the NAC group had better rOS (NAC: 67.3%, surgery: 31.5%; p = 0.049). Initial cancer stage (T4, N1-2), poorly differentiated histology, and >1 hepatic metastases were independent predictors of worse OS. Based on these factors, patients were divided into low-risk (≤1 risk factor, n = 115) and high-risk (≥2 risk factors, n = 166) groups. For high-risk patients, NAC yielded better OS than upfront surgery (NAC: 74.5%, surgery: 53.2%; p = 0.024). Although NAC and upfront surgery-treated patients had similar perioperative outcomes and OS, better postrecurrence survival was shown in patients with NAC. In addition, NAC may benefit patients with worse prognoses; therefore, physicians should consider patient disease risk before initiating treatment to identify patients who are most likely to benefit from chemotherapy.

Salvage Locoregional Therapy Following Progression After Radiotherapy for Hepatocellular Carcinoma Is Associated with Improved Outcomes

PurposeTo evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression following radiotherapy. MethodsThis single-institution retrospective analysis included consecutive HCC patients having intrahepatic tumor progression following radiotherapy during 2015–2019. Overall survival (OS) was calculated from the date of intrahepatic tumor progression after initial radiotherapy by using the Kaplan–Meier method. Log-rank tests and Cox regression models were used for univariable and multivariable analyses. An inverse probability weighting was used to estimate treatment effect of salvage-LT considering confounding factors. ResultsA total of 123 patients (mean age ± SD, 70 years ± 10; 97 men) were evaluated. Among those, 35 patients underwent 59 sessions of salvage-LT, including transarterial embolization/chemoembolization (n = 33), ablation (n = 11), selective internal radiotherapy (n = 7), and external beam radiotherapy (n = 8). At a median follow-up of 15.1 months (range, 3.4–54.5 months), the median OS was 23.3 months in patients who received salvage-LT and 6.6 months who did not. At multivariate analysis, ECOG performance status, Child–Pugh class, albumin-bilirubin grade, extrahepatic disease, and lack of salvage-LT were independent predictors of worse OS. After inverse probability weighting, salvage-LT was associated with a survival benefit of 8.9 months (95% CI: 1.1, 16.7 months; p = 0.03). ConclusionsSalvage locoregional therapy is associated with increased survival in HCC patients suffering from intrahepatic tumor progression following initial radiotherapy.

When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database.

e15631 Background: Rectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy specifically in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy. Methods: A retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004-2019) was performed. First, univariate and multivariate cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterwards, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group. Results: 1837 patients (49.8% female; mean age 56.6 ±12.3 years) underwent radical resection of a rectal neuroendocrine tumor. Tumors &gt; 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared to 15.9 months when neoadjuvant therapy was not given (p = 0.006). Conclusions: Neoadjuvant chemotherapy improved OS of patients with high-grade rNET by 15 months and may be indicated for this group.

Efficacy and safety of allogeneic hematopoietic cell transplantation in acute myeloid leukemia patients aged &gt; 65 years with unfavorable cytogenetics

Unrelated donor bone marrow transplantation (UR-BMT), unrelated donor cord blood stem cell transplantation (UR-CBT), and haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT) are the main alternative stem cell sources for allogeneic hematopoietic cell transplantation (HCT) in Japan. The present study aimed to identify factors associated with the outcomes of UR-BMT, UR-CBT, and Haplo-PBSCT in older patients with acute myeloid leukemia (AML) and intermediate- or poor-risk cytogenetics to improve the clinical efficacy and safety of allogeneic HCT. We retrospectively analyzed data for 448 AML patients aged > 65 years who received UR-BMT (n = 102), UR-CBT (n = 250), or Haplo-PBSCT (n = 96) between 2014 and 2020. Overall survival (OS) in the UR-BMT group was superior (P = 0.033) to that in the other groups. However, all patients without complete remission (non-CR) who had Karnofsky performance status (KPS) < 80 at HCT and poor-risk cytogenetics died within 1 year after HCT. Multivariate Cox regression analysis identified KPS <80 at HCT and poor-risk cytogenetics as independent predictors of worse OS in non-CR patients. KPS < 80 may be an alternative indicator for non-CR AML patients with poor-risk cytogenetics during the selection of HCT, alternative treatments, or best supportive therapy, and the optimal KPS is important for the success of HCT.

Trends in Incidence and Survival of 1496 Patients with Mucosal Melanoma in The Netherlands (1990–2019)

Mucosal melanoma (MM) is a rare tumour with a poor prognosis. Over the years, immune and targeted therapy have become available and have improved overall survival (OS) for patients with advanced cutaneous melanoma (CM). This study aimed to assess trends in the incidence and survival of MM in the Netherlands against the background of new effective treatments that became available for advanced melanoma. We obtained information on patients diagnosed with MM during 1990-2019 from the Netherlands Cancer Registry. The age-standardized incidence rate and estimated annual percentage change (EAPC) were calculated over the total study period. OS was calculated using the Kaplan-Meier method. Independent predictors for OS were assessed by applying multivariable Cox proportional hazards regression models. In total, 1496 patients were diagnosed with MM during 1990-2019, mostly in the female genital tract (43%) and the head and neck region (34%). The majority presented with local or locally advanced disease (66%). The incidence remained stable over time (EAPC 3.0%, p = 0.4). The 5-year OS was 24% (95%CI: 21.6-26.0%) with a median OS of 1.7 years (95%CI: 1.6-1.8). Age ≥ 70 years at diagnosis, higher stage at diagnosis, and respiratory tract location were independent predictors for worse OS. Diagnosis in the period 2014-2019, MM located in the female genital tract, and treatment with immune or targeted therapy were independent predictors for better OS. Since the introduction of immune and targeted therapies, OS has improved for patients with MM. However, the prognosis of MM patients is still lower compared to CM, and the median OS of patients treated with immune and targeted therapies remains fairly short. Further studies are needed to improve outcomes for patients with MM.

Impact of diabetes and chronic kidney disease on active surveillance outcomes for small renal masses: A cohort study.

The American Cancer Society estimates 79,000 individuals will be diagnosed with kidney cancer in 2022, most of which are initially found as small renal masses (SRMs). Proper management of SRM patients includes careful evaluation of risk factors such as medical comorbidities and renal function. To investigate the importance of these risk factors, we examined their effect on crossover to delayed intervention (DI) and overall survival (OS) in patients undergoing active surveillance (AS) for SRMs. This is an Institutional Review Board-approved retrospective analysis of AS patients presented at kidney tumor conferences with SRMs between 2007 and 2017. Univariable and multivariable logistic regression analyses were performed to determine how factors including estimated glomerular filtration rate (eGFR), diabetes, and chronic kidney disease are associated with DI and OS. A total of 111 cases were reviewed. In general, AS patients were elderly and had significant comorbidities. On univariate analysis, intervention was more likely to occur in patients with a younger age (P = 0.01), better kidney function (P = 0.01), and higher tumor growth rates (GRs) (P = 0.02). Higher eGFR was associated with better survival (P = 0.03), while higher tumor GRs (P = 0.014), greater Charlson Comorbidity Index (P = 0.01), and larger tumors (P = 0.01) were associated with worse OS. Of the comorbidities, diabetes was found to be an independent predictor of worse OS (P = 0.01). Patient-level factors - such as diabetes and eGFR - are associated with the rate of DI and OS among SRM patients. Consideration of these factors may facilitate better AS protocols and improve patient outcomes for those with SRMs.

PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer

AimTo determine the prognostic value of programmed death-ligand 1 (PD-L1) score in early-stage epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), contrasted against EGFR-wildtype NSCLC. MethodsConsecutive patients with Stage IA-IIIA NSCLC diagnosed 1st January 2010–31st December 2019 at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary end-points were 2-year disease-free survival (DFS) and 5-year overall survival (OS) by Kaplan–Meier method. Results455 patients were included (267 EGFR-mutated, EGFR-M+; 188 EGFR-wildtype, wt). Median age at diagnosis was 65 years, 52.3% (238/455) of patients were males, 62.9% (286/455) of patients were never-smokers and 92.5% (421/455) of patients had R0 resection. Stage IA comprised 42.4% (193/455) of patients, Stage IB comprised 23.1% (105/455) of patients, Stage IIA comprised 10.8% of patients (49/455), Stage IIB comprised 5.1% of patients (23/455) and Stage IIIA comprised 18.7% (85/455) of patients. Among EGFR-M+, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-M+ and EGFR-wt was 45.3% (121/267) and 54.8% (103/188) respectively (p = 0.047).At median follow-up of 47 months, 178 patients had relapsed. Among EGFR-M+, 2-year DFS comparing PD-L1 <1% and PD-L1 ≥1% was 78.1% and 67.6% (p = 0.007) while 5-year OS was 59.5% and 42.8% (p = 0.001), respectively. Controlling for age, gender, lymphovascular invasion, adjuvant therapy and resection margin status, PD-L1 ≥1% (hazard ratio, HR 2.18, 95% CI 1.04–4.54, p = 0.038), stage IIB (HR 7.78, 95% CI 1.72–35.27, p = 0.008) and stage IIIA (HR 4.45, 95% CI 1.44–13.80, p = 0.01) emerged as independent predictors of inferior OS on multivariable analysis.In exploratory analysis, genomic analysis of 81 EGFR-M+ tumours was performed. PD-L1 ≥1% tumours had significantly higher rates of TP53 mutations (36.1% versus 15.6%, p = 0.04), with predominantly missense mutations. ConclusionPD-L1 ≥1% is an independent predictor of worse OS among early-stage EGFR-mutated NSCLC and is associated with inferior DFS regardless of EGFR status. PD-L1 score as a risk stratification factor should be evaluated in prospective adjuvant studies among EGFR-mutated NSCLC.

Mutations in circulating tumor DNA detected in the postoperative period predict poor survival in patients with ovarian cancer

BackgroundWe investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens. MethodsBetween July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. ResultsThe study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79–46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07–40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042). ConclusionsctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS.

No survival benefit could be obtained from adjuvant radiotherapy in esophageal cancer treated with neoadjuvant chemotherapy followed by surgery: A SEER-based analysis.

BackgroundThe aim of this study is to assess the clinical benefit of postoperative radiotherapy (PORT) in patients with esophageal cancer (EC) who treated with neoadjuvant chemotherapy (NAC) and surgery via a national population-based database.MethodsPatients diagnosed with EC between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival analysis was used to compare the overall survival (OS) and cause-specific survival (CSS) difference between PORT vs. no-radiotherapy (RT) groups before and after propensity score matching (PSM). After PSM for baseline characteristics, Cox proportional hazard regression was performed to investigate the factors associated with OS.ResultsA total of 321 patients were included in the analysis. Of them, 91 patients (28%) received PORT. In the unmatched population, the no-RT group had improved OS compared with PORT (44 vs. 25 months, p = 0.002), and CSS was similar in patients undergoing NAC with or without PORT (42 vs. 71 months, p = 0.17). After PSM for baseline characteristics, the OS benefit of the no-RT group over the PORT group remained significant with a median OS of 46 vs. 27 months (p = 0.02), and CSS remained comparable between groups (83 vs. 81 months, p = 0.49). In subgroup analyses, PORT did not improve the OS among patients with adenocarcinoma in the subgroups of cN0, cN1, and cN2–3 (all p > 0.05). In Cox regression, aged ≥71 years old, cT3–4, cN2–3, and receiving PORT were independent predictors of worse OS, whereas cT4 and cN2–3 were independent predictors of worse CSS (all p < 0.05).ConclusionsThe present study demonstrated that no survival benefit could be obtained from the additional use of PORT after NAC and surgery in patients with EC. Well-designed prospective trials are needed to confirm our findings.

Development and validation of a prognosis prediction model based on 18 endoplasmic reticulum stress-related genes for patients with lung adenocarcinoma.

BackgroundEndoplasmic reticulum (ER) stress had a crucial impact on cell survival, proliferation, and metastasis in various cancers. However, the role of ER stress in lung adenocarcinoma remains unclear.MethodGene expression and clinical data of lung adenocarcinoma (LUAD) samples were extracted from The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. ER stress score (ERSS) was constructed based on hub genes selected from 799 ER stress-related genes by least absolute shrinkage and selection operator (LASSO) regression. A Cox regression model, integrating ERSS and the TNM stage, was developed to predict overall survival (OS) in TCGA cohort and was validated in GEO cohorts. Gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), and gene mutation analyses were performed to further understand the molecular features of ERSS. The tumor immune infiltration was evaluated by ESTIMATE, CIBERSORT, and xCell algorithms. The receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the risk model. p< 0.05 was considered statistically significant.ResultsOne hundred fifty-seven differentially expressed genes (DEGs) were identified between tumor and para-carcinoma tissues, and 45 of them significantly correlated with OS. Next, we identified 18 hub genes and constructed ERSS by LASSO regression. Multivariate analysis demonstrated that higher ERSS (p< 0.0001, hazard ratio (HR) = 3.8, 95%CI: 2.8–5.2) and TNM stage (p< 0.0001, HR = 1.55, 95%CI: 1.34–1.8) were independent predictors for worse OS. The prediction model integrating ERSS and TNM stage performed well in TCGA cohort (area under the curve (AUC) at five years = 0.748) and three GEO cohorts (AUC at 5 years = 0.658, 0.717, and 0.739). Pathway enrichment analysis showed that ERSS significantly correlated with unfolded protein response. Meanwhile, pathways associated with the cell cycle, growth, and metabolism were significantly enriched in the high ERSS group. Patients with SMARCA4, TP53, and EGFR mutations showed significantly higher ERSS (p = 4e−04, 0.0027, and 0.035, respectively). Tissues with high ERSS exhibited significantly higher infiltration of M1 macrophages, activated dendritic cells, and lower infiltration of CD8+ T cells and B cells, which indicate an activated tumor antigen-presenting but suppressive immune response status.ConclusionWe developed and validated an ER stress-related risk model that exhibited great predictive value for OS in patients with LUAD. Our work also expanded the understanding of the role of ER stress in LUAD.

Prognostic value of sarcopenia in patients with rectal cancer: A meta-analysis.

BackgroundSarcopenia is usually characterized by the loss of skeletal muscle mass and impaired muscle function which is commonly seen in the elderly. It has been found to be associated with poorer prognoses in many types of cancer. Computed tomography (CT) scan is frequently used to assess skeletal muscle mass and further calculate skeletal muscle index (SMI) at the third lumbar vertebra level (L3), which is used to define sarcopenia. The purpose of this meta-analysis was to assess the prognostic value of sarcopenia for overall survival (OS) in patients with rectal cancer.MethodsWe performed a systematic search to find relevant studies published up to 14 January 2021 in PubMed, Embase, Web of science and Scopus. In our meta-analysis, studies comparing OS in rectal cancer patients with sarcopenia versus those without were included. Quality assessment for included studies was evaluated according to the Quality in Prognosis Studies (QUIPS) tool. We directly extracted hazard ratios (HRs) with 95% confidence intervals (CIs) in both univariate and multivariate analyses from each study. The Cochrane Collaboration’s Review Manager 5.4 software was applied to analyze data. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines and website GRADEpro.ResultsFinally, a total of 7 studies involving 2377 patients were included. The pooled HRs were 2.10 (95% CI 1.33–3.32, P = 0.001) and 2.37 (95% CI 1.13–4.98, P = 0.02) using random-effects models in univariate and multivariate analyses, respectively. The results showed a significant association between sarcopenia and OS in patients with rectal cancer. The quality of the evidence for OS was moderate for both univariate and multivariate analyses.ConclusionCT-defined sarcopenia is an independent predictor for worse OS in patients with rectal cancer. Future studies with a more stringent definition of sarcopenia are required to further confirm our findings.

Usefulness of Procalcitonin as a Predictor of Long-Term Prognosis in the Early Postoperative Period after Esophagectomy for Esophageal Cancer.

The aim of this study was to investigate the relationship between serum procalcitonin (PCT) levels after esophagectomy and infectious complications and long-term prognosis. A total of 105 patients who underwent esophagectomy between 2012 and 2019 were stratified into two groups: PCT-High group of ≥1 ng/mL and PCT-Low group of <1 ng/mL. The clinical outcomes and prognostic factors were compared between the two groups 2 postoperative days (POD), 4 POD, and 7 POD after esophagectomy. As the postoperative days passed, the association between PCT and infectious complications became stronger, and the positive predictive value was 100% at 7 POD. At 2 POD, there was no significant association between PCT elevation and infectious complications. Patients in the PCT-Low group had significantly worse overall survival (OS) and recurrence-free survival (RFS) than those in the PCT-High group at 2 POD (p = 0.026 and p = 0.011, respectively). In multivariate analysis, advanced pathological stage (hazard ratio (HR), 5.348; 95% confidence interval (CI), 2.299–12.500; p < 0.001) and PCT-Low group at 2 POD (HR, 3.673; 95% CI, 1.116–12.092; p = 0.032) were also independent predictors of worse OS. PCT in the early postoperative period after esophagectomy could be a good predictor of prognosis.