Overall Survival In Squamous Cell Carcinoma Research Articles

The Prognostic Value of TTF-1/NKX2-1 in Lung Squamous Cell Carcinoma.

TTF-1/NKX2-1 is a lineage-specific transcription factor that is expressed in the thyroid gland, lung, and forehead. It functions as a key component in regulating lung morphogenesis and differentiation. It is mainly expressed in lung adenocarcinoma, while its prognostic value in non-small-cell lung cancer remains controversial. This study evaluates the prognostic value of TTF-1 in different cellular locations in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC). The expression of TTF-1 was analyzed by immunohistochemistry in 492 patients (ADC 340 and SCC 152) who had undergone surgery between June 2004 and June 2012. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Positive TTF-1 expression was 68.2% in ADC (located in the nucleus) and 29.6% in SCC (cytoplasm staining). The presence of TTF-1 was associated with better OS in SCC and ADC (P=0.000 and P=0.003, respectively). In SCC, an increased level of TTF-1 was associated with a longer disease-free survival (DFS). Positive TTF-1 expression was an independent favorable prognostic factor in SCC (P=0.020, HR: 2.789, 95%CI: 1.172-6.637) and ADC (P=0.025, HR: 1.680, 95%CI: 1.069-2.641). TTF-1 was largely located in the nucleus of ADC, while it always accumulated in the cytoplasm of SCC. The higher level of TTF-1 in the different subcellular locations of ADC and SCC was an independent, favorable prognostic factor, respectively. Increased TTF-1 in the cytoplasm of SCC was associated with a longer OS and DFS.

P-94 Unicentric real-world data from esophageal cancer neoadjuvant treatment according to the CROSS trial protocol

Locally advanced esophageal cancer (EC) remains a disease with poor prognosis, with a 5-year survival of around 40%. In 2012, the CROSS trial was a changing point in the treatment of EC by introducing neoadjuvant (NA) chemoradiotherapy (CRT), with carboplatin/paclitaxel and reduced-dose RT (41.4Gy), as a valid approach, with higher disease-free survival (DFS) and overall survival (OS) than had been seen before. These results had subgroup variations, with better OS in squamous cell carcinoma (SCC) patients when compared to adenocarcinoma (AC).

Radiooncological View on Therapy Outcome after Multidisciplinary Treatment of Sinonasal Tumors.

We report the outcome of a mono-institutional retrospective study of sinonasal carcinoma with the primary focus on GTV (gross tumor volume) and the effect of radiotherapy. 53 patients with sinonasal carcinoma and that of the nasal cavity, paranasal sinus or both except lymphoma were included. All patients were treated between 1999 and 2017. For tumor volume delineation, all pre-therapeutic images were fused to the planning CT (computed tomography). The median follow-up was 17 months [0.3-60], the median age 60 years, 35 males and 18 females were included. Squamous cell carcinoma (SCC) (60.4%) was the predominant histology, followed by adenocarcinoma (15.1%). The mean composite OS (overall survival) time was 33.3 ± 3.5 months. There was no significant difference in the 5 y composite OS between tumor localization or radiotherapy setting. The simultaneous integrated boost concept showed a trend towards improving five-year composite OS compared to the sequential boost concept. The only factor with a significant impact on the 5 y composite OS rate was the pre-therapeutic GTV (cutoff 75 cm3; p = 0.033). The GTV ≥ 100 cm3 has no effect on the 5 y composite OS rate for SCC. The pre-therapeutic GTV is a prognostic factor for five-year composite OS for the entire group of patients with sinonasal tumors, influencing the outcome after completion of all treatment strategies. The GTV seems to not influence five-year composite OS in SCC. For this rare tumor entity, an intensive, multidisciplinary discussion is essential to finding the best treatment option for the patient.

The prognostic value of 4.1 mRNA expression in non-small cell lung cancer.

BackgroundThe mechanism of 4.1 family in human cancer has not been elucidated. In this study we investigate the value as a prognostic factor of mRNA expression of 4.1 family in non-small cell lung cancer (NSCLC).MethodsA survival analysis was carried out through the Kaplan-Meier plotter (KM plotter) database. KM’s method was used to estimate the prognostic value of 4.1 mRNA expression in NSCLC.ResultsExpression of four members are linked to overall survival (OS) in NSCLC patients, among which 4.1G, 4.1B, 4.1R are concerned with first progression (FP), and 4.1G, 4.1R are correlated with post progression survival (PPS) besides. Only 4.1B expression is associated with OS in squamous cell carcinoma, as four members with OS in adenocarcinoma. What’s more, 4.1G, 4.1N high mRNA are linked to better FP in adenocarcinoma, and 4.1R overexpression is linked to better PPS. The expression of 4.1G is associated with the prognosis in female, whereas 4.1R in male. Furthermore, 4.1G and 4.1B play as protective roles in non-smoking populations, while 4.1N overexpression is related to poorer PPS. All the four family members are associated with early stage in NSCLC 4.1G, 4.1B and 4.1R are closely related to surgical resection, yet 4.1N has no prognostic significance in patients receiving treatments. However, the results need to be verified in clinical trials further.ConclusionsOur results offer new opinion about the prognostic value of 4.1 protein family in NSCLC, which may contribute to the development of new therapy for NSCLC.

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.

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.

The prognostic value of hypoxia-inducible factor-1α in advanced cancer survivors: a meta-analysis with trial sequential analysis.

Background:Expression of hypoxia-inducible factors (HIFs) has been observed, but their prognostic role in advanced cancers remains uncertain. We conducted a meta-analysis to establish the prognostic effect of HIFs and to better guide treatment planning for advanced cancers.Methods:Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was also performed. The clinical outcomes included overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), relapse/recurrence-free survival (RFS), and metastasis-free survival (MFS) in patients with advanced tumors according to multivariate analysis.Results:A total of 31 studies including 3453 cases who received chemotherapy, radiotherapy, or chemoradiotherapy were identified. Pooled analyses revealed that HIF-1α expression was correlated with worse OS (HR = 1.61, p < 0.001), DFS (HR = 1.61, p < 0.001), PFS (HR = 1.49, p = 0.01), CSS (HR = 1.65, p = 0.056), RFS (HR = 2.10, p = 0.015), or MFS (HR = 2.36, p = 0.002) in advanced cancers. HIF-1α expression was linked to shorter OS in the digestive tract, epithelial ovarian, breast, non-small cell lung, and clear cell renal cell carcinomas. Subgroup analysis by study region showed that HIF-1α expression was correlated with poor OS in Europeans and Asians, while an analysis by histologic subtypes found that HIF-1α expression was not associated with OS in squamous cell carcinoma. No relationship was found between HIF-2α expression and OS, DFS, PFS, or CSS.Conclusions:Targeting HIF-1α may be a useful therapeutic approach to improve survival for advanced cancer patients. Based on TSA, more randomized controlled trials are strongly suggested.

Preoperative chemoradiation may be more effective for esophageal squamous cell carcinoma compared with adenocarcinoma: results from 15 randomized controlled trials of 2,250 patients

Background: Although preoperative chemoradiation (CRT) is considered a standard treatment for patients with esophageal cancer, the results obtained from a variety studies concerning this treatment type still do not completely concur. The purpose of this study is to evaluate the efficacy of preoperative CRT on different histological types in the treatment of esophageal cancer, and to clarify the benefits of preoperative CRT for esophageal cancer. Methods: PubMed, EMBASE, Web of science and Cochrane library were searched for eligible studies published up to December 2017. Three primary out-comes were analyzed. Pooled hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated using a random effects or fixed effects. Heterogeneity of included studies was assessed using the I2 test. Publication bias was examined by the Begg’s funnel plot. Results: Fifteen RCTs totaling 2,250 patients were included, compared with surgery alone (SA), the HR (95% CI) for the overall survival (OS) was 0.88 (0.81–0.97), the disease-free survival (DFS) rate was 0.78 (0.64–0.96), and the progression-free survival (PFS) rate was 0.72 (0.56–0.91). To clarify the effect of histological differences on CRT, a subgroup analysis was performed, and the results showed that there was no statistically significant difference in the HR of the OS in squamous cell carcinoma (SCC) and adenocarcinoma (AC) for those treated with preoperative CRT compared with SA [HR of SCC =0.92 (0.83–1.01), P=0.085; HR of AC =0.77 (0.55–1.08), P=0.135]. There was however a statistically significant difference in the HR of the PFS in SCC and AC for those treated with preoperative CRT compared with SA [HR =0.48 (0.32–0.71) for SCC and =0.83 (0.57–1.21) for the AC]. The indirect compare results show there was no statistically significant difference between SCC and AC in OS, ROR (=1.19, 95% CI: 0.84–1.70), but have a statistically significant difference in PFS, ROR (=0.58, 95% CI: 0.33–1.00). Conclusions: Preoperative CRT can improve the OS, PFS and DFS of esophageal cancer. The results of subgroup analyses show that preoperative CRT can improve the PFS of esophageal SCC, but not esophageal AC. However, there was no significant difference in the OS of SCC and AC. And the indirect comparison results confirmed it.

Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer.

BackgroundIndoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC.ResultsHigh IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001).ConclusionsEC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC.Materials and MethodsmRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic analysis.

Chemoradiotherapy-induced hemoglobin nadir values and survival in patients with stage III non-small cell lung cancer

PurposeWe investigated the influence of change in hemoglobin (Hgb) levels during concurrent chemoradiotherapy (C-CRT) on outcomes of non-anemic patients with stage IIIA/B non-small cell lung cancer (NSCLC). MethodsWe identified 722 patients with stage IIIA/B NSCLC without anemia at baseline [hemoglobin (Hgb) <12 g/dL for women or <13 g/dL for men], either nonsmokers or ex-smokers, who received C-CRT between 2007 and 2012. All patients had received 1−3 cycles of platinum-based doublet chemotherapy during radiotherapy to 60−66 Gy and had documented Hgb measurements before treatment and at weekly intervals for 6 weeks during the C-CRT. Potential associations were assessed between baseline, nadir, extent of change in Hgb level, and anemia and overall survival (OS), locoregional progression-free survival (LRPFS), and PFS. ResultsThe median baseline Hgb level was 13.9 g/dL (range 12.0–16.8) and declined to a median 12.4 g/dL (range 7.9–16.1) during treatment. Anemia appeared in 237 patients (32.8%) and was more common among women (44.8% vs. 26.5%, P < 0.001). Neither baseline Hgb level nor change during treatment nor anemia emergence influenced any survival endpoint. Receiver operating curve analysis revealed an Hgb nadir of 11.1 g/dL to be associated with outcomes, in that a nadir Hgb <11.1 g/dL (in 156 patients) was linked with shorter median OS time (P < 0.001), LRPFS time (P < 0.001), and PFS time (P < 0.001); retained significance for all three endpoints in multivariate analyses; and was more strongly associated with OS in squamous cell carcinoma (P < 0.001) than in adenocarcinoma (P = 0.009). ConclusionNadir Hgb <11.1 g/dL levels during C-CRT were associated with significantly poorer survival times in initially non-anemic patients presenting with locally advanced NSCLC.

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.

Prognostic Roles of mRNA Expression of S100 in Non-Small-Cell Lung Cancer.

The S100 protein family is involved in cancer cell invasion and metastasis, but its prognostic value in non-small-cell lung cancer (NSCLC) has not been elucidated. In the present study we investigated the prognostic role of mRNA expression of each individual S100 in NSCLC patients through the Kaplan–Meier plotter (KM plotter) database. Expression of 14 members of the S100 family correlated with overall survival (OS) for all NSCLC patients; 18 members were associated with OS in adenocarcinoma, but none were associated with OS in squamous cell carcinoma. In particular, high mRNA expression level of S100B was associated with better OS in NSCLC patients. The prognostic value of S100 according to smoking status, pathological grades, clinical stages, and chemotherapeutic treatment of NSCLC was further assessed. Although the results should be further verified in clinical trials our findings provide new insights into the prognostic roles of S100 proteins in NSCLC and might promote development of S100-targeted inhibitors for the treatment of NSCLC.

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.

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.

Different Prognostic Implications of 18F-FDG PET Between Histological Subtypes in Patients With Cervical Cancer.

This study aimed to investigate whether the predictive values of intensity- and volume-based PET parameters are different between histological subtypes in patients with cervical cancer.Ninety patients, 65 with squamous cell carcinoma (SCC) and 25 with non-SCC (NSCC), who underwent pretreatment 18F-FDG PET/CT and pelvic MRI, were studied retrospectively. In addition to SUVmax and SUVmean, metabolic-tumor-volume (MTV) was determined by thresholding of 40% SUVmax and total-lesion-glycolysis (TLG) was calculated. Clinical factors and PET metabolic indices were compared between SCC and NSCC. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method with cut-offs determined by ROC analyses to stratify SCC and NSCC patients separately. Factors associated with survival were assessed with univariate and multivariate analyses using the Cox regression model.No significant differences were observed in clinical factors other than tumor size or 18F-FDG PET metabolic indices between SCC and NSCC. The Kaplan–Meier estimates of 2-year PFS and OS rates were 60% and 70% for SCC and 40% and 76% for NSCC, respectively. Multivariate analyses showed that MTV and TLG were the independent prognostic factors for PFS and OS in SCC; in contrast, SUVmax was the independent prognostic factor for PFS and OS in NSCC.Metabolic burden (MTV and TLG) could be beneficial for the prognostic prediction of cervical SCC patients; in contrast, metabolic intensity (SUVmax) could be beneficial for the prognostic prediction of NSCC patients. The different prognostic implications might be based on the differences of tissue integrity and histological heterogeneity between SCC and NSCC.

Nonmelanoma cutaneous cancers involving the skull base: outcomes of aggressive multimodal management.

A relative paucity of information exists regarding outcomes from craniofacial resection for advanced nonmelanoma skin cancers involving the skull base. In light of advances in surgical technique and adjuvant therapy protocols, the authors reviewed their surgical experience to determine disease control rates, overall survival (OS), morbidity, and mortality. A retrospective review of 24 patients with nonmelanoma cutaneous cancers with skull base involvement treated with craniofacial resection at The University of Texas MD Anderson Cancer Center from 1994 to 2012 was performed. Of these patients, 19 (79%) had squamous cell carcinoma (SCC), 4 (17%) had basosquamous carcinoma (BSCC), and 1 patient (4%) had adenocarcinoma. Factors as assessed were prior treatment, TNM staging, tumor involvement, extent of intracranial extension, margin status, postoperative complications, recurrence, disease status at last follow-up, and long-term survival. The majority of tumors were T4 (67%) according to the TNM classification; perineural extension was noted in 58%, cavernous sinus involvement in 25%, and dural involvement in 29%. Postoperative complications occurred in 4 patients (17%) including 1 death. Kaplan-Meier estimates were calculated for OS and progression-free survival (PFS). Median OS was 43.2 months with an 82% 1-year OS and 37% 5-year OS; the median PFS was 91.2 months. Margin status was positively associated with median OS in SCC (91 months [for negative margins] vs 57 months, p = 0.8) and in BSCC (23.7 vs 3.2 months, p < 0.05). Postoperative radiotherapy was associated with improved median OS (43.2 vs 22 months, p = 0.6). Brain involvement was uniformly fatal after 1 year, while cavernous sinus involvement (31 vs 43 months, p = 0.82), perineural disease (31 vs 54 months, p = 0.30), and T4 stage (22 vs 91.2 months, p = 0.09) were associated with worsened OS. Similar associations were found with median PFS. Aggressive multimodality management with surgery and postoperative radiotherapy can positively impact locoregional control and OS. With improvements in technique and adjuvant therapy protocols, treatment can still be considered in situations of perineural disease and cavernous sinus involvement and as a salvage option for patients in whom prior treatment has failed. As patients with advanced NMSCs often have few options, craniofacial resection, as part of a coordinated multimodal management plan, is justified if it can be performed safely.

Association of miR-141 and miR-200c with time to recurrence (TTR) and overall survival (OS) in resected non-small-cell lung cancer (NSCLC) adenocarcinoma (ADC) patients (p).

7547 Background: Surgical resection remains the standard curative treatment for early-stage NSCLC, but nearly 50% of p experience recurrence, highlighting the need for novel diagnostic and therapeutic strategies. Moreover, treatments in NSCLC are often histology-dependent, underlining the need for histology-related markers. MicroRNAs (miRNAs) are promising molecular markers in cancer, with marked differences in expression according to histology. miR-200 family members have been associated in vitro with the regulation of epithelial-mesenchymal transition. We have examined their impact on outcome in resected NSCLC p. Methods: We analyzed miRNA expression using TaqMan assays in 160 tumor samples from NSCLC p who had undergone surgical resection and correlated our findings with TTR and OS. Results: p characteristics: age, 67 (51-83); 140 male; 96 (60%) stage I, 34 (21.3%) stage II, 30 (18.7%) stage III; 77(48.1%) ADC, 71(44.4%) squamous cell carcinoma (SCC); 16 (9.1%) received adjuvant treatment. With a median follow-up of 28 months (m), 64 p (40%) had relapsed. TTR for the 107 p with high miR-200c was 26.7 m vs 100.2 m for the 52 p with low miR-200c (P=0.032). OS for p with high miR-200c was 71.2 m vs. 125 m for p with low miR-200c (P=0.01). TTR for 112 p with high miR-141 was 26.7 m vs. 100.2 m for 46 p with low miR-141 (P=0.06). OS for p with high miR-141 was 72 m vs. 118 m for p with low miR-141 (P=0.02). Interestingly, neither miR-200c nor miR-141 correlated with TTR or OS in SCC p. In contrast, in ADC p, the prognostic value of both miRNAs increased: miR-200c (TTR, P=0.01; OS, P&lt;0.0001) and miR-141 (TTR, P=0.003; OS, P&lt;0.0001). This prognostic value was maintained in the subgroup of stage I p: miR-200c (TTR, P=0.011; OS, P&lt;0.001) and miR-141 (TTR, P=0.018; OS, P&lt;0.001). In the multivariate analysis, miR-200c and miR-141 emerged as an independent prognostic factor for OS (OR: 3.2, P=0.006; OR:2.5, P=0.02, respectively) together with age&gt;65 (OR: 3.3, P=0.001) and stage I (OR: 0.3, P=0.004). Conclusions: miR-200c and miR-141 expression is associated with TTR and OS in resected ADC but not in SCC NSCLC p.