Internationale Contre Le Cancer Stage Research Articles

Notch Signaling Pathway in Pancreatobiliary Tumors.

Background and Objectives: The Notch signaling pathway plays an important role both in the development of the ductal systems of the pancreas and the bile ducts as well as in cancer development and progression. The aim of this study was to examine the expression of central proteins of the Notch signaling pathway in pancreatobiliary tumors and its influence on patient survival. Materials and Methods: We compared the receptors (Notch1, Notch4), activating splicing factors (ADAM17), and target genes (HES1) of the Notch pathway and progenitor cell markers with relevance for the Notch signaling pathway (CD44, MSI1) between pancreatic adenocarcinomas (PDAC, n = 14), intrahepatic cholangiocarcinoma (iCC, n = 24), and extrahepatic cholangiocarcinoma (eCC, n = 22) cholangiocarcinomas via immunohistochemistry and ImageJ software-assisted analysis. An Immunohistochemistry (IHC)-score was determined by the percentage and intensity of stained (positive) cells (scale 0–7) and normal and malignant tissue was compared. In the IHC results, patients’ (gender, age) and tumor (TNM Classification of Malignant Tumors, Union Internationale contre le Cancer (UICC) stages, grading, and lymphangitic carcinomatosa) characteristics were correlated to patient survival. Results: For eCC, the expression of CD44 (p = 0.043, IHC-score 3.94 vs. 3.54) and for iCC, the expression of CD44 (p = 0.026, IHC-score 4.04 vs. 3.48) and Notch1 (p < 0.001, IHC-score 2.87 vs. 1.78) was significantly higher in the tumor compared to non-malignant tissue. For PDAC, the expression of ADAM17 (p = 0.008, IHC-score 3.43 vs. 1.73), CD44 (p = 0.012, IHC-score 3.64 vs. 2.27), Notch1 (p = 0.012, IHC-score 2.21 vs. 0.64), and Notch4 (p = 0.008, IHC-score 2.86 vs. 0.91) was significantly higher in the tumor tissue. However, none of the analyzed Notch-signaling related components showed an association to patient survival. Conclusion: A significant overexpression of almost all studied components of the Notch signaling pathway can be found in the tumor tissue, however, without a significant influence on patient survival. Therefore, further studies are warranted to draw conclusions on Notch pathway’s relevance for patient survival.

Comparison of Postoperative Acute Kidney Injury Between Laparoscopic and Laparotomy Procedures in Elderly Patients Undergoing Colorectal Surgery.

Postoperative acute kidney injury (AKI) has an unfavorable impact on both short-term and long-term outcomes. The aim of this retrospective study was to compare the incidence of postoperative AKI between laparoscopic and laparotomy procedures in elderly patients undergoing colorectal surgery. Medical records of elderly (65 y and older) patients who underwent colorectal cancer surgery between May 2016 and July 2018 at our tertiary hospital were reviewed. Patients with Union Internationale Contre le Cancer (UICC) stage II and III colorectal cancer, without neoadjuvant treatment, were divided into laparoscopic procedure group and laparotomy group. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups, before and after propensity matching. Multivariable analysis was made to identify independent risk factors of AKI. In all, 285 patients met the study inclusion criteria. Postoperative AKI occurred only in 16 patients from the laparotomy group (n=212). The incidence of AKI was significantly lower in the laparoscopic procedure group (n=73) compared with the laparotomy group (0% vs. 7.5%; P=0.015). Seventy-three patients who underwent laparoscopic surgery were matched with 73 of 212 patients who underwent open surgery, by using propensity score analysis, and the incidence of AKI in the 2 groups was similar (0% vs. 8.3%; P=0.028). Multivariable analysis showed that intraoperative metaraminol dose >1 mg (odds ratio=2.742, P=0.042) is an independent risk factor for postoperative AKI. In elderly patients, the incidence of AKI after colorectal cancer surgery is lower in the laparoscopic procedure group, maybe related to hemodynamic stability and less vasoconstriction.

Correlations of UICC tumor stage and tumor regression on T2-weighted MRI sequences during definitive radiotherapy of cervical cancer.

The purpose of this study is to detect a correlation between the preradiation tumor staging and the relative volumetric regression of the primary tumor through external beam radiation therapy (EBRT). Clinical data of 32 patients with a mean age of 60±12 years treated with primary radiation therapy (RT) of cervical carcinoma were analyzed. Union Internationale Contre le Cancer (UICC) stages were T1 = 4 patients, T2 = 15 patients, T3 = 8 patients, T4 = 5 patients; N1 = 26 patients, N0 = 6 patients; and M0 = 25 patients, M1 = 7 patients. All patients received pelvic magnetic resonance imaging (MRI) before RT as well as during RT. The cervical primary tumor was delineated as gross tumor volume (ptGTV) in T2-weighted MRI sequences. We compared ptGTV reduction by stage, lymph node status, metastatic status, and grading. Mean ptGTV reduction during RT was 61.4±28.9%. T1 tumors shrank by 88.2±13.4%, T2 by 67.6±28.7%, T3 by 50.8±23.6%, and T4 by 38.7±27.2%. The difference in tumor shrinkage was statistically significant between the lower T stages and the higher T stages (p < 0.05). There was no statistical difference in the mean ptGTV before treatment in the group with lymph node metastases (LNM) (54.1±47.7 cm3) as compared to the group without LNM (76.6±52.2 cm3). Nonetheless, ptGTV shrank significantly differently: by 68.9±25.7% (N1 patients) and by 29.0±17.7% (N0 patients). No significant differences in ptGTV shrinkage were observed in M0 versus M1 and G2 versus G3 tumors. There is a correlation between mean ptGTV reduction during EBRT and tumor stages. Tumors with higher T stages shrank less under radiation treatment, and the ptGTV of N1 patients responded better than that of N0 patients.

Volumetric 18 F-FDG-PET parameters as predictors of locoregional failure in low-risk HPV-related oropharyngeal cancer after definitive chemoradiation therapy.

We sought to investigate the prognostic value of volumetric positron emission tomography (PET) parameters in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and a ≤10 pack-year smoking history treated with chemoradiation. A total of 142 patients were included. Maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of the primary tumor, involved regional lymph nodes, and total lesion were calculated. Cox proportional hazard modeling was used to evaluate associations of clinical and PET parameters with locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS). On univariate analysis, volumetric PET parameters were significantly associated with all endpoints, and 8th edition American Joint Committee on Cancer/Union Internationale Contre le Cancer staging was significantly associated with DMFS and OS. On multivariate analysis, total lesion TLG was significantly associated with LRFFS, while staging was most significantly prognostic for DMFS and OS. Volumetric PET parameters are uniquely prognostic of LRFFS in low-risk HPV-related OPSCC and may be useful for directing de-intensification strategies.

Staging of oropharyngeal carcinomas : New TNM classification as achallenge for head and neck cancer centers

The TNM (tumor, nodes, metastasis) classification is updated periodically according to the literature and international recommendations. With the 8th edition, notable changes have been developed especially with regard to oropharyngeal cancer. The modifications as well as the practicability of the classification for staging of oropharyngeal cancers are demonstrated on the basis of cases from the tumor database. The latest edition of the TNM classification realizes requirements to differentiate between human papilloma virus (HPV) positive and HPV-negative tumors during staging. Furthermore, the prognostic relevance of extranodal extension of lymph node metastases was integrated into the classification. While downstaging is performed regarding Ncategory and Union Internationale Contre le Cancer (UICC) stage in many p16-positive tumors, for p16-negative tumors, extranodal spread mostly leads to anotable upstaging. Due to limited specificity of the p16 immunostaining, the relevance of false positive results has to be underlined. Missing integration of smoking behavior, limited standardization of the extranodal extension examination technique, as well as high demands on the documentation quality should be kept in mind. Clinical trials will have to show whether deescalation strategies regarding p16-positive carcinomas are supported by the changes made in the TNM staging system. Aprospective multicenter study should examine the universal applicability, the appropriateness for all sublocations, as well as the prognostic significance of the current edition.

EGFR and Cortactin: Markers for potential double target therapy in oral squamous cell carcinoma.

Survival periods of patients following surgical therapy of oral squamous cell carcinoma (OSCC) have previously been demonstrated to decrease over recent decades. Epidermal growth factor receptor (EGFR) and Cortactin are molecular markers that are important in tumour progression and development, and interact within the EGF pathway. Although EGFR antibody therapy exists, sufficient efforts for increased survival are still lacking due to the present limited response rates. The aim of the present study was to examine the association between EGFR and Cortactin expression on survival rates of OSCC patients and to determine whether EGFR and Cortactin expression levels are associated with advanced tumor sizes and lymphnode-metastases. In total, 222 OSCC patients were included in the study. EGFR and Cortactin expression in tumor tissue was evaluated by immunohistochemistry. Cox regression was used for survival analysis. Categories were tested for associations by using cross tabs (Chi-square test). Groups were compared by the non-parametric Mann Whitney U-test. Probabilities of less than 0.05 were considered significant and significant expression of Cortactin was observed in Advanced Union Internationale Contre le Cancer stage (P=0.032), including advanced tumour stage (P=0.021) and lymph node metastasis (P=0.049). High Cortactin expression was significantly associated with poorer survival rates (P=0.037). Further Cortactin expression was not associated with extracapsular spread, however EGFR exhibited a significant association (P=0.034). Neither EGFR nor Cortactin expression was correlated to grading. EGFR and Cortactin co-expression was demonstrated to be significantly associated with poorer survival rates in OSCC patients, suggesting that identification of predictive biomarkers for adjuvant therapies are of primary concern in OSCC. In particular, efficient dual-target therapy may act as an appropriate therapy to improve survival time for patients at advanced OSCC tumor stages.

Clinicopathological Characteristics of Young Patients With Pancreatic Cancer: An Analysis of Data From Pancreatic Cancer Registry of Japan Pancreas Society.

The aim of this study was to determine the characteristics of patients with pancreatic ductal adenocarcinoma younger than 40 years. Data from the Japan Pancreas Society's nationwide Pancreatic Cancer Registry were analyzed retrospectively. Clinicopathological characteristics were compared in patients who were grouped according to age, namely, younger than 40 years versus 40 years and older. Of the 36 145 patients in the database, the younger group included 526 (1.5%) patients. A family history of pancreatic cancer was not more frequent in the younger group. The frequency of Union Internationale Contre le Cancer T4 and M1 were both significantly higher in younger patients, resulting in a higher percentage of patients with Union Internationale Contre le Cancer stage IV. Pancreatectomy was performed less frequently in the younger group, and R0 resection was also less frequent. The overall survival rate was significantly better in the older group, whereas in surgically resected patients, the overall survival and recurrence-free survival rates were not different between the 2 groups. Younger patients with pancreatic adenocarcinoma were more often diagnosed at advanced stages, and the overall survival rate was worse than that in older patients. Family genetic background and the prognoses of patients who underwent surgery were similar between the 2 groups.

MicroRNA-100 and microRNA-21 as markers of survival and chemotherapy response in pancreatic ductal adenocarcinoma UICC stage II.

BackgroundPancreatic ductal adenocarcinoma (PDAC) remains a highly chemoresistant tumor entity for which no reliable molecular targets exist to predict or influence the success of chemotherapy. Recently, we identified a panel of microRNAs associated with induced gemcitabine chemoresistance in human PDAC cell lines. This clinical study evaluates these microRNAs and associated molecular markers as prognostic markers of outcome in 98 PDAC patients Union Internationale Contre le Cancer (UICC) stage II undergoing curative surgery with adjuvant gemcitabine chemotherapy. The primary end points of this study are recurrence-free survival and overall survival.ResultsPoor response to chemotherapy was significantly correlated to overexpression of microRNA-21 (p = 0.029), microRNA-99a (p = 0.037), microRNA-100 (p = 0.028), and microRNA-210 (p = 0.021) in tissue samples of PDAC patients UICC stage II. Upregulation of these microRNAs was associated with a significantly shorter overall survival and recurrence-free survival (p < 0.05). Overexpression of phosphatase and tensin homolog (PTEN) (p = 0.039) and low expression of multidrug resistance (MDR)-1 (p = 0.043) and breast cancer resistance protein (BCRP)-1 (p = 0.038) were significantly correlated to improved response to adjuvant chemotherapy. Adjuvant gemcitabine treatment (p < 0.0001) and low tumor grading (p = 0.047) were correlated to better outcome. MicroRNA-100, microRNA-21, and its targets PTEN and MDR-1 were independent factors of survival in multivariate analysis.ConclusionsMultivariate survival analyses identified microRNA-21 and microRNA-100 as unfavorable prognostic factors in resected and adjuvant treated PDAC UICC stage II patients.

Survival in patients with colorectal cancer diagnosed by screening colonoscopy

In Germany, screening colonoscopy was first established in 2002 as part of the national cancer screening program. To evaluate whether colorectal cancer (CRC) survival differs when CRC is diagnosed by screening colonoscopy (S-CRC) versus diagnostic colonoscopy (D-CRC). Long-term, retrospective, multicenter, observational study. Study centers: 10 private gastroenterology practices in Germany. A total of 60 patients diagnosed with CRC during screening colonoscopy and 252 patients during diagnostic colonoscopy in 2002, 2003, and2004. Colonoscopy. Survival of patients up to December2013. Mean (± standard deviation [SD]) follow-up time was 81.0 (± 40.1) months. Union Internationale Contre le Cancer (UICC) stages I and II were found more often in S-CRC (81.6%) compared with D-CRC (59.9%; P< .002). Kaplan-Meier analysis showed significantly reduced overall survival for patients with D-CRC (mean [± SD] 86.9 [± 3.0] months; 95% confidence interval [CI], 81.0-92.8) compared with S-CRC (mean [±SD] 107.1 [± 4.9] months; 95% CI, 97.4-116.9; P= .003). When deaths not related to CRC were excluded, survival was still shorter for D-CRC patients (mean [± SD] 89.4 [± 3.0] months; 95% CI, 83.5-95.4) compared with S-CRC (mean [± SD] 109.6 [± 4.7] months; 95% CI, 100.2-119.0; P= .004). Retrospective study design. In this long-term, retrospective study, patients with CRC diagnosed during screening colonoscopy lived significantly longer when compared with patients with CRC diagnosed during diagnostic colonoscopy.

Assessment of bronchial and pulmonary blood supply in non-small cell lung cancer subtypes using computed tomography perfusion.

The aim of this study was to investigate the dual blood supply of non-small cell lung cancer (NSCLC) and its association with tumor subtype, size, and stage, using computed tomography perfusion (CTP). A total of 54 patients (median age, 65 years; range, 42-79 years; 15 women, 39 men) with suspected lung cancer underwent a CTP scan of the lung tumor. Pulmonary and bronchial vasculature regions of interest were used to calculate independently CTP parameters (blood flow [BF], blood volume [BV], and mean transit time [MTT]) of the tumor tissue. The mean and maximum pulmonary and bronchial perfusion indexes (PImean and PImax) were calculated. The tumoral volume and the largest tumoral diameter were assessed. Differences in CTP parameters and indexes among NSCLC subtypes, tumor stages and tumor dimensions were analyzed using non-parametric tests. According to biopsy, 37 patients had NSCLC (22 adenocarcinomas [ACs], 8 squamous cell carcinomas [SCCs], 7 large-cell carcinomas [LCC]). The mean bronchial BF/pulmonary BF, bronchial BV/pulmonary BV, and bronchial MTT/pulmonary MTT was 41.2 ± 30.0/36.9 ± 24.2 mL/100 mL/min, 11.4 ± 9.7/10.4 ± 9.4 mL/100 mL, and 11.4 ± 4.3/14.9 ± 4.4 seconds, respectively. In general, higher bronchial BF than pulmonary BF was observed in NSCLC (P = 0.014). Using a tumoral volume cutoff of 3.5 cm, a significant difference in pulmonary PImax was found (P = 0.028). There was a significantly higher mean pulmonary BF in LCCs and SCCs compared with ACs (P = 0.018 and P = 0.044, respectively), whereas the mean bronchial BF was only significantly higher in LCCs compared with ACs (P = 0.024). Correspondingly, the PImax was significantly higher in LCCs and SCCs than in ACs (P = 0.001 for both). Differences between bronchial and pulmonary PImean and PImax among T stages and Union Internationale Contre le Cancer stages were not statistically significant (P values ranging from 0.691 to 0.753). The known dual blood supply of NSCLC, which depends on tumor size and histological subtype, is reflected in CTP parameters, with parameters depending both on tumor size and histological subtype. This has to be accounted for when analyzing NSCLC with CTP.

Peritumoral eosinophils predict recurrence in colorectal cancer

In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; P<0.001) and with the intensity of the overall inflammatory cell reaction (R=0.318; P<0.001). Both increasing peri- and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58–0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52–0.93; P=0.01)—independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising readily assessable tool and should therefore routinely be commented on in the pathology report.

Correlation of β‐catenin, but not PIN1 and cyclin D1, overexpression with disease‐free and overall survival in patients with cancer of the parotid gland

Malignant tumors of the salivary glands comprise about 3% to 5% of all head and neck carcinomas. The purpose of our study was to find possible predictive and/or prognostic markers for parotid cancer. A total of 46 tissue samples of carcinomas of the parotid gland were immunohistochemically stained for ß-catenin, cyclin D1, and PIN1. The factors were analyzed regarding their prognostic value for disease-free and overall survival. An overexpression of the cytoplasmatic ß-catenin was linked to a statistically significant worse outcome regarding disease-free (p = .0296) and overall survival (p = .0416). The 5-year overall survival was 83.9% in patients without and 0% in patients presenting with overexpression of cytoplasmatic ß-catenin. Additionally, Union Internationale Contre le Cancer (UICC) stage correlated with overall survival (p = .0306) and disease-free survival (DFS; p = .0473). Multivariate analysis showed that overexpression of cytoplasmatic ß-catenin and the UICC stage are 2 independent prognostic markers for survival in patients with parotid cancer.

Risk Factors for Patients with Stage IVB Hepatocellular Carcinoma and Extension into the Heart: Prognostic and Therapeutic Implications

PurposeTo evaluate the risk factors of hepatocellular carcinoma (HCC) extension into the right atrium (RA) and determine poor prognostic factors for HCC extension to the heart.Materials and MethodsA total of 665 patients who were newly diagnosed with HCC were analyzed retrospectively from January 2004 to July 2012. The patients were divided into two groups: 33 patients with HCC extending into the RA and 632 HCC patients during the same period. The patients with HCC extending into the RA were subdivided into shorter survival group (<2 months) and longer survival group (≥2 months).ResultsThe prevalence of HCC extending to the RA was 4.96%. In multivariate analysis, a modified Union Internationale Contre le Cancer (UICC) stage higher than IVA, hepatic vein invasion, concomitant inferior vena cava and portal vein invasion, and multinodular tumor type were risk factors for HCC extending to the RA. In multivariate analysis, Cancer of the Liver Italian Program (CLIP) score >3 (p=0.016, OR: 13.89) and active treatment (p=0.024, OR: 0.054) were associated with prognostic factors in patients HCC extending into the RA. Active treatment such as radiation (n=1), transcatheter arterial chemoembolization (TACE) (n=11), Sorafenib (n=1), and combined modalities (n=2) were performed.ConclusionModified UICC stage higher than IVA, vascular invasion and multinodular tumor type are independent risk factors for HCC extending to the RA. Active treatment may prolong survival in patients HCC extending into the RA.

Comparison of Hand-assisted Laparoscopic and Open Radical Distal Gastrectomy for Obese Patients

To evaluate the feasibility and safety of hand-assisted laparoscopic surgery for gastric cancer in obese patients, we compare the operative outcomes in obese patients who underwent hand-assisted laparoscopic distal gastrectomy (HALDG) and open distal gastrectomy (ODG). One hundred sixty-two obese patients with gastric cancer operated on in our department from January 2009 to December 2011 were divided into two groups: the open distal gastrectomy group (the ODG group) and the hand-assisted laparoscopic distal gastrectomy group (the HALDG group). Operative time, estimated blood loss, number of lymph node retrieval, wound length, times of analgesic injection, time to the first flatus, and postoperative hospital stay were compared between the two groups. Estimated blood loss, wound length, times of analgesic injection, time to the first flatus, and postoperative hospital stay were significantly less or shorter in the HALDG group than in the ODG group. There were no significant differences in tumor size, retrieved lymph nodes, American Joint Cancer Committee /Union Internationale Contre le Cancer staging, and resection margins between the two groups. Obesity should not be seen as a contraindication for HALDG. HALDG for obese patients is a safe, feasible, and oncologically sound procedure and has advantages over ODG.

Clinical Outcome of IBD-Associated versus Sporadic Colorectal Cancer: A Matched-Pair Analysis

PurposeThis study assesses the perioperative course and long-term survival of inflammatory bowel disease (IBD)-associated vs. sporadic colorectal cancer (IBD-CRC vs. SCRC) after elimination of known confounders. MethodsBetween 1991 and 2007, n = 3,299 patients underwent surgery for CRC at our institution. Thirty-three IBD patients were identified and compared to 165 SCRC using a matched-pair analysis (1:5 scenario). As matching parameters were used: age, gender, Union Internationale Contre le Cancer (UICC) stage, site of primary lesion, and date of surgery. After univariate analysis of the perioperative course, a multivariate survival analysis (Cox) of all patients (n = 198) was performed. ResultsSignificant differences were shown for preoperative symptoms (p = 0.022), transfusion rate (p = 0.01), ileostomy construction rate (p = 0.001), total complication rate (p = 0.042), and hospital stay (15 vs. 11 days, p < 0.001). Local tumor recurrence was three times higher in IBD-CRC (p = 0.004), and the 5-year survival rate was lower (49 % vs. 67 %, p = 0.03). IBD, advanced UICC stage, and synchronous liver metastasis were identified as independent prognostic factors. ConclusionWe demonstrate for the first time survival differences between IBD-CRC and SCRC after elimination of five known confounders. This might be caused by a difference in tumor biology resulting in a higher local recurrence rate in IBD-CRC.

Positron emission tomography detection of synchronous colon cancer in a patient with chronic lymphocytic leukemia

Positron emission tomography detection of synchronous colon cancer in a patient with chronic lymphocytic leukemia

Ergebnisse beim Nasopharynxkarzinom im Erwachsenenalter

Nasopharyngeal carcinoma (NPC) is a rare tumor entity in Germany in contrast to endemic countries in Asia or Africa. This retrospective study investigated patient characteristics and prognostic factors with respect to different NPC treatment strategies. A total of 63 NPC patients treated during the period 1990-2009 at the University Hospital Bonn, Germany, were included. The median age of the patients was 56.4 years, the male:female ratio was 3.2:1, 23.8% were in Union Internationale Contre le Cancer (UICC) stage I/II and 76.2% were in stage III/IV. Most of the carcinomas were WHO type III (57.1%), followed by World Health Organization (WHO) type II (33.3%) and at last WHO type I (9.6%). The 5-year overall survival rate after concomitant chemoradiotherapy (RCT) was 75% and after radiotherapy (RT) 60%. The mortality rate increased by 3.5 times with each increase in T-stage (p ≤ 0.047). The recurrence rate (RR) after RCT was 34% and after RT alone 68% (p ≤ 0.04). Tumor ablation increased the RR significantly (p ≤ 0.047). Combined chemotherapy and RT is an effective treatment of NPC disease and clearly superior to RT alone. Tumor ablation before RCT/RT worsens the prognosis and is now obsolete.

Role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 expression in gastric carcinomas

The chemokine ligand CXC chemokine ligand 16 and its receptor chemokine (C-X-C motif) receptor 6 are up-regulated in many types of cancer and give rise to more aggressive behavior by regulating proliferation and angiogenesis. To clarify the role and clinicopathologic significance of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 expression in gastric carcinoma, their expression was examined by immunohistochemistry of tissue microarrays containing gastric carcinoma and nonneoplastic mucosa, reverse transcription-polymerase chain reaction, and Western blotting and by enzyme-linked immunosorbent assay to determine the CXC chemokine ligand 16 concentration in serum. Expression was compared with the clinicopathologic features of the carcinomas. All carcinoma and epithelial cells showed CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 messenger RNA expression to various degrees. Among 28 pairs of gastric carcinoma and normal tissues, there was higher CXC chemokine ligand 16 expression in carcinoma than in adjacent mucosa (P < .05), whereas the converse was true for chemokine (C-X-C motif) receptor 6 (P < .05). Nuclear CXC chemokine ligand 16 expression correlated inversely with the depth of invasion, lymphatic invasion, Union Internationale Contre le Cancer stage, and favorable prognosis. The serum CXC chemokine ligand 16 concentration was lower in male patients or patients 55 years or older than in female or younger patients, respectively (P < .05). Patients with lymphatic invasion or mixed-type carcinoma showed lower CXC chemokine ligand 16 concentrations than those with no lymphatic invasion or with diffuse-type carcinoma (P < .05). Aberrant expression of CXC chemokine ligand 16 and chemokine (C-X-C motif) receptor 6 might be involved in gastric carcinogenesis. The expression and serum concentration of CXC chemokine ligand 16 could indicate the aggressiveness and prognosis of gastric carcinomas.

Image-Guided Hypofractionated Small Volume Radiotherapy of Non-Small Cell Lung Cancer – Feasibility and Clinical Outcome

Purpose: Local hypofractionated stereotactic radiation treatment (hfSRT) of early stage non-small cell lung cancer (NSCLC) represents a highly effective treatment alternative in medically inoperable patients. Method: Between June 2007 and December 2010, 65 patients with NSCLC were treated with image-guided hypofractionated radiotherapy. The Union Internationale Contre le Cancer (UICC) stage distribution was: IA, n = 19; IB, n = 15; IIB, n = 5; IIIA, n = 10; IIIB, n = 6; and IV, n = 10. The fractionation schedule used was 3 × 12.5 Gy (n = 36) prescribed to the encompassing 67% isodose line for peripheral primary tumours, and 8 × 6 Gy (n = 26) or 8 × 5 Gy (n = 3) prescribed to the encompassing 80% isodose line for centrally located tumours. Results: Mean follow-up was 13.8 months (range 1–41 months). Until now 6 patients developed a local recurrence, 2 of them in combination with mediastinal lymph node failure. The 1-year actuarial local control rate was 93% and overall survival 79%. Pneumonitis was seen in 14 patients (21.5%) (Common Terminology Criteria for Adverse Events (CTCAE) grade I: n = 12, and II: n = 2) after a median time period of 9.5 months. No patient developed pneumonitis of CTCAE grade III or higher. Conclusion: Image-guided hfSRT is effective and feasible in patients with non-operable NSCLC, even in higher stages, whenever local control is crucial and there are contraindications against systemic therapy.

Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy

To validate the American Thyroid Association (ATA) initial risk of recurrence scheme and the Memorial Sloan Kettering Cancer Center (MSKCC) response to therapy re-stratification approach in a large cohort of patients with differentiated thyroid cancer (DTC) treated outside of the United States. Retrospective chart review. Five hundred and six patients with DTC followed for a median of 10 years after total thyroidectomy and RAI remnant ablation at a major cancer centre in Brazil. Final clinical outcomes were assessed based on American Joint Cancer Committee (AJCC)/Union Internationale Contre le Cancer (UICC) staging, ATA risk stratification and response to therapy assessment (excellent, acceptable, biochemical incomplete and structural incomplete). The AJCC/UICC staging system did not adequately stratify patients with regard to the risk of recurrence/persistent disease. However, the ATA system demonstrated a 13% risk of recurrent/persistent disease in low-risk patients, 36% in intermediate risk patients, and 68% in high-risk patients. Furthermore, an excellent response to therapy decreased the risk of recurrent/persistent disease to 1·4%. At the time of final follow-up, 34% of the biochemical incomplete response patients had been re-classified as having no evidence of disease (NED) without having received any additional therapy beyond continue levothyroxine suppression. Conversely, even after additional therapies, only 9% of the patients with an incomplete structural response were eventually re-classified as NED. These data validate the ATA risk classification as an excellent initial predictor of recurrent/persistent disease and confirm the clinical utility of the MSKCC dynamic risk assessment system in a cohort of patients evaluated and treated outside the United States.