Recent Chemotherapy Reduces the Sensitivity of [18F]Fluorodeoxyglucose Positron Emission Tomography in the Detection of Colorectal Metastase
http://www.100md.com
《临床肿瘤学》
the Departments of Surgery, Nuclear Medicine, and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
ABSTRACT
PURPOSE: [18F]2-fluoro-2-deoxyglucose (FDG) –positron emission tomography (PET) has become a useful tool in the assessment of patients with colorectal cancer. Patients often undergo chemotherapy as treatment for primary or metastatic colorectal malignancy. Because cytotoxic chemotherapy may decrease the cellular metabolic activity of tumor, we assessed the effects of chemotherapy on PET imaging.
PATIENTS AND METHODS: This is a prospective study examining detection of hepatic colorectal metastases by FDG-PET as related to use of chemotherapy. Pathologic analysis of the liver resection specimens was used as gold standard.
RESULTS: There was significantly decreased tumor FDG uptake (as measured by the maximal standardized uptake value) in patients treated preoperatively with chemotherapy, resulting in less efficient detection of cancerous lesions. One biologic basis of this change in accuracy of PET was a significant decrease in the activity of the key glycolytic enzyme hexokinase in tumors from patients treated with chemotherapy.
CONCLUSION: These results indicate that FDG-PET scanning should be interpreted in the context of concurrent cytotoxic therapy. FDG-PET scanning results may also be useful in assessment of response to such cytotoxic therapies.
INTRODUCTION
More than 150,000 people each year in Europe and in the United States will develop metastases from a colorectal malignancy.1 Many effective treatments have been developed for treatment of colorectal cancer including potentially curative surgical resections2-4 and palliative radiation and chemotherapeutic treatments.5-7 Choosing and planning the appropriate therapies depend on the use of noninvasive imaging that accurately identifies the extent of disease involvement. Conventional cross-sectional imaging, such as computed tomography and magnetic resonance imaging, are the standard staging modalities that are the basis for current therapy.8-10 Recently, whole-body positron emission tomography (PET) scanning after administration of [18F]2-fluoro-2-deoxyglucose (FDG) has emerged as a promising modality for staging of cancers.11-14 The biologic basis of FDG-PET is that tumors have higher glycolytic activity than noncancerous tissues. When the glucose analog [18F]FDG is administered to a patient with cancer, it is transported into the tumor cell via GLUT transporters and phosphorylated by the glycolytic enzyme hexokinase. The intratumoral [18F]FDG-6-phosphate so produced cannot proceed down the glycolytic pathway and, thus, accumulates, allowing the tumor cells to be imaged by the 511-keV photons released from the fluorine-18.
Many patients who are subjected to staging are under concurrent treatment with cytotoxic chemotherapy. Because chemotherapy seeks to decrease the metabolic activity of tumors, we postulated that such treatments would adversely affect sensitivity of FDG-PET scanning. To test this hypothesis and to determine the possible cellular basis of changes in FDG accumulation resulting from chemotherapy, we conducted a prospective evaluation of FDG-PET in a homogenous group of patients with hepatic metastatic colorectal cancer undergoing staging before liver resection. All findings were confirmed by pathologic analysis. Hexokinase activity of the tumor tissues harvested at resection was also correlated to the preoperative PET findings.
PATIENTS AND METHODS
This study was performed under the auspices of the Institutional Review Board of the Memorial Sloan-Kettering Cancer Center (New York, NY), and all enrolled patients gave informed consent. Forty-two patients (median age, 61 years; range, 30 to 78 years; 21 men and 19 women) who were being evaluated for resection of colorectal liver metastases were enrolled. Thirteen patients received fluorouracil-based chemotherapy within 3 months of their hepatic resection as either adjuvant treatment for the primary malignancy or preoperatively for liver disease. The remaining 29 patients did not receive chemotherapy within 3 months of PET scan.
All patients were imaged on a state of the art, high-resolution, high-sensitivity, dedicated bismuth germanate (BGO) PET system, the GE Advance (GEMS, Milwaukee, WI), after injection of 10 to 15 mCi (370 to 555 MBq) of [18F]FDG. Iteratively reconstructed images of the FDG-PET scans were read by the nuclear medicine physician, who was blinded to the results of other scanning. PET results were quantified by calculating the maximum standardized uptake value (SUV) for lesions detected.15 PET was also graded on a 5-point ordinal confidence scale (0 to 4), with a score of 0 to 2 classified as a negative PET and a score of 3 to 4 classified as a positive PET.
At the time of surgery, the number of tumors and site of each tumor within the liver were recorded. Serial thin slices of the resected specimen were then examined, and all tumor nodules were identified (and confirmed as cancers by histopathology). These pathologic findings were correlated with the blinded PET reading.
29 patients, sections that appeared macroscopically viable were also immediately frozen in liquid nitrogen and later analyzed for hexokinase (EC No. 2.7.1.1) activity as previously described.11 In total, 62 tumor nodules were analyzed. In the remaining 13 patients, there was insufficient viable tumor remaining after diagnostic pathologic examination to allow enzymatic analysis. Hexokinase activity was standardized to total protein content and expressed as units per milligram of protein.
Mixed-model regression analysis was performed to analyze the relationship of PET positivity as a binary variable (positive or negative) and as a continuous variable (SUV maximum values) to the chemotherapy status, the size of the tumor, and the hexokinase values in both univariate and multivariate analyses. This model was used because it corrects for the effect of the presence of multiple lesions per patient by considering the patients as a random effect. Tumor size was transformed using the natural logarithm to reduce the asymmetry of the distribution when needed. SAS statistical software (SAS Institute, Cary, NC) is used for all analyses.
RESULTS
Of the 42 patients evaluated, 13 patients underwent preoperative chemotherapy (41 lesions), and 29 patients did not undergo preoperative treatment (69 lesions). The average number of lesions per patient was 2.6 (Table 1). Maximum SUVs were significantly lower for patients treated with preoperative chemotherapy (mean SUV, 4.5; range, 2.2 to 8.1) compared with patients not undergoing preoperative treatment (mean SUV, 6.6; range, 2.2 to 13.0; P = .003; Table 2). Three patients in the preoperative chemotherapy group (one with a single metastasis and two with multiple liver lesions) had lesions confirmed on pathology that were all undetectable by PET. The phosphorylating activity of tumor hexokinase was also significantly lower in patients treated preoperatively with chemotherapy (mean, 14.4; range, 3.4 to 31.0 for chemotherapy-treated patients; and mean, 23.4; range, 8.4 to 40.4 for nontreated patients; P = .002; Fig 1).
PET detected 80 of the 110 total lesions confirmed as malignant by pathology. Thirty lesions (27%) were not detected. Of those patients treated with chemotherapy, 15 (37%) of 41 lesions were undetected by PET. For patients who did not receive preoperative treatment, 16 (23%) of 69 lesions were undetected by PET. When FDG-PET was used to evaluate patients not subjected to concurrent chemotherapy, no cancerous lesion greater than 1.2 cm was missed by PET. When FDG-PET was used to evaluate patients undergoing concurrent chemotherapy, a lesion as large as 3.2 cm was missed.
Multivariable regression analysis demonstrates that, when patients are untreated, a change in SUV is more strongly impacted by the change in tumor size compared with when the patients are treated with chemotherapy (P < .0001; Fig 2). When the binary variable of PET negative or positive is used, a similar result holds (P = .005). The regression analyses were repeated excluding small tumors ( 1 cm). The rationale for this subset analysis is that PET is thought to be insensitive in the detection of small tumors because of issues related to the resolution recovery of the camera. Despite the exclusion, the results remain unchanged.
DISCUSSION
The predilection of tumors for accelerated glucose uptake and utilization is the biologic basis for PET scanning using FDG. The current study further confirms the ability of FDG-PET to visualize the majority of pathologically confirmed tumors. However, a significant proportion of tumors, particularly small tumors, within the liver were not detectable by PET. Ninety-two percent of tumors 1 cm were not detected. This poor sensitivity in the liver is partly a result of the relatively high FDG uptake of normal hepatocytes. It is also partly a result of the acquisition parameters used in standard scans that seek to perform a whole-body survey within a reasonable length of time. Dedicated FDG-PET imaging of the liver with increased scan duration may improve the sensitivity for lesions less than 1 cm in size, but this is not practical at present. It is also possible that gating the scans to respiratory variations may increase the sensitivity of FDG-PET imaging and improve lesion detection.
Appearance of tumors on scans, such as FDG-PET, that measure metabolism clearly depend not only on the size and shape of the lesion, but also on the biologic activity. Cells with higher expression of GLUT transporters16 or the rate-limiting glycolytic enzyme hexokinase17 have been found to accumulate higher levels of FDG. Furthermore, conditions that alter host cell or tumor glucose metabolism have also been found to alter appearance of tumor on FDG-PET. Thus, diabetic patients have notoriously unreliable results of FDG-PET. Germ cell tumors that differentiate into more mature morphology have decreased accumulation of FDG.18 We postulated that use of chemotherapy might also alter FDG uptake by altering tumor metabolism. This was confirmed by current data, which demonstrated a 40% decrease in tumor cell hexokinase activity in those tumors resected from patients who had undergone recent chemotherapy. This was associated with a corresponding decrease in detection of tumors by FDG-PET.
Another important implication of these findings is that FDG-PET may be useful in assessing cytotoxic or ablative therapy. Other studies have suggested that FDG-PET may be useful in the assessment of response of primary rectal cancer to chemoradiotherapy.19 Preliminary data also indicate that FDG-PET may be useful in the assessment of completeness of cryoablation of hepatic colorectal metastases.20 In the current studies, a decrease in glycolytic metabolism was noted in equivalent-sized tumors of patients treated with chemotherapy. These data encourage investigation of FDG-PET in determining response early after chemotherapy, radiation therapy, or ablative therapy before changes are visible by cross-sectional imaging.
The most important implication of this decreased sensitivity of PET during chemotherapy is that PET should not be used as a sole determinant of presence of cancer in this clinical setting. On the basis of this study, it is apparent that a full knowledge of recent therapy is required to accurately interpret an FDG-PET scan result. A negative FDG-PET scan does not exclude the presence of viable disease in the setting of recent chemotherapy.
Authors' Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
NOTES
Supported by US Public Health Service Grants No. RO1CA76416, RO1CA72632, RO1CA80982 and RO1CA61524 from the National Institutes of Health and Grant No. MBC-99366 from the American Cancer Society and the Laurent and Alberta Gerschel Foundation.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
REFERENCES
Fong Y: Surgical therapy of hepatic colorectal metastasis. CA Cancer J Clin 49:231-255, 1999
Fong Y, Fortner J, Sun RL, et al: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases. Ann Surg 230:309-318, 1999
Scheele J: Liver resection for colorectal metastases. World J Surg 19:59-71, 1995
Nordlinger B, Guiguet M, Vaillant JC, et al: Surgical resection of colorectal carcinoma metastases to the liver: A prognostic scoring system to improve case selection, based on 1568 patients—Association Francaise de Chirurgie. Cancer 77:1254-1262, 1996
Masuda N, Kudoh S, Fukuoka M: Irinotecan (CPT-11): Pharmacology and clinical applications. Crit Rev Oncol Hematol 24:3-26, 1996
Allen-Mersh TG, Earlam S, Fordy C, et al: Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet 344:1255-1260, 1994
Cunningham D, Pyrhonen S, James RD, et al: Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352:1413-1418, 1998
Chezmar JL, Bernardino ME, Kaufman SH, et al: Combined CT arterial portography and CT hepatic angiography for evaluation of the hepatic resection candidate: Work in progress. Radiology 189:407-410, 1993
Little AF, Baron RL, Peterson MS, et al: Optimizing CT portography: A prospective comparison of injection into the splenic versus superior mesenteric artery. Radiology 193:651-655, 1994
Barish MA, Yucel EK, Ferrucci JT: Magnetic resonance cholangiopancreatography. N Engl J Med 341:258-264, 1999
Zhuang H, Sinha P, Pourdehnad M, et al: The role of positron emission tomography with fluorine-18-deoxyglucose in identifying colorectal cancer metastases to liver. Nucl Med Commun 21:793-798, 2000
Strasberg SM, Dehdashti F, Siegel BA, et al: Survival of patients evaluated by FDG-PET before hepatic resection for metastatic colorectal carcinoma: A prospective database study. Ann Surg 233:293-299, 2001
Fong Y, Saldinger PF, Akhurst T, et al: Utility of 18F-FDG-PET scanning on selection of patients for resection of hepatic colorectal metastases. Am J Surg 178:282-287, 1999
Meta J, Seltzer M, Schiepers C, et al: Impact of 18F-FDG PET on managing patients with colorectal cancer: The referring physician's perspective. J Nucl Med 42:586-590, 2001
Ramos CD, Erdi YE, Gonen M, et al: FDG-PET standardized uptake values in normal anatomical structures using iterative reconstruction segmented attenuation correction and filtered back-projection. Eur J Nucl Med 28:155-164, 2001
Higashi T, Tamaki N, Torizuka T, et al: FDG uptake, GLUT-1 glucose transporter and cellularity in human pancreatic tumors. J Nucl Med 39:1727-1735, 1998
Aloj L, Caraco C, Jagoda E, et al: Glut-1 and hexokinase expression: Relationship with 2-fluoro-2-deoxy-D-glucose uptake in A431 and T47D cells in culture. Cancer Res 59:4709-4714, 1999
Marymont JV, Dakhil SR, Travers H, et al: Chemical cholecystitis associated with hepatic arterial chemotherapy delivered by a permanently implanted pump. Hum Pathol 16:986-990, 1985
Guillem JG, Puig-La Calle J Jr, Akhurst T, et al: Prospective assessment of primary rectal cancer response to preoperative radiation and chemotherapy using 18-fluorodeoxyglucose positron emission tomography. Dis Colon Rectum 43:18-24, 2000
Akhurst T, Larson SM, Macapinlac H, et al: Fluorodeoxyglucose (FDG) positron emission tomography (PET) immediately post hepatic cryotherapy predicts recurrence of tumor in the liver. Proc Am Soc Clin Oncol 18:625a, 1999 (abstr 2415)(Timothy Akhurst, Tara J. )
ABSTRACT
PURPOSE: [18F]2-fluoro-2-deoxyglucose (FDG) –positron emission tomography (PET) has become a useful tool in the assessment of patients with colorectal cancer. Patients often undergo chemotherapy as treatment for primary or metastatic colorectal malignancy. Because cytotoxic chemotherapy may decrease the cellular metabolic activity of tumor, we assessed the effects of chemotherapy on PET imaging.
PATIENTS AND METHODS: This is a prospective study examining detection of hepatic colorectal metastases by FDG-PET as related to use of chemotherapy. Pathologic analysis of the liver resection specimens was used as gold standard.
RESULTS: There was significantly decreased tumor FDG uptake (as measured by the maximal standardized uptake value) in patients treated preoperatively with chemotherapy, resulting in less efficient detection of cancerous lesions. One biologic basis of this change in accuracy of PET was a significant decrease in the activity of the key glycolytic enzyme hexokinase in tumors from patients treated with chemotherapy.
CONCLUSION: These results indicate that FDG-PET scanning should be interpreted in the context of concurrent cytotoxic therapy. FDG-PET scanning results may also be useful in assessment of response to such cytotoxic therapies.
INTRODUCTION
More than 150,000 people each year in Europe and in the United States will develop metastases from a colorectal malignancy.1 Many effective treatments have been developed for treatment of colorectal cancer including potentially curative surgical resections2-4 and palliative radiation and chemotherapeutic treatments.5-7 Choosing and planning the appropriate therapies depend on the use of noninvasive imaging that accurately identifies the extent of disease involvement. Conventional cross-sectional imaging, such as computed tomography and magnetic resonance imaging, are the standard staging modalities that are the basis for current therapy.8-10 Recently, whole-body positron emission tomography (PET) scanning after administration of [18F]2-fluoro-2-deoxyglucose (FDG) has emerged as a promising modality for staging of cancers.11-14 The biologic basis of FDG-PET is that tumors have higher glycolytic activity than noncancerous tissues. When the glucose analog [18F]FDG is administered to a patient with cancer, it is transported into the tumor cell via GLUT transporters and phosphorylated by the glycolytic enzyme hexokinase. The intratumoral [18F]FDG-6-phosphate so produced cannot proceed down the glycolytic pathway and, thus, accumulates, allowing the tumor cells to be imaged by the 511-keV photons released from the fluorine-18.
Many patients who are subjected to staging are under concurrent treatment with cytotoxic chemotherapy. Because chemotherapy seeks to decrease the metabolic activity of tumors, we postulated that such treatments would adversely affect sensitivity of FDG-PET scanning. To test this hypothesis and to determine the possible cellular basis of changes in FDG accumulation resulting from chemotherapy, we conducted a prospective evaluation of FDG-PET in a homogenous group of patients with hepatic metastatic colorectal cancer undergoing staging before liver resection. All findings were confirmed by pathologic analysis. Hexokinase activity of the tumor tissues harvested at resection was also correlated to the preoperative PET findings.
PATIENTS AND METHODS
This study was performed under the auspices of the Institutional Review Board of the Memorial Sloan-Kettering Cancer Center (New York, NY), and all enrolled patients gave informed consent. Forty-two patients (median age, 61 years; range, 30 to 78 years; 21 men and 19 women) who were being evaluated for resection of colorectal liver metastases were enrolled. Thirteen patients received fluorouracil-based chemotherapy within 3 months of their hepatic resection as either adjuvant treatment for the primary malignancy or preoperatively for liver disease. The remaining 29 patients did not receive chemotherapy within 3 months of PET scan.
All patients were imaged on a state of the art, high-resolution, high-sensitivity, dedicated bismuth germanate (BGO) PET system, the GE Advance (GEMS, Milwaukee, WI), after injection of 10 to 15 mCi (370 to 555 MBq) of [18F]FDG. Iteratively reconstructed images of the FDG-PET scans were read by the nuclear medicine physician, who was blinded to the results of other scanning. PET results were quantified by calculating the maximum standardized uptake value (SUV) for lesions detected.15 PET was also graded on a 5-point ordinal confidence scale (0 to 4), with a score of 0 to 2 classified as a negative PET and a score of 3 to 4 classified as a positive PET.
At the time of surgery, the number of tumors and site of each tumor within the liver were recorded. Serial thin slices of the resected specimen were then examined, and all tumor nodules were identified (and confirmed as cancers by histopathology). These pathologic findings were correlated with the blinded PET reading.
29 patients, sections that appeared macroscopically viable were also immediately frozen in liquid nitrogen and later analyzed for hexokinase (EC No. 2.7.1.1) activity as previously described.11 In total, 62 tumor nodules were analyzed. In the remaining 13 patients, there was insufficient viable tumor remaining after diagnostic pathologic examination to allow enzymatic analysis. Hexokinase activity was standardized to total protein content and expressed as units per milligram of protein.
Mixed-model regression analysis was performed to analyze the relationship of PET positivity as a binary variable (positive or negative) and as a continuous variable (SUV maximum values) to the chemotherapy status, the size of the tumor, and the hexokinase values in both univariate and multivariate analyses. This model was used because it corrects for the effect of the presence of multiple lesions per patient by considering the patients as a random effect. Tumor size was transformed using the natural logarithm to reduce the asymmetry of the distribution when needed. SAS statistical software (SAS Institute, Cary, NC) is used for all analyses.
RESULTS
Of the 42 patients evaluated, 13 patients underwent preoperative chemotherapy (41 lesions), and 29 patients did not undergo preoperative treatment (69 lesions). The average number of lesions per patient was 2.6 (Table 1). Maximum SUVs were significantly lower for patients treated with preoperative chemotherapy (mean SUV, 4.5; range, 2.2 to 8.1) compared with patients not undergoing preoperative treatment (mean SUV, 6.6; range, 2.2 to 13.0; P = .003; Table 2). Three patients in the preoperative chemotherapy group (one with a single metastasis and two with multiple liver lesions) had lesions confirmed on pathology that were all undetectable by PET. The phosphorylating activity of tumor hexokinase was also significantly lower in patients treated preoperatively with chemotherapy (mean, 14.4; range, 3.4 to 31.0 for chemotherapy-treated patients; and mean, 23.4; range, 8.4 to 40.4 for nontreated patients; P = .002; Fig 1).
PET detected 80 of the 110 total lesions confirmed as malignant by pathology. Thirty lesions (27%) were not detected. Of those patients treated with chemotherapy, 15 (37%) of 41 lesions were undetected by PET. For patients who did not receive preoperative treatment, 16 (23%) of 69 lesions were undetected by PET. When FDG-PET was used to evaluate patients not subjected to concurrent chemotherapy, no cancerous lesion greater than 1.2 cm was missed by PET. When FDG-PET was used to evaluate patients undergoing concurrent chemotherapy, a lesion as large as 3.2 cm was missed.
Multivariable regression analysis demonstrates that, when patients are untreated, a change in SUV is more strongly impacted by the change in tumor size compared with when the patients are treated with chemotherapy (P < .0001; Fig 2). When the binary variable of PET negative or positive is used, a similar result holds (P = .005). The regression analyses were repeated excluding small tumors ( 1 cm). The rationale for this subset analysis is that PET is thought to be insensitive in the detection of small tumors because of issues related to the resolution recovery of the camera. Despite the exclusion, the results remain unchanged.
DISCUSSION
The predilection of tumors for accelerated glucose uptake and utilization is the biologic basis for PET scanning using FDG. The current study further confirms the ability of FDG-PET to visualize the majority of pathologically confirmed tumors. However, a significant proportion of tumors, particularly small tumors, within the liver were not detectable by PET. Ninety-two percent of tumors 1 cm were not detected. This poor sensitivity in the liver is partly a result of the relatively high FDG uptake of normal hepatocytes. It is also partly a result of the acquisition parameters used in standard scans that seek to perform a whole-body survey within a reasonable length of time. Dedicated FDG-PET imaging of the liver with increased scan duration may improve the sensitivity for lesions less than 1 cm in size, but this is not practical at present. It is also possible that gating the scans to respiratory variations may increase the sensitivity of FDG-PET imaging and improve lesion detection.
Appearance of tumors on scans, such as FDG-PET, that measure metabolism clearly depend not only on the size and shape of the lesion, but also on the biologic activity. Cells with higher expression of GLUT transporters16 or the rate-limiting glycolytic enzyme hexokinase17 have been found to accumulate higher levels of FDG. Furthermore, conditions that alter host cell or tumor glucose metabolism have also been found to alter appearance of tumor on FDG-PET. Thus, diabetic patients have notoriously unreliable results of FDG-PET. Germ cell tumors that differentiate into more mature morphology have decreased accumulation of FDG.18 We postulated that use of chemotherapy might also alter FDG uptake by altering tumor metabolism. This was confirmed by current data, which demonstrated a 40% decrease in tumor cell hexokinase activity in those tumors resected from patients who had undergone recent chemotherapy. This was associated with a corresponding decrease in detection of tumors by FDG-PET.
Another important implication of these findings is that FDG-PET may be useful in assessing cytotoxic or ablative therapy. Other studies have suggested that FDG-PET may be useful in the assessment of response of primary rectal cancer to chemoradiotherapy.19 Preliminary data also indicate that FDG-PET may be useful in the assessment of completeness of cryoablation of hepatic colorectal metastases.20 In the current studies, a decrease in glycolytic metabolism was noted in equivalent-sized tumors of patients treated with chemotherapy. These data encourage investigation of FDG-PET in determining response early after chemotherapy, radiation therapy, or ablative therapy before changes are visible by cross-sectional imaging.
The most important implication of this decreased sensitivity of PET during chemotherapy is that PET should not be used as a sole determinant of presence of cancer in this clinical setting. On the basis of this study, it is apparent that a full knowledge of recent therapy is required to accurately interpret an FDG-PET scan result. A negative FDG-PET scan does not exclude the presence of viable disease in the setting of recent chemotherapy.
Authors' Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
NOTES
Supported by US Public Health Service Grants No. RO1CA76416, RO1CA72632, RO1CA80982 and RO1CA61524 from the National Institutes of Health and Grant No. MBC-99366 from the American Cancer Society and the Laurent and Alberta Gerschel Foundation.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
REFERENCES
Fong Y: Surgical therapy of hepatic colorectal metastasis. CA Cancer J Clin 49:231-255, 1999
Fong Y, Fortner J, Sun RL, et al: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases. Ann Surg 230:309-318, 1999
Scheele J: Liver resection for colorectal metastases. World J Surg 19:59-71, 1995
Nordlinger B, Guiguet M, Vaillant JC, et al: Surgical resection of colorectal carcinoma metastases to the liver: A prognostic scoring system to improve case selection, based on 1568 patients—Association Francaise de Chirurgie. Cancer 77:1254-1262, 1996
Masuda N, Kudoh S, Fukuoka M: Irinotecan (CPT-11): Pharmacology and clinical applications. Crit Rev Oncol Hematol 24:3-26, 1996
Allen-Mersh TG, Earlam S, Fordy C, et al: Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet 344:1255-1260, 1994
Cunningham D, Pyrhonen S, James RD, et al: Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352:1413-1418, 1998
Chezmar JL, Bernardino ME, Kaufman SH, et al: Combined CT arterial portography and CT hepatic angiography for evaluation of the hepatic resection candidate: Work in progress. Radiology 189:407-410, 1993
Little AF, Baron RL, Peterson MS, et al: Optimizing CT portography: A prospective comparison of injection into the splenic versus superior mesenteric artery. Radiology 193:651-655, 1994
Barish MA, Yucel EK, Ferrucci JT: Magnetic resonance cholangiopancreatography. N Engl J Med 341:258-264, 1999
Zhuang H, Sinha P, Pourdehnad M, et al: The role of positron emission tomography with fluorine-18-deoxyglucose in identifying colorectal cancer metastases to liver. Nucl Med Commun 21:793-798, 2000
Strasberg SM, Dehdashti F, Siegel BA, et al: Survival of patients evaluated by FDG-PET before hepatic resection for metastatic colorectal carcinoma: A prospective database study. Ann Surg 233:293-299, 2001
Fong Y, Saldinger PF, Akhurst T, et al: Utility of 18F-FDG-PET scanning on selection of patients for resection of hepatic colorectal metastases. Am J Surg 178:282-287, 1999
Meta J, Seltzer M, Schiepers C, et al: Impact of 18F-FDG PET on managing patients with colorectal cancer: The referring physician's perspective. J Nucl Med 42:586-590, 2001
Ramos CD, Erdi YE, Gonen M, et al: FDG-PET standardized uptake values in normal anatomical structures using iterative reconstruction segmented attenuation correction and filtered back-projection. Eur J Nucl Med 28:155-164, 2001
Higashi T, Tamaki N, Torizuka T, et al: FDG uptake, GLUT-1 glucose transporter and cellularity in human pancreatic tumors. J Nucl Med 39:1727-1735, 1998
Aloj L, Caraco C, Jagoda E, et al: Glut-1 and hexokinase expression: Relationship with 2-fluoro-2-deoxy-D-glucose uptake in A431 and T47D cells in culture. Cancer Res 59:4709-4714, 1999
Marymont JV, Dakhil SR, Travers H, et al: Chemical cholecystitis associated with hepatic arterial chemotherapy delivered by a permanently implanted pump. Hum Pathol 16:986-990, 1985
Guillem JG, Puig-La Calle J Jr, Akhurst T, et al: Prospective assessment of primary rectal cancer response to preoperative radiation and chemotherapy using 18-fluorodeoxyglucose positron emission tomography. Dis Colon Rectum 43:18-24, 2000
Akhurst T, Larson SM, Macapinlac H, et al: Fluorodeoxyglucose (FDG) positron emission tomography (PET) immediately post hepatic cryotherapy predicts recurrence of tumor in the liver. Proc Am Soc Clin Oncol 18:625a, 1999 (abstr 2415)(Timothy Akhurst, Tara J. )