Clinical applications of FDG-PET in oncology

Positron emission tomography together with F-18-deoxyglucose (FDG) has emerged as a valuable clinical tool in the field of oncology. FDG-PET diagnoses, stages and restages most cancers with a high diagnostic accuracy. The effects of chemotherapy on tumour metabolism can be monitored with this whole-body technique. Recent studies have established a high prognostic accuracy of PET for predicting the clinical outcome of cancer patients. The current review addresses the role of FDG-PET for diagnosing, staging and restaging of lung cancer, colorectal cancer, lymphoma, melanoma and breast cancer staging and provides a brief outlook for future applications of clinical PET imaging.     

Complete remission of unresectable colon cancer after preoperative chemotherapy selected by adenosine triphosphate-based chemotherapy response assay

The adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is a chemosensitivity test that offers the potential of selecting cancer treatments based on the responsiveness of individual tumors. We report a case of 47-yr-old male, presented with sigmoid colon cancer with multiple liver and peritoneal metastases, in which there was a complete response for the primary colon cancer after administration of preoperative chemotherapy selected by ATP-CRA. Oxaliplatin was the most sensitive drug based on the ATP-CRA where the specimen obtained by ultrasound- guided percutaneous liver biopsy was used. After twelve cycles of oxaliplatincapecitabine chemotherapy, abdominopelvic computed tomography revealed marked shrinkage of the liver metastases and positron emission tomography showed no uptake of 18F-fluoro-deoxy-glucose (FDG) either in the liver or peritoneum except localized uptake in the sigmoid colon. The patient underwent an anterior resection and radiofrequency ablation of the liver metastases, which resulted in a macroscopic curative resection of the cancer cells. Histological examination revealed no residual cancer cells in the resected specimen of the sigmoid colon. This result suggested that preoperative chemotherapy chosen by ATP-CRA may be useful for treating advanced colon cancer with unresectable liver and peritoneal metastases.     

Fas/Fas ligand interaction in human colorectal hepatic metastases: A mechanism of hepatocyte destruction to facilitate local tumor invasion

This study demonstrates a novel role for the Fas pathway in the promotion of local tumor growth by inducing apoptotic cell death in normal hepatocytes at the tumor margin in colorectal hepatic metastases. Our results show that >85% of lymphocytes infiltrating colorectal liver cancer express high levels of Fas-ligand (Fas-L) by flow cytometry. Using immunohistochemistry of tumor tissue we showed strong Fas expression in noninvolved hepatocytes, whereas Fas-L expression was restricted to tumor cells and infiltrating lymphocytes at the tumor margin. Apoptosis was observed in 45 +/- 13% of the Fas(high) hepatocytes at the tumor margin whereas only 7 +/- 3% tumor cells were apoptotic (n = 10). In vitro, primary human hepatocytes expressed Fas receptor and crosslinking with anti-Fas antibody induced apoptosis in 44 +/- 5% of the cells compared with 4. 6 +/- 1.0% in untreated controls (P = 0.004). Both tumor-infiltrating lymphocytes (TIL) and human metastatic colon cancer cells cells are able to induce Fas-mediated apoptosis of primary human hepatocytes in coculture cytotoxic assays. TIL induced apoptosis in 47 +/- 9% hepatocytes compared with control 4.3 +/- 1. 0% (P = 0.009) and this effect was reduced by anti-human Fas-L mAb (18.7 +/- 1.3%, P = 0.009). SW620 cells induced apoptosis in 26 +/- 2% hepatocytes compared with control 5.6 +/- 1.7% (P = 0.004) and this was reduced to 11.2 +/- 1.8% (P = 0.004) in the presence of anti-human Fas-L mAb. These data suggest that the inflammatory response at the margin of colorectal liver metastases induces Fas expression in surrounding hepatocytes, allowing them to be killed by Fas-L-bearing TIL or tumor cells and facilitating the invasion of the tumor into surrounding liver tissue.     

Tissue-specific differences in 2-fluoro-2-deoxyglucose metabolism beyond FDG-6-P: a 19F NMR spectroscopy study in the rat

2-Fluoro-[(18)F]-2-deoxy-glucose (FDG) is a positron-emitting analogue of glucose used clinically in positron emission tomography (PET) to assess glucose utilization in diseased and healthy tissue. Originally developed to measure local cerebral glucose utilization rates, it has now found applications in tumour diagnosis and in the study of myocardial glucose uptake. Once taken up into the cell, FDG is phosphorylated to FDG-6-phosphate (FDG-6-P) by hexokinase and was originally believed to be trapped as a terminal metabolite. This 'metabolic trapping' of FDG-6-P forms the basis of the analysis of PET data. In this study, we have used (19)F NMR spectroscopy to investigate FDG metabolism following the injection of a bolus of the glucose tracer into the rat (n=6). Ninety minutes after the (19)FDG injection, the brain, heart, liver and kidneys were removed and the (19)FDG metabolites in each were extracted and quantified. We report that significant metabolism of FDG occurs beyond FDG-6-P in all organs examined and that the extent of this metabolism varies from tissue to tissue (degree of metabolism beyond FDG-6-P, expressed as percentage of total organ FDG content, was brain 45 +/- 3%; heart 29 +/- 2%; liver 22+/-3% and kidney 17 +/- 3%, mean +/- SEM n=6). Furthermore, we demonstrate that the relative accumulation of each metabolite was tissue-dependent and reflected the metabolic and regulatory characteristics of each organ. Such inter-tissue differences may have implications for the mathematical modelling of glucose uptake and phosphorylation using FDG as a glucose tracer.     

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium-DTPA-enhanced MRI and localized 19F MRS pharmacokinetic studies of 5-fluorouracil

Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of the drug in the tumor and by the amount of intracellular uptake, metabolic activation and catabolism, as well as other factors. The first aim of this study was to investigate the predictive value of DCE-MRI with the contrast agent Gd-DTPA for tumor response to first-line chemotherapy in patients with liver metastases of colorectal cancer. The second aim was to investigate the predictive value of 5-fluorouracil (FU) uptake, retention and catabolism as measured by localized (19)F MRS for tumor response to FU therapy. Since FU uptake, retention and metabolism may depend on tumor vascularization, the relationship between (19)F MRS and the DCE-MRI parameters k(ep), K(trans) and v(e) was also examined (1). In this study, 37 patients were included. The kinetic parameters of DCE-MRI, k(ep), K(trans) and v(e), before start of treatment did not predict tumor response after 2 months, suggesting that the delivery of chemotherapy by tumor vasculature is not a major factor determining response in first-line treatment. No evident correlations between (19)F MRS parameters and tumor response were found. This suggests that in liver metastases that are not selected on the basis of their tumor diameter, FU uptake and catabolism are not limiting factors for response. The transfer constant K(trans), as measured by DCE-MRI before start of treatment, was negatively correlated with FU half-life in the liver metastases, which suggests that, in metastases with a larger tumor blood flow or permeability surface area product, FU is rapidly washed out from the tumor.     

Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer

BACKGROUND: Two years after undergoing resection of liver metastases from colorectal cancer, about 65 percent of patients are alive and 25 percent are free of detectable disease. We tried to improve these outcomes by treating patients with hepatic arterial infusion of floxuridine plus systemic fluorouracil after liver resection. METHODS: We randomly assigned 156 patients at the time of resection of hepatic metastases from colorectal cancer to receive six cycles of hepatic arterial infusion with floxuridine and dexamethasone plus intravenous fluorouracil, with or without leucovorin, or six weeks of similar systemic therapy alone. Patients were stratified according to previous treatment and the number of liver metastases identified at operation. The study end points were overall survival, survival without recurrence of hepatic metastases, and survival without any metastases at two years. RESULTS: The actuarial rate of overall survival at two years was 86 percent in the group treated with local plus systemic chemotherapy and 72 percent in the group given systemic therapy alone (P=0.03). The median survival was 72.2 months in the combined-therapy group and 59.3 months in the monotherapy group, with a median follow-up of 62.7 months. After two years, the rates of survival free of hepatic recurrence were 90 percent in the monotherapy group and 60 percent in the monotherapy group (P<0.001), and the respective rates of progression-free survival were 57 percent and 42 percent (P=0.07). At two years, the risk ratio for death was 2.34 among patients treated with systemic therapy alone, as compared with patients who received combined therapy (95 percent confidence interval, 1.10 to 4.98; P=0.027), after adjustment for important variables. The rates of adverse effects of at least moderate severity were similar in the two groups, except for a higher frequency of diarrhea and hepatic effects in the combined-therapy group. CONCLUSIONS: For patients who undergo resection of liver metastases from colorectal cancer, postoperative treatment with a combination of hepatic arterial infusion of floxuridine and intravenous fluorouracil improves the outcome at two years.     

The clinical relevance of cytokeratin phenotyping in needle biopsy of liver metastasis

Although cytokeratin (CK) phenotyping of metastatic tumors is now routine in many laboratories, the clinical relevance of the procedure has seldom been addressed. We carried out a prospective clinical study of 134 consecutive cases of metastatic adenocarcinoma of the liver diagnosed by needle biopsies stained routinely for CK20 and CK7. The most probable localization of the primary tumor, deduced from this staining pattern, was stated in the original pathology report. The present study compared this assignment with the information available at the time of interpretation of the liver biopsy, to the results of the subsequent clinical investigation, and to the officially reported cause of death as outcome. As expected, the primary tumors were localized in the colon or in the rectum in 85% (34/40) of the CK20+/CK7- metastases. The definite diagnosis remained metastatic colorectal carcinoma in 83% (15/18) of the cases with diagnosed colorectal cancer before the liver biopsy. In the cases without a known primary tumor when the liver biopsy was interpreted, primary colorectal localization was accurately predicted in 86% (19/22) of the patients. Compared to the outcome, 77% (36/47) of the CK20+/CK7+ metastases had the expected pancreaticobiliary primary localization in 83% (30/36) without any primary tumor being known at the time of interpretation of the liver biopsy. In contrast, the majority of CK20- metastatic carcinomas had an unexpected primary localization, 50% (16/32) in the CK20-/CK7+ and 60% (9/15) in the CK20-/CK7- subgroup. In addition, the origin of the liver metastasis remained unknown in 37% (12/32) of CK20-/CK7+ cases. Thus, the CK20+/CK7- phenotype indicates a colorectal origin of the liver metastasis with considerable accuracy and independently of the available clinical information. The same is true for CK20+/CK7+ metastases, which indicate primary tumor localization in the pancreas or in the biliary tree. The results in the CK20- subgroups of the liver metastases are disappointing and cannot substantially help the clinical investigation.     

Utility of F-18 fluorodeoxyglucose pos?tron em?ss?on tomography/computed ?n carc?noma of unknown primary

Carcinoma of unknown primary (CUP) is a heterogeneous group of tumors with various clinical features causing diagnostic and therapeutic challenges. The aim of this study was to evaluate the ability of F-18 FDG PET/CT for localizing the primary tumor, disclosing additional metastases, and changing the treatment in patients with CUP. One hundred and twelve metastatic patients (female = 40, male = 72, median age = 60.5 years) in whom conventional diagnostic work-up failed to disclose the primary tumor were included in the study. F-18 FDG PET/CT imaging was performed in a standard protocol (patient supine, arms on patient’s side, vertex to thigh, 369.3 MBq (296-444 MBq) F-18 FDG, a 60-minute uptake period, 6-7 bed position). Histopathology was taken as the only reference standard. F-18 FDG PET/CT correctly detected primary tumor in 37 of 112 (33.03%) patients. The most common site of primary tumor detected by F-18 FDG PET/CT was lung (n = 18), which was followed by nasopharynx (n = 7), pancreas (n = 5), tonsil (n = 2), breast (n = 2), thyroid (n = 1), uterus (n = 1) and colon/rectum (n = 1). F-18 FDG PET/CT imaging disclosed additional previously undetected metastases in 32 (28.5%) and changed the treatment in 33 (29.4%) of 112 patients. There were false positive F-18 FDG PET/CT results in 21 (18.5%) patients. F-18 FDG PET/CT is able to disclose the primary tumor, disclose new metatases and change the treatment in about one third of patients with CUP.     

FDG-PET and CT features of non-small cell lung cancer based on tumor type

We determined if specific tumor types of non-small cell lung cancer can be identified by variance in FDG-PET standard uptake value (SUV) in combination with characteristics on CT. Staging FDG-PET and CT scans of 81 patients (34 men and 47 women, average age 67+/-11 years) with 82 lung cancers were analyzed. Mean tumor SUV was calculated at the location of maximum FDG uptake. Tumor size, margins, and location were analyzed on CT. Statistical analysis compared SUV between tumor subtypes, assessed relationship between tumor subtype and features on CT and determined if combination of CT and SUV patterns predicted tumor type. In total 35 adenocarcinomas (AC); 15 bronchioloalveolar cell carcinomas (BAC), 23 squamous cell carcinomas and 9 large cell carcinomas were evaluated. Significant differences were found between SUV of all AC and squamous cell (p<0.0001); between all AC and large cell (p=0.03); between non-BAC AC and squamous cell types (p=0.0005); BAC and non-BAC AC (p=0.04), BAC and squamous cell (p<0.0001); BAC and large cell (p=0.004). Ground glass was the most significant CT feature in distinguishing tumor types, which was seen in BAC (p<0.0003). In conclusion, SUVs for non-small cell lung cancer were most significantly different between BAC and all other NCLC cell subtypes. The presence of ground glass in a nodule on CT is a significant feature for BAC and should raise the suspicion for this tumor type despite low FDG uptake.     

TP53基因多态与结直肠癌肝转移遗传易感性的相关性

目的 探讨TP53基因C-8343G、C-1863T及第72密码子(R72P)单核苷酸多态性与结直肠癌(colorectal cancer,CRC)肝转移风险的关系.方法 采用TaqMan和聚合酶链反应-限制性片段长度多态性方法,检测121例伴肝转移CRC与性别、年龄匹配的280例不伴肝转移CRC的各单核苷酸多态性的基因型分布及差异.结果 C-8343G和C-1863T基因型分布在伴和不伴肝转移的两组CRC人群间差异均无统计学意义.R72P增加CRC肝转移的发生风险:与PP基因型相比,RP基因型、RR基因型和R等位基因携带者(RP或RR基因型)的肝转移风险分别增加至2.21倍(95%CI:1.13～4.33)、2.26倍(95%CI:1.03～4.94)和2.22倍(95%CI:1.16～4.26).CRC组织中P53表达状态的分层分析结果显示:对于P53表达阳性者,72R携带者的肝转移风险与PP基因型相比进一步增加至3.28倍(95%CI:1.21～8.88);而对于P53表达阴性者,PP基因型与72R携带者的肝转移风险差异无统计学意义(比值比为1.37,95%CI:0.52～3.62).结论 TP53增加CRC,特别是P53表达阳性CRC的肝转移风险,可作为CRC肝转移高危人群的筛选指标;C-8343G和C-1863T可能均与CRC肝转移风险无关.     

Accuracy of rigid CT-FDG-PET image registration of the liver

Diagnostic and surgical strategies could benefit from accurate localization of liver malignancies via CT-FDG-PET image registration. However, registration uncertainty occurs due to protocol differences in data-acquisition, the limited spatial resolution of positron emission tomography (PET) and the low uptake of 18F-fluorodeoxyglucose (FDG) in normal liver tissue. To assess this uncertainty, methods were presented to estimate registration precision and systematic bias. A semi-automatic, organ-focused method was investigated to minimize the uncertainty well beyond the typical uncertainty of 5-10 mm obtained by commonly available methods. By restricting registration to the liver region and by isolating the liver on computed tomography (CT) from surrounding structures using a thresholding technique, registration was achieved using the mutual information-based method as implemented in insight toolkit (ITK). CT and FDG-PET images of 10 patients with liver metastases were registered rigidly a number of times. Results of the organ-focused method were compared to results of three commonly available methods (a manual, a landmark-based and a 'standard' mutual information-based method) where no dedicated image processing was performed. The proposed method outperformed the other methods with a precision (mean+/-s.d.) of 2.5+/-1.3 mm and a bias of 1.9 mm with a 95% CI of [1.0, 2.8] mm. Unlike the commonly available methods, our approach allows for robust CT-FDG-PET registration of the liver, with an accuracy better than the spatial resolution of the PET scanner that was used.     

Prognostic significance of mature dendritic cells and factors associated with their accumulation in metastatic liver tumors from colorectal cancer

Although dendritic cells (DCs) play an important role in tumor immunity, their prognostic significance and factors related to mature DCs have not been addressed in metastatic liver tumors. In surgically resected, paraffin-embedded tissue sections from 70 patients with colorectal liver metastasis, CD83 (a marker of mature DCs) positive cells and cancer cells positive for the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were counted. Expression of gp96, which is considered to participate in the maturation of DCs, was also evaluated. CD83-positive cells were observed predominantly in the cancer invasive margin. Patients with CD83-positive cell counts of <2 per field had a significantly poorer prognosis (5-year survival rate 47.5% vs 23.1%; P=0.0184). Patients with >0.83% apoptotic cancer cells had significantly higher numbers of CD83-positive cells (7.3 +/- 7.3 vs 4.0 +/- 5.1; P=0.039). Patients with immunohistochemically positive gp96 expression in tumors had significantly higher numbers of CD83-positive cells than those with negative gp96 expression (6.0 +/- 6.5 vs 1.4 +/- 2.3; P=0.0108). Patients with metachronous occurrence of liver metastasis had significantly higher numbers of CD83 positive cells than those with synchronous detection (6.3 +/- 6.5 vs 3.9 +/- 5.9; P=0.0313). Although the number of apoptotic cancer cells, degree of tumor gp96 expression, and synchronous or metachronous occurrence of liver metastasis did not directly influence patient outcome, they did influence the number of CD83-positive cells in the cancer invasive margin, which was a significant prognostic factor in patients with colorectal liver metastasis.     

18F-fluorodeoxyglucose positron emission tomography in colorectal cancer: value in primary staging and follow-up

Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) is a encouraging imaging technique allowing a highly sensitive whole-body search for malignant foci detected by their increased glucose metabolism compared with benign tissues. Several studies are now available that indicate its added value for diagnosis and staging of colorectal cancer. In all, patient management seems to be changed in 20-30% of patients who undergo Fluorodeoxyglucose positron emission tomography in addition to standard staging procedures. Fluorodeoxyglucose positron emission tomography is also useful in monitoring radiation therapy and chemotherapy. Regarding preoperative staging of primary colorectal cancer the literature is very limited.     

Imaging of cellular proliferation in liver metastasis by [18F]fluorothymidine positron emission tomography: effect of therapy

Although [(18)F]fluorothymidine positron emission tomography (FLT-PET) permits estimation of tumor thymidine kinase-1 expression, and thus, cell proliferation, high physiological uptake of tracer in liver tissue can limit its utility. We evaluated FLT-PET combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT-PET(KSF)) for detecting drug response in liver metastases. FLT-PET and computed tomography data were collected from patients with confirmed breast or colorectal liver metastases before, and two weeks after the first cycle of chemotherapy. Changes in tumor FLT-PET and FLT-PET(KSF) variables were determined. Visual distinction between tumor and normal liver was seen in FLT-PET(KSF) images. Of the 33 metastases from 20 patients studied, 26 were visible after kinetic filtering. The net irreversible retention of the tracer (Ki; from unfiltered data) in the tumor, correlated strongly with tracer uptake when the imaging variable was an unfiltered average or maximal standardized uptake value, 60 min post-injection (SUV(60,av): r = 0.9, SUV(60,max): r = 0.7; p < 0.0001 for both) and occurrence of high intensity voxels derived from FLT-PET(KSF) (r = 0.7, p < 0.0001). Overall, a significant reduction in the imaging variables was seen in responders compared to non-responders; however, the two week time point selected for imaging was too early to allow prediction of long term clinical benefit from chemotherapy. FLT-PET and FLT-PET(KSF) detected changes in proliferation in liver metastases.     

Steatohepatitis bei der Chemotherapie kolorektaler Lebermetastasen (CASH)

Neoadjuvant chemotherapy provides an important treatment option for patients who, as a consequence of colorectal cancer, have developed liver metastases. Regression of metastases prior to surgery may substantially improve prognosis. However, chemotherapeutics may harm non-tumorous liver tissue, particularly if this is already impaired prior to chemotherapy. The present article discusses the risks of chemotherapeutics for liver tissue-including sinusoidal obstruction syndrome, nodular regenerative hyperplasia, and chemotherapy-associated steatohepatitis, amongst others-which should be borne in mind when selecting therapy.     

Prognostic significance of 18F-FDG uptake in primary osteosarcoma after but not before chemotherapy: a possible association with autocrine motility factor/phosphoglucose isomerase expression

Response to neoadjuvant chemotherapy is a significant prognostic factor for osteosarcoma (OS). 18-F-fluorodeoxy-D: -glucose (FDG) positron emission tomography (PET) is a noninvasive imaging modality that correlates with histological grading in musculoskeletal sarcomas. To determine the prognostic value of FDG PET in patients receiving chemotherapy, 13 patients were evaluated by FDG-PET, and followed for more than 4 years. FDG PET standardized uptake values before (SUV1) and after (SUV2) chemotherapy were analyzed and correlated with the expression of metastasis-related glycolytic enzyme, autocrine motility factor (AMF)/phosphoglucose isomerase (PGI) by immunohistochemical examination in surgically excised tumors. Although mean SUV1 for OS patients with metastatic lesions were similar to those in the completely disease-free (CDF) group (6.5 vs. 6.6, respectively, P = 0.975), mean SUV2 for OS with metastatic lesions were significantly higher than those in the CDF group (5.1 vs. 2.5, respectively, P = 0.0445). Interestingly, immunohistochemical analysis using anti-AMF/PGI antibody revealed that SUV2 correlated significantly with the AMF/PGI staining titers (P = 0.0303), while no correlation between SUV1 and the AMF/PGI staining titers existed (P = 0.964). The present study suggests that FDG PET after chemotherapy may provide information for AMF/PGI-related metastatic potentiality of residual tumors located out side of the area surgically resected afterward, and then lead to a useful prediction of the patients' prognosis.     

Key Enzymes of the Extracellular Matrix in Colorectal Cancer

The role of extracellular matrix enzymes in the development of distant metastases of colorectal cancer was studied. The expression of types 2 and 9 matrix metalloproteinases was evaluated in primary colorectal adenocarcinomas (264 patients) and their metastases in the lymph nodes (127 patients) and liver (109 patients). Increased expression of matrix metalloproteinase-9 was associated with the probable progress of tumor process and with a low level of histological differentiation of the tumor (p=0.048), deeper invasion of the tumor in the intestinal wall (p=0.012), unfavorable outcome (p=0.037), high risk of metastases in the liver, and worse overall and uneventful survival of patients with colorectal cancer (p=0.001 and p=0.01, respectively). High expression of matrix metalloproteinase-2 was less significant for the invasive potential and prognosis of colorectal tumors. It is suggested that matrix metalloproteinase-9 is an important marker for analysis of the postoperative prognosis and risk of metastases in the liver in patients with colorectal cancer. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 3, pp. 327–330, March, 2009     

Meeting the biologic challenge of colorectal metastases

An overview of colorectal cancer discussed (Philip Paty) the good outcome after primary management with local control in 90–95 % of colon and 85 % in rectal cancer patients with major progression to metastases and to death related to hematogenous dissemination. The major disease pathways include the APC, aneuploid pathway involving mutations of P53, KRAS, SMAD 4, or the CMP/MSI pathway, mismatched repair defect as characterized by Lynch syndrome, the major hereditary form which may also have KRAS and P53 mutations. The common sporadic colorectal cancers are MS1 high, with many patients having BRAF and KRAS mutations. The sentinel node biopsy in colorectal cancer surgery may provide more definitive staging and perhaps modification of the extent of resection with better outcome as suggested by Dr. Saha. The identification of sentinel lymph nodes outside of the planned bowel resection may increase the resection biologically indicated by the sentinel lymph node location leading to better outcome. In a small study by Dr. Saha, the operation was enhanced in 21 % by extending the length of bowel resection, which increased node recovery to 18.5 nodes versus 12 nodes with the more conventional resection, increasing nodal recovery, and positivity to 60 % with reduction to five year recurrence rate to 9 % versus 27 % with the conventional resection. A new (Swiss) technique for pathologic node examination, the OSNA (the One Step Nucleic Acid diagnostic system), was presented which demonstrated increased detection of micro-metastases in a focused pathology study of 22 patients (Zuber) to 11 out of 15 patients versus the 7 micro-metastases identified by the standard single slide per node, and compared to 14 out of 15 with an intensive multi-slide technique. This suggests value in pursuing OSNA study by other centers with relevant clinical trials to establish its true value. An analysis of liver resection for metastatic colorectal cancer (CRC) emphasized the value of 10-year follow-up (DeAngelica). The 10-year survival of 102 patients among 612 patients was 17 % (Memorial Sloan Kettering data). At the five-year point 99 of 102 survivors were NED and 86 have been free of disease since the resection. The usual five-year figure after hepatic resection reveals that one-third of five-year survivors die from recurrence of distant disease suggesting the value of longer term follow-up in these patients. An additional question reviewed related to the role of neoadjuvant systemic chemotherapy (with response rates in the 50 % range) to produce down staging of the hepatic metastases and allow one to retrieve these patients with possible residual disease. In a series of 116 patients who had hepatic resection of CRC metastases in presence of regional node metastases, post neoadjuvant chemotherapy (normally not candidates for resection) these patients were demonstrated to have a 95 % recurrence at median time of 9 months. This raises a cautionary note to the literature report of five-year survivals in the 20–30 % range for hepatic metastases in presence of extra hepatic disease. Such may reflect patient selection rather than a true measure of the biology of disease, and warrant clinical trial evaluation. Lastly, regional therapy and overall systemic therapy were addressed by Dr. Kemeny. The CALGB study of hepatic artery infusion (HAI) with FUDR, dexamethasone versus 5FU leucovorin showed an overall survival of 24.4 months with HAI versus 20 months with systemic therapy (P = 0.0034). An adjuvant trial of HAI at MSK in 156 patients showed an overall survival benefit at 2 year and recent long term 10yr follow-up showing a significant overall survival of 41 % with HAI versus 27 % with systemic therapy (5FU leucovorin). In the neoadjuvant Nordlinger trial for hepatic metastases, there was a significant outcome differences—the preoperative therapy group had 9.2 % increase of progression free survival versus the surgery alone group which suggests the value of combining neoadjuvant surgery in good risk liver resection candidates. Conclude the final lesson from this well presented mini symposium confirms the need for continued evaluation of the numerous discussion points by clinical trial.     

Deauville Scores 4 or 5 Assessed by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Early Post-Allotransplant Is Highly Predictive of Relapse in Lymphoma Patients

The impact of early fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) status on survival after allogeneic transplantation for lymphoma is poorly reported. This retrospective study included all adult Hodgkin lymphoma (HL) or non-Hodgkin lymphoma(NHL) patients (>18 years old) who benefited from FDG PET-CT before (within 1 month) and/or early (+3 months and within +6 to 9 months) after allogeneic stem cell transplantation in our institution between 2005 and 2015 and who were still without documented progression or relapse at the time of the FDG PET-CT. All FDG PET-CT were reviewed by a nuclear medicine expert in hematology and restaged according to the Deauville scale. FDG-PET CT was considered positive when the uptake was higher than liver background (Deauville score ≥ 4). The primary objective was to study the impact of pre- and post-transplant FDG PET-CT on lymphoma-free survival (LFS) and overall survival (OS). Inclusion criteria were fulfilled for 103 patients (69 men; median age, 51.6 years old; range, 22 to 67). Diagnoses were high-grade NHL (n = 47), low-grade NHL (n = 6), T cell lymphoma (n = 34), and HL (n = 16). More than half of the patients were in complete remission at the time of transplant (n = 56). A reduced-intensity conditioning regimen was applied in most cases (n = 90). With a median follow-up of 49.5 months (range, 6 to 140.5) for alive patients, median 3-year OS and LFS were, respectively, 81% (range, 71% to 87%) and 65% (range, 54% to 74%) for the entire cohort. In multivariate analysis, positive FDG PET-CT at 3 months was the strongest independent factor significantly associated with poorer LFS (hazard ratio, 9.22; 95% confidence interval, 1.88 to 645.2; P = .006). FDG PET-CT positivity at 3 months appears to be highly predictive of LFS in patients after allogeneic transplantation and may help to guide strategies to prevent relapse. These results need to be validated prospectively.     

Increased expression of thioredoxin-1, vascular endothelial growth factor, and redox factor-1 is associated with poor prognosis in patients with liver metastasis from colorectal cancer

We examined whether the expression of thioredoxin-1 (Trx-1) was associated with patient prognosis after liver resection for metastatic colorectal cancer. Eighty-four patients underwent resection of liver metastases from colorectal cancer, leaving no macroscopic evidence of residual tumor. Immunohistochemical study was performed to evaluate the relation among Trx-1, vascular endothelial growth factor (VEGF), and redox factor-1 (Ref-1) expression and the clinicopathologic characteristics and patient survival. Thirty-seven patients (44.0%) with Trx-1-positive metastases had shorter survival after primary liver resection (P = .0003) than the 47 patients (56.0%) with Trx-1-negative metastases. The percentage VEGF-positive and Ref-1-positive metastases was significantly higher in patients with Trx-1 expression (P = .0009 and .0002, respectively). Multivariate analysis revealed that Trx-1 expression was an independent prognostic factor. Expression of VEGF and Ref-1 is associated with Trx-1 overexpression, which is related to a poor prognosis in patients with liver metastases from colorectal cancer.