Eric Rohren

Clinical practice guidelines in oncology

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

Response Assessment of Aggressive Non-Hodgkin’s Lymphoma by Integrated International Workshop Criteria and Fluorine-18–Fluorodeoxyglucose Positron Emission Tomography

PURPOSE To determine whether a response classification based on integration of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) into the International Workshop Criteria (IWC) provides a more accurate response assessment than IWC alone in patients with non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS Fifty-four patients with aggressive NHL who underwent FDG-PET and computed tomography 1 to 16 weeks after four to eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone were assessed for complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) by the IWC and by integrated IWC and FDG-PET (IWC+PET). Progression-free survival (PFS) was also compared between IWC- and IWC+PET-assigned response designations. RESULTS By IWC, 17 patients had a CR, seven had a CRu, 19 had a PR, nine had SD, and two had PD. In comparison, by IWC+PET, 35 patients had a CR, 12 had a PR, six had SD, one had PD, and zero had a CRu. In separate multivariate models, PFS was significantly shorter in patients with PR than in those with a CR using IWC (hazard ratio [HR], 8.9; P = .021) or IWC+PET (HR, 29.7; P = .0003). However, when the two classifications were included in the same multivariate model, only IWC+PET was a statistically significant independent predictor for PFS (P = .008 v P = .72 for IWC). In addition, when patients with a PR by IWC and a CR by IWC+PET were compared with those with a CR by IWC and a CR by IWC+PET, there was no significant difference in PFS (HR, 1.6; P = .72), indicating that IWC+PET identified a subset of IWC-PR patients with a more favorable prognosis. CONCLUSION Compared with IWC, the IWC+PET-based assessment provides a more accurate response classification in patients with aggressive NHL.

Circulating Tumor Cells and [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Outcome Prediction in Metastatic Breast Cancer

PURPOSE Circulating tumor cells (CTCs) and [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) are two new promising tools for therapeutic monitoring. In this study, we compared the prognostic value of CTC and FDG-PET/CT monitoring during systemic therapy for metastatic breast cancer (MBC). PATIENTS AND METHODS A retrospective analyses of 115 MBC patients who started a new line of therapy and who had CTC counts and FDG-PET/CT scans performed at baseline and at 9 to 12 weeks during therapy (midtherapy) was performed. Patients were categorized according to midtherapy CTC counts as favorable (ie, < five CTCs/7.5 mL blood) or unfavorable (> or = five CTCs/7.5 mL blood) outcomes. CTC counts and FDG-PET/CT response at midtherapy were compared, and univariate and multivariate analyses were performed to identify factors associated with survival. RESULTS In 102 evaluable patients, the median overall survival time was 14 months (range, 1 to > 41 months). Midtherapy CTC levels correlated with FDG-PET/CT response in 68 (67%) of 102 evaluable patients. In univariate analysis, midtherapy CTC counts and FDG-PET/CT response predicted overall survival (P < .001 and P = .001, respectively). FDG-PET/CT predicted overall survival (P = .0086) in 31 (91%) of 34 discordant patients who had fewer than five CTCs at midtherapy. Only midtherapy CTC levels remained significant in a multivariate analysis (P = .004). CONCLUSION Detection of five or more CTCs during therapeutic monitoring can accurately predict prognosis in MBC beyond metabolic response. FDG-PET/CT deserves a role in patients who have fewer than five CTCs at midtherapy. Prospective trials should evaluate the most sensitive and cost-effective modality for therapeutic monitoring in MBC.

18F-FDG PET/CT as an Indicator of Progression-Free and Overall Survival in Osteosarcoma

The aim of our study was to retrospectively evaluate whether maximum standardized uptake value (SUVmax), total lesion gylcolysis (TLG), or change therein using 18F-FDG PET/CT performed before and after initial chemotherapy were indicators of patient outcome. Methods: Thirty-one consecutive patients who underwent 18F-FDG PET/CT before and after chemotherapy, followed by tumor resection, were retrospectively reviewed. Univariate Cox regression was used to analyze for relationships between covariates of interest (SUVmax before and after chemotherapy, change in SUVmax, TLG before and after chemotherapy, change in TLG, and tumor necrosis) and progression-free and overall survival. Logistic regression was used to evaluate tumor necrosis. Results: High SUVmax before and after chemotherapy (P = 0.008 and P = 0.009, respectively) was associated with worse progression-free survival. The cut point for SUVmax before chemotherapy was greater than 15 g/mL* (P = 0.015), and after chemotherapy it was greater than 5 g/mL* (P = 0.006), as measured at our institution and using lean body mass. Increase in TLG after chemotherapy was associated with worse progression-free survival (P = 0.016). High SUVmax after chemotherapy was associated with poor overall survival (P = 0.035). The cut point was above the median of 3.3 g/mL* (P = 0.043). High TLG before chemotherapy was associated with poor overall survival (P = 0.021). Good overall and progression-free survival was associated with a tumor necrosis greater than 90% (P = 0.018 and 0.08, respectively). A tumor necrosis greater than 90% was most strongly associated with a decrease in SUVmax (P = 0.015). Conclusion: 18F-FDG PET/CT can be used as a prognostic indicator for progression-free survival, overall survival, and tumor necrosis in osteosarcoma.

Imaging bone metastases in breast cancer: techniques and recommendations for diagnosis

Bone is the most common site of distant metastases from breast carcinoma. The presence of bone metastases affects a patients prognosis, quality of life, and the planning of their treatment. We discuss recent innovations in bone imaging and present algorithms, based on the strengths and weaknesses of each technique, to facilitate the most successful and cost-effective choice of imaging studies for the detection of osseous metastases. Skeletal scintigraphy (bone scan) is very sensitive in the detection of osseous metastases and is recommended as the first imaging study in patients who are asymptomatic. Radiographs are recommended for the assessment of abnormal radionuclide uptake or the risk of pathological fracture and as initial imaging studies in patients with bone pain. MRI or PET-CT can be considered for cases of abnormal radionuclide uptake that are not addressed by radiography. Osseous metastases can lead to emergent situations, such as spinal-cord compression or impending fracture of a weight-bearing bone, and imaging guidelines are essential for early detection and initiation of appropriate therapy. The imaging method used in non-emergent situations, such as assessment of the ribs, sternum, pelvis, hips, and joints, should be guided by the strengths and limitations of each technique.

Phase I trial of cixutumumab combined with temsirolimus in patients with advanced cancer

Purpose: Mammalian target of rapamycin (mTOR) inhibitors mediate AKT activation through a type 1 insulin-like growth factor receptor (IGF-1R)–dependent mechanism. Combining the mTOR inhibitor temsirolimus with cixutumumab, a fully human immunoglobulin G1 monoclonal antibody directed against IGF-1R, was expected to enhance mTOR-targeted anticancer activity by modulating resistance to mTOR inhibition. The objectives of this phase I study were to evaluate the tolerability and activity of temsirolimus and cixutumumab. Experimental Design: Patients in sequential cohorts (“3 + 3” design) received escalating doses of temsirolimus with cixutumumab weekly for 28 days. At the maximum tolerated dose (MTD), 21 patients were randomized into three separate drug sequence treatment groups for serial blood draws and 2[18F]fluoro-2-deoxy-d-glucose positron emission tomography combined with X-ray computed tomography (FDG-PET/CT) scans for pharmacodynamic analyses (PD). Results: Forty-two patients with advanced cancer (19 male/23 female, median age = 53, median number of prior therapies = 4) were enrolled. MTD was reached at cixutumumab, 6 mg/kg IV and temsirolimus, 25 mg IV. Dose-limiting toxicities included grade 3 mucositis, febrile neutropenia, and grade 4 thrombocytopenia. The most frequent toxicities were hypercholesterolemia, hypertriglyceridemia, hyperglycemia, thrombocytopenia, and mucositis. Tumor reduction was observed in 2 of 3 patients with Ewings sarcoma and in 4 of 10 patients with adrenocortical carcinoma. PD data suggest that cixutumumab alone or combined with temsirolimus increased plasma IGF-1 and IGF binding protein 3. FDG-PET/CT showed the odds of achieving stable disease decreased by 58% (P = 0.1213) with a one-unit increase in absolute change of standard uptake value from baseline to day 3. Conclusions: Temsirolimus combined with cixutumumab was well tolerated. We are currently enrolling expansion cohorts at the MTD for Ewings sarcoma and adrenocortical carcinoma. Clin Cancer Res; 17(18); 6052–60. ©2011 AACR.

The Role of F-18 Fdg Positron Emission Tomography in Preoperative Assessment of the Liver in Patients Being Considered for Curative Resection of Hepatic Metastases from Colorectal Cancer

Purpose The authors’ goal was to determine the sensitivity and specificity of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying patients with hepatic metastases from colorectal cancer and the accuracy of PET for determining the number and distribution of lesions within the liver. Intraoperative sonography and surgical inspection and palpation were used as the reference standard. Methods Twenty-three patients being evaluated for surgical resection of hepatic metastases from colorectal carcinoma underwent FDG PET before operation. Findings of the PET studies were reviewed in a blinded, retrospective manner, with the results compared with the findings of intraoperative sonography and surgical exploration. Lesions of all sizes were considered in the analysis. Results The FDG-PET results were positive in 21 of the 22 patients ultimately found to have metastatic disease to the liver, and they were negative in the single patient without metastases. Therefore, for identification of patients with hepatic metastatic disease, PET has a sensitivity of 95% and a specificity of 100%. In all, 48 metastatic lesions were identified in these patients, of which 38 (79%) were identified on PET images. The probability of lesion detection by PET was directly correlated with lesion size (P < 0.01). The assessment of lobar disease distribution in the liver was discordant between PET and surgery in 3 of 23 (13%) patients. Conclusions In patients being evaluated for potential curative resection of hepatic metastases from colorectal cancer, FDG PET is accurate for the identification of the presence or absence of metastatic disease to the liver. However, detection of individual lesions depends on their size, and determination of lesion number and distribution within the liver is more accurately accomplished with intraoperative sonography.

Clinical utility of PET/CT in lymphoma

OBJECTIVE The purpose of this review is to assist interpreting radiologists in becoming familiar with the role of PET/CT in baseline staging and therapeutic response assessment in the management of lymphoma, in becoming aware of imaging pitfalls, and in understanding the natural behavior of lymphoma and the therapeutic options. CONCLUSION Therapeutic strategies for the management of lymphoma are constantly being refined to improve long-term survival with the lowest risk of toxicity to the patient. PET/CT is accurate for baseline staging and yields important prognostic information for determining the most appropriate initial treatment. Used for evaluation of treatment response, PET/CT can depict residual viable malignant lesions with greater accuracy than can other imaging techniques. The findings thereby influence decisions about the need for additional or alternative treatment.

Retrospective Study of 18F-FDG PET/CT in the Diagnosis of Inflammatory Breast Cancer: Preliminary Data

Our objective was to retrospectively evaluate 18F-FDG PET/CT in the initial staging of inflammatory breast cancer (IBC). Methods: The institutional review board waived informed consent and approved this study, which was compliant with the Health Insurance Portability and Accountability Act. The cases of 41 women with a mean age of 50 y (range, 25–71 y) and newly diagnosed IBC who underwent 18F-FDG PET/CT at diagnosis were retrospectively reviewed. All PET/CT images were analyzed visually and semiquantitatively by 2 physicians. The maximum standardized uptake value in the primary breast, regional nodes (axillary, subpectoral, supraclavicular, internal mammary), and extranodal regions was documented. The accuracy of PET/CT image interpretation was assessed by histopathologic analysis, if available; concurrent or subsequent imaging findings (contrast-enhanced CT, contrast-enhanced MRI, sonography, or PET/CT follow-up); or clinical follow-up. Results: All patients presented with unilateral IBC. PET/CT showed hypermetabolic uptake in the skin in all patients, in the affected breast in 40 (98%), in the ipsilateral axillary nodes in 37 (90%), and in the ipsilateral subpectoral nodes in 18 (44%). Twenty patients (49%) were found to have distant metastases at staging, 7 (17%) of whom were not known to have metastases before undergoing PET/CT. Disease sites included bone, liver, contralateral axilla, lung, chest wall, pelvis, and the subpectoral, supraclavicular, internal mammary, mediastinal, and abdominal nodes. Conclusion: PET/CT should be considered in the initial staging of IBC, as the technique provided valuable information on locoregional and distant disease in this preliminary retrospective study.

False-positive lesions mimicking breast cancer on FDG PET and PET/CT

OBJECTIVE Incidental (18)F-FDG-avid breast lesions are commonly encountered in patients with cancer who undergo staging PET/CT. This pictorial essay discusses breast lesions that show increased FDG activity, mimicking breast cancer, with biopsy-confirmed benign diagnosis. CONCLUSION Acute and chronic inflammation, physiologic lactation, and benign breast masses, including silicone granuloma, fat necrosis, fibroadenoma, and postsurgical changes, may show increased FDG uptake on PET/CT. These conditions can often be differentiated from malignancy by correlative imaging, including mammography, sonography, or MRI.