Rituximab, cyclophosphamide-fractionated, vincristine, doxorubicin and dexamethasone alternating with rituximab, methotrexate and cytarabine overcomes risk features associated with inferior outcomes in treatment of newly diagnosed, high-risk diffuse large B-cell lymphoma.

Subtypes of diffuse large B-cell lymphoma (DLBCL) that have inferior outcomes after front-line therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) have been identified. While it is agreed that R-CHOP is probably not adequate in these patients, there is no standard treatment approach for patients with DLBCL with high-risk features. We present results of a retrospective cohort study of high-risk DLBCL (defined as having at least one unfavorable risk factor: non-germinal center [GC] subtype by immunohistochemistry [IHC], Ki-67 ≥ 80%, high International Prognostic Index [IPI], c-MYC rearrangement) treated with R-HCVAD/R-MTX-AraC (rituximab, cyclophosphamide-fractionated, vincristine, doxorubicin and dexamethasone alternating with rituximab, methotrexate and cytarabine; R-HCVAD) as front-line therapy. With a median follow-up of 25.3 months, the 3-year PFS and OS estimates are 79% (95% confidence interval [CI], 65-88%) and 76% (95% CI, 61-86%), respectively, which are higher than those for historical comparisons with R-CHOP data for high-risk patients. These data are in accord with other recent reports of dose-intense front-line therapy of high-risk DLBCL. This analysis represents the largest reported cohort of patients with DLBCL treated with R-HCVAD. These data suggest that R-HCVAD can overcome traditional poor risk features such as high IPI, high Ki-67 and non-GC IHC pattern. Future work will focus on identifying molecular markers for failure in patients with DLBCL treated with dose-intensive regimens.

Post-treatment (not interim) positron emission tomography-computed tomography scan status is highly predictive of outcome in mantle cell lymphoma patients treated with R-HyperCVAD.

BACKGROUND: Although convincing data exist regarding the prognostic utility of positron emission tomographic (PET)-computed tomographic (CT) imaging in Hodgkin lymphoma and diffuse large B-cell lymphoma, its prognostic utility both during treatment and immediately after treatment have not been systematically evaluated in a large mantle cell lymphoma (MCL) patient cohort to support its use in clinical practice. METHODS: The authors conducted a retrospective cohort study to examine the prognostic utility of PET-CT imaging in a uniform MCL patient cohort undergoing dose-intensive chemotherapy (R-HyCVAD) in the frontline setting. The primary study endpoints were progression-free survival (PFS) and overall survival (OS). PET-CT images were centrally reviewed for the purposes of this study using standardized response criteria. RESULTS: Fifty-three patients with advanced stage MCL with PET-CT data were identified. With median follow-up of 32 months, 3-year PFS and OS estimates were 76% (95% confidence interval [CI], 64%-84%) and 84% (95% CI, 72%-90%), respectively. Interim PET-CT status was not associated with PFS (hazard ratio [HR], 0.9; 95% CI, 0.3-2.7; P = .8) or OS (HR, 0.6; 95% CI, 0.1-2.9; P = .5). Post-treatment PET-CT status was statistically significantly associated with PFS (HR, 5.2; 95% CI, 2.0-13.6; P = .001) and trended toward significant for OS (HR, 2.8; 95% CI, 0.8-9.6; P = .07). CONCLUSIONS: These data do not support the prognostic utility of PET-CT in pretreatment and interim treatment settings. A positive PET-CT after the completion of therapy identifies a patient subset with an inferior PFS and a trend toward inferior OS.

Interpretation and reporting of positron emission tomography-computed tomographic scans.

Body oncology positron emission tomography-computed tomographic (PET-CT) exams are particularly complex and time-consuming studies to interpret and report. An integrated approach is required to provide the referring physician with the full clinical value of this combined modality. Special attention to the Positron Emission Tomography-Computed Tomographic Report Findings section and Impression section is necessary to insure all the information relevant to the patient's care are clearly communicated to the referring physicians.

Detection of clinically unexpected malignant and premalignant tumors with whole-body FDG PET: histopathologic comparison.

PURPOSE: To determine the clinical importance and malignant potential of unexpected abnormal foci of hypermetabolism at fluorodeoxyglucose (FDG) positron emission tomography (PET) performed for evaluation of malignancy. MATERIALS AND METHODS: A total of 1,750 FDG PET scans were obtained to evaluate a variety of known or suspected malignancies. Each scan was evaluated for abnormal unexpected hypermetabolism based on unusual location (ie, foci that did not conform to the usual distribution of metastases given the primary tumor for which the PET scan was requested) and discrete focal nature of an abnormality. Unexpected findings were followed by pathologic confirmation and were considered clinically important if the final pathologic diagnosis was cancerous, precancerous, or noncancerous but had the potential for local destruction or systemic physiologic effects. RESULTS: On the basis of the normal spread pattern of the primary lesion, 58 abnormal unexpected foci of hypermetabolism were identified in 53 patients. Forty-five of these abnormalities were followed up with computed tomography (CT), magnetic resonance imaging, and/or mammography, and 42 had subsequent tissue confirmation at endoscopic, CT-guided, or surgical biopsy. Of 42 histopathologically confirmed abnormalities, 30 (71%) were either malignant or premalignant tumors that differed from the cancer for which the patient was originally scanned. Nine other suspicious abnormal foci proved benign and three represented false-positive findings, with no abnormal findings at endoscopy. Three of nine nonmalignant lesions were considered clinically important because of the potential for local destruction and/or systemic effects. CONCLUSION: The identification of unexpected foci of hypermetabolism at whole-body FDG PET may signal the presence of tumors that are unrelated to the neoplasm for which the patient was scanned. Findings of this study emphasize the need for follow-up of these abnormalities because the majority represent either malignant or premalignant neoplasms, which were not clinically apparent.

Clinical role of FDG PET in evaluation of cancer patients.

Positron emission tomography (PET) is a diagnostic imaging technique that allows identification of biochemical and physiologic alterations in tumors. Use of PET performed with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) significantly improves the accuracy of tumor imaging. In terms of oncologic applications, FDG PET has already gained widespread acceptance in the initial staging of cancer, management of recurrent cancer, and monitoring the response to therapy. With conventional imaging modalities, size criteria are used to distinguish between benign and malignant disease in lymph nodes; conversely, FDG PET is based on identification of fundamental aspects of tumor metabolism. FDG uptake in tumors is proportional to the metabolic rate of viable tumor cells, which have an increased demand for glucose. The high sensitivity and high negative predictive value of FDG PET in most malignant tumors enable this technique to play an even greater role in tumor management at initial staging and follow-up.