Squamous Cell Cancer Patients Research Articles

Patterns of failure and prognostic factors for radically treated patients of oropharyngeal cancers planned by two-dimensional radiotherapy: An audit from a regional cancer center

Objectives: To review the patterns of failure and analyze various prognostic factors influencing the outcomes of radically treated patients of oropharyngeal squamous cell cancer treated at our institute with two-dimensional planning (2D). Materials and Methods: Case records of 100 oropharyngeal squamous cell cancers, which were treated radically with radiation or concurrent chemoradiation to an equivalent dose of 66 Gy in conventional fractionation, in our department between 2011 and 2013 were retrospectively analyzed for locoregional control (LRC), progression-free survival (PFS), patterns of failure, and various prognostic factors. Results: Median age of presentation was 53 years, 95% being males. Ninety-three percent had a history of tobacco use. Base of tongue was the most common site in 63% of patients followed by tonsil in 26%. All patients were of Stage III and IV. Among these patients, 27% received concurrent chemoradiation while others received radical radiation. At a median follow-up of 28 months, 57% of the patients were disease free and the LRC was 60%. Among the recurrences, 17% had local failures while 23% had nodal failures as the first site of recurrence. There were no marginal failures. On multivariate analysis, stage of the disease was the single most important prognostic factor determining the PFS and LRC. Conclusion: Stage appears to be the most important prognostic factor affecting LRC and PFS. Absence of marginal failures in our study implies adequacy of coverage with 2D treatment planning while in-field failures mandate attempts to use increased dose, chemosensitizers or nodal dissection postradical radiation.

Prognostic value of pathological response to neoadjuvant chemotherapy in bulky stage Ib2 and IIa cervical squamous cell cancer patients.

Neoadjuvant chemotherapy (NAC) is widely used to treat patients with locally advanced cervical cancer. Optimal pathological response to neoadjuvant therapy has proven to be a good prognostic indicator for patient survival, but the prognostic significance of a partial response remains unclear. The aim of this study was to identify prognostic predictors for patients with partial response. We included in the study 190 patients with bulky stage Ib2 or IIa cervical squamous cell cancer, who underwent neoadjuvant chemotherapy followed by surgery. A novel pathological grading system, including optimal response (complete disappearance of tumor, grade 1), viable tumor cells occupying <(2)/3 (grade 2) or >(2)/3 (grade 3) of the tumor bed area and extra-cervical tumor deposits (grade 4), was developed and associations with disease-free survival and overall survival were studied. Survival analysis was conducted using log-rank testing and Cox regression analysis. We found statistically significant differences between 4 different pathological response groups both in terms of disease-free survival (p = 0.001) and overall survival (p = 0.003). Combining adjacent survival curves in the pathological grading system allowed us to identify response grade 2 patients with disease-free and overall survival similar to those of optimal response patients (p = 0.000, p = 0.002). Multivariate analyses showed that the pathological response grading system is the only independent predictor for progression-free survival and overall survival (p = 0.001 and p = 0.007). A response grading system based on pathological parameters may be useful to predict both progression-free and overall survival in bulky stage Ib2 and IIa cervical squamous cell cancer patients treated with NAC.

Intraoperative photodynamic diagnosis of lymph node metastasis in esophageal cancer patients using 5-aminolevulinic acid.

Lymph node metastasis is the strongest prognostic factor in esophageal cancer patients who have undergone esophagectomy. The accurate diagnosis of lymph node metastasis is important, but the pre-operative diagnostic accuracy is poor. The intraoperative diagnosis based on histopathological examination of frozen tissue specimens is complicated and time-consuming. Therefore, the establishment of a simple and rapid intraoperative diagnostic method is essential. Exogenous application of 5-aminolevulinic acid (ALA) causes a selective accumulation of protoporphyrin IX, which is a fluorescent substrate, in cancer cells. The present study evaluated the feasibility of photodynamic diagnosis using ALA (ALA-PDD) for lymph node metastasis in esophageal cancer. A total of 292 lymph nodes were analyzed from 8 esophageal squamous cell cancer patients treated with esophagectomy. The patients were administered ALA orally prior to surgery. Excised lymph nodes were cut in half and examined by spectrometer. The diagnostic results of ALA-PDD were compared to those of the histopathological examination. Among the 292 lymph nodes, 19 nodes (6.5%) were histologically metastatic and 21 nodes (7.2%) were PDD-positive. The sensitivity and specificity of ALA-PDD were 84.2% (16/19) and 98.2% (268/273), respectively. The area of cancer nests of the PDD-negative lymph nodes was <2 mm2. Metastatic lymph nodes, including cancer nests >4 mm2, were correctly diagnosed by ALA-PDD. In conclusion, this study demonstrated that ALA-PDD of lymph node metastasis in patients with esophageal cancer is feasible. Further investigation would make this method a simple and rapid intraoperative diagnostic tool.

SU‐E‐J‐269: Tracking of Tumor Regression for Stage III Lung Cancer Using CBCT

Purpose:This study is to evaluate the tumor regression over the course of EBRT treatment and to determine the difference of tumor reduction for stage III lung squamous cell cancer (SCC) and adenocarcinoma using CBCT.Methods:Twenty three stage III lung cancer patients treated in our clinic who had daily cone beam CT (CBCT) were selected for this study (16 adenocarcinoma and 7 SCC cases). Patients received prescription dose in the range of 50Gy–71.4Gy (mean =60.3Gy, median =50Gy) at 1.8Gy or 2Gy per fraction. Treatments spanned over a minimum of five weeks. Initial mean volume of the gross tumor volume (GTV) was 123cc (range = 14.7cc–353.3cc). For this study, we choose six sets of CBCTs at an interval of one week, starting from the first fraction of treatment. Daily CBCTs from treatment linac computer were transferred to MIM Software version 6.0. An experienced physician contoured the primary GTV on each slices of the CBCT for these patients.Results:A consistent regression of the GTVs was observed in all patients, except in one patient (adeno case) where GTV did not change. Weekly volumetric reduction was in the range of 11.2%–16.6%. Maximum reductions were noticed in the first two weeks of the treatment cycle; mean overall (for adeno+SCC) reductions were 16.6%, 14.2% in week‐1 and week‐2, respectively. Mean reduction over five weeks of treatment was 49.8% (range = 0.1%–75.5%). Higher reduction was observed in SCC patients as compare to adenocarcinoma cases (54.9% vs. 47.6%); however, the difference was not statistically significant (p‐value &gt; 0.05).Conclusion:Large regression of tumors over the course of EBRT for stage III lung cancer patients was observed. Both SCC and adenocarcinoma responded well; overall reduction for SCC cases was higher. A future study is warranted for determining the co‐relation between tumor volume reduction and treatment outcome.

The prognostic value of hemoglobin level in cervical cancer patients

The present paper aim to assess the prognostic value of pretreatment hemoglobin (Hb) level in cervical cancer patients. A number of 142 adenocarcinoma (AC) and 242 squamous cell cancer (SCC) patients, FIGO stage I-IVA, treated with surgery and radiotherapy (RT) or RT alone, were analyzed retrospectively. Factors as the pretreatment Hb level, FIGO stage, the tumor diameter, the histopathology, and WHO status were analyzed. As the cut-off value of Hb level, 10 g/dl and 13 g/dl was accepted. Independently of the other factors, the pretreatment Hb level in cervical SCC patients had statistically significant association with overall survival (OS) (p=0.031) and disease free survival (DFS) (p=0.019). In patients with AC, Hb level was not statistically significant for OS (p=0.58) and DFS (p=0.29). The pretreatment Hb concentration in patients with SCC of the uterine cervix seems to be an important prognostic factor.

Risk Patterns of Subsequent Primary Cancers following Esophagectomy in Early-Stage Thoracic Esophageal Squamous Cell Cancer Patients

Subsequent primary cancers (SPCs) have been demonstrated to be the major causes of death among patients with thoracic esophageal squamous cell cancer (ESCC) negative for lymph node involvement. We designed this study to investigate clinical characteristics and risk patterns of SPCs following esophagectomy in patients with early-stage thoracic ESCC. We retrospectively analyzed clinical factors in 512 patients with early-stage thoracic ESCC collected from 3 independent hospitals over a 10-year interval. The overall standard incidence rate (SIR) of SPCs was 3.84 (95% confidence interval 2.98-4.95). The most common SPCs were head and neck cancers, lung cancer, and stomach cancer. The risk patterns of SPCs varied across organs. A 3-phase risk pattern with a U-shaped curve between 2 rising phases was seen for head and neck cancers, while for the other cancers, the risk patterns all displayed as an approximately linear upward trend. It was further noted that sex, smoking habits, and cancer histories among first-degree relatives were 3 significant independent risk factors in the development of SPCs. We observed significant associations between early-stage ESCC and SPCs arising from anatomically adjacent sites. The different risk patterns of SPCs indicated that follow-up strategies should be established accordingly in different organs at different times, with particularly close follow-up for head and neck cancers in the first 5 years and beyond 15 years after diagnosis of ESCC.

Low expression of Bin1, along with high expression of IDO in tumor tissue and draining lymph nodes, are predictors of poor prognosis for esophageal squamous cell cancer patients.

Indoleamine 2,3-dioxygenase (IDO) has been reported to be involved in esophageal squamous cell cancer (ESCC) progression by promoting immune escape. Previous studies have revealed bridging integrator-1 (Bin1) can inhibit cancer cell growth by suppressing expression of IDO, thus we investigated the correlation between the expression of Bin1 and IDO and their prognostic significances for ESCC patients. Specimens were collected from 196 ESCC patients and detected with flow cytometry, reverse transcription-polymerase chain reaction and immunohistochemistry. We found that in tumor microenvironment (TME) and tumor draining lymph node (TDLN), the proportions of CD3(+) CD4(+) T cell, CD3(+) CD8(+) T cell and CD3(-) CD16(+) CD56(+) NK cell were lower while the proportions of CD3(-) CD19(+) B cell and CD4(+) CD25(+) Treg were higher in specimens with high IDO expression when compared to the specimens with low IDO expression (p < 0.01). In addition, IDO expression was negatively correlated with Bin1 expression at gene and protein level in TME and TDLN. Both the expression of Bin1 and IDO were associated with some clinicopathological parameters including differentiation grade, TNM stage, invasion range, lymph node metastasis (p < 0.05). Moreover, multivariate survival analysis suggested that, along with some other parameters, low expression of Bin1 and high expression of IDO might be independent prognostic factor for ESCC patients. Our results demonstrate that low expression of Bin1, along with high expression of IDO, are predictor for poor prognosis in ESCC and thereby could be used to establish new therapeutic strategies.

Prognostic significance of SLC9A9 in patients with resectable esophageal squamous cell carcinoma.

The survival rate of esophageal squamous cell cancer (ESCC) patients is still dismal. Therefore, novel prognostic biomarkers are critically needed for patients with ESCC. SLC9A9 has been reported to be downregulated in hormone-sensitive prostate cancer; however, the correlations between SLC9A9 and ESCC prognosis are unclear. The aim of this study is to evaluate the expression and prognostic significance of SLC9A9 in resectable ESCC. Fresh frozen or paraffin-embedded samples were collected from 167 or 59 patients with resectable ESCC, respectively. The expression of SLC9A9 was assessed by reverse transcription and quantitative real-time polymerase chain reaction analysis (167 patients) and immunohistochemistry (61 patients). The expression of SLC9A9 was not associated with patient clinicopathological characteristics at both transcription and protein levels. The 5-year overall survival in the high SLC9A9 messenger RNA (mRNA) group (n = 106) was poorer than that in the low expression group (n = 61) (34.6 vs. 65.9 %, P < 0.001). Notably, higher SLC9A9 protein expression was also correlated with lower 5-year overall survival (33.1 vs. 66.5 %, P = 0.023). Moreover, multivariate analysis revealed that SLC9A9 mRNA (HR, 2.41; 95 % CI, 1.47-3.97; P = 0.001) and protein (HR, 2.31; 95 %CI, 1.06-5.02; P = 0.034) were independent prognostic factors. In conclusion, the expression of SLC9A9 can be a prognostic predictor for ESCC.

A clinical trial of multiple peptides vaccination for advanced head and neck cancer patients induced immune responses and prolonged OS

A phase II clinical trial for head and neck squamous cell cancer (HNSCC) patients using multiple peptides vaccine derived from tumor-associated antigens (TAAs) was performed. The therapy was well tolerated and overall survival was statistically significantly longer in vaccinated patients, and the patients exhibiting cytotoxic T lymphocytes (CTL) responses to multiple peptides exhibited better prognosis.

Associations of PI3KR1 and mTOR Polymorphisms with Esophageal Squamous Cell Carcinoma Risk and Gene-Environment Interactions in Eastern Chinese Populations

Single nucleotide polymorphisms (SNPs) in the PI3K/PTEN/AKT/mTOR signaling pathway may contribute to carcinogenesis. We genotyped five potentially functional PIK3R1 and mTOR SNPs in 1116 esophageal squamous cell cancer (ESCC) patients and 1117 cancer-free controls to assess their associations with ESCC risk. We observed no association with ESCC risk for any of the selected SNPs. However, the combined analysis of these SNPs revealed that subjects with one-to-three risk genotypes had an increased ESCC risk. Stratified analysis by body mass index (BMI) found that ESCC risk was significantly associated with each of three mTOR SNPs among subjects with BMI < 25.0. Specifically, we found that subjects carrying ≥ 1 risk genotypes had significantly increased ESCC risk, particularly for males, ever-smokers, ever-drinkers, and those with age > 60, or BMI < 25.0. Moreover, three mTOR haplotypes were associated with an increase in ESCC risk. Our meta-analysis of mTOR rs2295080 and cancer risk provided further evidence that mTOR SNPs might modulate cancer susceptibility. In this population, such risk effects might be modified by other risk factors, highlighting the importance of gene-environment interaction in esophageal carcinogenesis. Additional, larger studies are warranted to validate our findings.

Evaluation of Combined Argon Plasma Coagulation and Savary Bougienage for the Relief of Anastomotic-Stenosis after Esophageal Squamous Cancer Surgery

Background: Several endoscopic dilation techniques have been reported for treatment of anastomotic-stenosis of esophageal cancer, but the high incidence of dysphagia has remained unchanged. The aim of this study was to compare the effect of Argon Plasma Coagulation (APC) combined with Savary Bougienage (SB) compared to APC alone or SB alone for anastomotic-stenosis after radical operation for squamous cell carcinoma of the esophagus. Methods: Patients with anastomotic-stenosis that was diagnosed for the first time following esophageal squamous cell carcinoma resection surgery were randomly assigned to undergo APC combined with SB, APC alone, or SB alone. Primary endpoints were the dysphagia-free survival (DFS defined as the time from first dilatation of effectively relieved dysphagia to dysphagia relapse expressed in days) after 6 months of follow up. Results: A total of 90 patients from the Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology were entered into the study (APC group, n = 30, SB group, n = 30, combination group [APC combined with SB], n = 30). Primary endpoints: 6 months after treatment, DFS of combination group (115.63 days; 95% CI, 105.31-125.95) was significantly longer than the APC alone group (39.53 days; 95% CI, 35.95-43.11, p = 0.000) and the SB alone group (16.93 days; 95% CI, 15.01-18.84, p = 0.000). No severe complications occurred within the three treatment groups. Conclusions: APC combined with SB was a safe and well-tolerated method for relieving dysphagia of esophageal squamous cell cancer patients with anastomotic-stenosis. (Registered with randomized controlled trials, ChiCRT, registration number ChiCTR-TRC-13003757.)

The prognostic value of squamous cell carcinoma antigen for predicting tumor recurrence in cervical squamous cell carcinoma patients.

ObjectiveThe aim of this study was to evaluate the prognostic value of squamous cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting recurrence in cervical squamous cell carcinoma patients with complete remission after primary treatment.MethodsWe reviewed the records of 783 cervical squamous cell cancer patients who underwent primary therapy and showed complete remission at our institution between January 2000 and April 2014. A receiver operating characteristic curve was used to determine the optimal SCC-Ag threshold to predict recurrence. Cox regression model for disease free survival was used to assess differences in outcome.ResultsThe median follow-up period was 41.2 months, and 154 patients (19.7%) had recurrent disease. The median pretreatment and posttreatment SCC-Ag level was 2.6 ng/mL (range, 0.1 to 532.0 ng/mL) and 0.7 ng/mL (range, 0.0 to 46.8 ng/mL), respectively. Both pretreatment and posttreatment SCC-Ag levels were higher in the recurrence group (P=0.017 and P=0.039). Optimal cut-off value of pretreatment and posttreatment SCC-Ag for predicting recurrence was 1.86 ng/mL (area under the curve, 0.663; P=0.000), and 0.9 ng/mL (area under the curve, 0.581; P=0.002), respectively. In the multivariate Cox regression model, pretreatment SCC-Ag >1.86 ng/mL (odds ratio, 2.11; 95% confidence interval, 1.38 to 3.22; P=0.001) and posttreatment SCC-Ag >0.9 ng/mL (odds ratio, 1.64; 95% confidence interval, 1.18 to 2.28; P=0.003) were significantly associated with poor disease free survival.ConclusionPatients with pretreatment SCC-Ag >1.86 ng/mL or posttreatment SCC-Ag >0.9 ng/mL should be considered at high risk for cancer recurrence after complete remission, and therefore, closer surveillance is needed.

O2-11-3 - Implications for the Ajcc Staging Systems on Esophageal Squamous Cell Cancer Patients Receiving Multimodality Therapy

Background: The 7th edition of the American Joint Committee on Cancer (AJCC) staging system is based on pathologic data from esophageal cancers treated by surgery alone. The objective of this study was to evaluate the prognostic impact of the pre-treatment clinical stage (cTNM) and post-treatment pathologic stage (ypTNM) on esophageal cancer patients undergoing neoadjuvant chemotherapy followed by surgery (NAC-S).Methods: Information on 235 consecutive esophageal squamous cell carcinoma patients undergoing NAC-S was reviewed. Data collected included demographics, cTNM, ypTNM, and survival. Statistical methods included the Cox regression model, Akaike information criterion (AIC) within the Cox proportional hazard regression model, and Kaplan-Meier analyses.Results: The overall three-year survival rate was 67.6%. There were significant differences between stages II and III in cTNM and ypTNM stage, respectively (P < 0.01, respectively). There were no significant survival differences between stages I and II, between stages III and IV in each TNM stage. For all patients, cN stage (cN0 vs. cN1-3), ypT stage (ypT0-2 vs. ypT3-4), and ypM stage were the better predictor of outcome for patients who underwent Neo-S than downstage or treatment effect by multivariate analysis (P < 0.05). Compared with cTNM stage, ypTNM stage has a smaller AIC value, which described the optimum prognostic stratification.Conclusions: Our study indicates that the cTNM stage of 7th edition of AJCC staging system also does not accurately predict survival in esophageal squamous cell cancer patients receiving multimodality therapy.

Predictive value of SUV-based parameters derived from pre-treatment (18)F-FLT PET/CT for short-term outcome with head and neck cancers.

The aim of this study was to investigate the predictive potential of pre-treatment 3'-deoxy-3'-[18F]-fluorothymidine (FLT) uptake parameters for short-term outcome of primary head and neck squamous cell cancer (HNSCC) patients. A total of 32 patients undergoing pre-treatment FLT positron emission tomography/computed tomography (PET/CT) from May 2010 to May 2013 were evaluated. Semi-quantitative assessment was used to determine mean, peak and maximum standardized uptake values (SUVmean, SUVpeak and SUVmax), metabolic tumor volume (MTV) and total lesion proliferation (TLP). Clinicopathologic factors and PET/CT parameters were analyzed for their association with 2-year loco-regional control (LRC) and overall survival (OS). The mean (±SD) SUVmean, SUVpeak, SUVmax, MTV and TLP were 5.97±3.16, 6.71±3.75, 10.05±5.37, 7.31±8.05 and 44.95±52.82, respectively. In univariate analyses, N category was associated with OS (P=0.037). Increased MTV ≥13ml was associated with decreased LRC and OS (P<0.0001). TLP ≥69.3g was also linked with both LRC and OS (P=0.009 and 0.015, respectively). Regarding SUVs, only the SUVpeak was associated with LRC and OS (P=0.035 and 0.049, respectively). Pre-treatment MTV is the most useful parameter with FLT PET/CT. TLP and SUVpeak may also provide important prognostic information for patients with HNSCCs.

FDG volumetric parameters and survival outcomes after definitive chemoradiotherapy in patients with recurrent head and neck squamous cell carcinoma.

The purpose of this study was to establish the predictive value of (18)F-FDG parameters for overall survival in biopsy-proven recurrent head and neck squamous cell cancer (HNSCC) patients after definitive chemoradiotherapy. We conducted a retrospective study including 34 patients with HNSCC who had biopsy-proven recurrence between April 2004 and March 2012 and underwent FDG PET/CT at our institution at the time of recurrence. Maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. The primary outcome measure was overall survival. ROC analysis, univariate and multivariate Cox regression models, and Kaplan-Meir survival curves were performed. In univariate analyses, human papillomavirus (HPV) status (p = 0.04), primary site recurrence of MTV (p = 0.03), metastasis of MTV (p = 0.02), metastasis of TLG (p = 0.02), total MTV (p = 0.002), and total TLG (p = 0.04) were significantly associated with overall survival outcome. Total MTV remained as significant independent prognostic factor when adjusted for all other covariates except for primary site recurrence SUVmax and SUVpeak and lymph node SUVmax and SUVpeak. There was a significant difference in time to survival between patients with total MTV above and below the 50th percentile (Mantel-Cox log-rank test, p = 0.05 and Gehan-Breslow-Wilcoxon test, p = 0.03) and the optimum threshold of 16.8 mL (Mantel-Cox log-rank test, p = 0.01 and Gehan-Breslow-Wilcoxon test, p = 0.01; hazard ratio [HR], 0.25). FDG PET/CT-based total MTV and clinical HPV status may be significant prognostic markers for overall survival of patients with recurrent HNSCC after definitive chemoradiotherapy.

Comparison of Quality of Life in Head and Neck Stage IV Squamous Cell Cancer Patients Treated With Surgery and Reconstruction Versus Radical Radiotherapy

This study aimed to analyze the differences in quality of life (QOL) in head and neck stage IV squamous cell cancer patients treated with surgery and reconstruction versus radical radiotherapy.The QOL was analyzed in 2 groups of patients. All patients had the same demographic and oncologic features but were treated differently. Group 1 (n = 16) was compound with patients treated with surgery and radiotherapy, whereas group 2 (n = 14) was formed with those who received radical radiotherapy. The University of Washington questionnaire was used for this purpose.A total of 30 questionnaires were received. The total score of the questionnaires ranged from 485 to 1120. The mean values were 837.8 for group 1 and 827.85 for group 2, with no statistical significance. Significant differences were found in several domains. By using a validated questionnaire, it is possible to estimate the impact in QOL of these patients.

Invited Commentary

As we collectively gain a greater understanding of the biology of cancers, the number of factors conveying prognostic significance will continue to expand and may become incorporated into the traditional TNM staging system. Histologic subtype, gene mutations, expression profiles, micro-RNAs, and single nucleotide polymorphisms are among the factors previously associated with long-term survival. Zhang and colleagues [1Zhang W. Zhu H. Liu X. et al.Epidermal growth factor receptor is a prognosis predictor in patients with esophageal squamous cell carcinoma.Ann Thorac Surg. 2014; 98: 513-520Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar] should be congratulated for the current study investigating the prognostic role of epidermal growth factor receptor (EGFR) expression among patients with esophageal squamous cell carcinoma. As new prognostic factors are evaluated, they must be interpreted in the context of our existing literature. In the current series of 441 patients, 390 (88%) were found to have pathologic T3 to T4a lesions. Despite the large number of patients with advanced T stage tumors, 213 (48%) did not have any lymph node involvement, which appears surprisingly low. The authors also indicated that patient survival could be better predicted by EGFR expression status than by T stage among patients who were pathologically node negative. This finding is impressive and needs to be validated by other studies. Importantly, the current findings are congruent with previous reports indicating the prognostic significance of EFGR expression among patients with esophageal cancer [2Gibson M.K. Abraham S.C. Wu T.T. et al.Epidermal growth factor receptor, p53 mutation and the pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemotherapy.Clin Cancer Res. 2003; 9: 6461-6468PubMed Google Scholar]. Understanding the role of EGFR in esophageal cancer progression is particularly important because of the clinical availability of EFGR targeting agents, and some have been investigated in patients with esophageal cancer. The recently published American College of Surgeons Oncology Group (ACOSOG) Z4051 trial used neoadjuvant cisplatin, docetaxel, and radiotherapy plus the EGFR inhibitor, panitumumab, to prospectively treat patients with locally advanced esophageal adenocarcinoma. A favorable pathologic complete response rate of 33.3% was observed, and an additional 20.4% had a nearly pathologic complete response, defined as less than 10% viability of malignant cells [3Lockhart A.C. Reed C.E. Decker P.A. et al.Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab plus radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051).Ann Oncol. 2014; ([Epub ahead of print])http://dx.doi.org/10.1093/annonc/mdu091PubMed Google Scholar]. Unfortunately, the induction therapy was fairly toxic and this contributed to a median survival of only 26.3 months. This was substantially lower than the survival observed in the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) trial, which used only traditional neoadjuvant chemotherapy and radiotherapy [4van Hagen P. Hulshof M.C. van Lanschot J.J. et al.Preoperative chemoradiotherapy for esophageal or junctional cancer.N Engl J Med. 2012; 366: 2074-2084Crossref PubMed Scopus (3580) Google Scholar]. Similar disappointing results were also found with EGFR inhibition in the Eastern Cooperative Oncology Group (ECOF) 2205 trial, which included the addition of cetuximab to oxaliplatin, 5-fluorouracil, and radiotherapy and in the Randomized Trial of EOC With or Without Panitumumab for Advanced and Locally Advanced Esophagogastric Cancer (REAL3) trial where panitumumab was added to standard epirubicin, oxaliplatin and capecitabine for metastatic esophageal cancer [5Kleinberg L.R. Catalano P.J. Gibson M.K. ECOG 2205: a phase II study to measure response rate and toxicity of the neo-adjuvant chemoradiotherapy (CRT)(IMRT permitted) with oxaliplatin (O) and infusional 5-fluorouracil (5FU) plus cetuximab (C225) in patients with operable adenocarcinoma of the esophagus: high risk of post-op adult respiratory distress syndrome (ARDS).Int J Radiot Oncol Biol Phys. 2010; 78: S72Abstract Full Text Full Text PDF PubMed Google Scholar, 6Waddell T.S. Chau I. Barbachano Y. et al.A randomized multicenter trial of epirubicin, oxaliplatin and cepacetabine (EOC) plus panitumumab in advanced esophagogastric cancer (REAL3).J Clin Onocl. 2012; 30 (abst LBA4000)PubMed Google Scholar]. As the role of EFGR is further clarified in esophageal cancers, proper patient selection for targeted therapy may provide improved outcomes in this disease as it has with our current selection criteria for patients with bronchogenic adenocarcinoma. Epidermal Growth Factor Receptor Is a Prognosis Predictor in Patients With Esophageal Squamous Cell CarcinomaThe Annals of Thoracic SurgeryVol. 98Issue 2PreviewOur previous study indicated the survival rate for esophageal squamous cell cancer (ESCC) patients in stage III and positive lymph node groups with postoperative radiation therapy was significantly increased compared with surgery alone. But a predictive biomarker was needed to identify the patients who would benefit from postoperative radiotherapy. This study aims to evaluate epidermal growth factor receptor (EGFR) as an indicator to predict the prognosis of ESCC and to identify the patients who would benefit from postoperative radiotherapy. Full-Text PDF

Hyperglycemia 3 Days After Esophageal Cancer Surgery Is Associated with an Increased Risk of Postoperative Infection

PurposePostoperative hyperglycemia is associated with infectious complications after various types of surgery. Our objective was to determine whether postoperative blood glucose levels up to 1 week after highly invasive esophageal cancer surgery are associated with the incidence of postoperative infections (POIs). MethodsWe conducted a retrospective chart review of 109 consecutive thoracic esophageal squamous cell cancer patients who underwent invasive esophagectomy with thoracotomy and laparotomy. The incidence of postoperative POIs and risk factors for POIs, including postoperative blood glucose levels, were evaluated. ResultsOf the 109 patients, 37 (34.0 %) developed POIs. Clinically, 73.0 % of the POIs became evident on or after postoperative day 4 (median, 5.25 days; interquartile range, 3.00–9.25 days). On and after postoperative day 3, chronological changes in blood glucose levels were significantly different between two groups of patients with or without POIs, as indicated by repeated measures ANOVA (P = 0.006). Multivariate logistic regression analysis results showed that an increased blood glucose concentration on postoperative day 3 was a significant risk factor for POIs. ConclusionsOur findings suggested that postoperative hyperglycemia on postoperative day 3 was a predictive factor of POIs after highly invasive esophageal cancer surgery.

Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)-interreader reliability, accuracy, and survival outcomes.

There has been no established qualitative system of interpretation for therapy response assessment using PET/CT for head and neck cancers. The objective of this study was to validate the Hopkins interpretation system to assess therapy response and survival outcome in head and neck squamous cell cancer patients (HNSCC). The study included 214 biopsy-proven HNSCC patients who underwent a posttherapy PET/CT study, between 5 and 24 wk after completion of treatment. The median follow-up was 27 mo. PET/CT studies were interpreted by 3 nuclear medicine physicians, independently. The studies were scored using a qualitative 5-point scale, for the primary tumor, for the right and left neck, and for overall assessment. Scores 1, 2, and 3 were considered negative for tumors, and scores 4 and 5 were considered positive for tumors. The Cohen κ coefficient (κ) was calculated to measure interreader agreement. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier plots with a Mantel-Cox log-rank test and Gehan Breslow Wilcoxon test for comparisons. Of the 214 patients, 175 were men and 39 were women. There was 85.98%, 95.33%, 93.46%, and 87.38% agreement between the readers for overall, left neck, right neck, and primary tumor site response scores, respectively. The corresponding κ coefficients for interreader agreement between readers were, 0.69-0.79, 0.68-0.83, 0.69-0.87, and 0.79-0.86 for overall, left neck, right neck, and primary tumor site response, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the therapy assessment were 68.1%, 92.2%, 71.1%, 91.1%, and 86.9%, respectively. Cox multivariate regression analysis showed human papillomavirus (HPV) status and PET/CT interpretation were the only factors associated with PFS and OS. Among the HPV-positive patients (n = 123), there was a significant difference in PFS (hazard ratio [HR], 0.14; 95% confidence interval, 0.03-0.57; P = 0.0063) and OS (HR, 0.01; 95% confidence interval, 0.00-0.13; P = 0.0006) between the patients who had a score negative for residual tumor versus positive for residual tumor. A similar significant difference was observed in PFS and OS for all patients. There was also a significant difference in the PFS of patients with PET-avid residual disease in one site versus multiple sites in the neck (HR, 0.23; log-rank P = 0.004). The Hopkins 5-point qualitative therapy response interpretation criteria for head and neck PET/CT has substantial interreader agreement and excellent negative predictive value and predicts OS and PFS in patients with HPV-positive HNSCC.

Epidermal Growth Factor Receptor Is a Prognosis Predictor in Patients With Esophageal Squamous Cell Carcinoma

Our previous study indicated the survival rate for esophageal squamous cell cancer (ESCC) patients in stage III and positive lymph node groups with postoperative radiation therapy was significantly increased compared with surgery alone. But a predictive biomarker was needed to identify the patients who would benefit from postoperative radiotherapy. This study aims to evaluate epidermal growth factor receptor (EGFR) as an indicator to predict the prognosis of ESCC and to identify the patients who would benefit from postoperative radiotherapy. Tissue samples were collected from our previous randomized study: 243 in the surgery alone group and 198 in the surgery plus radiotherapy group. Expression of EGFR was analyzed by immunohistochemical staining. The expression of EGFR is correlated with depth of tumor invasion (p=0.005), lymph node metastasis (p<0.001), and pathologic stage (p<0.001). The survival rate of patients with high EGFR expression is significantly lower than that of patients with low EGFR expression (p=0.000). Notably, in stage IIA cases, the 5-year survival rate is 57.6% in the low EGFR expression group and 36.6% in the high expression group (p=0.020). EGFR is one of the independent variants that influence the prognosis. Moreover, for high EGFR expression patients the survival rate of the surgery plus radiotherapy group is higher than that of the surgery alone group (p=0.034). Expression of EGFR can be a prognostic predictor for ESCC. Patients with high expression of EGFR may benefit from postoperative radiation therapy.