Impact of a previous cancer history on the overall survival of patients with primary gastric cancer: A SEER population-based study

BackgroundThe impact of previous cancers on the survival of gastric cancer (GC) patients is still uncertain. To evaluate the impact of a prior cancer history on the overall survival of patients with primary GC.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database provided data on patients diagnosed with GC as the first or second primary malignancy between 2010 and 2015 in this retrospective cohort study. Cox proportional hazards models, Kaplan-Meier curves and forest plots were utilized to analyze overall survival. Subgroup analysis was performed based on age, gender, race and prior cancer type.ResultsTotally 39,379 were eligible for this study, including 7403 (18.8%) with a previous cancer history. A previous cancer was an independent risk factor for overall survival [hazard ratio (HR) = 1.103, 95% confidence interval (CI): 1.070–1.138]. For GC patients aged 40–60 years (HR = 1.191, 95% CI: 1.084–1.308) and ≥60 years (HR = 1.093, 95% CI: 1.058–1.13) at diagnosis, a previous cancer was significantly associated with worse overall survival. GC patients with previous oral cavity and pharynx cancer (HR = 1.249, 95% CI: 1.038–1.501), respiratory system cancer (HR = 1.177, 95% CI: 1.076–1.286), female genital system cancer (HR = 1.169, 95% CI: 1.011–1.351), or lymphoma cancer (HR = 1.192, 95% CI: 1.023–1.389) had shorter overall survival than GC patients without a previous cancer.ConclusionA previous cancer adversely affected the overall survival of GC patients. Specifically, GC patients aged ≥40 years, or with oral cavity and pharynx cancer, respiratory system cancer, female genital system cancer, or lymphoma cancer had inferior overall survival. These patients should obtain more attention and get individualized treatment to improve prognosis, and clinical trial eligibility criteria could be reconsidered for particular age and cancer types.     

Treatment and outcome trends and predictors of overall survival of rectal melanoma: Analysis of the National Cancer Database

BackgroundWe aimed to assess characteristics, treatment, and outcomes of rectal melanoma (RM).MethodsThis retrospective cohort study looked at patients with RM from National Cancer Database (2004–2019) analyzed characteristics and outcomes of the entire cohort and across three time periods (2004–2009; 2010–2014; 2015–2019). Main outcome measures were change in treatment and survival trends across time periods and overall survival (OS).Results641 patients (58.5% female; mean age: 68.2 ± 13.6 years) were included. OS rate was 26%; median survival duration was 17.9 (IQR: 15.93–20.67) months. There was a significant decrease in the use of chemotherapy (17.3%–6.6%; p = 0.001) and surgery (62.9%–41.8%; p = 0.00004) but increased use of immunotherapy (11.9%–52%; p < 0.001) across time periods. OS was longer in the last time period than in the first two (21.8 vs 16.8 vs 16.5 months; p = 0.09). Surgical excision was an independent predictor of improved OS (HR = 0.266, 95%CI: 0.089–0.789, p = 0.017) whereas older age (HR = 1.039, 95%CI: 1.007–1.072, p = 0.016), positive resection margins (HR = 5.06, 95%CI: 1.902–13.48, p = 0.001) and metastasis (HR = 34.62, 95%CI: 3.973–301.6, p = 0.001) were predictors of poor survival.ConclusionsOver time, chemotherapy and surgery have been used less often in the treatment of RM while the use of immunotherapy increased by more than four-fold. Older age, surgical treatment, positive resection margins, and metastasis were predictive of survival of RM.     

Role of Postoperative Radiotherapy in Pathologic Stage IIIA (N2) Non–Small Cell Lung Cancer in a Prospective Nationwide Oncology Outcomes Database

IntroductionThe role of postoperative radiotherapy (PORT) in the treatment of pathologic stage IIIA (N2) NSCLC remains controversial. We investigated practice patterns and outcomes for these patients in a prospectively maintained nationwide oncology outcomes database.MethodsPatients with known histologic features of pathologic stage IIIA (N2) NSCLC who underwent an operation with negative margins and received adjuvant multiagent chemotherapy from 2004 to 2013 were identified from the National Cancer Data Base and stratified by the use of PORT. Multivariable logistic regression modeling was used to examine factors associated with receiving PORT, and multivariable proportional hazards regression was used to examine the association of treatment and mortality, adjusting for demographic, socioeconomic and clinicopathologic factors. Landmark analysis and covariate balancing propensity score (CBPS) weighting were also explored to account for immortal time bias and nonrandomization.ResultsA total of 2691 patients were identified, with a median follow-up of 32.32 months. In multivariable analysis, improved overall survival was associated with multiple factors, including younger age, female sex, lower Charlson-Deyo comorbidity index, histologic type (with squamous cell being better than adenocarcinoma), smaller tumor size, lower pathologic T stage, surgical procedure (with pneumonectomy or lobectomy being better than sublobar resection), and receipt of PORT (all p < 0.05). Before landmark analysis, the hazard ratio (HR) showed an overall survival benefit for patients receiving PORT (adjusted HR = 0.83, 95% CI [confidence interval]: 0.72–0.95; p = 0.008). This benefit remained significant after CBPS weighting (HR = 0.81, 95% CI: 0.70–0.94, p = 0.005), almost significant after landmark analysis (adjusted HR = 0.84, 95% CI: 0.69–1.007, p = 0.059), and significant after landmark analysis with CBPS weighting (HR = 0.77, 95% CI: 0.63–0.94, p = 0.009). Median survival past landmark time was 27.43 months in the PORT group and 25.86 months in the non-PORT group. Factors significantly associated with receiving PORT were facility location, facility type, Charlson-Deyo comorbidity index, and grade (all p < 0.05).ConclusionsImproved survival is associated with receipt of PORT for patients with pathologic stage IIIA (N2) NSCLC treated with complete resection and multiagent chemotherapy.     

Prognostic value of sarcopenia in adults with solid tumours: A meta-analysis and systematic review

BackgroundBody composition plays an important role in predicting treatment outcomes in adults with cancer. Using existing computed tomographic (CT) cross-sectional imaging and readily available software, the assessment of skeletal muscle mass to evaluate sarcopenia has become simplified. We performed a systematic review and meta-analysis to quantify the prognostic value of skeletal muscle index (SMI) obtained from cross-sectional CT imaging on clinical outcomes in non-haematologic solid tumours.MethodsWe searched PubMed and the American Society Clinical Oncology online database of meeting abstracts up to October 2015 for relevant studies. We included studies assessing the prognostic impact of pre-treatment SMI on clinical outcomes in patients with non-haematologic solid tumours. The primary outcome was overall survival (OS) and the secondary outcomes included cancer-specific survival (CSS), disease-free survival (DFS), and progression-free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated.ResultsA total of 7843 patients from 38 studies were included. SMI lower than the cut-off was associated with poor OS (HR = 1.44, 95% CI = 1.32–1.56, p < 0.001). The effect of SMI on OS was observed among various tumour types and across disease stages. Worse CSS was also associated with low SMI (HR = 1.93, 95% CI = 1.38–2.70, p < 0.001) as well as DFS (HR = 1.16, 95% CI = 1.00–1.30, p = 0.014), but not PFS (HR = 1.54, 95% CI = 0.90–2.64, p = 0.117).ConclusionsThis meta-analysis demonstrates that low SMI at cancer diagnosis is associated with worse survival in patients with solid tumours. Further research into understanding and mitigating the negative effects of sarcopenia in adults with cancer is needed.     

Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: A literature based meta-analysis of randomized trials

BackgroundSeveral novel androgen receptor pathway targeted agents have recently entered on to therapeutic landscape for metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the effect of these novel androgen receptor pathway targeted agents in improving outcome of CRPC patients.MethodsA literature-based meta-analysis of randomized controlled trials (RCTs) in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology meetings were searched. The primary outcome was overall survival. The secondary end-points were time to the first symptomatic skeletal event, progression-free survival, prostatic antigen specific (PSA) response rate, time to PSA progression and safety.ResultsPooled analysis from RCTs of novel androgen receptor pathway targeted agents revealed significantly increased overall survival compared with placebo or prednisone (hazard ratio [HR] for death: 0.79, 95% confidence interval [CI]: 0.71–0.87; P < 0.00001). All secondary end-points favoured the androgen receptor pathway targeted agents, although heterogeneity was high in some cases. The pooled analysis revealed that the androgen receptor pathway targeted agents significantly improved time to the first skeletal event (HR = 0.69, 95% CI: 0.63–0.75; P < 0.00001), progression-free survival (HR = 0.48, 95% CI: 0.37–0.62; P < 0.00001), time to PSA progression (HR = 0.37, 95% CI: 0.24–0.59; P < 0.0001) and PSA response rate (relative risk [RR] = 4.46, 95% CI: 2.63–7.55; P < 0.00001). The incidence of grade ≥3 adverse events was moderately higher with androgen receptor pathway targeted agents as compared with the control arms (RR = 1.11, 95% CI: 0.98–1.25; P = 0.09).ConclusionThis study confirmed the efficacy and safety of the novel androgen receptor pathway targeted agents.     

Prognostic Value of Primary Tumor Volume Changes on kV-CBCT during Definitive Chemoradiotherapy for Stage III Non–Small Cell Lung Cancer

IntroductionKilovoltge cone beam computed tomography (kV-CBCT) allows for tumor localization and response assessment during definitive chemoradiotherapy for locally advanced NSCLC. We hypothesize that significant tumor volume loss occurs early during radiotherapy and that the extent of volume loss correlates with clinical outcomes.MethodsA total of 52 patients with locally advanced NSCLC treated with definitive chemoradiotherapy were reviewed. kV-CBCT images were used to contour primary gross tumor volumes at four time points during treatment. Patients were dichotomized according to absolute and relative volume changes at each time point. Statistical analyses were performed to evaluate correlations between volume changes and clinical outcomes.ResultsThe median gross tumor volumes were 77.1, 48.3, 42.5, and 29.9 cm³ for fractions 1, 11, 21, and final, respectively. Greater relative volume loss between fractions 1 and 21 correlated with improved distant control (hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.13–0.94, p = 0.038) and overall survival (HR = 0.40, 95% CI: 0.16–0.98, p = 0.046). Greater relative volume loss between fractions 11 and 21 correlated with improved progression-free survival (HR = 0.39, 95% CI: 0.17–0.88, p = 0.02) and trended toward improved overall survival (HR = 0.43, 95% CI: 0.17–1.06, p = 0.07). On multivariate analysis, greater relative volume loss between fractions 11 and 21 correlated with improved progression-free survival (HR = 0.39, 95% CI: 0.16–0.97, p = 0.041) and overall survival (HR = 0.31, 95% CI: 0.11–0.88, p = 0.027).ConclusionsSignificant primary tumor volume loss occurs early during radiotherapy for locally advanced NSCLC. Greater relative tumor volume loss during treatment correlates with improved disease control and overall survival. Thus, kV-CBCT has potential to be used as a practical prognostic imaging marker.     

Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database

ObjectivesIn this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer.Materials and methodsCox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate.ResultsA total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4–2.3, p < 0.001; HR = 1.9, 95% CI: 1.6–2.3, p < 0.001; HR = 1.4, 95% CI: 1.0–1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2–1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3–1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9–1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects.ConclusionPatients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients.     

IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain

IntroductionFinal overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase 3 IMpower150 study (NCT02366143) evaluating atezolizumab plus bevacizumab plus carboplatin and paclitaxel (ABCP) or atezolizumab plus carboplatin and paclitaxel (ACP) versus bevacizumab plus carboplatin and paclitaxel (BCP).MethodsOverall, 1202 patients (intention-to-treat population) with chemotherapy-naive, metastatic, nonsquamous NSCLC were randomized to ABCP, ACP, or BCP. Patients with treated, stable brain metastases were permitted. OS was evaluated in EGFR mutations and baseline liver metastases subgroups; rate and time to development of new brain metastases were evaluated in the intention-to-treat patients.ResultsAt data cutoff (September 13, 2019; median follow-up, 39.3 mo), OS improvements were sustained with ABCP versus BCP in sensitizing EGFR mutations (all: hazard ratio [HR] = 0.60; 95% confidence interval [CI]: 0.31–1.14; previous tyrosine kinase inhibitor [TKI]: HR = 0.74; 95% CI: 0.38–1.46) and baseline liver metastases (HR = 0.68; 95% CI: 0.45–1.02) subgroups. ACP did not have survival benefit versus BCP in sensitizing EGFR mutations (all: HR = 1.0; 95% CI: 0.57–1.74; previous TKI: HR = 1.22; 95% CI: 0.68–2.22) or liver metastases (HR = 1.01; 95% CI: 0.68–1.51) subgroups. Overall, 100 patients (8.3%) developed new brain metastases. Although not formally evaluated, an improvement toward delayed time to development was found with ABCP versus BCP (HR = 0.68; 95% CI: 0.39–1.19).ConclusionsThis final exploratory analysis revealed OS benefits for ABCP versus BCP in patients with sensitizing EGFR mutations, including those with previous TKI failures, and with liver metastases, although these results should be interpreted with caution. The impact of ABCP on delaying the development of new brain lesions requires further investigation.     

Efficacy of Neoadjuvant Chemohormonal Therapy in Oligometastatic Hormone-Sensitive Prostate Cancer: A Prospective,Three-Arm,Comparative Propensity Score Match Analysis

BackgroundThe study aimed to investigate the efficacy and safety outcomes in hormone-sensitive oligometastatic prostate cancer (OMPC) patients treated with docetaxel-based neoadjuvant chemohormonal therapy (NCHT) prior to radical prostatectomy (RP) compared with direct RP and standard androgen deprivation therapy (ADT) alone using propensity score match (PSM) analysis.Patients and MethodsA single-center, prospective, three-arm study was conducted with hormone-sensitive OMPC patients. Eligible patients (N = 130) were divided into three groups—NCHT, RP, and standard treatment (ST)—and received their respective treatments. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were pathological response rate, radiographic progression-free survival (rPFS), and overall survival (OS). Further, propensity scores were calculated and group-wise comparisons were carried out: NCHT versus RP, ST versus RP, and ST versus NCHT.ResultsAfter PSM, in the NCHT group, two patients (11.76%) and four patients (23.52%) had complete and partial pathological responses, respectively. Univariate and multivariate Cox regression analysis showed that PFS and rPFS were significantly higher in the NCHT group. For NCHT versus RP, the PFS hazard ratio (HR) = 0.11 (95% confidence interval [CI], 0.02-0.51; P = .004) and HR = 0.016 (95% CI, 0.0015-0.17; P < .001); the rPFS HR = 0.088 (95% CI, 0.011-0.71; P = .023) and HR = 0.03 (95% CI, 0.0025-0.36; P = .006). Further, the median OS of the ST group was 44.6 months for ST versus RP, and it was 49.3 months for ST versus NCHT; it was not reached in either the NCHT or RP group. Furthermore, 17.65% and 47.06% patients had positive surgical margins in the NCHT and RP groups, respectively, and no therapy-related deaths were observed during the study period.ConclusionsPSM analysis revealed NCHT before RP in OMPC patients has potential therapeutic benefits with acceptable toxicities and lower incidence of postoperative positive surgical margins.     

Prognostic factors and outcomes of adult spermatic cord sarcoma. A study from the French Sarcoma Group

PurposeTo evaluate the outcomes of adult patients with spermatic cord sarcoma (SCS).MethodsAll consecutive patients with SCS managed by the French Sarcoma Group from 1980 to 2017 were analysed retrospectively. Multivariate analysis (MVA) was used to identify independent correlates of overall survival (OS), metastasis-free survival (MFS), and local relapse-free survival (LRFS).ResultsA total of 224 patients were recorded. The median age was 65.1 years. Forty-one (20.1%) SCSs were discovered unexpectedly during inguinal hernia surgery. The most common subtypes were liposarcoma (LPS) (73%) and leiomyosarcoma (LMS) (12.5%). The initial treatment was surgery for 218 (97.3%) patients. Forty-two patients (18.8%) received radiotherapy, 17 patients (7.6%) received chemotherapy. The median follow-up was 5.1 years. The median OS was 13.9 years. In MVA, OS decreased significantly with histology (HR, well-differentiated LPS versus others = 0.096; p = 0.0224), high grade (HR, 3 versus 1–2 = 2.7; p = 0.0111), previous cancer and metastasis at diagnosis (HR = 6.8; p = 0.0006). The five-year MFS was 85.9% [95% CI: 79.3–90.6]. In MVA, significant factors associated with MFS were LMS subtype (HR = 4.517; p < 10-4) and grade 3 (HR = 3.664; p < 10-3). The five-year LRFS survival rate was 67.9% [95% CI: 59.6–74.9]. In MVA, significant factors associated with local relapse were margins and wide reresection (WRR) after incomplete resection. OS was not significantly different between patients with initial R0/R1 resection and R2 patients who underwent WRR.ConclusionsUnplanned surgery affected 20.1% of SCSs. A nonreducible painless inguinal lump should suggest a sarcoma. WRR with R0 resection achieved similar OS to patients with correct surgery upfront.     

Determining the role of adjuvant therapy in Invasive Intraductal Papillary Mucinous Neoplasms; a systematic review and meta-analysis

BackgroundConflicting evidence exists regarding the role of adjuvant therapy for Invasive Intraductal Papillary Mucinous Neoplasms (i-IPMN). This meta-analysis assessed whether adjuvant therapy improves Overall Survival (OS) in patients with resected i-IPMN.MethodsA systematic review and meta-analysis was performed. The primary endpoint was the effect of adjuvant therapy on OS. Secondary endpoint evaluated adjuvant therapy with regard to nodal disease, positive resection margins, tumour grade and differentiation. A meta-analysis of pooled hazard ratios (HRs) with an inverse variance and a random-effects model was performed. Risk of bias was determined with the GRADE approach and MINORS criteria.ResultsTen articles with a total of 3252 patients were included. No statistically significant difference in the OS was noted with adjuvant therapy for i-IPMN in the entire cohort (HR = 1; 95% CI = 0.75–1.35; P = 0.98). However, a survival benefit was noted in a subgroup of patients with an aggressive disease phenotype; nodal involvement (HR = 0.56; 95% CI = 0.39–0.79; P = 0.001) and advanced staged tumours (≥stage 2, HR = 1.42; 95% CI = 1.11–1.82; P = 0.005)ConclusionsThe concurrent evidence base for adjuvant therapy for i-IPMN is limited. After acknowledging the limitations of the data, the current literature suggests that adjuvant therapy should be reserved for patients with resected i-IPMN that have adverse tumour biology.     

Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab

BackgroundAlternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms.Patients and MethodsFormalin-fixed, paraffin-embedded primary tumors from metastatic CRC patients treated with first-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) + bevacizumab (n = 285) or FOLFIRI only (n = 75) were collected. The relative expression of VEGFA121a, 121b, 145a, 145b, 165a, and 165b was assessed with custom TaqMan-MGB assays and quantitative PCR.ResultsAt a median follow-up of 101.5 months, left-sided primary CRC was a favorable prognosticator (median survival, 29.2 vs. 18.2 months; P = .015). Positive high VEGFA145b was an unfavorable factor for progression-free survival (PFS; hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.13-2.44; P = .009) in patients who received FOLFIRI + bevacizumab, without prognostic significance in FOLFIRI-only patients (HR = 0.70; 95% CI, 0.34-1.44; P = .33). The adverse effect on PFS of 145b was more pronounced in patients with right-sided colon cancer (HR = 2.62; 95% CI, 1.35-5.12; P = .005), especially in those who received bevacizumab (HR = 2.85; 95% CI, 1.31-6.21; P = .008). In patients with right-sided colon primary tumors, isoform 121b correlated with inferior PFS (HR = 1.73; 95% CI, 0.94-3.18; P = .076) and overall survival (OS; HR = 2.0; 95% CI, 1.08-3.72; P = .028). In patients with left-sided primary tumors, positive high 165b correlated with superior PFS (HR = 0.76; 95% CI, 0.59-0.99; P = .044) and OS (HR = 0.68; 95% CI, 0.52-0.90; P = .006). At multivariate analysis, right-sided primary tumor was associated with inferior PFS (HR = 1.28; 95% CI, 1.00-1.64), while 145b consistently retained predictive significance for lack of benefit in PFS with bevacizumab (HR = 1.71; 95% CI, 1.16-2.53). Multivariate analysis for OS showed that VEGFA165b expression was favorable in patients with left-sided but unfavorable in patients with right-sided primary tumors (P_interaction < .001).ConclusionThe antiangiogenic isoform VEGFA145b messenger RNA may predict resistance to bevacizumab. Differences in biological relevance and prognostic significance of various VEGFA isoforms were found for right- versus left-sided primary tumors.     

Postoperative Radiotherapy for Completely Resected Masaoka/Masaoka-Koga Stage II/III Thymoma Improves Overall Survival: An Updated Meta-Analysis of 4746 Patients

IntroductionOur systematic review and meta-analysis aimed to evaluate the effect of postoperative radiotherapy (PORT) on completely resected Masaoka/Masaoka-Koga (M/MK) stage II/III thymomas.MethodsWe systematically searched four online databases and included studies that compared surgery alone versus surgery plus a PORT for completely resected M/MK stage II/III thymoma. The multivariate-adjusted hazard ratios (HRs) of overall survival (OS) and disease-free survival were evaluated as the primary and secondary end points, respectively. We performed a subgroup analysis for OS with respect to M/MK stage II, III, and inseparable II/III cases. A generic inverse variance meta-analysis using a random model was conducted.ResultsFive studies including 4746 patients (among them, 2408 patients received PORT) met our selection criteria. A meta-analysis of these five studies revealed that PORT was associated with a significantly better OS (HR = 0.68, 95% confidence interval [CI]: 0.57–0.83, p < 0.001, I² = 0%, p for heterogeneity = 0.97). Subgroup analyses for M/MK stage II disease (HR = 0.63, 95% CI: 0.44–0.91, p = 0.01, I² = 0%, p for heterogeneity = 0.80) and M/MK stage III disease (HR = 0.72, 95% CI: 0.55–0.95, p = 0.02, I² = 0%, p for heterogeneity = 0.84) revealed similar results. PORT was not associated with an improved disease-free survival (HR = 0.96, 95% CI: 0.70–1.33, p = 0.83, I² = 0%, p for heterogeneity = 0.72).ConclusionsCurrently available evidence from observational studies suggests PORT for patients with completely resected M/MK stage II/III thymoma. A randomized trial is warranted.     

Improved Survival of Stage I Non–Small Cell Lung Cancer: A VA Central Cancer Registry Analysis

IntroductionThe combined impact of advances in diagnosis and treatment of stage I NSCLC has not been assessed comprehensively. To define the survival impact of modern staging and treatment techniques for clinical stage I NSCLC, the Veterans Administration Central Cancer Registry, a database of U.S. veterans in whom the disease was diagnosed in the Veteran’s Health Administration, was queried. From this database, patients who had stage I NSCLC diagnosed from 2001 to 2010 and were treated with either surgery or radiation were identified.MethodsOverall survival (OS) and lung cancer–specific survival were determined. Propensity score matching and Cox multivariate analysis were used to adjust for baseline patient characteristics.ResultsA total of 11,997 patients were identified. The 4-year OS rate increased from 38.9% to 53.2% from 2001 to 2010 for all patients. Positron emission tomography and endobronchial ultrasound did not improve OS. Survival of radiated patients improved from 12.7% to 28.5%. The introduction of stereotactic body radiation therapy (SBRT) significantly improved OS (hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.54–0.68) and lung cancer–specific survival (HR = 0.39, 95% CI: 0.32–0.46) compared with conventionally fractionated radiation. The 4-year OS rate also improved after surgery (from 51.5% to 66.5%). This increase was associated with use of adjuvant chemotherapy, increased use of video-assisted thoracoscopic surgical procedures, and decreased pneumonectomy rates, with similar survival between open and video-assisted thoracoscopic surgical procedures. OS after lobectomy was superior to that after sublobar resection (HR = 0.82, 95% CI: 0.75–0.89). In the era of available SBRT (2008–2010), 4-year OS was not significantly different after sublobar resection or lobectomy for medically unfit patients (Charlson comorbidity index = 2) (55.4% and 58.1%, respectively; p = 0.69) but was significantly worse for fit patients (Charlson comorbidity index = 0–1) undergoing sublobar resection (55.5% and 68.0%, respectively; p < 0.001).OS (HR = 0.36, 95% CI: 0.35–0.38) and lung cancer–specific survival (HR = 0.31, 95% CI: 0.29–0.33) were improved after surgery as compared with after radiation, with the improvement maintained on matched comparison of lobectomy and SBRT.ConclusionsOS increased in veterans with a diagnosis of stage I NSCLC from 2001 to 2010; the increase was coincident with improved radiation and surgical techniques.     

Extracapsular lymph node involvement is a robust survival predictor in esophageal cancer patients: A pooled analysis

BackgroundAlthough extracapsular lymph node involvement (EC-LNI) has been proposed to be incorporated into the staging system of esophageal cancer, the prognostic value of EC-LNI remains controversial with conflicting data available, especially in the era of neoadjuvant therapy.MethodsAn electronic literature search was undertaken using four public databases. Studies investigating the effects of EC-LNI on survival were included. In addition to analysis of the entire cohort, subset analyses were also performed to assess the impact of EC-LNI on patients receiving different treatment modalities.ResultsA total of 20 studies were included in this meta-analysis. Pooling 13 studies on overall survival (OS), we observed that presence of EC-LNI was associated with significantly worse OS (HR = 2.09, 95%CI: 1.63–2.68; p < 0.01). Nine studies describing disease-free survival (DFS) included, the pooled data revealed that presence of EC-LNI was associated with significantly worse DFS (HR = 1.89, 95%CI: 1.63–2.20; p < 0.001). Subset analyses of patients receiving neoadjuvant therapy demonstrated a survival disadvantage of EC-LNI on OS (HR = 1.928, 95%CI: 1.196–3.107; p = 0.007) and DFS (HR = 1.985, 95%CI: 1.585–2.487; p < 0.001). Similar result was also seen in patients receiving primary surgery (OS: HR = 2.219, 95%CI: 1.720–2.864; p < 0.001; DFS: HR = 1.659, 95%CI: 1.285–2.141; p < 0.001).ConclusionEC-LNI is a strong prognostic predictor of inferior survival in patients with esophageal cancer irrespective of treatment modality. The currently pooled evidence indicates that EC-LNI has great potential to be incorporated into the future staging system.     

Risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 or BRCA2 mutation carriers: A systematic review and meta-analysis

AimBRCA mutation carriers have a high lifetime risk of developing breast cancer (BC) and ovarian cancer (OC). Risk-reducing salpingo-oophorectomy (RRSO) has been shown to reduce OC risk. This meta-analysis was aim to analyze the effect of RRSO on the BC risk among BRCA1/2 mutation carriers.MethodsEmbase, PubMed, Web of Science, and Cochrane databases were searched for all studies investigating the effect of RRSO on BC risk. The pooled results were used to evaluate the association between RRSO and BC risk.ResultsThis meta-analysis included 13,965 BRCA1 and 7,057 BRCA2 mutation carriers from 14 observational studies. The pooled results showed that RRSO lowered BC risk among BRCA1 mutation carriers [hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.49–0.81, P < 0.01] and BRCA2 mutation carriers (HR = 0.51, 95% CI: 0.34–0.75, P < 0.01). RRSO reduced BC risk in younger women with BRCA1 mutation (HR = 0.48, 95% CI: 0.30–0.77, P < 0.01) and BRCA2 mutation (HR = 0.22, 95% CI: 0.08–0.65, P < 0.01). Analysis of the efficacy of RRSO at different time intervals after surgery showed a reduction of BC risk at <5 years after surgery in BRCA1 mutation carriers (HR = 0.60, 95% CI: 0.40–0.89, P = 0.01) and BRCA2 mutation carriers (HR = 0.42, 95% CI: 0.20–0.86, P = 0.02).ConclusionsRRSO is an effective way to reduce BC risk among women with BRCA1/2 mutation, especially in younger women. BRCA1/2 mutation carriers could benefit from RRSO in the immediate 5 years after surgery.     

Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study

PurposeFactors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC).MethodsBetween 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation.ResultsMedian age was 46 (23–70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24–172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14–5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16–5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89–5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44–3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63–5.79).ConclusionALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.     

Tumor and Tumor-Associated Macrophage Programmed Death-Ligand 1 Expression Is Associated With Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma

IntroductionPatients with stage II to III lung adenocarcinomas are treated with adjuvant chemotherapy (ACT) to target the premetastatic niche that persists after curative-intent resection. We hypothesized that the premetastatic niche is a scion of resected lung tumor microenvironment and that analysis of tumor microenvironment can stratify survival benefit from ACT.MethodsUsing tumor and tumoral stroma from 475 treatment-naive patients with stage II to III lung adenocarcinomas, we constructed a tissue microarray and performed multiplex immunofluorescent staining for immune markers (programmed death-ligand 1 [PD-L1], tumor-associated macrophages [TAMs], and myeloid-derived suppressor cells) and derived myeloid-lymphoid ratio. The association between immune markers and survival was evaluated using Cox models adjusted for pathologic stage.ResultsPatients with high PD-L1 expression on TAMs or tumor cells in resected tumors had improved survival with ACT (TAMs: hazard ratio [HR] = 1.79, 95% confidence interval [CI]: 1.12–2.85; tumor cells: HR = 3.02, 95% CI: 1.69–5.40). Among patients with high PD-L1 expression on TAMs alone or TAMs and tumor cells, ACT survival benefit is pronounced with high myeloid-lymphoid ratio (TAMs: HR = 3.87, 95% CI: 1.79–8.37; TAMs and tumor cells: HR = 2.19, 95% CI: 1.02–4.71) or with high stromal myeloid-derived suppressor cell ratio (TAMs: HR = 2.53, 95% CI: 1.29–4.96; TAMs and tumor cells: HR = 3.21, 95% CI: 1.23–8.35). Patients with low or no PD-L1 expression on TAMs or tumor cells had no survival benefit from ACT.ConclusionsOur observation that PD-L1 expression on TAMs or tumor cells is associated with improved survival with ACT provides rationale for prospective investigation and developing chemoimmunotherapy strategies for patients with lung adenocarcinoma.     

Surgical Prognosis of Synchronous Multiple Primary Lung Cancer: Systematic Review and Meta-Analysis

BackgroundWe evaluated the long-term prognosis of synchronous multiple primary lung cancer (SMPLC) patients after surgical treatment and explored prognostic factors for overall survival (OS).Materials and MethodsA systematic review and meta-analysis was performed regarding the surgical prognosis of SMPLC. A literature search was performed using online databases. All studies were rigorously categorized following the 8th edition of the tumor, node, metastasis classification (TNM) staging rules for multiple lung cancers: SMPLC and multifocal ground-glass/lepidic (GG/L) lung cancers. Five-year OS after surgery was pooled, and hazard ratios (HRs) for prognostic factors were synthesized. Specific subgroup analysis and sensitivity analysis were conducted (PROSPERO registration CRD42019142420).ResultsAn analysis of 26 studies including 1788 patients was performed. The pooled 5-year OS was 45% (95% confidence interval [CI], 37-53) of true SMPLC patients and 62% (95% CI, 57-67) of patients with pathologic stage I disease, which was different from the 5-year OS of 93% (95% CI, 85-100) of patients with multifocal GG/L lung cancers. Poor prognostic factors for SMPLC were lymph node metastasis (HR = 2.36; 95% CI, 1.75-3.20; P < .001) and pneumonectomy (HR = 2.96; 95% CI, 1.36-6.45; P = .006], whereas histology (HR = 1.11; 95% CI, 0.82-1.50; P = .508), laterality (HR = 1.16; 95% CI, 0.93-1.44, P = .190), sublobar resection (HR = 1.29; 95% CI, 0.90-1.84; P = .159), and adjuvant therapy (HR = 1.07; 95% CI, 0.64-1.80; P = .791) were not found to influence the outcome.ConclusionThe long-term prognosis of SMPLC patients after surgery is acceptable, especially in patients with early-stage disease. Sublobar resection can be applied, although pneumonectomy should be avoided. Advanced criteria are needed to diagnose SMPLC and distinguish it from multifocal GG/L lung cancer to perform accurate surgical evaluation.     

Prognostic impact of infectious complications after curative gastric cancer surgery

IntroductionThere have been few studies about the effect of infectious complications on recurrence or long-term survival outcome after curative gastric cancer surgery in large populations. This study was conducted to investigate the impact of infectious complications on long-term survival after curative gastrectomy in high volume center.MethodFrom January 2002 to December 2012, patients who underwent curative gastrectomy were enrolled. Infectious complications were defined as wound infection, intra-abdominal infection or postoperative pneumonia. Five-year overall survival was compared between two groups and followed by multivariable analysis using a Cox proportional hazards model.ResultOf 6585 patients who underwent curative gastrectomy, 413 (6.2%) had infectious complications after curative gastrectomy. The five-year overall survival rate was 86.0% in non-complication patients and 74.1% in infectious complications patients (P < 0.001). In univariate analysis, Age over 70 years, male sex, higher ASA score, total or proximal gastrectomy, advanced stage and infectious complication had statistically worse survival. A Cox proportional hazards model indicated that the infectious complication was independent prognostic factor (HR = 1.478, CI 95% 1.242–1.757 p < 0.001) as well as age over 70 years (HR = 2.434, CI 95% 2.168–2.734 p < 0.001), male sex (HR = 1.153, CI 95% 1.022–1.302 p = 0.014), higher ASA score (p < 0.001) and advanced Stage (p < 0.001). Local recurrence (P = 0.044), LN recurrence (P = 0.038) and hematologic recurrence (P = 0.033) were significantly associated with infectious complications.ConclusionPostoperative infectious complication was an independent prognostic factor for five-year overall survival after curative gastrectomy as well as known factors. A significant association between infectious complications and recurrence were also noted. The surgeon should try to prevent the infectious complications in gastric cancer surgery to improve the long term survival.