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.     

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.     

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.     

Is the Outcome of a Salvage Surgery for T4 Thoracic Esophageal Squamous Cell Carcinoma Really Poor?

Background

Among patients with T4 thoracic esophageal squamous cell carcinoma (TESCC), it is unclear whether the outcomes of late responders who undergo high-dose chemoradiotherapy (CRT) followed by salvage esophagectomy differs from those of early responders who undergo low-dose CRT followed by esophagectomy.

Methods

A total of 153 patients with T4 TESCC were treated with CRT. The first evaluation was performed after 40 Gy of CRT for downstaging. Of these, 28 patients could be downstaged, and underwent subsequent surgery (early responders). For the remaining patients, additional CRT was administered, and patients were re-evaluated after treatment and underwent salvage surgery. In total, 40 patients (early + late responders) were analyzed.

Results

The primary tumors exhibited a grade 3 response in six (21.4 %) of the early responders and two (16.7 %) of the late responders (p = 1.000). The rate of residual tumor in the primary tumor was 80 % (32/40 patients). The proportions of resected lymph nodes and positive metastatic nodes were similar between early and late responders (p = 0.406 and p = 0.859, respectively). The 5-year overall survival rates among the early and late responders were 25.9 and 36.5 %, respectively, and the median survival times were 24.8 and 24.3 months (p = 0.925), respectively. The 5-year cause-specific survival rates in the early and late responder groups were 61.5 and 72.9 % (p = 0.425), respectively.

Conclusion

The outcomes of both early and late responders to CRT were similar, and salvage surgery for T4 TESCC outweighs the risks in patients with T4 TESCC.     

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.     

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.

     

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.     

Outcome Standards for an Organ Preservation Strategy in Stage II and III Rectal Adenocarcinoma after Neoadjuvant Chemoradiation

Background

Neoadjuvant chemoradiotherapy is the standard of care for patients with locally advanced mid and distal rectal cancer. Tumor regression is variable, and this study was designed to evaluate the pathological response and impact on long-term disease control in responders and nonresponders.

Methods

A total of 303 consecutive patients with cStage II and III mid and distal rectal adenocarcinoma were identified. The mean age was 64 years and 63% were men. Patients received neoadjuvant chemoradiotherapy (45 Gy) with a continuous infusion of 5-fluorouracil. Total mesorectal excision (TME) was performed after an interval of 6–8 weeks. Tumors were stratified as responders (ypT0 or ypT1) and nonresponders (≥ypT3). All ypT2 were separately categorized.

Results

Tumors of 84 patients were classified as responders (27.5%) versus nonresponders in 144 patients (47.5%). Pathological tumor stage was ypT2 in 75 patients (25%). After a median follow-up of 55 months, the 5-year cancer-specific survival rate was 98% and the disease-free survival rate was 91% in responders versus 82% (P < 0.0025) and 60% (P < 0.0001), respectively, for the nonresponders.

Conclusions

After neoadjuvant chemoradiotherapy and TME surgery for locally advanced rectal cancer and complete or near-complete pathological tumor response oncological outcome is very good. These results set the standards for a rectum-sparing strategy.     

Selective Lateral Pelvic Lymph Node Dissection in Patients with Advanced Low Rectal Cancer Treated with Preoperative Chemoradiotherapy Based on Pretreatment Imaging

Background

The significance of lateral pelvic lymph node (LPLN) metastasis in advanced low rectal cancer treated with preoperative chemoradiotherapy (CRT) remains unclear. The objective of this study was to evaluate the outcomes of selective LPLN dissection (LPLD) based on the pretreatment imaging in patients with advanced low rectal cancer treated with preoperative CRT.

Methods

We reviewed 127 consecutive patients with clinical stage II–III low rectal cancer below the peritoneal reflection who underwent preoperative CRT and curative resection. LPLD was performed in patients with suspected LPLN metastasis based on MDCT or MRI before CRT (LPLD group, N = 38), and only total mesorectal excision (TME) was performed in patients without suspected LPLN metastasis (TME group, N = 89). Clinical characteristics and the oncological outcome were compared between groups.

Results

The median tumor-to-anal verge distance was 40 mm in both groups. The median maximum long-axis LPLN diameter before CRT was 0 mm in the TME group and 10.5 mm in the LPLD group. Pathological LPLN metastasis was confirmed in 25 patients (66 %) in the LPLD group. Local recurrence at LPLN developed in 3 patients (3.4 %) in the TME group and in none (0 %) of the LPLD group. Multivariate analysis showed that only ypN was an independent prognostic factor for relapse-free survival (RFS), but LPLN metastasis was not associated with poor RFS.

Conclusions

The incidence of LPLN metastasis is high even after preoperative CRT, and LPLD might improve local control and survival of patients with LPLN metastasis in advanced low rectal cancer treated with preoperative CRT.     

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.     

Circulating Cell-Free DNA: A Promising Marker of Pathologic Tumor Response in Rectal Cancer Patients Receiving Preoperative Chemoradiotherapy

Purpose

The circulating cell-free DNA (cfDNA) in plasma has been reported to be a marker of cancer detection. The aim of this study was to investigate whether the cfDNA has a role as response biomarker in patients receiving preoperative chemoradiotherapy (CRT) for rectal cancer.

Methods

Sixty-seven patients (median age 61 years; male/female 42/25) who underwent CRT for rectal cancer were evaluated. After tumor regression grade (TRG) classification was made, the patients were classified as having disease that responded (TRG 1–2) and that did not respond (TRG 3–5) to therapy. Plasma samples were obtained from patients before and after CRT. The cfDNA levels were analyzed by quantitative real-time polymerase chain reaction of β-globin. On the basis of the Alu repeats, the cfDNA was considered as either total (fragments of 115 bp, Alu 115) or tumoral (fragments of 247 bp, Alu 247). The association between the pre- or post-CRT levels and between variations during CRT of the Alu 247, Alu 115 repeat, and Alu 247/115 ratio (cfDNA integrity index) and the pathologic tumor response was analyzed.

Results

The baseline levels of cfDNA were not associated with tumor response. The post-CRT levels of the cfDNA integrity index were significantly lower in responsive compared to nonresponsive disease (P = 0.0009). Both the median value of the Alu 247 repeat and the cfDNA integrity index decreased after CRT in disease that responded to therapy (P < 0.005 and P < 0.005, respectively) compared to disease that did not respond to therapy (P = 0.83 and P = 0.726, respectively). The results of the multivariable logistic regression analysis showed that only the cfDNA integrity index was significantly and independently associated with tumor response to treatment.

Conclusions

The plasma levels of the longer fragments (Alu 247) of cfDNA and the cfDNA integrity index are promising markers to predict tumor response after preoperative CRT for rectal cancer.     

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.     

Volume of Resected Stomach as a Predictor of Excess Weight Loss After Sleeve Gastrectomy

Background

Laparoscopic sleeve gastrectomy (LSG) is gaining popularity for the treatment of obesity. The objective of this study was to evaluate the volume of the resected stomach (VRS) as a predictor of the percentage of excess weight loss (%EWL) 1 year after LSG.

Methods

This was a single-surgeon study of prospectively collected data of patients who underwent LSG at Jordan University Hospital (February 2009 to February 2012). The VRS was measured using a standardized technique. The %EWL was calculated at 3, 6, and 12 months postoperatively. The correlation between the VRS and %EWL was statistically evaluated.

Results

Ninety patients underwent LSG during the study period. Of these, 73 patients (57 female) completed at least 1 year of follow-up and were analyzed; their body mass index was 45?±?7.6 kg/m² (33–81). The VRS was 1,337.4?±?435.2 ml (600–2,800). The %EWL was 33.6?±?11.1 % at 3 months, 48.6?±?15.5 % at 6 months, and 56.8?±?18.9 % at 12 months. A significant correlation was observed between the VRS and %EWL at 1 year (p?=?0.003). Patients with a VRS of >1,100 ml (n?=?43) achieved significantly greater %EWL at 12 months than did those with a VRS of ≤1,100 (n?=?30). Removal of >1,100 ml of gastric volume was associated with a sensitivity and specificity of 75.5 and 46.2 %, respectively, for achieving a %EWL of ≥50 %.

Conclusion

The VRS can be used as an indicator of excess weight loss 1 year after LSG.     

Different Recurrence Pattern After Neoadjuvant Chemoradiotherapy Compared to Surgery Alone in Esophageal Cancer Patients

Purpose

To evaluate the rate and pattern of recurrences after neoadjuvant chemoradiotherapy (CRT) in esophageal cancer patients.

Methods

We described survival and differences in recurrences from a single center between neoadjuvant CRT (carboplatin/paclitaxel and 41.4 Gy) and surgery alone for the period 2000–2011. To reduce bias, we performed a propensity score matched analysis.

Results

A total of 204 patients were analyzed, 75 treated with neoadjuvant CRT and 129 with surgery alone. The pathologic response to neoadjuvant CRT was 69 % with a complete response rate of 25 %. After matching, baseline characteristics between the groups (both n = 75) were equally distributed. The 3- and 5-year disease-free survival was 53 and 42 % in the neoadjuvant CRT group compared with 24 and 18 % in the surgery-alone group (P = 0.011). After 3 and 5 years’ CRT, patients had an estimated locoregional recurrence-free survival of 83 and 73 % compared with 52 and 49 % in the surgery-alone group (P = 0.015). The distant recurrence-free survival was comparable in both groups. Locoregional recurrences were located less in the paraesophageal lymph nodes in the CRT group than in the surgery-alone group, 9 versus 21 %, respectively (P = 0.041). With respect to differences in distant recurrences, we observed more skeletal recurrences in the surgery-alone group compared to CRT, 12 versus 1 % (P = 0.009).

Conclusions

The neoadjuvant CRT regimen we used offers a significant improvement in outcome, with a different recurrence pattern compared with surgery alone. This effect is probably due to both the pathologic complete response and eradication of micrometastases in CRT group.     

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.     

Pulmonary resection after chemoradiotherapy for advanced non-small cell lung cancer: the impact of presurgical radiation therapy

Purpose

Chemoradiation therapy (CRT) is recommended as standard care for stage III non-small cell lung cancer (NSCLC), but some patients experience local recurrence after the treatment. Surgical resection after CRT involves high surgical risk, but is expected to increase the curability. This study was performed to investigate the impact of presurgical CRT on the postoperative outcome, focusing especially on the effect of radiation therapy.

Methods

Twenty-six patients with stage III (N2 or T3-4) NSCLC underwent pulmonary resection after CRT. A radiation dose up to 40–70 Gy was given with concurrent chemotherapy. The morbidity, mortality and survival after surgical resection were examined.

Results

Lung resection was performed as lobectomy (73 %) or pneumonectomy (19 %). Postoperative complications occurred in 12 patients (morbidity 46.1 %). The overall 5-year survival of the entire cohort was 69.7 %. The factors associated with favorable long-term survival included a pathological complete response (CR) and mediastinal node negative condition after CRT, and microscopic complete resection.

Conclusion

Surgical resection for stage III patients after CRT may provide a survival benefit with acceptable morbidity. The surgical morbidity may be increased by prior radiation therapy, thus, surgeons should be familiar with the available countermeasures to reduce the surgical risk.     

The Usefulness of Neoadjuvant Chemoradiation Therapy for Locally Advanced Esophageal Cancer with Multiple Lymph-Node Metastases

Background

The prognosis of patients with esophageal squamous-cell cancer (ESCC) and multiple lymph-node metastases is quite poor. We examined whether neoadjuvant chemoradiation therapy (CRT) has a beneficial effect in such patients.

Methods

A total of 50 consecutive patients with T3–4 tumors and without organ metastases were prospectively enrolled. Of those patients, 20, who had four or more nodal metastases, underwent neoadjuvant CRT (CRT group), and the remaining 30 patients, who had three or fewer nodal metastases, underwent surgery alone (surgery group). CRT consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The groups’ clinical outcomes were compared.

Results

Surgery was performed in 48 patients: all enrolled patients except for 2 who had organ metastasis after CRT. In the CRT group, the number of patients with pathological complete response was observed in 8 patients (44 %), mean nodal metastases number was changed from 8.2 to 2.6 and 9 patients had pN0. The 3-year survival rate was 76 % in the CRT group (4 patients relapsed) and 68 % in the surgery group (8 patients relapsed), which is not a statistically significant difference (P = 0.61).

Conclusions

Neoadjuvant CRT is beneficial for locally advanced ESCC with four or more lymph-node metastases.     

Retrospective Evaluation of the Influence of Postoperative Tumor Marker Status on Survival and Patterns of Recurrence After Surgery for Pancreatic Cancer Based on RECIST Guidelines

Purpose

The purpose of this study was to obtain a comprehensive understanding of the impact of postoperative tumor marker (TM) normalization on survival after pancreatectomy for pancreatic carcinoma. We propose the concept of surgical RECIST based on residual tumor and TM status.

Methods

A total of consecutive patients with pancreatic carcinoma underwent pancreatectomy between August 1, 1989, and August 1, 2008. Pre- and postoperative TM values were available for 194 patients. The relationship between TM status, survival, and other clinical and demographic data was determined with univariate log-rank tests and Cox proportional hazards analysis.

Results

Postoperative TM levels remained elevated in 92 patients (47.4%; partial responders). TM levels normalized in 102 patients (52.6%; complete responders). Lymph node metastases, portal vein resection, absence of retroperitoneal clearance, residual tumor, preoperative high CA19-9, and surgical partial response were associated with decreased survival. Nodal stage (P = 0.0227) and surgical RECIST (P = 0.025) were significant predictors of survival. Partial responders had a significantly lower median survival time (P = 0.0008) and significantly higher frequency of hepatic metastasis (P = 0.0299).

Conclusions

Postresection TM normalization is a strong prognostic factor for pancreatic cancer. The efficacy of pancreatic cancer surgery should be evaluated in the context of both local clearance and serum TM kinetics.     

Prognostic Impact of Circumferential Resection Margin in Rectal Cancer Treated with Preoperative Chemoradiotherapy

Background

The circumferential resection margin (CRM) is a strong prognostic factor in rectal cancer. The purpose of this study was to investigate the relationship between CRM distance and recurrence in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy (CRT).

Methods

We analyzed data for 561 patients who underwent preoperative CRT and curative surgery for locally advanced rectal cancer between August 2001 and December 2008. CRM was divided into four groups: group 1, CRM > 2 mm; group 2, 1.1–2.0 mm; group 3, 0.1–1.0 mm; and group 4, 0 mm. We assessed the associations of CRM with local recurrence and disease-free survival.

Results

Groups 1, 2, 3, and 4 comprised 487, 36, 20, and 18 patients, respectively. The local recurrence rate was highest and the disease-free survival rate was lowest in group 4, followed by groups 3, 2, and 1. Survival was similar between groups 2 and 1. Local recurrence rates were lower in groups 3, 2, and 1 than in group 4 [hazard ratio (HR) 0.28, 95 % confidence interval (CI) 0.09–0.91, P = 0.035; HR 0.11, 95 % CI 0.03–0.46, P = 0.002; HR 0.18, 95 % CI 0.08–0.42, P < 0.0001, respectively]. Disease-free survival rates were higher in groups 3, 2, and 1 than in group 4 (HR 0.32, 95 % CI 0.13–0.75, P = 0.009; HR 0.24, 95 % CI 0.10–0.54, P = 0.001; HR 0.26, 95 % CI 0.14–0.48, P < 0.0001, respectively).

Conclusions

After preoperative CRT, CRM distance provides useful information for risk stratification in the recurrence of rectal cancer.     

Diagnostic value of 18F-FDG PET/CT for lymph node metastasis of esophageal squamous cell carcinoma

Purpose

This study investigated the diagnostic accuracy of hybrid positron-emission tomography/computed tomography (PET/CT) for lymph node (LN) metastasis of esophageal cancer. We also investigated the correlation between the size of metastatic nests and the detection by PET/CT.

Methods

Two hundred and fifty-eight patients with esophageal squamous cell carcinoma who underwent esophagectomy with two- or three-field radical lymphadenectomy were analyzed retrospectively. We compared the diagnosis of preoperative PET/CT to the postoperative histopathological examination by each anatomical field (n = 1,231) in all 258 patients. The metastatic LNs resected from PET/CT positive fields were classified as belonging to the PET/CT-N-positive group (n = 229) and those from negative fields as belonging to the PET/CT-N-negative group (n = 352). The cross-sectional areas of metastatic nests were measured in each metastatic LN.

Results

Of the 1,231 fields, 275 (22 %) were positive for metastasis, including 581 LNs from 408 regional LN stations. The sensitivity and specificity of PET/CT examined by each anatomical field were 25.8 and 97.8 %, respectively. The median area of metastatic nests was 17.7 mm² in the PET/CT-N-positive group, and 7.7 mm² in the PET/CT-N-negative group (p < 0.001).

Conclusions

A significant correlation was suggested between the nest size and detection by PET/CT. Because of its low sensitivity, PET/CT alone is insufficient to determine the surgical procedures, especially when considering reduction surgery.