Metabolic Response to Preoperative Chemotherapy Predicts Prognosis for Patients Undergoing Surgical Resection of Colorectal Cancer Metastatic to the Liver

Background

Biological characteristics of colorectal cancer liver metastases (CRCLM) are increasingly recognized as major determinants of patient outcome. The purpose of this study was to evaluate the prognostic value of metabolic response to preoperative chemotherapy as quantified by ¹⁸F-FDG positron emission tomography (PET) for patients undergoing liver resection of CRCLM.

Methods

All patients (n = 80) who had staging PET before liver resection for CRCLM at Austin Health in Melbourne between 2004 and 2011 were included. Thirty-seven patients had PET and CT imaging before and after preoperative chemotherapy. Semiquantitative PET parameters—maximum standardized uptake variable (SUV_max), metabolic tumour volume (MTV), and total glycolytic volume (TGV)—were derived. Metabolic response was determined by the proportional change in PET parameters (?SUV_max, ?MTV, ?TGV). Prognostic scores, CT RECIST response, and tumour regression grading (TRG) were also assessed. Correlation to recurrence-free (RFS) and overall survival (OS) was assessed using Kaplan–Meier survival and multivariate analysis.

Results

Semiquantitative parameters on staging PET before chemotherapy were not predictive of prognosis, whereas all parameters after chemotherapy were prognostic for RFS and OS. Only ?SUV_max was predictive of RFS and OS on multivariate analysis. Patients with metabolically responsive tumours had an OS of 86 % at 3 years vs. 38 % with nonresponsive or progressive tumours (p = 0.003). RECIST and TRG did not predict outcome.

Conclusions

Tumour metabolic response to preoperative chemotherapy as quantified by PET is predictive of prognosis in patients undergoing resection of CRCLM. Assessing metabolic response uniquely characterizes tumour biology, which may allow future optimization of patient and treatment selection.     

Acute exacerbation of interstitial lung disease with lung cancer after surgery: evaluation with 2-[18]-fluoro-2-deoxy-d-glucose positron emission tomography

Purpose

Interstitial lung disease (ILD) has been associated with primary lung cancer and an increased risk of postoperative acute exacerbation (AE). The effectiveness of 2-[18]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography (PET) for staging lung cancer is well established. This study investigates the association of FDG uptake on PET in patients with AE of ILD.

Methods

The subjects of this retrospective study were 1309 patients with lung cancer, who underwent pulmonary resection at Shizuoka Cancer Center between September, 2002 and January, 2011. ILD was diagnosed with chest computed tomography in 95 patients, 81 of whom underwent ¹⁸F-FDG PET before surgery. Six patients suffered from AE after surgery (AE group), while the remaining 75 (non-AE group) did not. We investigated the clinico-pathological findings and the results of FDG uptake on PET using the value of the I/M ratio, which is the ratio of the peak of standardized uptake value (SUV) of the ILD area to the mean SUV of the mediastinum.

Results

There was no significant difference in clinico-pathological findings, but a significance difference in the I/M ratio (P = 0.0102).

Conclusion

The FDG uptake in PET may be a predictive factor for AE of ILD in patients who have undergone lung cancer surgery.     

Positron Emission Tomography (PET) has Limited Utility in the Staging of Pancreatic Adenocarcinoma

Background

Positron emission tomography (PET) as an adjunct to conventional imaging in the staging of pancreatic adenocarcinoma is controversial. Herein, we assess the utility of PET in identifying metastatic disease and evaluate the prognostic potential of standard uptake value (SUV).

Methods

Imaging and follow-up data for patients diagnosed with pancreatic adenocarcinoma were reviewed retrospectively. Resectability was assessed based on established criteria, and sensitivity, specificity, and accuracy of PET were compared to those of conventional imaging modalities.

Results

For 123 patients evaluated 2005–2011, PET and CT/MRI were concordant in 108 (88 %) cases; however, PET identified occult metastatic lesions in seven (5.6 %). False-positive PETs delayed surgery for three (8.3 %) patients. In a cohort free of metastatic disease in 78.9 % of cases, the sensitivity and specificity of PET for metastases were 89.3 and 85.1 %, respectively, compared with 62.5 and 93.5 % for CT and 61.5 and 100.0 % for MRI. Positive predictive value and negative predictive value of PET were 64.1 and 96.4 %, respectively, compared with 75.0 and 88.9 % for CT and 100.0 and 91.9 % for MRI. Average difference in maximum SUV of resectable and unresectable lesions was not statistically significant (5.65 vs. 6.5, p?=?0.224) nor was maximum SUV a statistically significant predictor of survival (p?=?0.18).

Conclusion

PET is more sensitive in identifying metastatic lesions than CT or MRI; however, it has a lower specificity, lower positive predictive value, and in some cases, can delay definitive surgical management. Therefore, PET has limited utility as an adjunctive modality in staging of pancreatic adenocarcinoma.     

Role of the standardized uptake value of 18-fluorodeoxyglucose positron emission tomography–computed tomography in detecting the primary tumor and lymph node metastasis in colorectal cancers

Purpose

To assess the role of positron emission tomography–computed tomography (PET–CT) and multidetector-row CT (MD-CT) in detecting the primary lesion and lymph node metastasis in patients with colorectal cancers.

Methods

A collective total of 80 lesions resected from 77 patients were examined pathologically. We analyzed the significance of the standardized uptake value (SUV) and its relationship with the clinicopathologic findings of primary lesions and lymph node metastasis. The detectability of primary lesions and lymph node metastases on PET–CT images was compared with that on MD-CT images.

Results

The detectability of primary lesions was better on PET–CT images than on MD-CT images (p = 0.0023). We observed no significant differences in the SUV with respect to staging, tumor grade, lymphatic or vessel invasion, and macroscopic type; however, primary tumor size analysis revealed that tumors larger than 3 cm had a higher SUV than those smaller than 3 cm. The sensitivity of PET–CT for detecting lymph node metastasis was lower than that of MD-CT, but the specificity of PET–CT was higher than that of MD-CT.

Conclusions

The SUV of primary cancers tends to increase in proportion to tumor size. Although the value of PET–CT in detecting lymph node metastasis is limited, PET -positive lymph nodes can be considered metastatic.     

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 value of post-treatment metabolic tumor volume from <Superscript>11</Superscript>C-methionine PET/CT in recurrent malignant glioma

We investigated the diagnostic and prognostic significance of metabolic parameters from ¹¹C-methionine (MET) positron emission tomography (PET) in patients with malignant glioma. The MET-PET was examined in 42 patients who had been previously treated with adjuvant treatment for malignant glioma. Both ratios of maximal MET uptake of the tumors to those of the contralateral normal gray matter (T/N ratio) and metabolic tumor volume (MTV) were estimated in each lesion. The diagnostic performance for recurrence was investigated in all enrolled patients. A definitive diagnosis was done with pathologic confirmation or clinical follow-up. Among recurrent patients, we evaluated the prognostic value of metabolic parameters (T/N ratio and MTV) as well as clinical factors. Among 42 patients, 35 patients were revealed with recurrence. Both T/N ratios (p?=?0.009) and MTV (p?=?0.001) exhibited statistical significance to differentiate between recurrence and post-treatment radiation effect. A T/N ratio of 1.43 provided the best sensitivity and specificity for recurrence (91.4 and 100 %, respectively), and a MTV of 6.72 cm³ provided the best sensitivity and specificity (77.1 % and 100 %, respectively). To evaluate the prognostic impact, different cutoffs of MTV were examined in patients with recurrent tumor and a threshold of 60 cm³ was determined as a best cutoff value to separate the patients in two prognostic groups. Univariate analysis revealed improved overall survival (OS) for patients with Karnofsky performance scale (KPS) score ≥70 (p?<?0.001) or MTV <60 cm³ (p?=?0.049). Multivariate analysis showed that patients with KPS score ≥70 (p?<?0.001; hazard ratio?=?0.104; 95 % CI, 0.029–0.371) or MTV?<?60 cm³ (p?=?0.031; hazard ratio?=?0.288; 95 % CI, 0.093–0.895) were significantly associated with a longer OS. However, T/N ratio was not correlated with patients’ outcome. Metabolic parameters had the diagnostic value to differentiate recurrence from post-treatment radiation effect. Compared with T/N ratio, MTV was an independent significant prognostic factor with KPS score in patients with recurrent tumor. Our study had a potential to manage these patients according to prognostic information using MET-PET.     

Lymph Node Ratio May Be Supplementary to TNM Nodal Classification in Node-positive Breast Carcinoma Based on the Results of 2,151 Patients

Background

The aim of the present study was to determine how lymph node ratio (LNR; the ratio of the number of metastatic lymph nodes to the number of removed lymph nodes) can supplement the TNM nodal classification in breast carcinoma.

Methods

We retrospectively reviewed the file records of 2,151 patients.

Results

Lymph node ratio-based low- (LNR ≤ 0.20), intermediate- (LNR 0.21–0.65), and high-risk (LNR > 0.65) patient groups had significantly different disease-free survival (DFS) (P < 0.001). The DFS of patients with N1, N2, and N3 disease was significantly different (P < 0.001). When LNR and TNM nodal groupings were included together in the Cox analysis, both groupings had independent prognostic significance (P < 0.001 and P < 0.001, respectively). The most significant LNR threshold value separating patients in low-risk and high-risk groups in terms of disease recurrence was 0.20 for N1 disease (P < 0.001), 0.35 for N2 disease (P < 0.001), and 0.90 for N3 disease (P < 0.001).

Conclusions

Lymph node ratio and TNM nodal groupings show no superiority over each other in categorizing patients with node-positive breast carcinoma into prognostic groups of low-, intermediate-, and high-risk. However, LNR grouping may supplement TNM nodal classification by categorizing patients within each TNM nodal group into low-risk and high-risk groups with significantly different survival.     

Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using 18FDG-PET/CT

Background

Pathologic complete response (pCR) after neoadjuvant chemoradiation (CRT) has been observed in 15?C30% of patients with locally advanced rectal cancer (LARC). The objective of this study was to determine whether PET/CT can predict pCR and disease-free survival in patients receiving CRT with LARC.

Methods

This is a retrospective review of patients with EUS-staged T3?CT4, N?+?rectal tumors treated with CRT, who underwent pre/post-treatment PET/CT from 2002?C2009. All patients were treated with CRT and surgical resection. Standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and surgery, compared with pCR. Kaplan?CMeier estimation evaluated significant predictors of survival.

Results

Seventy patients (age 62?years; 42M:28F) with preoperative stage T3 (n?=?61) and T4 (n?=?9) underwent pre- and post-CRT PET/CT followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas the median post-CRT SUV was 4 (P?=?0.001). Patients with pCR had a lower median post-CRT SUV compared with those without (2.7 vs. 4.5, P?=?0.01). Median SUV decrease was 63% (7.5?C95.5%) and predicted pCR (P?=?0.002). Patients with a pCR had a greater time interval between CRT and surgery (median, 58 vs. 50?days) than those without (P?=?0.02). Patients with post-CRT SUV?P?=?0.03). Patients with SUV decrease ??63% had improved overall survival at median follow-up of 40?months than those without (P?=?0.006).

Conclusions

PET/CT can predict response to CRT in patients with LARC. Posttreatment SUV, %SUV decrease, and greater time from CRT to surgery correlate with pCR. Post-CRT, SUV?相似文献   

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.     

Expression of β-tubulin isotypes in urothelial carcinoma of the bladder

Purpose

Our study aims to investigate the expressions of β-tubulin isotypes and their significances in urothelial carcinoma of the bladder (UCB) as altered expression of a specific β-tubulin isotype is associated with chemoresistance and poor prognosis in other malignancies.

Materials and methods

Expression of β-tubulin isotypes was retrospectively examined in 342 UCB samples obtained from 1995 to 2010 by immunohistochemistry.

Results

TUBB1 (307/342, 89.8 %) was most frequently overexpressed in the cytoplasm of UCB cases, followed by TUBB4 (101/342, 29.5 %), TUBB2 (85/342, 24.9 %), and TUBB3 (60/342, 17.5 %). TUBB1 overexpression was associated with older age (p = 0.032), high WHO grade (p = 0.001), and advanced TNM stage (p = 0.006). High levels of TUBB2 expression were associated with high WHO grade (p < 0.001), advanced TNM stage (p < 0.001), and non-papillary growth pattern (p = 0.007). TUBB3 overexpression was related to high WHO grade (p = 0.029). In univariate and multivariate survival analyses, TUBB1 overexpression was associated with poor recurrence-free survival (RFS) rates of all cases (hazard ratio 1.98, p = 0.031) and of the patients with transurethral and/or partial resection (hazard ratio 2.12, p = 0.031). TUBB2 overexpression was correlated with a short RFS of the patients with T2–T4 stages (hazard ratio 3.48, p = 0.007). TUBB3 overexpression was related to a poor RFS of the patients undergoing radical cystectomy (hazard ratio 5.90, p = 0.002).

Conclusions

High TUBB1, TUBB2, and TUBB3 expressions are associated with unfavorable clinicopathologic factors and are independent prognostic factors for recurrence-free survival of UCB.     

BRAFV600E Mutation Analysis in Papillary Thyroid Carcinoma: Is it Useful for all Patients?

Background

The BRAF^V600E mutation has been adopted as a prognostic factor in papillary thyroid carcinoma (PTC). However, it remains unclear whether routine BRAF mutation analysis is useful in establishing a prognosis for PTC patients. In the present study we investigated BRAF mutation analysis in a large number of PTC patients with long-term follow-up.

Patients and methods

We enrolled 766 patients from our hospital who underwent initial surgery for PTC without distant metastasis at diagnosis between 1996 and 2001, and whose BRAF mutation of primary lesions could be analyzed. The average age and follow-up period were 51 years and 130 months, respectively.

Results

To date, 77 (10 %) and 37 (5 %) patients have developed lymph node and distant recurrence, respectively, and 10 (1 %) have died of PTC. The BRAF mutation was positive in 281 patients (37 %), and it had no prognostic impact on lymph node recurrence-free (LNRFS) (p = 0.700), distant recurrence-free (DRFS) (p = 0.696), and cause-specific (CSS) (p = 0.125) survival in our entire series. However, CSS of BRAF mutation-positive high-risk patients based on AMES (p = 0.030), MACIS (score >6) (p = 0.017), the UICC stage (IVa) (p = 0.021), CIH classification (Sugitani et al. Surgery 135:139–148, 2004) (p = 0.015), and our own classification system (Ito et al. World J Surg 34:2570–2580, 2010) (p = 0.010) were significantly poorer than CSS of mutation-negative high-risk patients. The BFAF mutation did not affect CSS of non-high-risk patients, although the incidence of the BRAF mutation did not significantly differ between high-risk and non-high-risk groups based on these classification systems. The BRAF mutation was not related to LNRFS and DRFS in the subsets of high-risk and non-high-risk patients.

Conclusions

BRAF mutation analysis is useful in estimating the CSS of high-risk PTC patients based on the representative classification systems. It was not related to the prognosis in non-high-risk patients, at least those living in Japan.     

Preoperative Consolidation-to-Tumor Ratio and SUVmax Stratify the Risk of Recurrence in Patients Undergoing Limited Resection for Lung Adenocarcinoma ≤2 cm

Purpose

Limited resection is an increasingly utilized option for treatment of clinical stage IA lung adenocarcinoma (ADC) ≤2 cm (T1aN0M0), yet there are no validated predictive factors for postoperative recurrence. We investigated the prognostic value of preoperative consolidation/tumor (C/T) ratio [on computed tomography (CT) scan] and maximum standardized uptake value (SUVmax) on ¹⁸F-fluorodeoxyglucose-positron emission tomography (PET) scan.

Methods

We retrospectively reviewed 962 consecutive patients who underwent limited resection for lung cancer at Memorial Sloan-Kettering between 2000 and 2008. Patients with available CT and PET scans were included in the analysis. C/T ratio of 25 % (in accordance with the Japan Clinical Oncology Group 0201) and SUVmax of 2.2 (cohort median) were used as cutoffs. Cumulative incidence of recurrence (CIR) was assessed.

Results

A total of 181 patients met the study inclusion criteria. Patients with a low C/T ratio (n = 15) had a significantly lower 5-year recurrence rate compared with patients with a high C/T ratio (n = 166) (5-year CIR, 0 vs. 33 %; p = 0.015), as did patients with low SUVmax (n = 86) compared with patients with high SUVmax (n = 95; 5-year CIR, 18 vs. 40 %; p = 0.002). Furthermore, within the high C/T ratio group, SUVmax further stratified risk of recurrence [5-year CIR, 22 % (low) vs. 40 % (high); p = 0.018].

Conclusions

With the expected increase in diagnoses of small lung ADC as a result of more widespread use of CT screening, C/T ratio and SUVmax are widely available markers that can be used to stratify the risk of recurrence among cT1aN0M0 patients after limited resection.     

Incidental Thyroid Carcinoma by FDG-PET/CT: A Study of Clinicopathological Characteristics

Background

The rising incidence of incidental thyroid carcinoma (ITC) detected during fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scanning poses a challenge to clinicians. The present study aims to critically evaluate the clinicopathological characteristics of ITC detected by FDG-PET/CT.

Methods

Among the 557 patients managed at our institution, 40 (7.2%) patients were identified as having ITC. Of these, 22 patients had their tumor detected by FDG-PET/CT (PET group) and 11 by ultrasonography (USG group). Additional bedside ultrasonography ± fine-needle aspiration (FNA) was done in all patients at their clinic visit. The clinicopathological characteristics were compared between the PET and USG groups.

Results

The PET group had significantly more patients with history of nonthyroidal malignancy (P < 0.001). Papillary carcinoma was the most common histological type in both groups. Despite having similar histological and prognostic features including tumor size, tumor multifocality, capsular invasion, extrathyroidal extension, and lymph node metastases, tumor bilaterality (or presence of contralateral tumor focus) was significantly more frequent in the PET than the USG group (P = 0.04). The tumors were also more advanced by the tumor–node–metastasis (TNM) staging system in the PET group (P = 0.021). None of the contralateral tumor foci were evident preoperatively. One patient in the USG group developed metastatic thyroid carcinoma in neck lymph nodes 28 months after thyroid resection.

Conclusion

ITC by FDG-PET/CT had higher incidence of tumor bilaterality than those detected by ultrasonography. Total thyroidectomy should be considered for ITC detected by FDG-PET/CT even for tumor size <10 mm.     

Blood Neutrophil-to-Lymphocyte Ratio is Prognostic in Gastrointestinal Stromal Tumor

Background

The immune system has been shown to play an important role in gastrointestinal stromal tumor (GIST). The neutrophil-to-lymphocyte ratio (NLR) in blood is an easily assessable parameter of systemic inflammatory response. The aim of this study was to determine whether the NLR is prognostic in GIST.

Methods

A total of 339 previously untreated patients with primary, localized GIST operated at our institution between 1995 and 2010 were identified from a prospectively collected sarcoma database. NLR was assessed preoperatively. Patients who received adjuvant imatinib treatment were excluded from the analysis (n = 64). Cox regression models were calculated and correlation analyses were performed.

Results

On univariate analysis, NLR was associated with recurrence-free survival (RFS) (P = 0.003, hazard ratio 3.3, 95 % confidence interval 1.5–7.4). Patients with a low NLR had a 1- and 5-year RFS of 98 and 91 %, compared with 89 and 76 % in those with a high NLR. The median RFS was not reached. Positive correlations were found between NLR and mitotic rate (Pearson correlation coefficient [r] = 0.15, P = 0.03), and NLR and tumor size (r = 0.36, P = 0.0001). RFS in patients with a GIST >5 cm with low NLR was significantly longer compared to patients with high NLR (P = 0.002). Flow cytometry analysis of freshly obtained GISTs revealed that neutrophils constituted a minimal percentage of intratumoral immune cells.

Conclusions

NLR is a surrogate for high-risk tumor features. Elevated blood NLR appears to represent systemic inflammation in patients with high-risk GIST.     

Is Lymph-node Ratio a Superior Predictor than Lymph Node Status for Recurrence-free and Overall Survival in Patients with Head and Neck Squamous Cell Carcinoma?

Introduction

TNM status is questioned as an exact predictor of survival in different tumour entities. Recently, lymph node ratio (LNR) has been described as a predictor of survival in patients with HNSCC. The purpose of this study was to evaluate to which degree LNR could be used as a more accurate predictor than TNM staging?

Methods

A total of 291 patients, with a follow-up of at least 3 years, were analyzed using log-rank statistic, univariate and multivariate data analyzes, and p values, for prediction of lymph node ratio on overall and recurrence-free survival.

Results

Survival differed significantly if patients were stratified for LNR. Impact of LNR on survival was significantly different even in patients with extracapsular spread. Patients with pN0 had no survival benefit compared with patients with pN1 or higher with a LNR lower than 6 %.

Conclusions

LNR is a prognostic tool in patients with a lymph node status pN0–pN2b. LNR remained significant even in patients with extracapsular spread, contrary to TNM status. With LNR, stratification for high-risk patients (higher than 6 % LNR) can be evaluated easily. We would suggest using LNR in the clinical routine.     

Impact of total PSA, PSA doubling time and PSA velocity on detection rates of 11C-Choline positron emission tomography in recurrent prostate cancer

Purpose

To evaluate the effect of total PSA (tPSA) and PSA kinetics on the detection rates of ¹¹C-Choline PET in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) or external beam radiotherapy (EBRT).

Methods

We included 185 patients with BCR after RP (PSA >0.2 ng/ml) or after EBRT (ASTRO definition). After injection of 400 MBq ¹¹C-Choline i.v., a scan was made using the ECAT HR + PET camera with CT fusion images or Siemens mCT PET/CT. Biopsy-proven histology, confirmative imaging (CT or bone scan) and/or clinical follow-up (PSA) were used as composite reference. Statistical analysis was performed using PASW Statistics 18.

Results

¹¹C-Choline PET was positive in 124/185 cases (65 %) (in 22/61 (36 %) after RP, 102/124 (82 %) after EBRT). In 79 patients a local recurrence was identified, and 45 patients showed locoregional metastases on PET/CT. In 20 cases a proven false-negative PET scan was observed. Positive PET scans were confirmed by histology in 87/124 (70 %) cases, by confirmatory imaging in 34/124 (28 %) and by clinical follow-up after salvage treatment in 3 (2 %) cases. The ROC analysis to detect a recurrence showed significant difference in area under the curve (AUC) of tPSA 0.721(p < 0.001) and PSA velocity 0.730 (p < 0.001). PSA doubling time showed no significant difference with an AUC of 0.542 (p = 0.354). Detection rates are <50 % in tPSA <2 ng/ml and/or PSA velocity <1 ng/ml/year.

Conclusions

Total serum PSA and PSA velocity have significant effect on the detection rates of ¹¹C-Choline PET/CT in men with a BCR after RP or EBRT.     

Prognostic Value of the Number and Size of Venous Invasions in pT3 Colorectal Cancer: A Prospective Observational Study

Background

Although venous invasion is reportedly a clinically useful prognostic marker for colorectal cancer, suitable grading criteria have not been established.

Objective

This prospective observational study aimed to investigate the prognostic value of the number and size of venous invasions in patients with pT3 colorectal cancer.

Methods

We recruited 139 consecutive patients with pT3 colorectal carcinomas resected between October 2001 and August 2003. We used slides of whole-tissue sections stained with Elastica van Gieson. Venous invasion was classified according to the number of veins with carcinoma infiltration per slide with most venous invasions (V-number classification): V(n)-low 0–3 and V(n)-high ≥4. Additionally, the findings were classified according to the maximal size of veins containing carcinoma infiltration (V-size classification): V(s)-low <1 mm and V(s)-high ≥1 mm. The grades of venous invasions were evaluated just after surgery.

Results

The 5-year survival rate of V(n)-low and V(n)-high were 89.9 and 59.1 %, respectively (p < 0.0001). Comparisons between overall survival curves revealed that V-number classification (but not V-size classification) had a significant prognostic value in patients with pT3 cancer, especially in stage II patients (98.2 and 64.2 %, respectively; p < 0.0001). Multivariate analysis revealed distant metastasis, age, and V-number classification (hazard ratio 3.1; p = 0.0071) as independent prognostic indicators.

Conclusions

V-number classification may be a useful prognostic system when evaluating and sub-grouping patients with pT3 colorectal cancer.     

The Prognostic Value of Lymph Node Ratio in Node-Positive Breast Cancer: A Dutch Nationwide Population-Based Study

Background

The absolute number of involved axillary lymph nodes (LNs) is considered the most important prognostic factor in breast cancer. Over the last decade, several studies indicated that the lymph node ratio (LNR) might predict outcome better than the number of positive LNs. In this study we test the applicability of earlier published LNR cutoff values and study the prognostic value of the LNR on a nationwide level.

Methods

A nationwide population-based study was performed, using data from the Netherlands Cancer Registry, including all women diagnosed with node-positive breast cancer between 1999 and 2005 (N = 25,315). Patients were divided into 3 LNR risk groups (low, ≤0.20; intermediate, 0.21–0.65; and high, >0.65). Kaplan–Meier survival analysis was performed. In order to evaluate whether LNR was associated with overall survival (OS), Cox proportional hazards modeling was used.

Results

For the entire cohort, 5- and 10-year OS rates were 78 % and 62 %, respectively. The number of positive LNs correlated with OS (5-year OS 84 %, 72 %, and 55 % for patients with 1–3, 4–9, and 10 or more positive LNs, respectively, P < .001). LNR also correlated with OS (5-year OS 86 %, 75 %, and 54 % for low-, intermediate-, and high-risk groups, respectively, P < .001). In the multivariable analysis, the risk of death increased with increasing LNR (P < .001).

Conclusions

The LNR has an important prognostic value in node-positive patients, independent of traditional clinicopathological factors. LNR should be added as an independent prognostic variable to the current staging system.     

Efficacy of Para-Aortic Lymphadenectomy in Early-Stage Endometrioid Uterine Corpus Cancer

Purpose

The objective of this study was to assess whether para-aortic lymphadenectomy has therapeutic efficacy for patients with early-stage endometrioid uterine cancer who underwent systematic pelvic lymphadenectomy.

Methods

The authors retrospectively reviewed the medical records and pathological findings of 547 patients with histologically proven FIGO stage I-II endometrioid uterine cancer, based on comprehensive surgical staging, including pelvic with or without para-aortic lymphadenectomy.

Results

Among 547 patients, 330 patients had systematic pelvic lymphadenectomy only, and 217 had systematic pelvic with para-aortic lymphadenectomy. There were no significant differences in histopathological factors in the high-risk group, even though deep myometrial invasion (p = 0.02) and lymphvascular space invasion (p = 0.01) were more common in patients who underwent systematic pelvic with para-aortic lymphadenectomy in all study populations. Within a median follow-up of 31 (range, 5–120) months, there was no significant difference in overall survival between the pelvic lymphadenectomy only and pelvic with para-aortic lymphadenectomy groups in all populations (p = 0.77), even in high-risk patients (p = 0.82). Upon multivariate analysis, patients with lymphvascular space invasion had significantly worse overall survival (odds ratio (OR) = 7.38; 95% confidence interval (CI) = 1.86–29.23; p = 0.004).

Conclusions

Although a prospective, randomized study needs to be performed for confirmation, our data suggest that the therapeutic benefit of para-aortic lymphadenectomy is uncertain in stage I and II endometrioid uterine corpus cancer, even in patients at high-risk for recurrence.