Squamous Cell Carcinoma Histology Research Articles

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort

AimsTo report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region. Materials and methodsBetween January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients. ResultsAfter a median follow-up of 37 months (range: 7–110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up. ConclusionICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.

Clinicopathological relevance of tumor expression of NK group 2 member D ligands in resected non-small cell lung cancer

UL16-binding protein (ULBP) 1-6 and MHC class I chain-related molecule A and B (MICA/B) are NK group 2, member D (NKG2D) ligands, which are specifically expressed in infected or transformed cells and are recognized by NK cells via NKG2D-NKG2D ligand interactions. We previously reported that MICA/B overexpression predicted improved clinical outcomes in patients with resected non-small cell lung cancer (NSCLC). However, the clinicopathological features and prognostic significance of ULBPs in NSCLC remain unclear. Here,ULBP1-6 expression was evaluated based on immunohistochemistry of 91 NSCLC samples from patients following radical surgery. ULBPs were expressed by the majority of NSCLC. Either ULBP1 or ULBP2/5/6 overexpression was associated with squamous-cell carcinoma histology, whereas ULBP4 overexpression was associated with younger age and adenocarcinoma histology. Although overexpression of ULBP1-6 did not impact clinical outcomes in NSCLC patients, integrative profiling with cluster analysis classified patients into 3 subgroups based on the expression pattern of NKG2D ligands. The subgroup characterized by ULBP1 or ULBP2/5/6 high expressing but ULBP4 low expressing tumors showed poor overall survival. Taken together with previous results, NSCLC histological subtype strongly correlates with NKG2D ligands expression pattern. NKG2D ligands expression levels assessed by multiple immune parameters could predict clinical outcomes of patients with NSCLC.

Endoscopic features and associated histology of an basaloid squamous cell carcinoma of the esophagus at the very early stage

BackgroundBasaloid squamous cell carcinoma of the esophagus (BSCCE) is generally detected at advanced stage and the prognosis is poorer than advanced conventional esophageal squamous cell carcinoma. Therefore, early detection is a critical to improve patients’ survival. However, only a few cases of early BSCCE have been reported and the endoscopic features of early BSCCE are not well described. We herein report the endoscopic features and associated histology of an early BSCCE limited within the mucosal lamina propria (m2). To our knowledge, this is the earliest BSCCE reported to date.Case presentationA 62-year-old male patient was admitted to our hospital because of epigastric pain for 3 months. White light endoscopy revealed a flat lesion with mild sloping at the periphery. The lesion was covered with leukoplakia, and normal vascular network could not be seen in the lesion. Magnifying endoscopy with narrow-band imaging showed abnormal intra-papillary capillary loop categorized as type B1 according to the classification of the Japan Esophageal Society. Iodine staining revealed a less-stained lesion. The lesion was completely resected through endoscopic submucosal dissection. Histopathologically, tumor cells, which were limited within the mucosal lamina propria, formed solid nests and lobule structures, with ribbon-like arrangement of sparse cytoplasm and round to ovoid hyperchromatic nuclei. A final diagnosis of early BSCCE was established.ConclusionsThis is the earliest BSCCE reported to date. The prominent lesion with a gentle rising slope and less-staining or abnormal stain might be initial feature of early BSCCE.

Prognostic value of ADC quantification for clinical outcome in uterine cervical cancer treated with concurrent chemoradiotherapy.

To investigate the prognostic value of diffusion-weighted imaging (DWI) in predicting clinical outcome in patients with cervical cancer after concurrent chemoradiotherapy (CCRT). We enrolled 124 cervical cancer patients who received definitive CCRT and underwent 3T-MRI before and 1month after initiating treatment. The mean apparent diffusion coefficient (ADC) value was measured on the tumor and the changes in ADC percentage (ΔADCmean) between the two time points were calculated. The Cox proportion hazard model was used to evaluate the associations between imaging or clinical variables and progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). In multivariate analysis, ΔADCmean was the only independent predictor of PFS (hazard ratio [HR] = 0.2379, p = 0.005), CSS (HR = 0.310, p = 0.024), and OS (HR = 0.217, p = 0.002). Squamous cell carcinoma antigen, histology, and pretreatment tumor size were significantly independent predictors of PFS. Tumor size response was significantly independent predictor of CSS and OS. Using the cutoff values of ΔADCmean, the PFS was significantly lower for ΔADCmean < 27.8% (p = 0.001). The CSS and OS were significantly lower for ΔADCmean < 16.1% (p = 0.002 and p < 0.001, respectively). The percentage change in tumor ADC may be a useful predictor of disease progression and survival in patients with cervical cancer treated with CCRT. • DWI is widely used as a potential marker of tumor viability. • Percentage change in tumor ADC (ΔADC mean ) was an independent marker of PFS, CSS, and OS. • Survival was better in patients with ≥ ΔADC mean cutoff value than with < the cutoff value.

A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer

Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11–199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.

Positron emission tomography for staging locally advanced cervical cancer and assessing intensity modulated radiotherapy approach.

To evaluate toxicity and outcome of concomitant chemotherapy and intensity modulated radiotherapy (IMRT) with 18-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) based simultaneous integrated boost (SIB) of locally advanced cervical cancer (LACC). Patients with LACC underwent chemo-radiation with IMRT and SIB. Staging and follow-up were performed with clinical evaluation and CT, MRI, 18FDG-PET/CT. SIB was done on positive nodes with 18FDG-PET/CT based planning. CT-based planning high-dose-rate brachytherapy (HDR-BT) was delivered as subsequent boost to the primary tumor. Cisplatin concomitant chemotherapy was administered during IMRT. Fourteen patients with cervical cancer were prospectively recruited between August 2014 and June 2017, 13 (93%) had a LACC, one (7%) patient was not evaluable because 18FDG-PET/CT evidenced metastases to the liver undetected by previous CT/MRI. Patients had a median age of 59years, a median Karnofsky performance status of 100%, and a prevalence of squamous cell carcinoma histology (85%). SIB was delivered on 23 positive lymph nodes. IMRT median dose to the pelvis was 48.6Gy in 27 fractions, SIB median dose 54Gy in 27 fractions, HDR-BT boost median dose 21Gy in 3 fractions. After a median follow-up of 30months, 2-year local control and distant control were 86% and 86%, respectively. There were no grade 4 acute and/or late toxicities. The 18FDG-PET/CT influenced stage assessment and RT treatment planning due to its high specificity in distant metastases and nodal involvement detection. The IMRT with SIB for positive nodes was an effective therapy with acceptable toxicity in LACC.

Next Generation Sequencing and Genetic Alterations in Squamous Cell Lung Carcinoma: Where Are We Today?

Lung cancer is the leading cause of cancer-related mortality and will affect ~6% of the population. It is divided into two broad categories, small cell lung cancer and non-small cell lung cancer (NSCLC), the latter representing 85% of all lung cancers. It mainly comprises adenocarcinoma (65%) and squamous cell carcinoma (30%) histologies. In recent years, there have been two major therapeutic advances in NSCLC. The first, immunotherapy, has greatly improved the prognosis of adenocarcinomas and squamous cell carcinomas. The second, the treatment of targetable driver mutations, has so far only benefited adenocarcinomas. Squamous cell carcinoma carries a high rate of mutations and is found mostly among smokers. This raises two important problems: identifying driver mutations and finding those of clinical relevance. Large-scale genomic analyses such as The Cancer Genome Atlas have allowed for the identification of frequent gene alterations, although their role and potential for targeted therapy remain unknown. The emergence of next generation sequencing has changed the landscape of precision medicine, in particular in lung cancer. In this review, we discuss the landscape of genetic alterations found in squamous cell lung cancer, the results of current targeted therapy trials, the difficulties in identifying and treating these alterations and how to integrate modern tools in clinical practice.

Radiotherapy is an independent prognostic marker of favorable prognosis in non-small cell lung cancer patients after treatment with the immune checkpoint inhibitor, nivolumab.

BackgroundIt remains unclear why radiation clinically provides a synergistic effect when combined with immune checkpoint inhibitors such as nivolumab. The purpose of our study was to retrospectively evaluate whether the therapeutic efficacy of nivolumab is improved as a result of a history of radiotherapy (RT) in patients with previously treated advanced non‐small cell lung cancer (NSCLC).MethodsFrom February 2016 to December 2017, 124 consecutive patients were administered nivolumab for pretreated advanced NSCLC. The patients were divided into RT and non‐RT groups.ResultsSixty‐six (53%) of the 124 patients had been administered RT before the initiation of nivolumab, 52 (42%) received extracranial RT, and 40 (32%) were treated with thoracic RT. The median number of nivolumab cycles was 4 (range: 1–43). The overall response rate (ORR) and disease control rate (DCR) of nivolumab in all patients were 28.0% and 58.4%, respectively. The ORR (36.4%) was significantly higher in patients who had received previous RT than in patients who had not received any RT (19%). The therapeutic efficacy of nivolumab was particularly noteworthy in patients with non‐adenocarcinoma and squamous cell carcinoma histology administered extracranial RT, with ORRs of 48.3% and 52.6%, and DCRs of 87.1% and 84.2%, respectively.ConclusionPrevious RT was an independent prognostic marker of favorable prognosis after nivolumab administration and improved the response rate to nivolumab treatment. Previous RT was clinically identified to have a synergistic effect with nivolumab treatment, increasing the response rate and improving the outcome of patients with advanced NSCLC.

The impact of histology (adenocarcinoma vs. SCC) on outcomes in nonmetastatic pancreatic cancer.

419 Background: Outcomes in squamous cell carcinoma (SCC) of the pancreas are generally thought to be poor compared with adenocarcinoma; however, this has not been sufficiently demonstrated in prior studies. This is the first NCDB analysis of the prognostic role of SCC histology in non-metastatic pancreatic cancer. Methods: We analyzed patients with non-metastatic pancreatic cancer using the National Cancer Database (NCDB) diagnosed from 2006-2014. Patients were analyzed according to histology—only adenocarcinoma, adenosquamous carcinoma, or SCC were selected for. The primary endpoint was overall survival (OS) from the time of diagnosis. Kaplan-Meier and Cox proportional hazard modeling were used to analyze OS. Results: A total of 94,928 patients were included; 94,016 in the adenocarcinoma group, 757 in the adenosquamous group, and 155 in the SCC group. There was a statistically significant decrease in median OS for patients with SCC (MS = 8.67 months, 95% CI: 7.23–9.92 months), compared to patients with adenosquamous carcinoma (MS = 12.7 months, 95% CI: 11.9–13.7 months) and adenocarcinoma (MS = 14.0 months, 95% CI: 13.86–14.06 months, p &lt; .001). On multivariate Cox regression, both adenocarcinoma and adenosquamous carcinoma were associated with a longer OS compared with SCC (for adenocarcinoma, HR 0.45, 95% CI: 0.31–0.66, p &lt; .001; for adenosquamous carcinoma, HR 0.60, 95% CI: 0.39–0.92, p = 0.02). On subgroup analysis, this OS improvement for adenocarcinoma histology was seen for patients with resectable/borderline resectable disease (HR 0.50, 95% CI: 0.32–0.79, p =.003) and for those with unresectable disease (HR 0.39, 95% CI: 0.19–0.77, p = 0.01). Conclusions: In patients with non-metastatic pancreatic cancer, there was a statistically significant detriment in OS for those with SCC histology compared with adenosquamous carcinoma or adenocarcinoma histology. On subgroup analysis, this difference persisted for those with resectable/borderline resectable disease and for those with unresectable disease. [Table: see text]

The impact of squamous histology on survival in patients with muscle-invasive bladder cancer

BackgroundBladder cancer is the ninth most common noncutaneous malignancy worldwide, though a fraction (2%–5%) are diagnosed as squamous cell carcinoma (SCC) in the Western world. Current understanding is based on small, single-institution studies and SEER-database reviews with conflicting results. We used the National Cancer Database to explore clinical characteristics and outcomes from a large cohort of invasive bladder SCC. MethodsWe queried the National Cancer Database for diagnoses of urothelial carcinoma (UC) or SCC using International Classification of Disease-O-3 morphologic codes from cases reported between 2004 and 2015. Primary outcome was overall survival in cT2-4N0M0 bladder cancer. Statistical analysis performed using chi-squared test, Kaplan-Meier survival, binomial logistic regression, and Cox proportional hazards. ResultsThe final cohort included 394,979 bladder cancer patients, of which 4,783 (1.2%) were classified as SCC histology. In comparison to UC, patients with SCC were more likely female (49% vs. 24%; P < 0.01) and African American (11% vs. 5%; P < 0.01). Patients with SCC presented at a higher stage than UC with muscle-invasive bladder cancer (MIBC) present at diagnosis in 70% vs. 19%. On multivariate analysis, SCC independently predicted poorer prognosis (hazard-ratio [HR] 1.79, P < 0.01) when controlling for patient characteristics and treatment modality. Unlike UC, there was no benefit with the use of NAC over radical cystectomy alone (HR 0.93, P = 0.69) for patients with SCC. ConclusionsInvasive SCC of the bladder carries a worse prognosis as compared to UC histology, both overall and on a stage-for-stage basis. As opposed to UC, we did not observe a survival benefit for NAC among SCC patients treated with cystectomy.

Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy.

Maximal resection of tumor while preserving the adjacent healthy tissue is particularly important for larynx surgery, hence precise and rapid intraoperative histology of laryngeal tissue is crucial for providing optimal surgical outcomes. We hypothesized that deep-learning based stimulated Raman scattering (SRS) microscopy could provide automated and accurate diagnosis of laryngeal squamous cell carcinoma on fresh, unprocessed surgical specimens without fixation, sectioning or staining.Methods: We first compared 80 pairs of adjacent frozen sections imaged with SRS and standard hematoxylin and eosin histology to evaluate their concordance. We then applied SRS imaging on fresh surgical tissues from 45 patients to reveal key diagnostic features, based on which we have constructed a deep learning based model to generate automated histologic results. 18,750 SRS fields of views were used to train and cross-validate our 34-layered residual convolutional neural network, which was used to classify 33 untrained fresh larynx surgical samples into normal and neoplasia. Furthermore, we simulated intraoperative evaluation of resection margins on totally removed larynxes.Results: We demonstrated near-perfect diagnostic concordance (Cohen's kappa, κ > 0.90) between SRS and standard histology as evaluated by three pathologists. And deep-learning based SRS correctly classified 33 independent surgical specimens with 100% accuracy. We also demonstrated that our method could identify tissue neoplasia at the simulated resection margins that appear grossly normal with naked eyes.Conclusion: Our results indicated that SRS histology integrated with deep learning algorithm provides potential for delivering rapid intraoperative diagnosis that could aid the surgical management of laryngeal cancer.

Stereotactic ablative radiotherapy (SABR) in early stage non-small cell lung cancer: Comparing survival outcomes in adenocarcinoma and squamous cell carcinoma

PurposeRecent retrospective studies have demonstrated mixed results regarding the histologic association of squamous cell carcinoma (SCC) with reduced overall survival in patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiotherapy (SABR). MethodsWe queried the National Cancer Database (NCDB) for ES-NSCLC (T1-2N0, Stage I-IIA) patients with SCC or adenocarcinoma (ADC) treated with SABR. Univariable and multivariable analyses identified characteristics predictive of overall survival. Cox proportional hazard ratios with propensity adjustment were used to mitigate indication bias between the two histologic arms. ResultsUltimately 15,110 ES-NSCLC patients with either ADC (n = 8,924) or SCC (n = 6,186) were eligible for analysis. Univariable analysis demonstrated a median overall survival of 44 months and 33 months (p < 0.0001) and 5-year overall survival of 36% and 24% (p < 0.0001) in patients diagnosed with ADC and SCC, respectively. SCC histology, remained an independent predictor of worse survival on propensity score matched multivariable comparison (p < 0.0001). Patients with SCC were more likely to have T2 lesions and poorly differentiated grade. Females, African American race, T1 lesions, and age <75 years were also associated with improved survival.Conclusion SCC histology was an independent prognosticator of worse survival in patients with ES-NSCLC treated with SABR, thus corroborating the results of previous studies. Randomized, prospective studies are needed to further validate these findings.

Phosphatidylinositol 3-kinase pathway genomic alterations in 60,991 diverse solid tumors informs targeted therapy opportunities.

BackgroundThe phosphatidylinositol 3‐kinase (PI3K) pathway is frequently altered in cancer. This report describes the landscape of PI3K alterations in solid tumors as well as co‐alterations serving as potential resistance/attenuation mechanisms.MethodsConsecutive samples were analyzed in a commercial Clinical Laboratory Improvement Amendment‐certified laboratory using comprehensive genomic profiling performed by next‐generation sequencing (315 genes). The co‐alterations evaluated included the Erb‐B2 receptor tyrosine kinase 2 (ERBB2), ERBB3, ERBB4, RAS, MET proto‐oncogene tyrosine kinase (MET), and mitogen‐activated protein kinase kinase (MAP2K) genes as well as tumor protein 53 (TP53), estrogen receptor 1 (ESR1), and androgen receptor (AR). ResultsAlterations in any of 18 PI3K‐pathway associated genes were identified in 44% of 60,991 tumors. Although single base and insertions/deletions (indels) were the most frequent alterations, copy number changes and rearrangements were identified in 11% and 0.9% of patients, respectively. Overall, the most frequently altered genes were PIK3 catalytic subunit α (PIK3CA) (13%), phosphatase and tensin homolog (PTEN) (9%), and serine/threonine kinase 11 (STK11) (5%). Tumor types that frequently harbored at least 1 PI3K alteration were uterine (77%), cervical (62%), anal (59%), and breast (58%) cancers. Alterations also were discerned frequently in tumors with carcinosarcoma (89%) and squamous cell carcinoma (62%) histologies. Tumors with a greater likelihood of co‐occurring PI3K pathway and MAPK pathway alterations included colorectal cancers (odds ratio [OR], 1.64; P < .001), mesotheliomas (OR, 2.67; P = .024), anal cancers (OR, 1.98; P = .03), and nonsquamous head and neck cancers (OR, 2.03; P = .019). The co‐occurrence of ESR1 and/or AR alterations with PI3K alterations was statistically significant in bladder, colorectal, uterine, prostate, and unknown primary cancers.ConclusionsComprehensive genomic profiling reveals altered PI3K‐related genes in 44% of solid malignancies, including rare disease and histology types. The frequency of alterations and the co‐occurrence of resistance pathways vary by tumor type, directly affecting opportunities for targeted therapy.

Second primary lung malignancy following head and neck squamous cell carcinoma.

Analyze the characteristics of second primary lung malignancies (SPLMs) following an index head and neck squamous cell carcinoma (HNSCC). Retrospective cohort study. The Surveillance, Epidemiology and End Results database was queried for all cases of HNSCC between 1973 and 2014 (N = 101,856). This population was compared to a standard population to assess relative risk for lung cancer, calculated as the standardized incidence ratio (SIR). Patients who developed SPLMs were extracted (N = 8,116) and compared to all other cases of lung cancer (N = 1,160,853) to assess histopathological differences. SPLM subpopulations divided by head and neck primary site were compared for lung cancer histology and time interval between cancer diagnoses. Overall, 8.0% of HNSCC patients developed SPLMs (SIR = 4.22, P < .001), diagnosed an average of 6.7 years later. Patients with HNSCC of the supraglottis and hypopharynx were at the highest risk relative to a standard population, with SIRs of 8.10 and 6.34, respectively. When comparing SPLMs to all other lung cancers, there was no difference in the distribution of lung lobe affected, but SPLMs were significantly more likely to be of squamous cell carcinoma histology (42.0% vs. 21.0%, P < .001). Among head and neck subsites, lung cancers following larynx tumors had a significantly higher proportion of small cell histology, and those following oropharyngeal or hypopharyngeal tumors had significantly higher proportions of squamous cell histology. Patients who undergo curative treatment of HNSCC are at high risk for developing SPLMs. Subsite-specific differences may help elucidate the degree of risk attributable to smoking, genetic susceptibility, human papillomavirus infection, or metastasis masquerading as an SPLM. 4 Laryngoscope, 129:903-909, 2019.

The role of inguinal lymph node dissection in men with urethral squamous cell carcinoma

IntroductionUrethral squamous cell cancer is a rare disease with limited clinical recommendations regarding management of the inguinal lymph nodes. Despite the similarities to penile cancer in terms of squamous cell carcinoma (SCC) histology and lymphatic drainage, there is not enough evidence to recommend for or against a prophylactic inguinal lymph node dissection (ILND) in patients with clinically negative groins and a primary tumor stage of T1b or higher. The objective of the study was to identify the rate of prophylactic inguinal lymph node dissection, node positive rate, and overall survival in patients with clinical T1 to T4 stage. The patients were separated into clinical N stage and the rates of node positivity were compared. We hypothesize that the node positivity rate would be similar to that observed in penile cancer of similar clinical T and N stage and provide evidence for prophylactic inguinal lymph node dissection in urethral squamous cancer. We also sought to determine the value of ILND in clinically node positive (cN+) and clinically node negative (cN−) patients. MethodsThe National Cancer Database was queried for all cases of primary urethral cancer in men from 2004 to 2014. Patients with other cancer diagnoses, metastasis, nonsquamous histology, female patients, and patients with a history of radiation therapy were excluded. Male patients with urethral squamous cell cancer of the anterior urethra with T1 or higher T stage were included in this study. All-cause mortality was compared using multivariable Cox regression controlling for covariates. ResultsThe study included 725 men with urethral SCC with T1 or higher clinical T stage. The median age was 63 years (33–83 interquartile range). Of the 725 men, 536 men did not receive an ILND and 189 (26%) underwent ILND. Patients who received LND had significantly higher clinical T and clinical N stage. There was no difference in age, sex, or histology between those with ILND versus no ILND. In patients with T1 to T4 and clinical N0, the ILND rate was 21.8% (89/396). The lymph node positive rate in patients with N0 and T1 to T4 primary tumor was 9%. In patients with clinically node positive disease (N1/N2), the overall ILND rate was 76%. The lymph node positive rate for patients with clinical nodal disease was 84%. On multivariable analysis cox regression, lymph node positivity was associated with worse overall survival when controlling for T stage, clinical N stage, and age (HR 1.56, 95% 1.3–1.9, P = 0.000). On multivariable analysis after controlling for T stage, sex, and age, having an ILND was associated with improved OS in patients with clinical N1 or N2 disease (HR 0.46, 95% 0.28–0.78 P = 0.002). ConclusionThe node positivity rate in patients with T1 to T4 and N0 is 9%, much lower than reported in penile cancer with a high-risk primary tumor but clinically negative groins. This argues against routine prophylactic inguinal ILND in patients with urethral SCC who are clinically N0, perhaps suggesting different biological behavior of urethral SCC compared to penile SCC. Performing a lymph node dissection in patients with clinically N1 or N2 disease is associated with improved OS.

Clinical fate of T0N1 esophageal cancer: results from the National Cancer Database.

The long-term survival for patients with locally advanced esophageal cancer (EC) remains poor despite improvements in multi-modality care. Neoadjuvant chemoradiation (NCR) followed by surgical resection remains pivotal in the management of patients with EC. However, the outcome of patients whose primary tumor exhibits a complete response with residual regional nodal disease (T0N1) remains unclear as well as the role for adjuvant therapy.Utilizing the National Cancer Database we identified patients with EC who underwent NCR followed by esophagectomy who had subsequent pathology of T0N1. Baseline univariate comparisons of patient characteristics were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests as appropriate. Pearson's Chi-square test was used to compare categorical variables. Unadjusted survival analyses were performed using the Kaplan-Meier method comparing survival curves with the log-rank test. All statistical tests were two-sided and α (type I) error <0.05 was considered statistically significant.We identified 7,116 patients diagnosed with EC; 6,235 (87.6%) adenocarcinoma (AC), 881 (12.4%) squamous cell carcinoma (SCC) with a median age of 62 [21-88] years. There were 6,031 (84.8%) males and 1,085 (15.2%) females. R0 resections were achieved in 6,668 (93.7%) patients and this correlated to improved median survival 39.5 (R0) and 20.1 (R1) months respectively, P<0.001. The median nodes harvested were 13 [0-83] with a mean positive LN's of 1.4±2.9. Pathologic complete response (pCR) was achieved in 1,334 (18.7%), partial response (pPR) 2,812 (39.5%) and non-response (pNR) 2,970 (41.7%). There were 230 (3.2%) patients deemed as pathologic T0N1. The median survival of patients with pCR was 61.7 months compared to 32.1 months in the T0N1 patients P<0.001. T0N1 patients did not demonstrate an improved survival over T1/2 patients who had a median survival of 30.5 months, P=0.79. However, T0N1 did reveal an improved survival over T3/4 patients who had a median survival of 24.6 months, P=0.02. Adjuvant chemotherapy in T0N1 did not provide a benefit in survival, median survival adjuvant versus no adjuvant 30.8 vs. 32.1 months respectively, P=0.08. Multivariate analysis in T0N1 patients demonstrated only number of LN's positive, and histology SCC vs. ACC as predictive of survival, HR, 1.22, 95% CI: 1.10-1.36, P<0.001; HR, 0.43, 95% CI: 0.24-0.75, P=0.003, respectively.Patients with EC who exhibit a pathologic T0N1 after NCR have oncologic fates similar to node positive patients. Patients with pCR of the primary tumor and regional lymph nodes continue to demonstrate significant survival benefits over all remaining pathologic cohorts.

A multicenter, open-label, phase II trial of S-1 plus carboplatin in advanced non-small cell lung cancer patients with interstitial lung disease

ObjectivesThe clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remain unclear. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of S-1 in combination with carboplatin (CBDCA) in NSCLC patients with ILD. Materials and methodsA total of 33 advanced or recurrent NSCLC patients with ILD were prospectively enrolled in this multicenter, open-label, phase II study. Every 4 weeks, CBDCA at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered. The primary endpoint was the investigator-assessed objective response rate. ResultsThe median age at initiating chemotherapy was 70. Sixteen patients (48.5%) had squamous cell carcinoma histology. With respect to the types of ILD, the usual interstitial pneumonia pattern was dominant (66.7%). The median number of cycles administered was 3, and the overall response rate and disease control rate were 33.3% and 78.8%, respectively. The median progression-free survival, the median survival time and the 1-year survival rate were 4.8 months, 12.8 months and 51.4%, respectively. Acute exacerbation of ILD caused by chemotherapy was noted in 2 patients (6.1%). ConclusionThis is the first prospective study designed to evaluate the efficacy of a specific chemotherapeutic regimen as the primary endpoint in patients with advanced NSCLC with ILD. The combination of S-1 with CBDCA may be a treatment option for advanced NSCLC patients with ILD (The clinical trial registration number: UMIN000011046).

Response to Combination Chemotherapy With Paclitaxel/Ifosfamide/Platinum Versus Paclitaxel/Platinum for Patients With Metastatic, Recurrent, or Persistent Carcinoma of the Uterine Cervix: A Retrospective Analysis.

Paclitaxel/ifosfamide/cisplatin triplet has shown a higher response rate than paclitaxel/cisplatin doublet, but the toxicity profile hindered the use of the triplet regimen. In this study, we adjusted the dosage of the triplet regimen and introduced carboplatin in cisplatin-intolerable patients. We tested the efficacy and toxicity of the modified triplet regimen in patients with recurrent or persistent cervical cancer. We retrospectively reviewed the medical records of patients with recurrent or persistent cervical cancer who were treated between 2003 and 2015 at Samsung Medical Center. Response rate, progression-free survival (PFS), overall survival (OS), and toxicity of paclitaxel/ifosfamide/platinum (TIP) and paclitaxel/platinum (TP) were compared. The overall response rate of TIP was significantly higher than that of TP (52.7% vs 36.4%, P = 0.031). In the TP group, response rate was higher in patients with progression-free interval longer than 12 months (P = 0.028) and those with squamous cell histology (P = 0.028). In TIP group, patients with older than 50 years (P = 0.017), progression-free interval longer than 12 months (P = 0.046), and squamous cell carcinoma histology (P < 0.001) showed higher response rates; but TIP showed higher response on all occasions. Median OS and median PFS were similar for TP and TIP (OS, 22.43 months vs 18.5 months, P = 0.44; PFS, 6.37 months vs 8.3 months, P = 0.48). Paclitaxel/ifosfamide/platinum showed a higher response rate than TP in patients with recurrent cervical cancer without an increase in severe complications. Considering the high response rate, TIP may be an option for persistent or recurrent cervical cancer.

Comparison of Single- and Five-fraction Regimens of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non–small-cell Lung Cancer: A Two-institution Propensity-matched Analysis

PurposeTo evaluate differences in local control (LC), disease-specific (DC), and overall survival (OS) of patients with early-stage non–small-cell lung cancer (NSCLC) treated with single- (SF) versus 5-fraction (FF) stereotactic body radiation therapy (SBRT) at 2 institutions. Patients and MethodsPeripheral early-stage NSCLC cases treated with a median dose of 30 Gy in SF or a median dose of 50 Gy in FF were included per institutional practice. Kaplan-Meier and Cox models were used to assess survival. A matched-pair analysis was performed to account for imbalances. Toxicities including Common Terminology Criteria for Adverse Events (CTCAE) grade 3 pneumonitis, chest wall pain requiring long-acting narcotics, and hospitalization for respiratory events 6 months posttreatment were recorded. ResultsA total of 163 lesions were treated between 2007 and 2015; 65 received SF SBRT and 98 received FF SBRT. Most tumors were T1 (n = 92) and T2 (n = 34) lesions and had adenocarcinoma (n = 77) and squamous cell carcinoma (n = 46) histologies, respectively. In the matched cohort, there were no differences in OS, LC, DC, or progression-free survival between the groups. LC and OS at 1 year in the matched cohort was 95% and 88%, and 87% and 84% in the SF and FF cohorts, respectively. There was 1 grade 3 pneumonitis in the FF group, and 9 total hospitalizations post-SBRT, 3 (5%) in the SF group and 6 (6%) in the FF group. ConclusionsNo statistically significant differences were seen in LC or DC following SF or FF SBRT in this matched cohort of peripheral lesions. No grade 4 or higher toxicities were reported.

Timing of esophagectomy after neoadjuvant chemoradiation treatment in squamous cell carcinoma

BackgroundTime interval between neoadjuvant (combined) chemotherapy and radiation (nCRT) and surgery has been linked to pathologic response rates and outcomes in patients with various solid cancers. The optimal timing between nCRT and esophagectomy in patients with esophageal squamous cell carcinoma (SCC), however, is not known. Our aim was to analyze the relation between elapsed time from completion of nCRT to esophagectomy and postsurgical mortality and overall survival. MethodsWe reviewed the National Cancer Database for patients with SCC (n = 1,244) of the esophagus diagnosed between 2003 and 2011 who were treated with nCRT followed by esophagectomy within 26 weeks after completion of nCRT. ResultsThirty-day mortality was 5.6% and 90-day mortality was 11.1%. The duration of post-nCRT interval was not a predictor of 30-day and 90-day postoperative mortality in multivariate models, but 30-day postoperative mortality was predictable based on increasing Charlson-Deyo comorbidities (adjusted odds ratio [aOR] 1.77, P = .054) and improved in academic institutions (aOR 0.66, P = .005). Similar findings were found for 90-day mortality (comorbidity index aOR 1.58, P = .046) and for treatment at an academic facility (0.82, P = .062). In a multivariate survival analysis, the duration of the post-nCRT interval was not found to be a predictor of overall survival (P = .769), whereas increasing age (hazard ratio [HR] 1.02, P = .005), increasing comorbidity score (HR 1.38, P = .005), treatment at an academic hospital (HR 0.84, P = .001), and post-treatment nodal status (HR 1.73, P < .001) were predictors. ConclusionPerioperative mortality and overall survival are not affected by the time interval between completion of nCRT and esophagectomy among patients with SCC histology.