Evaluation of 18F-FDG-PET for Early Detection of Suboptimal Response of Rectal Cancer to Preoperative Chemoradiotherapy: A Prospective Analysis

Background

Early identification of inadequate response to preoperative chemoradiotherapy (CRT) may spare rectal cancer patients the toxicity of ineffective treatment. We prospectively evaluated tumor response with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) early in the course of preoperative CRT.

Methods

A total of 27 prospectively accrued patients with locally advanced rectal cancer (T_3–4/N₁) received preoperative CRT (5040 cGy + 5FU-based chemotherapy). Patients underwent PET scanning before and 8–14 days after commencement of CRT. Scans were interpreted using 3 standard parameters: SUV_max, SUV_avg, and total lesion glycolysis (TLG) as well as an investigational parameter: visual response score (VRS). Percent pathologic response was quantified as a continuous variable. All PET parameters were correlated with pathology. Pathologic complete/near-complete response was defined as ≥95% tumor destruction, suboptimal response as <95%. Statistical analysis was performed using the Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis.

Results

Of the 27 patients, 11 (41%) had pathologic complete/near-complete response; 16 (59%) had suboptimal response. SUV_max, SUV_avg, and TLG did not discriminate between responders and nonresponders. Visual response score (VRS) was statistically significantly higher for complete/near-complete responders than for suboptimal responders (65 vs. 33%, P = 0.02). Suboptimal responders were identified with 94% sensitivity and 78% accuracy using a VRS cut-off of 50%.

Conclusions

In this pilot study, FDG-PET at 8–14 days after the beginning of preoperative CRT was unsuccessful at predicting pathological response with enough accuracy to justify an early change in therapy.     

18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography total glycolytic volume in thymic epithelial neoplasms evaluation: a reproducible image biomarker

Introduction

¹⁸Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography is not yet accepted as a standard pretreatment evaluation of thymic epithelial neoplasm (TEN). Statistical correlation between standardized uptake value of tumor/mediastinum ratio and patients’ WHO risk class has been reported. PET metabolic tumor volume (MTV) and total glycolytic volume (TGV) have been reported as additional prognostic imaging biomarkers in several human tumors. Purpose of study was to establish whether MTV and TGV add prognostic information in TEN.

Materials and methods

A retrospective dynamic cohort study of prospectively collected data (2006–2012) on 23 consecutive patients with pathologically proven TEN (no thymic carcinoma) was conducted. All patients underwent chest CT, and PET for staging. SUV T/M ratio, semi-quantitative and volumetric analyses of TEN were calculated. Patients were categorized according to WHO classification (low-risk and high-risk thymomas). Statistical analysis was performed with bootstrap method. Multi-collinearity was established using Pearson correlation coefficient. Cut-off point for TGV was compared using Mantel Cox log rank test.

Results

SUV T/M ratio, MTV, and TGV correlate with low- and high-risk TEN. However, the statistical correlation between TGV and WHO classification (ρ = 0.897) was higher than SUV T/M ratio (ρ = 0.873). Since sample distributions were not uniformly smooth, only one cut-off value was identified: a TGV of 383 served as a cut-off value between low-risk and high-risk TEN.

Conclusion

TGV is a PET reproducible imaging marker in patients with TEN, provides prognostic information, and could be useful in pretreatment stratification of patients. Nevertheless, it needs validation in larger cohort studies.     

Early Assessment of Axillary Response with 18F-FDG PET/CT during Neoadjuvant Chemotherapy in Stage II–III Breast Cancer: Implications for Surgical Management of the Axilla

Background

If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography–computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential ¹⁸F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II–III breast cancer.

Methods

A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUV_max) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard.

Results

A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUV_max was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68–0.92) and 0.65 (95 % confidence interval 0.52–0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %—that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy.

Conclusions

¹⁸F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.     

18F-Fluorodeoxyglucose Positron Emission Tomography versus Computed Tomography in Predicting Histopathological Response to Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor Treatment in Resectable Non-Small Cell Lung Cancer

Purpose

To prospectively evaluate diagnostic computed tomography (CT) and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for identification of histopathologic response to neoadjuvant erlotinib, an epidermal growth factor receptor–tyrosine kinase inhibitor in patients with resectable non-small cell lung cancer (NSCLC).

Methods

This study was designed as an open-label phase 2 trial, performed in four hospitals in the Netherlands. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. CT and FDG-PET/CT were performed at baseline and after 3 weeks of treatment. CT was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. FDG-PET/CT, tumor FDG uptake, and changes were measured by standardized uptake values (SUV). Radiologic and metabolic responses were compared to the histopathological response.

Results

Sixty patients were enrolled onto this study. In 53 patients (22 men, 31 women), the combination of CT, FDG-PET/CT, and histopathological evaluation was available for analysis. Three patients (6 %) had radiologic response. According to European Organisation for Research and Treatment of Cancer (EORTC) criteria, 15 patients (28 %) showed metabolic response. In 11 patients, histopathologic response (≥50 % necrosis) was seen. In predicting histopathologic response, relative FDG change in SUV_max showed more SUV_max decrease in the histopathologic response group (?32 %) versus the group with no pathologic response (?4 %) (p = 0.0132). Relative change in tumor size on diagnostic CT was similar in these groups with means close to 0.

Conclusions

FDG-PET/CT has an advantage over CT as a predictive tool to identify histopathologic response after 3 weeks of EGFR–TKI treatment in NSCLC patients.     

Prognostic Value of Preoperative Metabolic Tumor Volume and Total Lesion Glycolysis in Patients with Epithelial Ovarian Cancer

Purpose

Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) uptake on PET/CT images. The purpose of this study was to investigate the relationship between functional tumor parameters (MTV and TLG) and clinical outcomes in patients with epithelial ovarian cancer (EOC).

Methods

Fifty-five patients with EOC who had undergone [¹⁸F]FDG PET/CT before surgical staging were included in this retrospectively study. For each patient, we determined the highest (SUV_max and SUV_avg), the cumulative TLG, and the sum of all MTV, and compared their predictive value of recurrence and the effects of pretreatment functional tumor activity on progression-free interval (PFI).

Results

The median duration of PFI was 11 (range 3?C43) months, and 20 patients (36.4%) experienced recurrence. Poor outcome was associated with higher values for both the MTV (P?=?0.022, hazard ratio 5.571, 95% confidence interval 1.279?C24.272) and the TLG (P?=?0.037, hazard ratio 2.967, 95% confidence interval 1.065?C8.265). The Kaplan?CMeier survival graphs showed a significant difference in PFI between the groups categorized by MTV and TLG, respectively (P?=?0.01 for MTV, P?=?0.0287 for TLG, log rank test).

Conclusions

Pretreatment metabolic parameters such as MTV and TLG showed statistically significant association with recurrence in patients with EOC. These values can be useful quantitative criteria for disease prognostication in patients with EOC before treatment.     

Molecular Imaging of Proliferation and Glucose Utilization: Utility for Monitoring Response and Prognosis after Neoadjuvant Therapy in Locally Advanced Gastric Cancer

Background

Metabolic imaging of gastric cancer is limited due to the 30% of primary tumors that are not ¹⁸F-fluorodeoxyglucose (FDG) avid. In contrast, the proliferation marker ¹⁸F-fluorothymidine (FLT) has been shown to visualize also non-FDG-avid gastric tumors. In this study we tested whether FLT-positron emission tomography (PET) can improve the predictive potential of molecular imaging for assessing response to neoadjuvant therapy in gastric cancer compared with FDG-PET.

Methods

45 patients with gastric cancer underwent FDG- and FLT-PET before and 2 weeks after initiation of chemotherapy. FDG/FLT-PET findings and Ki67 immunohistochemistry were correlated with clinical and histopathological response and survival.

Results

14 patients had non-FDG-avid tumors, whereas all tumors could be visualized by FLT-PET. No significant association of clinical or histopathological response with any of the analyzed metabolic parameters [initial standardized uptake value (SUV), SUV after 2 weeks, change of SUV for FDG/FLT] was found. Univariate Cox regression analysis for Ki67 and metabolic parameters revealed significant prognostic impact for survival only for FLT SUV_mean day 14 (p = 0.048) and Ki67 (p = 0.006). Multivariate Cox regression analysis (including clinical response, Lauren type, ypN category, and FLT SUV_mean day 14) revealed Lauren type and FLT SUV_mean day 14 as the only significant prognostic factors (p = 0.006, p = 0.002).

Conclusions

FLT uptake 2 weeks after initiation of therapy was shown to be the only imaging parameter with significant prognostic impact. Neither FLT-PET nor FDG-PET were correlated with histopathological or clinical response. However, these data must be interpreted with caution due to the single-center trial study design, relatively short follow-up, poor response rates, and unfavorable prognosis.     

Prognostic Impact of Clinicopathological Features and Expression of Biomarkers Related to 18F-FDG Uptake in Esophageal Cancer

Purpose

To analyze the association between pretreatment 18-F-fluoro-deoxyglucose (FDG) uptake and characteristics of aggressive tumor biology in predicting outcome in esophageal cancer (EC).

Methods

Tumor FDG-uptake was measured by maximum standardized uptake values (SUV_max) in 47 patients undergoing esophagectomy with curative intent. ROC analyses were used to predict an optimal SUV_max cutoff for survival. Expression of hexokinase-II (HK-II), glucose transporter I (GLUT-I), hypoxia inducible factor-1α (HIF-Iα), vascular endothelial growth factor-C (VEGF-C), p53, and proliferative activity (Ki-67) were correlated with SUV_max values and clinicopathological characteristics.

Results

A SUV_max > 3.67 predicted a significantly lower disease-free survival (DFS) and distant recurrence-free survival (p = 0.022 and p = 0.005). High HK-II expression was correlated with reduced SUV_max values (p = 0.002) and was significantly higher in esophageal adenocarcinoma compared with squamous cell carcinoma (p = 0.005). Preoperative high FDG uptake in primary tumors was associated with nodal metastases (pN1; Spearman correlation 0.39, p = 0.01). We found no positive correlation between SUV_max and GLUT-1, HK-1, HIF-Iα 1, VEGF-C, p53, and Ki-67 expression.

Conclusions

High preoperative FDG-uptake strongly predicts poor survival outcome and is associated with lymph node metastases in EC patients. HK-II expression was related to SUV_max and DFS.     

18F-FDG Uptake at Initial Staging of the Adrenocortical Cancers: A Diagnostic Tool but Not of Prognostic Value

Background

Adrenocortical carcinoma (ACC) is a rare cancer for which little level evidence exists to guide management. ¹⁸F-FDG PET (¹⁸F-fluorodeoxyglucose positron emission tomography) is an increasingly used diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In some other solid tumors, ¹⁸F-FDG PET may offer prognostic information that can guide optimal patient treatment. The aim of the present study was to evaluate whether preoperative ¹⁸F-FDG PET based on SUVs assessments has a prognostic value in ACC patients.

Methods

A retrospective analysis was performed in patients who underwent ¹⁸F-FDG PET/CT for the evaluation of ACC. Inclusion criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis available; ¹⁸F-FDG PET/CT performed prior to surgery or other treatment of the primary tumor; a minimum of 6-months follow-up for surviving patients. All ¹⁸F-FDG PET/CT procedures were reinterpreted in a blind fashion.

Results

Thirty-seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled the study criteria. Median uptake values were tumor standardized uptake values (SUV)_max = 11 (range: 3–56) and a tumor/liver SUV_max ratio = 4.2 (range: 1.3–15). Median follow-up was 20 months. Although classic risk factors (tumoral stage, Weiss score) were associated with poor outcome, there was no correlation between primary tumor FDG uptake with overall survival (OS) and disease free survival (DFS) in M0 patients and with overall survival in M1 patients. ¹⁸F-FDG uptake correlated inconsistently with sinister histological features, such as atypical mitoses or necrosis.

Conclusions

At initial staging, primary tumor FDG uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient prognosis and treatment strategy should not be based on uptake values.     

18-Fluorodeoxyglucose Positron Emission Tomography Predicts Recurrence in Resected Pancreatic Ductal Adenocarcinoma

Background

We aimed to determine whether treatment should be stratified according to 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) maximum standardized uptake values (SUV_max) in pancreatic ductal adenocarcinoma.

Methods

Patients who underwent preoperative 18F-FDG PET/CT between 2006 and 2014 (n = 138) were stratified into high (≥ 4.85) and low (< 4.85) PET groups. The clinicopathological characteristics and prognostic outcomes were analyzed retrospectively.

Results

The primary tumor SUV_max was positively correlated with preoperative CA19-9 levels (P < 0.001). The high PET group failed to achieve postoperative CA19-9 normalization (P = 0.014). Disease-specific (P < 0.001), recurrence-free (P < 0.001), liver recurrence-free (P < 0.001), and peritoneal recurrence-free (P = 0.020) survivals were significantly shorter in the high PET group. The primary tumor SUV_max was an independent predictive risk factor for liver metastasis (hazard ratio 3.46, 95% confidence interval 1.61–7.87; P = 0.001) and peritoneal recurrence (hazard ratio 3.36, 95% confidence interval 1.18–10.89; P = 0.023).

Conclusions

Surgical resection failed to achieve CA19-9 normalization in the high PET group and distant recurrence was frequent. This suggests the potential for residual cancer at distant sites, even after curative resection. Stronger preoperative systemic chemotherapy is preferred for the high PET group patients.

     

Clinical Usefulness of AJCC Response Criteria for Neoadjuvant Chemotherapy in Breast Cancer

Purpose

Recently, the American Joint Committee on Cancer (AJCC) 7th edition proposed new response criteria for neoadjuvant chemotherapy (NAC) in breast cancer. The purpose of this study was to evaluate the clinical usefulness of AJCC response criteria.

Methods

A total of 398 consecutive stage II or III breast cancer patients who received NAC were enrolled in this study. AJCC response criteria were as follows: (1) complete response (CR)—absence of invasive carcinoma in the breast and node; (2) partial response (PR)—decrease in either or both T or N stage; (3) no response (NR)—no change or increase in either or both T or N stage.

Results

Complete response, PR, and NR by AJCC criteria were 9.8, 59.3, and 30.7 %, respectively. Among the 398 patients, 337 patients were available for both paired pre- and post- breast MRI and chest CT. AJCC response criteria were significantly associated with RECIST criteria (P < 0.001). AJCC response was significantly associated with relapse-free survival (RFS) and overall survival (OS). The 5-year RFS rates were 89.6 % in CR, 74.1 % in PR, and 62.6 % in NR (P = 0.002). The 5-year OS rates were 97.4 % in CR, 88.6 % in PR, and 78.3 % in NR (P = 0.012). When adjusting potential prognostic factors, AJCC response was independently associated with RFS and OS.

Conclusions

AJCC response criteria for NAC in breast cancer have clinical usefulness in evaluating response of NAC, as well as predicting survival. AJCC response criteria can discriminate among patient subgroups with respect to survival.     

Regulatory T Cell Infiltration Predicts Outcome Following Resection of Colorectal Cancer Liver Metastases

Background

Tumor-infiltrating lymphocyte (TIL) counts in colorectal cancer liver metastases (CRCLM) predict survival following resection. While CD4 and CD8 T cells have been correlated with outcome following CRCLM resection, the role of regulatory T cells (Treg) is not well defined.

Methods

TIL in 188 patients who underwent CRCLM resection between 1998 and 2000 were analyzed by immunohistochemistry using tissue microarrays. Correlation between TIL composition and outcome was determined while controlling for established prognostic factors. Total T cells (CD3), helper T cells (CD4), cytotoxic T cells (CD8), and Treg (FoxP3) were analyzed.

Results

Median follow-up time was 40 months for all patients and 95 months for survivors. Overall survival (OS) at 5 and 10 years was 40 and 25 %, respectively. The CD4 T cell count correlated with OS (p = .02) and recurrence-free survival (p = .04). A high number of CD8 T cells relative to total T cells (CD8:CD3 ratio) predicted longer OS times (p = .05). Analysis of Treg revealed that high FoxP3:CD4 (p = .03) and FoxP3:CD8 (p = .05) ratios were independent predictors of shorter OS. Patients with a high clinical risk score (CRS) were more likely to have a high number of intratumoral Treg, and patients ≥65 years old had a less robust CRCLM T cell infiltration.

Conclusions

A high number of Treg relative to CD4 or CD8 T cells predicted poor outcome, suggesting an immunosuppressive role for FoxP3 + TIL. The intratumoral immune response was an independent predictor of outcome in patients with colorectal liver metastases.     

Discrepancy Between Recurrence-Free Survival and Overall Survival in Patients with Resectable Colorectal Liver Metastases: A Potential Surrogate Endpoint for Time to Surgical Failure

Background

Recurrence-free survival (RFS) may not be a surrogate for overall survival (OS) in patients with resectable colorectal liver metastases (CLM). We investigated whether a new composite tool—time to surgical failure (TSF)—is a suitable endpoint.

Methods

The medical records of consecutive patients who underwent curative resection for CLM at our center over a 17-year period were reviewed. Patients with liver-limited tumors (n = 371) who had not received previous treatment for metastasis were eligible for analysis. TSF was defined as the time until unresectable relapse or death. The correlations between TSF and OS, and between RFS and OS, were assessed for all the eligible patients.

Results

The median OS, TSF, and RFS were 5.7, 2.7, and 0.7 years, respectively, and the 5-year OS, TSF, and RFS rates were 52.6, 39.8, and 23.7 %, respectively, for all patients. The rates of first, second, and third relapse were 75.5, 77.6, and 70.8 %, respectively, and repeat resections were performed in 54.3 % (first relapses), 40.7 % (second relapses), and 47.1 % (third relapses) of patients. The concordance proportions of TSF and RFS for OS events were 0.83 and 0.65, respectively. The correlation between TSF and OS was stronger than that between RFS and OS in terms of the predicted probabilities.

Conclusions

The correlation between TSF and OS was stronger than that between RFS and OS after curative hepatic resection. TSF could be a suitable endpoint for CLM overall management.     

Effects of a proton pump inhibitor on the physiological accumulation of fluoro-2-deoxy-d-glucose (FDG) in FDG-positron emission tomography

Purposes

The physiological accumulation of fluoro-2-deoxy-d-glucose (FDG) is common in medical examinations of the digestive tract conducted using FDG-positron emission tomography (PET). The aim of this study was to determine the effects of a proton pump inhibitor (PPI) on the physiological FDG accumulation in the digestive tract.

Methods

A total of 130 patients examined from July 2007 to October 2008 were included in the final analysis. A PPI was administered orally prior to FDG-PET in 65 patients. The remaining 65 patients underwent FDG-PET without administration of the PPI. The assessments used visual and quantitative evaluations.

Results

Visual evaluation showed that physiological FDG accumulation in the stomach was significantly reduced (p = 0.037) in the PPI group compared with the control group. The quantitative evaluation also revealed a significant reduction in the maximum standardized uptake values (SUV_max) in the stomach in the PPI group compared with the control group (p < 0.0001). Physiological FDG accumulation in the colon showed a decreasing trend on visual evaluation in the PPI group compared with the control group, and the quantitative evaluation found a significant reduction in the physiological FDG accumulation in the colon in the PPI group (p = 0.045).

Conclusions

The oral administration of a PPI was effective for reducing the physiological accumulation of the FDG in the alimentary tract. However, based on the error associated with SUV_max measurement, a quantitative evaluation should therefore be combined with the visual evaluation.     

Perioperative complications influence recurrence and survival after resection of hepatic colorectal metastases

Background

Perioperative outcomes, such as blood loss, transfusions, and morbidity, have been linked to cancer-specific survival, but this is largely unsupported by prospective data.

Methods

Patients from a previous, randomized trial that evaluated acute normovolemic hemodilution during major hepatectomy (≥3 segments) were reevaluated and those with metastatic colorectal cancer (n = 90) were selected for analysis. Survival data were obtained from the medical record. Disease extent was measured using a clinical-risk score (CRS). Log-rank test and Cox proportional hazard model were used to evaluate recurrence-free survival (RFS) and overall survival (OS).

Results

Median follow-up was 71 months. The CRS was ≥3 in 45 % of patients; 59 % had extrahepatic procedures. Morbidity and mortality were 33 and 2 %, respectively. Postoperative chemotherapy was given to 87 % of patients (78/90) starting at a median of 6 weeks. RFS and OS were 29 and 60 months, respectively. Postoperative morbidity significantly reduced RFS (23 vs. 69 months; P < 0.001) and OS (28 vs. 74 months; P < 0.001) on uni- and multi-variate analysis; positive resection margins and high CRS also were significant factors. Delayed initiation of postoperative chemotherapy (≥8 weeks) was common in patients with complications (37 vs. 12 %; P = 0.01).

Conclusions

In this selected cohort of patients from a previous RCT, perioperative morbidity was strongly (and independently) associated with cancer-specific outcome. It also was associated with delayed initiation of postoperative chemotherapy, the impact of which on survival is unclear.     

Interval Between Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma: Does Delayed Surgery Impact Outcome?

Background

Although esophagectomy traditionally is recommended to perform within 8 weeks after neoadjuvant chemoradiotherapy (nCRT), data from neoadjuvantly treated rectal cancer patients demonstrate that delayed surgery (>8 weeks) can maximize the effect of CRT. Despite these promising data, investigators are concerned that delayed surgery may lead to tumor repopulation. We report the impact of delayed surgery in patients with esophageal cancer who were treated with nCRT.

Methods

We retrospectively studied 276 esophageal cancer patients treated with nCRT and surgery between 2002 and 2008. We compared perioperative complication, rate of pathological complete response (pCR), distribution of tumor regression grade (TRG), and overall survival (OS) in patients who underwent surgery within 8 weeks (group A) and after 8 weeks (group B) after nCRT.

Results

There were 138 patients in each group with similar pre/post-nCRT characteristics. Delayed surgery did not result in lower surgical risk or higher pCR rate. Survival outcome also did not improve following a longer surgery interval (5-year OS: group A vs. group B, 29 vs. 23 %; P = 0.3). On the contrary, a subgroup analysis showed that delayed surgery might be hazardous, especially in patients who demonstrate a good response after nCRT. The amount of residual cancer, as measured by TRG, increased significantly after a longer surgical interval (P = 0.024). Survival also decreased after a longer surgical interval (5-year OS ≤8 vs. >8 weeks, 50 vs. 35 %; P = 0.038).

Conclusions

After nCRT, esophagectomy should be performed within 8 weeks, especially in patients with good response.     

Differences in histopathological evaluation of standard lymph node dissections result in differences in nodal count but not in survival

Objective

To analyse whether the reported differences in nodal yield at pelvic lymph node dissection (PLND) for bladder cancer, between two hospitals, are reflected in the survival rates.

Patients and methods

We assessed follow-up data of all 174 patients (mean age: 62.7, median follow-up: 3 years) who underwent PLND between 1 January 2007 and 31 December 2009 at two different hospitals. PLND was performed according to a standardized template by the same urologists for comparable bladder cancer patients. Mean number of reported lymph nodes was 16 at hospital A versus 28 at hospital B. We compared the overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) between both cohorts and performed a multivariate analysis.

Results

The cumulative probability for 2-year OS, DSS and RFS for hospital A are 61, 64 and 54 %, versus 58, 58 and 53 % for hospital B, respectively. Kaplan–Meier survival curves did not reveal statistically significant differences between both groups (OS: p log-rank = 0.75, DSS: p log-rank = 0.56, and RFS: p log-rank = 0.80). Also after adjustment for pT stage and neoadjuvant chemotherapy, survival was not significantly different between hospital A and hospital B.

Conclusion

Despite differences in lymph node yield in PLND specimens, this study reveals no significant differences in survival outcomes between both hospitals. Standardized histopathological methods should be agreed upon by pathologists before integrating nodal yield and subsequent lymph node density as indicators of the quality of surgery and as prognostic factors.     

Relationship Between <Superscript>18</Superscript>F-fluorodeoxyglucose Accumulation and the <Emphasis Type="Italic">BRAF</Emphasis><Superscript>V600E</Superscript> Mutation in Papillary Thyroid Cancer

Background

To determine whether ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG)-PET/CT is useful for predicting the BRAF ^V600E mutation status of a primary papillary thyroid carcinoma (PTC).

Methods

A retrospective analysis was performed in 108 patients who underwent ¹⁸F-FDG positron emission tomography–computed tomography (PET/CT) for staging before thyroidectomy and BRAF analysis in biopsy-confirmed PTC. The maximum standardized uptake value (SUV_max) of the primary tumor was calculated according to FDG accumulation. Univariate and multivariate analyses were performed to assess the association between the SUV_max and clinicopathological variables.

Results

The BRAF ^V600E mutation was detected in 71 of 108 (65.7%) patients. In all subjects, the tumor size and BRAF ^V600E mutation were independently related to the SUV_max according to multivariate analyses (P = 0.002 and 0.007, respectively). The SUV_max was significantly higher in tumors with the BRAF ^V600E mutation than in tumors with wild-type BRAF (10.24 ± 11.89 versus 4.02 ± 3.86; P = 0.007). In the tumor size >1 cm subgroup, the BRAF ^V600E mutation was the only factor significantly associated with the SUV_max (P = 0.016). A SUV_max cutoff level of 4.9 was determined to be significant for predicting the BRAF ^V600E mutation status (sensitivity 77.4%, specificity 100.0%, area under the curve 0.929; P < 0.0001) according to ROC curve analysis.

Conclusions

The BRAF ^V600E mutation is independently associated with high ¹⁸F-FDG uptake in PTC, especially in those with a tumor size >1 cm.

     

Sinusoidal Obstruction Syndrome Impairs Long-Term Outcome of Colorectal Liver Metastases Treated with Resection after Neoadjuvant Chemotherapy

Background

Chemotherapy-induced liver injury is a considerable problem in patients undergoing surgery for colorectal liver metastases, since an increase in postoperative morbidity and mortality has been observed. We investigated whether liver damage had further implications on long-term outcome in these patients.

Materials and Methods

Liver specimens from 196 patients resected for colorectal liver metastases were evaluated for chemotherapy-associated hepatic damage in the nontumorous liver. Injury patterns were correlated with recurrence free (RFS) and overall survival (OS). Factors leading to sinusoidal injury were identified.

Results

Patients who developed grade 2 or 3 sinusoidal dilatation had a significantly shorter RFS (hazard ratio [HR] 2.05; 95% confidence interval [95% CI] 1.23–3.39, P = .005) and OS (HR 2.90; 95% CI 1.61–6.19, P < .001), compared to patients without this alteration. Those patients also had significantly more intrahepatic recurrences (66.7% vs 30.5%, P = .003). Other patterns of chemotherapy-associated liver damage (nonalcoholic steatohepatitis, fibrosis) were not associated with impaired survival. Factors indicating sinusoidal injury were oxaliplatin-based chemotherapy, tumor size >5 cm, and elevated alkaline phosphatase or gamma glutamyltransferase.

Conclusions

Sinusoidal obstruction syndrome due to oxaliplatin-based chemotherapy may not only compromise perioperative outcome, but can lead to early recurrence and decreased survival in the long term. Strategies to prevent this condition are clearly needed.     

Long-term oncologic outcomes of endoscopic stenting as a bridge to surgery for malignant colonic obstruction: comparison with emergency surgery

Background

Self-expandable metallic stents (SEMS) are now regarded as an effective and safe intervention for malignant colorectal obstruction (MCO). However, manipulation of the tumor might lead to the spillage of tumor cells and result in distant metastases. We aimed to compare the long-term oncologic outcomes of SEMS as a bridge to surgery with those of emergency surgery for MCO.

Methods

Between June 2005 and December 2011, 60 patients who underwent elective curative resection after endoscopic SEMS insertion were included in the “SEMS group”. The SEMS group was matched to 180 patients who underwent emergency curative surgery for MCO during the same period [“Emergency surgery (ES) group”]. The clinicopathologic characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between the two groups.

Results

There were no significant differences in demographics, tumor stage, location, and histology between the SEMS group and the ES group. The median follow-up times were 41.4 months (IQR, 22.2–60.0 months) for the SEMS group and 45.0 months (IQR, 20.9–68.1 months) for the ES group. The proportions of patients who received postoperative adjuvant chemotherapy were comparable (SEMS group vs. ES group, 68.3 % vs. 77.8 %; P = 0.210). The long-term prognosis did not significantly differ between two groups in either the 5-year RFS rate (79.6 % vs. 70.2 %; P = 0.218) or the 5-year OS rate (97.8 % vs. 94.3 %; P = 0.469).

Conclusions

Long-term oncologic outcomes of SEMS insertion as a bridge to surgery were comparable to those of primary curative surgery.     

Esophageal Carcinosarcoma: A Unique Entity with Better Prognosis

Background

Esophageal carcinosarcoma is a rare kind of malignancy, and how to identify the patients with poor prognosis is critical for improving treatment efficacy and survival outcome.

Methods

The clinical characteristics, pathologic features, treatments, and outcomes of esophageal carcinosarcoma were analyzed in 33 patients. Meanwhile, we hypothesized that elevated neutrophil to lymphocyte ratio (NLR) correlates with poor prognosis.

Results

Most patients had polypoid tumors, and the carcinomatous elements were squamous in all patients except one with adenosquamous carcinoma. Eight patients had elevated NLR (≥5). The median follow-up time was 39.1 (range, 0.5–178.2) months. The median overall survival time (OS) was 43.5 months, and the 1-, 3-, and 5-year OS rates were 74, 57, and 48 %, respectively. Tumor recurrence occurred in 15 patients, and the median relapse-free survival time (RFS) was 23.9 months, and the 2-year RFS rate was 50 %. For patients who received curative resection, OS and RFS were significantly associated with preoperative NLR. In the multivariate Cox regression model, higher NLR was an independent prognostic factor (P value was 0.001 for both OS and RFS).

Conclusions

Our study identified the baseline NLR to be an independently prognostic factor for curatively resected esophageal carcinosarcoma.