Survival In Squamous Cell Carcinoma Research Articles

Patient-Reported Bowel and Urinary Function in Long-Term Survivors of Squamous Cell Carcinoma of the Anus Treated With Definitive Intensity Modulated Radiation Therapy And Concurrent Chemotherapy

Definitive radiation therapy with concurrent chemotherapy is curative for nonmetastatic squamous cell carcinoma of the anus (SCCA). However, the true effect of chemoradiation on long-term functional outcomes is poorly understood owing to limited follow-up and patient-reported outcomes (PROs). We conducted a cross-sectional survey of 248 patients with SCCA treated with definitive intensity modulated radiation and concurrent chemotherapy from 2010 to 2018 who were alive and without recurrence. PRO measures were collected, including Functional Assessment of Cancer Therapy-General (FACT-G7), Fecal Incontinence Quality of Life (FIQoL), Low Anterior Resection Syndrome (LARS), and International Consultation on Incontinence Questionnaires (ICIQ). Models were used to determine the association between demographic, tumor, treatment, and dosimetric data with PROs. One hundred twelve (45%) patients completed PROs. Median [interquartile range (IQR)] time from radiation completion to survey was 51 [37-85] months. The median scores [IQR] for FACT-G7, FIQoL, and LARS were 21 [15-24], 14 [11-16], and 32 [25-37], respectively. For men, median subscores [IQR] for ICIQ voiding and incontinence subscores were 5 [2-6] and 1 [1-3], respectively. For women, median subscores [IQR] for ICIQ voiding, incontinence, and filling were 1 [1-3], 5 [3-8], and 4 [2-5], respectively. Higher (better) FIQoL scores were associated with higher (better) FACT-G7 scores (β=0.83; 95% confidence interval, 0.58-1.09; P < .001), and higher (worse) LARS scores were associated with lower (worse) FACT-G7 scores (β=-0.22; 95% confidence interval, -0.31 to -0.13; P < .001). A separate multivariable analysis revealed higher bowel bag D1% was associated with lower (worse) FIQoL (P=.001) and higher (worse) LARS (P=.003) scores. Higher bladder V40 Gy was associated with increased (worse) ICIQ voiding subscore (P=.001). Patients treated with modern chemoradiation for SCCA experience significant long-term bowel toxic effects with considerable effect on quality of life. Minimizing bowel hotspots and bladder V40 Gy may improve bowel and urinary function. Other interventions to reduce long-term toxic effects and improve quality of life are needed.

Predictive Role of Tumor-Stroma Ratio for Survival of Patients With Non-Small Cell Lung Cancer: A Meta-Analysis.

Background: Role of tumor-stroma ratio (TSR) as a predictor of survival in patients with non-small cell lung cancer (NSCLC) remains not clear. A systematic review and meta-analysis was conducted to summarize current evidence for the role of TSR in NSCLC. Methods: Relevant cohort studies were retrieved via search of Medline, Embase, and Web of Science databases. The data was combined with a random-effect model by incorporating the between-study heterogeneity. Specifically, subgroup and meta-regression analyses were performed to explore the association between TSR and survival in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). Results: Nine cohort studies with 2031 patients with NSCLC were eligible for the meta-analysis. Pooled results showed that compared to those stroma-poor tumor, patients with stroma rich NSCLC were associated with worse recurrence-free survival (RFS, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.07 to 2.16, p = 0.02) and overall survival (OS, HR = 1.48, 95% CI: 1.20 to 1.82, p < 0.001). Subgroup analyses showed that stroma-rich tumor may be associated with a worse survival of SCC (HR = 1.89 and 1.47 for PFS and OS), but a possibly favorable survival of AC (HR = 0.28 and 0.69 for PFS and OS). Results of meta-regression analysis also showed that higher proportion of patients with SCC was correlated with higher HRs for RFS (Coefficient = 0.012, p = 0.03) and OS (Coefficient = 0.014, p = 0.02) in the included patients, while higher proportion of patients with AC was correlated with lower HRs for RFS (Coefficient = −0.012, p = 0.03) and OS (Coefficient = −0.013, p = 0.04), respectively. Conclusion: Tumor TSR could be used as a predictor of survival in patients with NSCLC. The relative proportion of patients with SCC/AC in the included NSCLC patients may be an important determinant for the association between TSR and survival in NSCLC. Stroma richness may be a predictor of poor survival in patients with lung SCC, but a predictor of better survival in patients with lung AC.

Invasive extramammary Paget's disease of the vulva: incidence, trends and outcomes

<h3>Objectives:</h3> To explore the incidence, trends and survival outcomes of invasive extramammary vulvar Paget's disease compared to squamous and basal cell vulvar cancers. <h3>Methods:</h3> Incidence data were extrapolated from the United States Cancer Statistics (USCS) from 2001 to 2017 by SEER*Stat. Trends analysis was performed by Joinpoint regression program and presented by average annual percent change (AAPC). Clinical data on demographics, disease and treatment were recorded from the National Cancer Database from the same period. Chi-squared test, Kaplan-Meier survival estimates, and Cox proportional hazards model adjusted for covariates were used. <h3>Results:</h3> From 2001-2017, there were 3,715 cases of malignant extramammary Paget's disease of the vulva. Whites comprised 3,172 cases (85.4%), followed by Asian/Pacific Islanders with 227 cases (6.1%), Hispanics with 198 cases (5.3%), and Blacks with 44 cases (1.2%). Most cases had localized disease (73.1%), 10.4% had regional spread and 1.2% had distant disease. The overall incidence was 0.12/100,000 women per year in 2017. The incidence increased with an average percent increase of 0.4% per year from 2001 to 2017 (p<0.01). Of 1,388 patients with invasive vulvar Paget's disease from the NCDB, the median age was 72 (range: 63-80) years. Local excision was performed in 77.4% of cases, and 10.7% underwent radical surgery. The overall five-year survival was 85.9%. Older age (HR=7.95, p<0.001), advanced disease (HR=6.0, P<0.001), positive LVSI (HR=2.81, p<0.001), and Charlson comorbidity index ≥ 1 (HR 2.17, p<0.001) had worse survival. Using the NCDB, we compared the 5 year survival rates of vulvar squamous cell carcinoma (SCC) (n=28,587) and basal cell carcinoma (BCC) (n=1,720) to invasive Paget's disease. The survival of SCC and BCC were 63.5% and 77.9% compared to 85.9% for invasive Paget's disease. More specifically, the survival of early stage I and II were SCC: 73.7% and 59.3%, BCC: 79.5% and 60.5% and Paget's: 83.6% and 81.3%. Survival of advanced stage III and IV were SCC: 45.3% and 24.8%, BCC: 71.4% and 50.0% and Paget's: 52.5% and 41.7%. <h3>Conclusions:</h3> Invasive extramammary Paget's disease of the vulva is uncommon though the incidence is increasing. Older age and advanced stage are associated with poorer survival. Patients with metastatic vulvar Paget's disease and squamous cell carcinoma have a poorer survival compared to metastatic vulvar basal cell carcinoma.

Prevalence of hyposalivation and associated factors in survivors of head and neck cancer treated with radiotherapy.

Hyposalivation and sensation of dry mouth (xerostomia) are one of the most common adverse effects in the treatment of patients with head and neck cancer.Objective:This study evaluates the prevalence of late hyposalivation and associated factors in survivors of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx treated with radiotherapy with or without concomitant chemotherapy.Methodology:A cross-sectional study was conducted with 88 patients who had concluded radiotherapy at least three months before the study, at a referral center for the treatment of head and neck cancer in the Southern region of Brazil. Hyposalivation was evaluated based on the stimulated salivary flow rate using the spitting method. Multivariate analysis using binary logistic regression was performed to determine the associations between hyposalivation and clinical and demographic variables.Results:Hyposalivation was found in 78.41% of the sample and the mean radiation dose was 63.01 Gy (±9.58). In the crude model of the multivariate analysis, hyposalivation was associated with higher doses of radiation (p=0.038), treatment with concomitant radiotherapy and chemotherapy (p=0.005), and time elapsed since the end of radiotherapy (p=0.025). In the adjusted model of the multivariate analysis, hyposalivation was only associated with dose and time elapsed. Patient who received higher doses of radiation had a 4.25-fold greater chance of presenting hyposalivation, whereas a longer time elapsed since the end of radiotherapy exerted a 75% protective effect against the occurrence of hyposalivation.Conclusion:Hyposalivation is a highly prevalence late-onset side effect of radiotherapy in patients treated for head and neck cancer, with a greater chance of occurrence among those who received higher doses of radiation and those who ended therapy less than 22 months before our study. Concomitant chemotherapy and radiotherapy does not seem to increase the chances of hyposalivation compared to radiotherapy alone.

Prognostic significance of KRT19 in Lung Squamous Cancer.

Backgroud: Keratin 19 (KRT19) is the intermediate filament that constitutes the cytoskeleton and regulates cell-cycle and cell death.Objective: We aimed to assess whether KRT19 was involved in lung cancer development.Methods: The expression of KRT19 in lung cancer was evaluated from mRNA expression on open databse and protein abundance on tumor tissue array.Results: Using open microarray gene expression datasets and differential expression analysis, we found that KRT19 was upregulated in lung cancer compared with normal tissue. Further analysis suggested that KRT19 mRNA expression was correlated with tumor progression and overall survival in lung cancer patients. As KRT19 was overexpressed in adenocarcinoma (AC) and squamous cell carcinoma (SCC), we examined the prognostic value of KRT19 protein abundance by tissue microarray (TMA). The results suggested that protein expression of KRT19 was significantly associated with overall survival of SCC.Conclusions: Giving the prognostic role of KRT19 in lung cancer, KRT19 could be considered as an potential molecular marker in lung cancer, especially in SCC.

Upper Urinary Tract Tumors: Variant Histology Versus Urothelial Carcinoma.

To evaluate stage at presentation and cancer-specific mortality (CSM) in upper urinary tract tumors according to histologic subtype. Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), we identified patients with upper urinary tract tumors with pure variant histology (UTVH) and pure upper urinary tract urothelial carcinoma (UTUC). Cumulative incidence plots, after propensity score matching for tumor and patient characteristics, addressed CSM. Subgroup analyses addressed efficacy of radical nephroureterectomy (RNU) in stage T1-2 and of chemotherapy in metastatic UTVH patients. Of all 11,809 upper urinary tract tumor patients, 154 (1.3%) harbored squamous cell carcinoma (SCC), 86 (0.7%) adenocarcinoma, 39 (0.3%) neuroendocrine carcinoma, 38 (0.3%) other UTVH, and 11,492 (97.3%) UTUC. UTVH patients were more likely to exhibit metastatic stage disease at diagnosis than UTUC (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P< .01). After detailed matching for performance status, only SCC showed significantly higher CSM than UTUC (multivariate HR= 1.71; P< .01). Subgroup analyses in stage T1-2 RNU patients showed, relative to UTUC patients, no CSM differences for SCC or adenocarcinoma patients. No significant survival benefit for chemotherapy administration was identified in patients with metastatic SCC or metastatic adenocarcinoma. This study is limited by its sample size and the missing centralized pathologic review. Disease stage at diagnosis is more advanced in UTVH patients than UTUC. Across all stages, CSM is higher for SCC than for UTUC. However, in T1-2 stage disease, RNU results in similar survival in SCC or adenocarcinoma versus UTUC.

Patterns of Care and Outcomes of Low-Lying Adenocarcinoma and Squamous Cell Carcinoma of the Rectum.

Squamous cell carcinoma (SCC) of the rectum is a unique entity that lacks definitive guidelines regarding prognosis and treatment. This study aimed to analyze patterns of care and survival for SCC and adenocarcinoma (AC) of the rectum. This was a retrospective analysis of patients with stage I-III SCC or AC of the rectum treated from 2004 to 2016 from the National Cancer Database. The treatment groups analyzed were surgery alone (S), chemoradiation followed by surgery (CRT + S), surgery followed by chemoradiation (S + CRT), and definitive chemoradiation (CRT). Patient- and clinical-related factors were compared. Overall survival was assessed with the Kaplan-Meier method and Cox proportional regression models. Of the patients studied, 21,587 (97.1%) were AC and 640 (2.9%) were SCC. Among patients with AC, most (n = 8549, 59.4%) received chemoradiation followed by surgery; those with SCC (n = 305, 66.4%) received definitive chemoradiation. Among patients who received surgery, the majority (69.2%) with AC histology had a low anterior resection while the majority (52.1%) of SCC had an abdominoperineal resection. Five-year overall survival of AC versus SCC in the entire cohort was 61.6% versus 56.1%, respectively (p < 0.001). On multivariable analysis for AC, CRT + S (HR 0.61, p < 0.001), or S + CRT (HR 0.67, p < 0.001) had improved survival compared to S alone while those who had definitive CRT (HR 1.55, p < 0.001) had worse survival. SCC of the rectum tends to be treated like anal cancers with definitive chemoradiation, with similar survival to historical reports of anal cancer. AC of the rectum is most commonly treated under the rectal cancer paradigm.

Comparison of survival outcomes of locally advanced cervical cancer by histopathological types in the surveillance, epidemiology, and end results (SEER) database: a propensity score matching study

BackgroundThere has been limited research on the comparison of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of cervical cancer and that lack of information may have significant bearing on the treatment of patients. We compared survival outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer patients and examined factors related to the prognosis of cervical cancer.MethodsWe identified 4131 patients with stage IB2-IVA cervical cancer patients diagnosed between 2010 and 2015 by using the Surveillance, Epidemiology, and End Results (SEER) database. Variables related to the prognosis of cervical cancer were compared using both univariate and multivariate Cox models and log-rank method before and after propensity score matching. We compared the efficacy of radiotherapy alone to radiotherapy combined with chemotherapy or/and surgery in overall survival of SCC and AC.ResultsOur sample included 3385 patients with SCC (81.9%) and 746 patients with AC (18.1%). The 5-year overall survival on comparing the squamous cell carcinoma group and adenocarcinoma group was not significant (P > 0.05). Using propensity score matching, 676 pairs of patients were selected. The 5-year overall survival of matched patients did not differ significantly (P > 0.05). Histology was not independently associated with overall survival in multivariate Cox model (P > 0.05). Factors affecting overall survival included FIGO stage IVA (P < 0.05), chemotherapy (P < 0.05), and external radiation combined with brachytherapy (P < 0.05). Patients with SCC that were treated with radiation alone had significantly worse OS than AC patients receiving radiation only (P < 0.05).ConclusionsThe OS in AC of the cervix is similar to that SCC in when treated with radiotherapy combined with chemotherapy and/or surgery but better when treated with radiation alone.

Can serial evaluation of serum SCC-Ag-level predict tumor recurrence and patient survival in squamous-cell carcinoma of uterine cervix treated with definitive chemoradiotherapy? A multi-institutional analysis.

Tumor marker screening may be useful to evaluate tumor response and detect tumor recurrence. However, usefulness and cut-off value of squamous-cell carcinoma antigen (SCC-Ag) for recurrence and survival has not yet established in cervical cancer. From January 2010 to October 2016, 304 patients with cervical squamous-cell carcinomas with FIGO stage IB-IVA who underwent curative chemoradiotherapy followed by brachytherapy at four institutions were included in this study. Serum SCC-Ag level was measured before treatment, re-measured after completion of treatment, and again at the time of relapse during follow-up. SCC-Ag levels at each measurement point were analyzed using receiver operating characteristic (ROC) curve. Their associations with recurrence-free survival (RFS) and overall survival (OS) were analyzed. During a median follow-up time of 36.5months, there were 66 (21.7%) recurrences and 76 (25.0%) deaths. The ROC curve showed optimal Youden indices were 4, 1.5, and 4ng/mL at pretreatment, treatment, and recurrence, respectively. In patients with SCC-Ag ≥ 4ng/mL, not SCC-Ag < 4ng/mL before treatment, post-treatment SCC-Ag level (≥ 1.5ng/mL vs. < 1.5ng/mL) showed significant differences in 3-year RFS (65.5% vs. 45.0%, p < 0.001) and OS (78.5% vs. 55.4%, p < 0.001). In 66 recurrent patients, patients with SCC-Ag ≥ 4ng/mL at recurrence showed a significantly lower OS rate than others (59.5% vs. 33.0%, p = 0.041). SCC-Ag level after treatment and at recurrence was useful for predicting recurrence and survival only when its pretreatment value was high (≥ 4ng/mL).

Second primary malignancy in patients with esophageal adenocarcinoma and squamous cell carcinoma

There have been no studies on implementing effective screening models for esophageal adenocarcinoma and squamous cell carcinoma survivors. We used a proportional subdistribution hazards model to estimate second primary malignancy risks among patients with esophageal adenocarcinoma and squamous cell carcinoma. We validated models using a bootstrap cross-validation method and performed decision curve analysis to evaluate their clinical utility. Age group and SEER historic stage were significantly associated with second primary malignancy risk after diagnosis of esophageal adenocarcinoma and squamous cell carcinoma. Saving positive lymph nodes and distant metastasis were significant factors in the adenocarcinoma group, and marital status, tumor location, and chemotherapy were significant factors in the squamous cell carcinoma group. Calibration plots show good concordance between predicted and actual outcomes except in high-probability areas for the risk of a second primary malignancy in patients with esophageal squamous cell carcinoma. Discrimination performances of the Fine-Gray models were evaluated using c-indices, which were 0.691 and 0.662 for second primary malignancies in patients with esophageal adenocarcinoma and squamous cell carcinoma, respectively. Decision curve analysis yielded a range of threshold probabilities (0.020-0.177 and 0.021-0.133 for patients with esophageal adenocarcinoma and squamous cell carcinoma, respectively) at which the clinical net benefit of the risk model was larger than those of hypothetical all-screening and no-screening scenarios. Our nomograms enable selection of patient populations at high risk for a second primary malignancy and thus will facilitate the design of prevention trials for affected populations.

Multiple primary malignancies for squamous cell carcinoma and adenocarcinoma of the esophagus.

Patients with esophageal cancer (EC) frequently have multiple primary cancers. We conducted the present study to assess the risk of multiple primary malignancies for patients with squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus and to investigate the influence of multiple primary tumors on the prognosis of EC patients. Using the data of 44,091 EC patients from the Surveillance Epidemiology and End Results (SEER) database, we calculated the standardized incidence ratios (SIRs) for overall multiple primary cancers and cancers at particular sites among EC survivors. The SIRs of esophageal SCC and AC patients were compared using Poisson regression. The Kaplan-Meier (KM) method was used for survival analysis. Multiple primary cancer risk was significantly increased among both esophageal SCC and AC survivors (SIR: 2.28 and 1.57, respectively; P<0.001). Among SCC patients, the highest SIRs were found in the oral cavity and pharynx (SIR: 16.54), esophagus (SIR: 10.02), and larynx (SIR: 10.34). Also, the highest SIRs following AC cases were observed in the esophagus (SIR: 8.81), stomach (SIR: 9.29), and small intestine (SIR: 4.95). SIRs for the oral cavity and pharynx, lung, and larynx were significantly higher among SCC survivors than AC survivors (all P<0.05). KM analysis revealed no significant difference of overall survival (OS) for multiple primary cancers, including those of the esophagus, stomach, oral cavity and pharynx, and lung among EC patients (log rank =2.04; P=0.564), except for prostate cancer (log rank =96.65; P<0.001). Multiple primary malignancy risk differed by the histological type of esophageal SSC and AC survivor. However, no significant relationship between survival and the multiple primary cancer sites, except for prostate cancer, was observed.

Significance of elevated SCC-Ag level on tumor recurrence and patient survival in patients with squamous-cell carcinoma of uterine cervix following definitive chemoradiotherapy: a multi-institutional analysis

ObjectiveThere is no definitive guideline for the significance and cut-off value of squamous-cell carcinoma antigen (SCC-Ag) in cervical cancer. Thus, we analyzed the significance and optimal cut-off value of SCC-Ag for predicting tumor recurrence and patient survival in squamous-cell carcinoma of uterine cervix.MethodsFrom January 2010 to October 2016, we enrolled 304 cervical cancer patients with squamous-cell carcinoma staging International Federation of Gynecology and Obstetrics (FIGO) Ib–IVa and treated with definitive chemoradiotherapy (CRT) followed by intra-cavitary radiotherapy (ICR). The cut-off value of SCC-Ag level for tumor recurrence was calculated using the receiver operating characteristic (ROC) curve. The recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan-Meier method to estimate the significance of SCC-Ag level.ResultsThe optimal cut-off value of SCC-Ag level for predicting tumor recurrence was calculated and set at 4.0 ng/mL in the ROC curve. After a median follow-up period of 36.5 months, the 3-year RFS (56.6% vs. 80.2%, p<0.001) and OS (72.1% vs. 86.8%, p=0.005) were significantly lower in SCC-Ag ≥4 ng/mL arm than in <4 ng/mL arm. The 3-year locoregional recurrence (17.6% vs. 7.0%, p=0.012), distant metastasis (20.4% vs. 6.9%, p=0.002), and para-aortic recurrence (9.4% vs. 2.1%, p=0.012) rates were significantly higher in SCC-Ag ≥4 ng/mL arm than in SCC-Ag <4 ng/mL arm.ConclusionPre-treatment SCC-Ag level higher than 4 ng/mL may be a useful predictor of tumor recurrence in patients with squamous-cell carcinoma of uterine cervix treated with definitive CRT and ICR.

PSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus

Signal transducers and activator of transcription (STAT)-3 is activated in cancers, where it promotes growth, inflammation, angiogenesis, and inhibits apoptosis. Tissue microarrays were generated using tissues from 154 patients, with oesophageal adenocarcinoma (OAC) (n = 116) or squamous cell carcinoma (SCC) (n = 38) tumours. The tissues were stained for pSTAT3 and IL-6R using immunohistochemistry. The OE33 (OAC) and OE21 (SCC) cell lines were treated with the STAT3 inhibitor, STATTIC. The Univariate cox regression analysis revealed that a positive pSTAT3 in SCC was adversely associated with survival (Hazard ratio (HR) 6.382, 95% CI 1.266–32.184), while a protective effect was demonstrated with the higher pSTAT3 levels in OAC epithelium (HR 0.74, 95% CI 0.574–0.953). The IL-6R intensity levels were higher in the SCC tumours compared with the OAC tumours for the core and leading edge tumour tissue. The pSTAT3 levels correlated positively with the IL-6R levels in both the OAC and SCC. The treatment of OE21 and OE33 cells with the STAT3 inhibitor STATTIC in vitro resulted in decreased survival, proliferation, migration, and increased apoptosis. The pSTAT3 expression was associated with adverse survival in SCC, but not in the OAC patients. The inhibition of STAT3 in both of the tumour subtypes resulted in alterations in the survival, proliferation, migration, and apoptosis, suggesting a potential role for therapeutically targeting STAT3.

Impact of prior malignancy on outcomes of stage IV esophageal carcinoma: SEER based study

ABSTRACT Introduction Usually, clinical trials on esophageal cancer exclude patients with a prior malignancy, assuming that this may influence survival outcomes. However, little is known about the impact of a prior malignancy on its prognosis. Methodology The Surveillance, Epidemiology, and End Results database (SEER) was used to review patients with stage IV squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus during 1973–2014. We calculated overall and esophageal cancer-specific survival using unadjusted Kaplan-Meier and multivariable covariate-adjusted Cox models. Results A total of 7,807 patients with stage IV SCC, and 11,238 patients with stage IV AC were reviewed, of which 652 and 840 patients, respectively, had a prior malignancy. Kaplan-Meier curves did not show difference in overall survival of SCC or AC in patients with prior malignancy. Stage IV AC patients with prior malignancy did not show different esophageal cancer-specific survival. However, esophageal cancer-specific survival was better among stage IV SCC patients with prior malignancy. Similar results were observed in Cox models after adjustment for: age, sex, race, marital status, grade, site in esophagus, and undergoing surgery. Conclusion Prior malignancy does not adversely impact survival of stage IV esophageal cancer. These results should be taken into consideration when designing clinical trials.

Diagnostic and prognostic value of 18F-FDG PET, CT, and MRI in perineural spread of head and neck malignancies.

We assessed whether quantitative imaging biomarkers derived from fluorodeoxyglucose-positron emission tomography (18F-FDG PET) could be extracted from perineural spread (PNS) in head and neck malignancies (HNM) to improve patient risk stratification. A case-control exploratory study (1:2 ratio) enrolled 81 patients with FDG-avid HNM. The case-group comprised 28 patients with documented PNS (reference: expert consensus), including 14 squamous cell carcinomas (SCC). Imaging biomarkers were extracted from the PNS on 18F-FDG PET, CT-scan, and MRI. The control-group enrolled 53 SCCs. The Cox proportional-hazards regression model explored the association with overall survival by univariate and multivariate analyses. The rate of PNS detection by 18F-FDG PET was 100% in the case-group. Quantitative imaging biomarkers were not associated with the presence of sensory (p>0.20) or motor (p>0.10) symptoms. In SCC patients (case: 14; control: 53), PNS was associated with a hazard ratio of death of 5.5 (95%CI: 1.4:20.9) by multivariate analysis. Increased cranial nerve SUVmax was significantly associated with poorer overall survival by univariate analysis (p=0.001). Our pilot study showed the feasibility of extracting 18F-FDG PET biomarkers from PNS in FDG-avid HNM. Our results encourage the development of new PET/CT- or PET/MRI-guided management strategies in further prospective studies. • 18F-FDG PET/CT detects PNS in FDG-avid HNM. • PNS metabolism is more heterogeneous than healthy tissue. • PNS diagnosis is crucial: most patients were asymptomatic, N0 and M0. • PNS diagnosis is associated with poorer overall survival in SCC. • PET/CT- or PET/MRI-guided management strategies should be evaluated.

Impact of Extracapsular Lymph Node Involvement After Neoadjuvant Chemoradiation Therapy Followed by Surgery in Carcinoma of the Esophagus: A Multicenter Study.

The current study aims to examine the impact of extracapsular lymph node involvement (EC-LNI) on survival for both esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery. Studies have demonstrated the negative prognostic value of EC-LNI in primary surgery, but its impact after nCRT remains unclear. From the databases of 6 European high-volume centers 1505 patients with R0 resections were withheld. Oncologic variables, including ypT, ypN, number of positive lymph nodes, and lymph node capsular status: EC-LNI and intracapsular lymph node involvement (IC-LNI), were examined. Statistical analysis was performed by Cox proportional hazards modeling. In SCC 182 patients (31.6%) had positive lymph nodes, of whom 60 (33.0%) showed EC-LNI. In AC 391 patients (42.1%) had positive lymph nodes, of whom 147 (37.6%) showed EC-LNI. Overall 5-year survival (O5YS) in SCC was 42.0%. Presence of EC-LNI meant a significantly worse O5YS than IC-LNI or pN0 (10.6%, 39.5%, and 47.4%, respectively; P < 0.05). O5YS in AC was 41.2%. No significant difference was observed between EC-LNI and IC-LNI (P = 0.322). In the multivariate analysis, among the examined possible prognosticators, presence of EC-LNI showed the highest hazard ratio (2.29, confidence interval: 1.52-3.47) as an independent prognosticator for overall survival in SCC, but it was not in AC. Based on this international multicenter study, the presence of EC-LNI after nCRT is at least as important as N-stage for survival and EC-LNI is the strongest prognosticator for overall survival in SCC but not in AC.

JCES01.11 Altered Expression of Programmed Death-Ligand 1 after Neo-Adjuvant Chemotherapy in Patients with Lung Squamous Cell Carcinoma

Programmed death-ligand 1 (PD-L1) is known to be over-expressed in non-small cell lung cancer (NSCLC). However, the impact of chemotherapy on the altered status of PD-L1 expression has not been examined for NSCLC. The present study was intended to examine the impact of neoadjuvant chemotherapy on PD-L1 expression and its prognostic significance in lung squamous cell carcinoma (SCC). Matched tumor samples were obtained from SCC patients prior to and after neoadjuvant chemotherapy. The expression of PD-L1 was evaluated by immunohistochemistry. Survival analysis was performed by the Kaplan-Meier method. A total of 76 eligible SCC patients were recruited. There were 51 males and 25 females with a median age of 60 (39-72) years. The smoking status was former (n=46) and never (n=34). Prior to neoadjuvant chemotherapy, PD-L1 expression was identified in 52.6% (40/76) of SCC patients while 61.8% (47/76) were positive for PD-L1 expression after neoadjuvant chemotherapy . Nine patients switched from negative to positive while another two patients’ samples showed the reverse of the above result. Multivariate analysis demonstrated that postoperative expression of PD-L1 was an independent prognostic factor for overall survival (HR=0.50, P=0.003), but not for PD-L1 expression prior to neoadjuvant chemotherapy. Neoadjuvant chemotherapy may up-regulate the expression of PD-L1. As compared with the status of PD-L1 expression prior to chemotherapy, the postoperative expression of PD-L1 is a better prognostic factor for overall survival in SCC.

Expression and survival significance of B-cell-specific Moloney murine leukemia virus integration site 1 and matrix metalloproteinase-9 in non-small-cell lung cancer.

One of the main challenges in lung cancer research is identifying patients at high risk of progression and metastasis following surgical resection. In the present study, the prognostic significance of B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and matrix metalloproteinase-9 (MMP9) in non-small-cell lung cancer (NSCLC) was evaluated. BMI1 and MMP9 expression in tumors from 132 surgical NSCLC patients [squamous cell carcinoma (SCC), n=79; and adenocarcinoma (AD), n=53] was evaluated by immunohistochemistry. The clinical significance was determined using multivariate Cox regression analysis, Kaplan-Meier curves and the log-rank test. High BMI1 expression was more frequent in SCC compared with that in AD (P=0.015). Comparisons between the expression of BMI1 and that of other known biological markers revealed that the expression of BMI1 was correlated with that of MMP9 (χ2=4.241, P=0.039) in SCC. Although an association was not identified between high BMI1 expression and overall survival (OS) in NSCLC or AD, high BMI1 expression was an unfavorable predictor of survival in SCC according to the survival curves (P=0.038). In addition, combined high BMI1 and MMP9 expression levels were significantly correlated with SCC nodal/distant metastasis (χ2=6.392, P=0.014). Multivariate Cox proportional model analysis demonstrated that this combined marker was an independent prognostic indicator of OS in SCC (P=0.025; hazard ratio = 12.963; 95% confidence interval: 1.142–7.637). Therefore, this study demonstrated that combined BMI1 and MMP9 expression may be used as a marker for the progression and metastasis of SCC. These results may aid in the elucidation of the potential mechanism underlying the involvement of BMI1 and MMP9 in tissue-specific SCC progression.

Use of NRP1, a novel biomarker, along with VEGF-C, VEGFR-3, CCR7 and SEMA3E, to predict lymph node metastasis in squamous cell carcinoma of the tongue.

Lymph node (LN) metastasis has been suggested as a major prognostic factor for oral cancer. Knockdown of the growth factors and receptors involved in these metastatic mechanisms could significantly reduce LN metastasis and improve the survival of oral cancer patients after treatment. The present study, therefore, aimed to evaluate the expression levels of the following growth factors and receptors in squamous cell carcinoma (SCC) of the tongue: the vascular endothelial growth factor (VEGF)-C and VEGF-D, which bind to the cell surface tyrosine kinase receptor VEGF receptor-3 (VEGFR-3); C-C motif chemokine receptor 7 (CCR7); neuropilin (NRP)1 and NRP2; and semaphorin 3E (SEMA3E). Furthermore, we assessed microvessel density (MVD) and lymphatic vessel density (LVD) to demonstrate the correlation between these factors and regional LN metastasis, with respect to the clinicopathological features. Finally, we analyzed the correlation between these proteins and overall or disease-free survival, in order to demonstrate their prognostic value. Univariate analysis revealed a significant association between LN metastasis and the expression levels of VEGF-C, VEGFR-3, CCR7, NRP1, and SEMA3E, as well as LVD, in SCC cells. In contrast, multivariate analysis identified associations between LN metastasis and NRP1 expression, as well as between LN metastasis and LVD; however, no correlation was found between LN metastasis and the expression levels of the other proteins. The expression levels of VEGF-C, VEGFR-3, NRP1, and SEMA3E, as well as LVD, were correlated with disease-free survival time. These results indicate that LN metastasis is associated with poor survival in SCC. This study suggests that NRP1 expression and LVD are independent factors that are likely to predict the risk of LN metastasis in SCC of the tongue, whereas the expression of VEGF-C, VEGFR-3, CCR7, and SEMA3E are non-independent predictive factors.

Altered expression of programmed death-ligand 1 after neo-adjuvant chemotherapy in patients with lung squamous cell carcinoma

ObjectiveProgrammed death-ligand 1 (PD-L1) is known to be over-expressed in non-small cell lung cancer (NSCLC). However, the impact of chemotherapy on the altered status of PD-L1 expression has not been examined for NSCLC. The present study was intended to examine the impact of neoadjuvant chemotherapy on PD-L1 expression and its prognostic significance in lung squamous cell carcinoma (SCC). Patients and methodsMatched tumor samples were obtained from 76 SCC patients prior to and after neoadjuvant chemotherapy. The expression of PD-L1 was evaluated by immunohistochemistry. Survival analysis was performed by the Kaplan-Meier method. ResultsPrior to neoadjuvant chemotherapy, PD-L1 expression was identified in 52.6% (40/76) of SCC patients while 61.8% (47/76) were positive for PD-L1 expression after neoadjuvant chemotherapy. Nine patients switched from negative to positive while another two patients’ samples showed the reverse of the above result. Multivariate analysis demonstrated that postoperative expression of PD-L1 was an independent prognostic factor for overall survival (HR=0.50, P=0.003), but not for PD-L1 expression prior to neoadjuvant chemotherapy. ConclusionNeoadjuvant chemotherapy may up-regulate the expression of PD-L1. As compared with the status of PD-L1 expression prior to chemotherapy, the postoperative expression of PD-L1 is a better prognostic factor for overall survival in SCC.