Farrokh Dehdashti

Five-Year Survival After Resection of Hepatic Metastases From Colorectal Cancer in Patients Screened by Positron Emission Tomography With F-18 Fluorodeoxyglucose (FDG-PET)

Objective:To report the first 5-year overall survival results in patients with colorectal carcinoma metastatic to the liver who have undergone hepatic resection after staging with [18F] fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). Summary Background Data:The 5-year overall survival after hepatic resection for colorectal cancer metastases without preoperative FDG-PET has been established in 19 studies (6070 patients). The median 5-year overall survival rate in these studies is 30% and has not improved over time. FDG-PET detects unsuspected tumor in 25% of patients considered to have resectable hepatic metastasis by conventional staging. Methods:From March 1995 to June 2002, all patients having hepatic resection for colorectal cancer metastases had preoperative FDG-PET. A prospective database was maintained. Results:One hundred patients (56 men, 44 women) were studied. Metastases were synchronous in 52, single in 63, unilateral in 78, and <5 cm in diameter in 60. Resections were major (>3 segments) in 75 and resection margins were ≥1 cm in 52. Median follow up was 31 months, with 12 actual greater than 5-year survivors. There was 1 postoperative death. The actuarial 5-year overall survival was 58% (95% confidence interval, 46–72%). Primary tumor grade was the only prognostic variable significantly correlated with overall survival. Conclusions:Screening by FDG-PET is associated with excellent postresection 5-year overall survival for patients undergoing resection of hepatic metastases from colorectal cancer. FDG-PET appears to define a new cohort of patients in whom tumor grade is a very important prognostic variable.

Lymph Node Staging by Positron Emission Tomography in Patients With Carcinoma of the Cervix

PURPOSE The aim of this study was to compare the results of computed tomography (CT) and positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) for lymph node staging in patients with carcinoma of the cervix and to evaluate the relationship of the imaging findings to prognosis. PATIENTS AND METHODS We retrospectively compared the results of CT lymph node staging and whole-body FDG-PET in 101 consecutive patients with carcinoma of the cervix. Patients were treated with standard irradiation and chemotherapy (as clinically indicated) and observed at 3-month intervals for a median of 15.4 months (range, 2.5 to 30 months). Progression-free survival was evaluated by the Kaplan-Meier method. RESULTS CT demonstrated abnormally enlarged pelvic lymph nodes in 20 (20%) and para-aortic lymph nodes in seven (7%) of the 101 patients. PET demonstrated abnormal FDG uptake in pelvic lymph nodes in 67 (67%), in para-aortic lymph nodes in 21 (21%), and in supraclavicular lymph node in eight (8%). The 2-year progression-free survival, based solely on para-aortic lymph node status, was 64% in CT-negative and PET-negative patients, 18% in CT-negative and PET-positive patients, and 14% in CT-positive and PET-positive patients (P <.0001). A multivariate analysis demonstrated that the most significant prognostic factor for progression-free survival was the presence of positive para-aortic lymph nodes as detected by PET imaging (P =.025). CONCLUSION This study demonstrates that FDG-PET detects abnormal lymph node regions more often than does CT and that the findings on PET are a better predictor of survival than those of CT in patients with carcinoma of the cervix.

Metabolic Flare: Indicator of Hormone Responsiveness in Advanced Breast Cancer

PURPOSE The purpose of this study was to investigate whether positron emission tomography (PET) with the glucose analog [(18)F]fluorodeoxyglucose (FDG) and the estrogen analog 16 alpha-[(18)F]fluoroestradiol-17 beta (FES), performed before and after treatment with tamoxifen, could be used to detect hormone-induced changes in tumor metabolism (metabolic flare) and changes in available levels of estrogen receptor (ER). In addition, we investigated whether these PET findings would predict hormonally responsive breast cancer. PATIENTS AND METHODS Forty women with biopsy-proved advanced ER-positive (ER(+)) breast cancer underwent PET with FDG and FES before and 7 to 10 days after initiation of tamoxifen therapy; 70 lesions were evaluated. Tumor FDG and FES uptake were assessed semiquantitatively by the standardized uptake value (SUV) method. The PET results were correlated with response to hormonal therapy. RESULTS In the responders, the tumor FDG uptake increased after tamoxifen by 28.4% +/- 23.3% (mean +/- SD); only five of these patients had evidence of a clinical flare reaction. In nonresponders, there was no significant change in tumor FDG uptake from baseline (mean change, 10.1% +/- 16.2%; P =.0002 v responders). Lesions of responders had higher baseline FES uptake (SUV, 4.3 +/- 2.4) than those of nonresponders (SUV, 1.8 +/- 1.3; P =.0007). All patients had evidence of blockade of the tumor ERs 7 to 10 days after initiation of tamoxifen therapy; however, the degree of ER blockade was greater in the responders (mean percentage decrease, 54.8% +/- 14.2%) than in the nonresponders (mean percentage decrease, 19.4% +/- 17.3%; P =.0003). CONCLUSION The functional status of tumor ERs can be characterized in vivo by PET with FDG and FES. The results of PET are predictive of responsiveness to tamoxifen therapy in patients with advanced ER(+) breast cancer.

In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM

Tumor hypoxia is recognized as an important determinant of response to therapy. In this study we investigated the feasibility of clinical imaging with copper-60 diacetyl-bis(N4-methylthiosemicarbazone) (60Cu-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of 60Cu-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with 60Cu-ATSM before initiation of therapy. 60Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M). All patients also underwent PET with fluorine-18 fluorodeoxyglucose (FDG) prior to institution of therapy. The PET results were correlated with follow-up evaluation (2–46 months). It was demonstrated that PET imaging with 60Cu-ATSM in patients with NCSLC is feasible. The tumor of one patient had no discernible 60Cu-ATSM uptake, whereas the tumor uptake in the remaining patients was variable, as expected. Response was evaluated in 14 patients; the mean T/M for 60Cu-ATSM was significantly lower in responders (1.5±0.4) than in nonresponders (3.4±0.8) (P=0.002). However, the mean SUV for 60Cu-ATSM was not significantly different in responders (2.8±1.1) and nonresponders (3.5±1.0) (P=0.2). An arbitrarily selected T/M threshold of 3.0 discriminated those likely to respond to therapy: all eight responders had a T/M <3.0 and all six nonresponders had a T/M ≥3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P=0.7) and did not correlate with 60Cu-ATSM uptake (r=0.04; P=0.9). 60Cu-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of 60Cu-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.

Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: Relationship to therapeutic response—a preliminary report

PURPOSE Tumor hypoxia is associated with poor response to therapy. We have investigated whether pretreatment tumor hypoxia assessed by positron emission tomography (PET) with Cu-60 diacetyl-bis(N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) predicts responsiveness to subsequent therapy in cervical cancer. METHODS AND MATERIALS Fourteen patients with biopsy-proved cervical cancer were studied by PET with (60)Cu-ATSM before initiation of radiotherapy and chemotherapy. (60)Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M) and peak slope index of tumor tracer uptake. All patients also underwent clinical PET with F-18 fluorodeoxyglucose (FDG) before institution of therapy. The PET results were correlated with follow-up evaluation (14-24 months). RESULTS Tumor uptake of (60)Cu-ATSM was inversely related to progression-free survival and overall survival (log-rank p = 0.0005 and p = 0.015, respectively). An arbitrarily selected T/M threshold of 3.5 discriminated those likely to develop recurrence; 6 of 9 patients with normoxic tumors (T/M < 3.5) are free of disease at last follow-up, whereas all of 5 patients with hypoxic tumors (T/M > 3.5) have already developed recurrence. Similar discrimination was achieved with the peak slope index. The frequency of locoregional nodal metastasis was greater in hypoxic tumors (p = 0.03). Tumor FDG uptake did not correlate with (60)Cu-ATSM uptake (r = 0.04; p = 0.80), and there was no significant difference in tumor FDG uptake between patients with hypoxic tumors and those with normoxic tumors. CONCLUSION (60)Cu-ATSM-PET in patients with cervical cancer revealed clinically relevant information about tumor oxygenation that was predictive of tumor behavior and response to therapy in this small study.

Detection of recurrent and metastatic colorectal cancer: Comparison of positron emission tomography and computed tomography

AbstractBackground: This study evaluates the clinical value of positron emission tomography (PET) with 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) as compared to computed tomography (CT) in patients with suspected recurrent or metastatic colorectal cancer (CRC). Methods: A retrospective review of the records of 58 patients who had FDG-PET for evaluation of recurrent or advanced primary CRC was performed. FDG-PET results were compared with those of CT and correlated with operative and histopathologic findings, or with clinical course and autopsy reports. Results: Recurrent or advanced primary CRC was diagnosed in 40 and 11 patients, respectively. The sensitivity and specificity of FDG-PET were 91% and 100% for detecting local pelvic recurrence, and 95% and 100% for hepatic metastases. These values were superior to CT, which had sensitivity and specificity of 52% and 80% for detecting pelvic recurrence, and 74% and 85% for hepatic metastases. FDG-PET correctly identified pelvic recurrence in 19 of 21 patients; CT was negative in 6 of these patients and equivocal in 4. FDG-PET was superior to CT in detecting multiple hepatic lesions and influenced clinical management in 10 of 23 (43%) patients. Conclusion: FDG-PET is more sensitive than CT in the clinical assessment of patients with recurrent or metastatic CRC, and provides an accurate means of selecting appropriate treatment for these patients.

Usefulness of FDG-PET scan in the assessment of suspected metastatic or recurrent adenocarcinoma of the colon and rectum

PURPOSE: The purpose of this study was to evaluate the clinical efficacy of positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose compared with computed tomography plus other conventional diagnostic studies in patients suspected of having metastatic or recurrent colorectal adenocarcinoma. METHODS: The records of 105 patients who underwent 101 computed tomography and 109 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography scans for suspected metastatic or recurrent colorectal adenocarcinoma were reviewed. Clinical correlation was confirmed at time of operation, histopathologically, or by clinical course. RESULTS: The overall sensitivity and specificity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detection of clinically relevant tumor were higher (87 and 68 percent) than for computed tomography plus other conventional diagnostic studies (66 and 59 percent). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting mucinous cancer was lower (58 percent; n=16) than for nonmucinous cancer (92 percent; n=93). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting locoregional recurrence (n=70) was higher than for computed tomography plus colonoscopy (90vs. 71 percent, respectively). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting hepatic metastasis (n=101) was higher than for computed tomography (89vs. 71 percent). The sensitivity of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in detecting extrahepatic metastases exclusive of locoregional recurrence (n=101) was higher than for computed tomography plus other conventional diagnostic studies (94vs. 67 percent). 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography altered clinical management in a beneficial manner in 26 percent of cases (26/101) when compared with evaluation by computed tomography plus other conventional diagnostic studies. CONCLUSION: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is more sensitive than computed tomography for the detection of metastatic or recurrent colorectal cancer and may improve clinical management in one-quarter of cases. However, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography is not as sensitive in detecting mucinous adenocarcinoma, possibly because of the relative hypocellularity of these tumors.

Improvement in Staging of Esophageal Cancer With the Addition of Positron Emission Tomography

BACKGROUND Positron emission tomography with the glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose (FDG) has been used to detect and stage a variety of malignancies. We hypothesized that FDG-positron emission tomography would improve staging of patients with esophageal cancer and thereby facilitate selection of candidates for resection. METHODS Fifty-eight patients (42 men and 16 women) with biopsy-proven esophageal cancer were evaluated with both FDG-positron emission tomography and computed tomography. RESULTS In all but 2 patients, increased FDG uptake was identified at the site of the primary tumor. Six patients were not operative candidates. Seventeen patients were not candidates for resection because of metastatic disease. Positron emission tomography identified the metastatic disease in all 17 (12 of whom underwent confirmatory biopsy), whereas computed tomography was positive for metastases in only 5. The remaining 35 patients underwent surgical exploration, were judged to have resectable disease and had esophagectomy. Pathologic examination of resected specimens identified lymph node metastases in 21 patients. These nodes were detected by positron emission tomography in 11 patients and by computed tomography in 6. CONCLUSIONS Positron emission tomography improved staging and facilitated selection of patients for operation by detecting distant disease not identified by computed tomography alone.

Utility of FDG-PET for investigating unexplained plasma CEA elevation in patients with colorectal cancer.

OBJECTIVE To assess the potential role of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in patients with unexplained rising carcinoembryonic antigen (CEA) levels after the treatment of colorectal cancer. BACKGROUND A rising CEA level after the resection of colorectal cancer is an early indicator of tumor recurrence. However, conventional imaging techniques have limited sensitivity for detecting recurrent disease in such patients. Especially after surgical intervention, FDG-PET is rapidly gaining an important role in establishing the extent of disease in the oncology patient. METHODS Twenty-two patients with abnormal CEA levels and normal results of conventional methods of tumor detection were studied with FDG-PET. The PET results were compared with pathologic findings (n = 9) and long-term radiologic and clinical follow-up (n = 13). RESULTS FDG-PET was abnormal in 17 of 22 patients. Tissue sampling was available in 7 of these 17 patients; all of these had recurrent disease. Definitive curative surgical intervention was performed in four patients. Subsequent dedicated imaging findings and clinical course confirmed the presence of extensive disease in 8 of the remaining 10 patients; the PET results in the other 2 patients were considered falsely positive. FDG-PET was negative in 5 of 22 patients. No disease was found by tissue sampling (n = 2) and clinical follow-up (n = 3). Overall, the positive-predictive value for PET was 89%, (15 of 17) and the negative-predictive value was 100% (5 of 5). CONCLUSIONS When conventional examinations are normal, FDG-PET is a valuable imaging tool in patients who have a rising CEA level after colorectal surgery.

Lower-Dose vs High-Dose Oral Estradiol Therapy of Hormone Receptor-Positive, Aromatase Inhibitor-Resistant Advanced Breast Cancer: A Phase 2 Randomized Study

CONTEXT Estrogen deprivation therapy with aromatase inhibitors has been hypothesized to paradoxically sensitize hormone-receptor-positive breast cancer tumor cells to low-dose estradiol therapy. OBJECTIVE To determine whether 6 mg of estradiol (daily) is a viable therapy for postmenopausal women with advanced aromatase inhibitor-resistant hormone receptor-positive breast cancer. DESIGN, SETTING, AND PATIENTS A phase 2 randomized trial of 6 mg vs 30 mg of oral estradiol used daily (April 2004-February 2008 [enrollment closed]). Eligible patients (66 randomized) had metastatic breast cancer treated with an aromatase inhibitor with progression-free survival (> or = 24 wk) or relapse (after > or = 2 y) of adjuvant aromatase inhibitor use. Patients at high risk of estradiol-related adverse events were excluded. Patients were examined after 1 and 2 weeks for clinical and laboratory toxicities and flare reactions and thereafter every 4 weeks. Tumor radiological assessment occurred every 12 weeks. At least 1 measurable lesion or 4 measurable lesions (bone-only disease) were evaluated for tumor response. INTERVENTION Randomization to receive 1 oral 2-mg generic estradiol tablet 3 times daily or five 2-mg tablets 3 times daily. MAIN OUTCOME MEASURES Primary end point: clinical benefit rate (response plus stable disease at 24 weeks). SECONDARY OUTCOMES toxicity, progression-free survival, time to treatment failure, quality of life, and the predictive properties of the metabolic flare reaction detected by positron emission tomography/computed tomography with fluorodeoxyglucose F 18. RESULTS The adverse event rate (> or = grade 3) in the 30-mg group (11/32 [34%]; 95% confidence interval [CI], 23%-47%) was higher than in the 6-mg group (4/34 [18%]; 95% CI, 5%-22%; P = .03). Clinical benefit rates were 9 of 32 (28%; 95% CI, 18%-41%) in the 30-mg group and 10 of 34 (29%; 95% CI, 19%-42%) in the 6-mg group. An estradiol-stimulated increase in fluorodeoxyglucose F 18 uptake (> or = 12% prospectively defined) was predictive of response (positive predictive value, 80%; 95% CI, 61%-92%). Seven patients with estradiol-sensitive disease were re-treated with aromatase inhibitors at estradiol progression, among which 2 had partial response and 1 had stable disease, suggesting resensitization to estrogen deprivation. CONCLUSIONS In women with advanced breast cancer and acquired resistance to aromatase inhibitors, a daily dose of 6 mg of estradiol provided a similar clinical benefit rate as 30 mg, with fewer serious adverse events. The efficacy of treatment with the lower dose should be further examined in phase 3 clinical trials. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00324259.