Lymphatic Invasion is an Independent Adverse Prognostic Factor in Patients with Colorectal Liver Metastasis.

BACKGROUND: For a selection of patients with colorectal liver metastases (CRLM), liver resection is a curative option. In order to predict long-term survival, clinicopathologic risk scores have been developed, but little is known about histologic factors and their prognostic value for disease-free and overall survival. The objective of the present study was to assess possible prognostic histologic factors in patients with solitary CRLM treated with liver resection who did not receive neoadjuvant treatment. METHODS: Patients with solitary CRLM who underwent liver resection between 1992 and 2011 were evaluated for clinical prognostic factors. Histologic analyses on tumor thickness at the tumor-normal interface, presence of a fibrotic capsule, intrahepatic vascular invasion, lymphatic invasion, or bile duct invasion and perineural growth were performed, using immunohistochemistry. RESULTS: A total of 124 patients were analyzed with a median follow-up of 41 months (range 1-232 months). There was no association between histologic factors and disease-free survival in multivariate analysis. In multivariate analysis, intrahepatic lymphatic invasion was associated with a decreased overall survival (41.9 vs. 61.0 months; p = 0.041), especially in combination with vascular invasion (n = 15) (28.1 vs. 62.2 months; p < 0.0001). In addition, size over 50 mm (29.2 vs. 65.9 months; p = 0.004) and interval less than 12 months between resection of the primary tumor and diagnosis of liver metastasis (49.0 vs. 91.5 months: p = 0.019) were also independent adverse prognostic factors. CONCLUSIONS: Intrahepatic lymphatic invasion, especially in combination with vascular invasion, is an important adverse prognostic factor for overall survival in patients with solitary CRLM after liver resection.

Oncological outcomes of unsuspected pN2 in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Optimal treatment of stage IIIA (N2) non-small-cell lung cancer (NSCLC) is controversial. Guidelines advise induction therapy before surgical resection. A proportion of patients with cN0 NSCLC are postoperatively upstaged due to unsuspected N2 disease. Survival of unsuspected N2 NSCLC treated with surgery varies and technical feasibility of video-assisted thoracic surgery (VATS) is unknown. The purpose of this study was to assess prevalence and survival of unsuspected N2 NSCLC treated with thoracotomy or VATS. METHODS: A systematic review and meta-analysis was performed of all available literatures through Pubmed, Cochrane, EMBASE, Web of Science, Trials registries and System for Information on Grey Literature (SIGLE) from 2000 to 2019. Outcomes of interest were prevalence, overall survival (OS) and disease-free survival of unsuspected N2 NSCLC. Secondary outcomes were number of harvested lymph nodes, postoperative complications and survival of unsuspected N2 NSCLC treated with VATS. RESULTS: Seventeen studies with patients with clinical stage N0-1 and unsuspected pN2 NSCLC were included. Prevalence of unsuspected pN2 was 8.6%. Three- and 5-year OS was 58% [95% confidence interval (CI) 37-78%) (N = 4337] and 35% (95% CI 28-43%) (N = 4337). Three- and 5-y ear disease-free survival was 48% (95% CI 30-66%) (N = 109) and 35% (95% CI 24-46%) (N = 517). VATS resulted in a low complication rate with similar 5-year OS as thoracotomy. CONCLUSIONS: In patients with cN0-1 NSCLC, a minority has unsuspected pN2 NSCLC. Even for these patients, 5-year OS and disease-free survival are reasonable. VATS with adequate lymph node dissection is the treatment of choice when in experienced hands. Adjuvant therapy should be provided in absence of relevant comorbidity.

Oncologic Outcomes of Surgery Versus SBRT for Non-Small-Cell Lung Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: The optimal treatment of stage I non-small-cell lung carcinoma is subject to debate. The aim of this study was to compare overall survival and oncologic outcomes of lobar resection (LR), sublobar resection (SR), and stereotactic body radiotherapy (SBRT). METHODS: A systematic review and meta-analysis of oncologic outcomes of propensity matched comparative and noncomparative cohort studies was performed. Outcomes of interest were overall survival and disease-free survival. The inverse variance method and the random-effects method for meta-analysis were utilized to assess the pooled estimates. RESULTS: A total of 100 studies with patients treated for clinical stage I non-small-cell lung carcinoma were included. Long-term overall and disease-free survival after LR was superior over SBRT in all comparisons, and for most comparisons, SR was superior to SBRT. Noncomparative studies showed superior long-term overall and disease-free survival for both LR and SR over SBRT. Although the papers were heterogeneous and of low quality, results remained essentially the same throughout a large number of stratifications and sensitivity analyses. CONCLUSION: Results of this systematic review and meta-analysis showed that LR has superior outcomes compared to SBRT for cI non-small-cell lung carcinoma. New trials are underway evaluating long-term results of SBRT in potentially operable patients.

A Clinical Decision Tool for Selection of Patients With Symptomatic Cholelithiasis for Cholecystectomy Based on Reduction of Pain and a Pain-Free State Following Surgery.

Importance: There is currently no consensus on the indication for cholecystectomy in patients with uncomplicated gallstone disease. Objective: To report on the development and validation of a multivariable prediction model to better select patients for surgery. Design, Setting, and Participants: This study evaluates data from 2 multicenter prospective trials (the previously published Scrutinizing (In)efficient Use of Cholecystectomy: A Randomized Trial Concerning Variation in Practice [SECURE] and the Standardized Work-up for Symptomatic Cholecystolithiasis [Success] trial) collected from the outpatient clinics of 25 Dutch hospitals between April 2014 and June 2019 and including 1561 patients with symptomatic uncomplicated cholelithiasis, defined as gallstone disease without signs of complicated cholelithiasis (ie, biliary pancreatitis, cholangitis, common bile duct stones or cholecystitis). Data were analyzed from January 2020 to June 2020. Exposures: Patient characteristics, comorbidity, surgical outcomes, pain, and symptoms measured at baseline and at 6 months' follow-up. Main Outcomes and Measures: A multivariable regression model to predict a pain-free state or a clinically relevant reduction in pain after surgery. Model performance was evaluated using calibration and discrimination. Results: A total of 1561 patients were included (494 patients in 7 hospitals in the development cohort and 1067 patients in 24 hospitals in the validation cohort; 6 hospitals included patients in both cohorts). In the development cohort, 395 patients (80.0%) underwent cholecystectomy. After surgery, 225 patients (57.0%) reported that they were pain free and 295 (74.7%) reported a clinically relevant reduction in pain. A multivariable prediction model showed that increased age, no history of abdominal surgery, increased visual analog scale pain score at baseline, pain radiation to the back, pain reduction with simple analgesics, nausea, and no heartburn were independent predictors of clinically relevant pain reduction after cholecystectomy. After internal validation, good discrimination was found (C statistic, 0.80; 95% CI, 0.74-0.84) between patients with and without clinically relevant pain reduction. The model had very good overall calibration and minimal underestimation of the probability. External validation indicated a good discrimination between patients with and without clinically relevant pain reduction (C statistic, 0.74; 95% CI, 0.70-0.78) and fair calibration with some overestimation of probability by the model. Conclusions and Relevance: The model validated in this study may help predict the probability of pain reduction after cholecystectomy and thus aid surgeons in deciding whether patients with uncomplicated cholelithiasis will benefit from cholecystectomy.

Improved selection of patients for hepatic surgery of colorectal liver metastases with (18)F-FDG PET: a randomized study.

UNLABELLED: With the increasing possibilities for surgical treatment of colorectal liver metastases, careful selection of patients who may benefit from surgical treatment becomes critical. The addition of PET to (18)F-FDG may significantly improve conventional staging by CT. Up to now, definitive evidence that the addition of (18)F-FDG PET to conventional staging leads to superior clinical results and improved clinical management in these patients has been lacking. In this randomized controlled trial in patients with colorectal liver metastases, we investigated whether the addition of (18)F-FDG PET is beneficial and reduces the number of futile laparotomies. METHODS: A total of 150 patients with colorectal liver metastases selected for surgical treatment by imaging with CT were randomly assigned to CT only (n = 75) or CT plus (18)F-FDG PET (n = 75). Patients were followed up for at least 3 y. The primary outcome measure was futile laparotomy, defined as any laparotomy that did not result in complete tumor treatment, that revealed benign disease, or that did not result in a disease-free survival period longer than 6 mo. RESULTS: Patient and tumor characteristics were similar for both groups. The number of futile laparotomies was 34 (45%) in the control arm without (18)F-FDG PET and 21 (28%) in the experimental arm with (18)F-FDG PET; the relative risk reduction was 38% (95% confidence interval, 4%-60%, P = 0.042). CONCLUSION: The number of futile laparotomies was reduced from 45% to 28%; thus, the addition of (18)F-FDG PET to the work-up for surgical resection of colorectal liver metastases prevents unnecessary surgery in 1 of 6 patients.

Survival After Stereotactic Body Radiation Therapy for Clinically Diagnosed or Biopsy-Proven Early-Stage NSCLC: A Systematic Review and Meta-Analysis.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is a promising curative treatment for early-stage NSCLC. It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients. In this systematic review and meta-analysis, we assess survival outcomes after SBRT in studies with patients with clinically diagnosed versus biopsy-proven early-stage NSCLC. METHODS: The main databases were searched for trials and cohort studies without restrictions to publication status or language. Two independent researchers performed the screening and selection of eligible studies. Outcomes were overall survival, cancer-specific survival, and disease-free survival. The inverse variance method and the random effects method for meta-analysis were used to assess pooled survival estimates. RESULTS: A total of 11,195 nonduplicate records were identified by the original search strategy. After screening by title and abstract, 1051 potentially eligible records were identified. A total of 43 articles were included. The comparative studies showed lower 3-year overall survival and lower 2-year and 5-year cancer-specific survival for biopsy-proven disease compared to clinical disease. However, 5-year overall survival was the same for both groups. For the pooled estimates, 3-year disease-free survival and 2-year cancer-specific survival were lower for biopsied disease. CONCLUSIONS: Results of this systematic review and meta-analysis show a discrepancy in oncological outcomes for patients undergoing SBRT for suspected early-stage NSCLC in whom there is pathologic conformation of malignancy and those who there is only a clinical diagnose of NSCLC. These results emphasize the importance of obtaining pathologic proof of malignancy.

Controversies in the management of colorectal liver metastases: role of PET and PET/CT.

Positron emission tomography (PET) using [F-18]-2-deoxy-2-fluoro-D-glucose (FDG) has emerged as a promising diagnostic modality in recurrent colorectal cancer. Data in the literature show that the addition of FDG-PET changes patient management in up to 30% of patients with potentially resectable liver metastases, mainly by detecting previously unknown extrahepatic disease. Furthermore, FDG-PET is useful in the follow-up of patients who underwent surgical procedures of the liver, since it is sensitive in detecting residual or relapse malignancy in scarred liver tissue following both resection and local ablative techniques. For follow-up during systemic therapy, early FDG-PET appears predictive for response to therapy. FDG-PET, computerized tomography and magnetic resonance imaging are complementary techniques in staging and restaging patients with advanced colorectal cancer. A combination of FDG-PET and CT scanning characteristics seems promising, and integrated PET/ CT is becoming more widely available, although the exact clinical value and efficacy is not yet fully established. In addition, assessment of these modalities in joint reading sessions with radiologist, nuclear medicine physician, medical and surgical oncologists significantly impacts upon patient management. This review evaluates the potential of FDG-PET and combined PET/CT in patients with colorectal liver metastases and discusses potential future possibilities.

A novel iterative method for lesion delineation and volumetric quantification with FDG PET.

OBJECTIVES: The determination of lesion boundaries on FDG PET is difficult due to the point-spread blurring and unknown uptake of activity within a lesion. Standard threshold-based methods for volumetric quantification on PET usually neglect any size dependence and are biased by dependence on the signal-to-background ratio (SBR). A novel, model-based method is hypothesized to provide threshold levels independent f the SBR and to allow accurate measurement of volumes down to the resolution of the PET scanner. METHODS: A background-subtracted relative-threshold level (RTL) method was derived, based on a convolution of the point-spread function and a sphere with diameter D. Validation of the RTL method was performed using PET imaging of a Jaszczak phantom with seven hollow spheres (D=10-60 mm). Activity concentrations for the background and spheres (signal) were varied to obtain SBRs of 1.5-10. An iterative procedure was introduced for volumetric quantification, as the optimal RTL depends on a priori knowledge of the volume. The feasibility of the RTL method was tested in two patients with liver metastases and compared to a standard method using a fixed percentage of the signal. RESULTS: Phantom data validated that the theoretically optimal RTL depends on the sphere size, but not on the SBR. Typically, RTL=40% (D=15-60 mm), and RTL>50% for small spheres (D<12 mm). The RTL method is better applicable to patient data than the standard method. CONCLUSIONS: Based on an iterative procedure, the RTL method has been shown to provide optimal threshold levels independent of the SBR and to be applicable in phantom and in patient studies. It is a promising tool for lesion delineation and volumetric quantification of PET lesions.

Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer.

PURPOSE: To investigate hypoxia measured by pimonidazole binding, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CA-IX) expression, proliferation, and vascularity in liver metastases of colorectal cancer and to compare GLUT1 and CA-IX expression in corresponding primary tumors. METHODS AND MATERIALS: Twenty-five patients with liver metastases of colorectal cancer, planned for metastasectomy, were included. The hypoxia marker pimonidazole and proliferation marker iododeoxyuridine were administered before surgery. After immunofluorescent staining of the frozen metastases, pimonidazole binding, vascularity, and proliferation were analyzed quantitatively. Thirteen paraffin-embedded primary tumors were stained immunohistochemically for GLUT1 and CA-IX expression, which was analyzed semiquantitatively in primary tumors and corresponding liver metastases. RESULTS: In liver metastases, pimonidazole binding showed a pattern consistent with diffusion-limited hypoxia. The mean pimonidazole-positive fraction was 0.146; the mean distance from vessels to pimonidazole-positive areas was 80 microm. When expressed, often co-localization was observed between pimonidazole binding and GLUT1 or CA-IX expression, but microregional areas of mismatch were also observed. No correlation between the level of pimonidazole binding and GLUT1 or CA-IX expression was observed. In some patients, a large fraction (up to 30%) of proliferating cells was present in pimonidazole-stained areas. Expression of CA-IX in primary tumors and metastases showed a significant correlation, which was absent for GLUT1 expression. CONCLUSIONS: Compared with other tumor types, liver metastases of colorectal cancer contain large amounts of hypoxic cells. The lack of correlation with pimonidazole binding brings into question the value of GLUT1 and CA-IX as endogenous markers of hypoxia.

Management of liver metastases in colorectal cancer patients: A retrospective case-control study of systemic therapy versus liver resection.

OBJECTIVE: To evaluate and compare the overall survival (OS) in case-matched patient groups treated either with systemic therapy or surgery for colorectal liver metastases (CRLM). METHODS: Patients with CRLM, without extra-hepatic disease, treated with chemotherapy with or without targeted therapy in two phase III studies (n = 480) were selected and case-matched to patients who underwent liver resection (n = 632). Matching criteria were sex, age, established prognostic factors for survival (clinical risk score). Available computed tomography (CT)-scans of patients treated with systemic therapies were reviewed by three independent liver surgeons for resectability. Survival was compared between patients with resectable CRLM (based on CT-scan review) who were treated with systemic therapy versus patients who underwent liver resection. RESULTS: A total of 96 patients treated with systemic therapy were included. Pre-treatment CT-scans of the liver were available for review in 56 of the systemically treated patients, and metastases were unanimously considered resectable in 36 patients (64.3%) (complex resectable: n = 25; 69%). These 36 patients were case-matched with 36 patients who underwent liver resection (wedge resection or segmentectomy: n = 26; 72%). Median OS in the patient group treated with systemic therapy was 26.5 months (range 0-81 months), which was significantly lower than that in case-matched patients who underwent liver resection (median OS 56 months; range 6-116) (p = 0.027). CONCLUSIONS: In this case-matched control study, surgery provided superior OS rates compared to systemic therapy for CRLM. Resection of CRLM should always be considered, preferably in a dedicated liver centre, since not all patients that qualify for resection are identified as such.

Role of FDG-PET in the diagnosis and treatment of colorectal liver metastases.

Positron emission tomography (PET) using [(18)F]-2-deoxy-2-fluoro-d-glucose (FDG) has emerged as a promising diagnostic modality in recurrent colorectal cancer. Data in the literature show that the addition of FDG-PET changes disease management in up to 30% of patients with potentially resectable liver metastases, mainly by detecting previously unknown extrahepatic disease. Furthermore, FDG-PET is useful in the follow-up of patients who underwent surgical procedures of the liver, since it is exquisitely sensitive in detecting residual or relapse malignancy in scarred liver tissue following both resection and local ablative techniques. For follow-up during systemic therapy, early FDG-PET appears predictive for response to therapy. However, at present, the available data are insufficient to justify the FDG-PET-driven management of patients treated with chemotherapy. FDG-PET and computerized tomography are complimentary techniques in staging and restaging patients with advanced colorectal cancer. The combination of these two modalities significantly impacts upon patient management.

Added value of positron emission tomography imaging in the surgical treatment of colorectal liver metastases.

OBJECTIVE: [F-18]-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is used increasingly in the work-up to surgery for patients with potentially resectable colorectal liver metastases. This study evaluates the clinical effectiveness, impact on health care resources and cost-effectiveness of adding FDG-PET to the diagnostic algorithm alongside a randomized clinical trial from a health care perspective. METHODS: In a randomized clinical trial, the net monetary benefit (NMB) of FDG-PET added to conventional diagnostic work-up (CWU) was determined in patients with colorectal liver metastases. Seventy-five patients were included in each arm. Change in clinical management, futile laparotomies, preoperative findings and all relevant health care consumption were prospectively documented during 3 years. To assess health-related quality of life European Quality of Life-5 Dimensions was administered at the time of randomization, 3 and 6 weeks postoperatively, and every 3 months postoperatively for 3 years. Quality-adjusted life years (QALYs) were calculated based on European Quality of Life-5 Dimensions outcomes. RESULTS: In adding FDG-PET, diagnostic performance increased and futile laparotomies were reduced by 38%. Both health-related quality of life and QALYs showed no significant difference between the CWU and PET groups. For CWU and PET groups costs were euro 92,836 and euro 81,776, respectively, accumulated in 3 years after randomization. NMB ranged from euro 1004 to euro 11,060 depending on the monetary value given to a QALY. When costs for chemotherapy were disregarded, costs amounted to euro 15,874 for CWU and euro 18,664 for PET group. CONCLUSION: Additional costs of FDG-PET in the diagnostic work-up of patients with potentially resectable colorectal liver metastases were compensated by a reduction in futile laparotomies. The NMB analysis showed savings over a relevant range of willingness to pay for a QALY.

Comparison between local ablative therapy and chemotherapy for non-resectable colorectal liver metastases: a prospective study.

BACKGROUND: There is a growing interest for the use of local ablative techniques in patients with non-resectable colorectal liver metastases. Evidence on the efficacy over systemic chemotherapy is, however, extremely weak. In this prospective study we aim to assess the additional benefits of local tumour ablation. METHODS: A consecutive series of 201 colorectal cancer patients, without extrahepatic disease, that underwent laparotomy for surgical treatment of liver metastases, were prospectively followed for survival and HRQoL. At laparotomy three groups were identified: patients in whom radical resection of metastases proved feasible, patients in whom resection was not feasible and received local ablative therapy, and patients in whom resection or local ablation was not feasible for technical reasons and who received systemic chemotherapy. FINDINGS: Patients in the chemotherapy and in local ablation group were comparable for all prognostic variables tested. For the local ablation group overall survival at 2 and 5 years was 56 and 27%, respectively (median 31 months, n = 45), for the chemotherapy group 51 and 15%, respectively (median 26 months, n = 39) (P = 0.252). After resection these figures were 83 and 51%, respectively (median 61 months, n = 117) (P < 0.001). The median DFS after local ablation was 9 months, HRQoL was restored within 3 months. Patients after local ablation gained far more QALY's (317) than in the chemotherapy group (165) (P < 0.001). INTERPRETATION: Although overall survival did not reached statistical significance, the median DFS of 9 months suggests a beneficial effect of local tumour ablation for non-resectable colorectal liver metastases. Moreover, compared with systemic chemotherapy more QALY's were gained after local ablative therapy.

The impact of fluor-18-deoxyglucose-positron emission tomography in the management of colorectal liver metastases.

Fluor-18-deoxyglucose-positron emission tomography (FDG-PET) has emerged as a promising diagnostic modality in recurrent colorectal carcinoma. Whole-body FDG-PET may be an accurate diagnostic modality to determine whether patients with recurrent hepatic disease are suitable candidates for curative resection. Reports on the use of FDG-PET in patients with recurrent colorectal carcinoma are scarce, especially those on colorectal liver metastases. To assess the usefulness of this emerging modality for the selection of patients to undergo resection for colorectal liver metastases, a systematic (meta)-analysis of the current literature was conducted. In the absence of randomized controlled clinical trials, a traditional meta-analysis could not be performed. An alternative strategy was designed to evaluate the current literature. After a literature search, an index score was devised to evaluate the articles with regard to the impact of FDG-PET in patients with colorectal liver metastases. The index scored articles on several items and, as such, could be considered an objective approach for the assessment of diagnostic, nonrandomized clinical trials. The proposed index proved to be an independent instrument for judging several research questions and was used systematically to address the sensitivity, specificity, and clinical impact of FDG-PET in patients with colorectal liver metastases. For FDG-PET, the pooled sensitivity and specificity results were 88.0% and 96.1%, respectively, for hepatic disease and 91.5% and 95.4%, respectively, for extrahepatic disease. For the 6 articles that reported the highest scores on the index, the sensitivity and specificity of FDG-PET for hepatic metastatic disease were 79.9% and 92.3%, respectively, and 91.2% and 98.4%, respectively, for extrahepatic disease, respectively. For computed tomography, the pooled sensitivity and specificity results were 82.7% and 84.1%, respectively, for hepatic lesions and 60.9% and 91.1%, respectively, for extrahepatic lesions. The percentage change in clinical management due to FDG-PET was 31.6% (range, 20.0-58.0%) in the articles that scored above the mean and reported this item. For the 6 highest scoring studies, the percentage change in clinical management was 25.0% (range, 20.0-32.0%). Despite apparent omissions in the literature, the combined sensitivity and specificity of FDG-PET clearly indicated that FDG-PET has added value in the diagnostic workup of patients with colorectal liver metastases. FDG-PET can be considered a useful tool in preoperative staging and produced superior results compared with conventional diagnostic modalities, especially for excluding or detecting extrahepatic disease.

Colorectal cancer: the role of PET/CT in recurrence.

Many imaging modalities and scanning techniques, such as contrast enhanced CT, MRI and FDG-PET, are available for assessment of recurrent colorectal carcinoma. In addition, integrated PET/CT is becoming increasingly available. Intuitively, a synergistic combination of scanning characteristics sounds promising. However, the exact clinical value has not yet been fully established. The role of PET/CT image fusion must be weighed carefully against other available modalities. In this review we evaluate the potential of combined PET/CT in recurrent colorectal carcinoma. When available, PET/CT currently appears the diagnostic tool of choice. In the near future, combined PET/MRI may further enhance the diagnostic algorithm.

Gadopentetate dimeglumine and FDG uptake in liver metastases of colorectal carcinoma as determined with MR imaging and PET.

PURPOSE: To examine the in vivo relationship between fluorine 18 fluorodeoxyglucose (FDG) uptake, as measured with positron emission tomography (PET), and functional tumor vasculature, as measured with dynamic contrast material-enhanced magnetic resonance (MR) imaging, in patients with liver metastases of colorectal cancer. MATERIALS AND METHODS: All patients provided written informed consent, and the study was approved by the institutional review board. A total of 26 patients (12 men and 14 women; mean age, 59 years) who were suspected of having liver metastases of histologically proved colorectal cancer and underwent work-up for liver metastasectomy were included. Patients underwent whole-body FDG PET, and tumor-to-nontumor ratio of FDG uptake in metastases was calculated. Dynamic contrast-enhanced MR imaging was performed, and the rate constant k(ep) (s(-1)) of gadopentetate dimeglumine uptake in metastases was determined. Pimonidazole was used to determine tumor hypoxia and vascular density of metastases. To assess the relationship between FDG uptake, rate constant k(ep) of gadopentetate dimeglumine uptake, hypoxic fraction, and vascular density, the Pearson correlation coefficient was calculated. RESULTS: Negative correlation between tumor-to-nontumor ratio of FDG uptake and rate constant k(ep) was observed (r = -0.421, P = .082). No correlation between tumor hypoxia and tumor-to-nontumor ratio of FDG uptake or rate constant k(ep) was found. A positive correlation was observed between vascular density and rate constant k(ep) (r = 0.458, P = .034) but not between tumor-to-nontumor ratio of FDG uptake. CONCLUSION: Negative correlation between tumor-to-nontumor ratio of FDG uptake and rate constant k(ep) suggests that lower values of gadopentetate dimeglumine uptake imply an acutely reduced supply of oxygen, which necessitates a higher uptake of glucose to maintain tumor energy levels. The positive correlation of vascular density with rate constant k(ep), but not with tumor-to-nontumor ratio of FDG uptake, emphasizes the potential of dynamic contrast-enhanced MR imaging to enable measurement of tumor vascularity in vivo and its additional value compared with ex vivo methods.