PET Response Criteria In Solid Tumors Research Articles

Therapy response evaluation with FDG-PET/CT in small cell lung cancer: a prognostic and comparison study of the PERCIST and EORTC criteria

Introduction: Small cell lung cancer (SCLC) is an aggressive form of lung cancer with poor prognosis. Adequate staging and therapeutic evaluation is necessary for therapy planning. Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been shown to be useful for staging and therapy response evaluation. The European Organization for Research and Treatment of Cancer (EORTC) and Positron Emission Tomography Response Criteria In Solid Tumors (PERCIST) criteria were compared in the evaluation of response assessment and prognostic factors were defined in a cohort of SCLC patients. Methods: Twenty-nine consecutive patients with SCLC were included in this study. Sixteen patients had extensive disease and 13 had limited disease. All patients had chemotherapy, 21 had thoracic radiotherapy. FDG-PET/CT scans were performed before and after therapy to evaluate treatment response. Metabolic responses were assessed using the EORTC criteria and PERCIST criteria. Univariate and multivariate analysis were performed using a Cox model to investigate the association between progression-free and overall survival time with a number of covariates. Results: There was perfect concordance between the EORTC and PERCIST criteria. Eight patients had a complete metabolic response (CMR), 9 had a partial metabolic response (PMR), 5 had stable metabolic disease (SMD) and 7 had progressive metabolic disease (PMD). Overall survival time in patients with CMR was significantly longer compared with patients who did not have CMR. The initial or delayed CMR and post-therapeutic standardized uptake value corrected for lean body mass were significantly associated with overall survival. Conclusion: CMR on post-therapeutic FDG-PET/CT in patients with SCLC is an important prognostic factor and may help decision making for therapeutic management.

Prognostic value of quantitative parameters derived on initial staging 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with high-grade non-Hodgkin’s lymphoma

This study was carried out to evaluate the role of quantitative parameters in staging PET in predicting prognosis in patients with high-grade non-Hodgkin's lymphoma (NHL). A total of 51 histopathologically proven high-grade NHL patients treated with conventional chemotherapy regimens were included in the study. Total lesion glycolysis (TLG) and functional volumes (FVs) were defined as per the PET Response Criteria in Solid Tumors (PERCIST) criteria. All patients were followed up for a minimum period of 1 year or until an event, whichever occurred earlier. Of the four semiquantitative parameters studied, SUV max and SUV mean did not show a statistically significant correlation with progression-free survival or overall survival, whereas TLG and FV showed a weak but statistically significant negative correlation. Using the receiver operating characteristic curve analysis, optimal cut-offs were derived for FV and TLG to predict progression and death. Using the cut-off values of 416 cm3 and 3340 g for FV and TLG, respectively, a statistically significant difference in progression-free survival and overall survival was obtained in the groups with FV and TLG above and below the threshold. On multivariate analysis of all the conventional prognostic factors and TLG more than 3340 and FV more than 416 cm3, only age greater than 60 years (P=0.013) and FV more than 416 cm3 (P=0.012) were found to be independently associated with disease progression. Our results indicate that FV and TLG in staging PET/CT could be useful indices in predicting outcomes in patients with high-grade NHL treated with standard first-line chemotherapy regimens.

A case series of low dose bevacizumab and chemotherapy in heavily pretreated patients with epithelial ovarian cancer.

BackgroundThe addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first line treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and activity of a lower dose of bevacizumab in pretreated advanced stage EOC.MethodsWe treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior cytotoxic regimens, with bevacizumab 5–7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor response was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT.ResultsThe median number of bevacizumab cycles was 21 (range 3–59). The median baseline CA125 was 272 U/ml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial response (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 – 95.8) according to Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall metabolic response rate of 67% (95%CI, 42.8 – 90.6) according to PET Response Criteria in Solid Tumors (PERCIST). Median progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment was delayed in five patients for nasal bleeding or uncontrolled hypertension.ConclusionsLow-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated population of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC.

Evaluation of Response to Neoadjuvant Chemotherapy for Esophageal Cancer: PET Response Criteria in Solid Tumors Versus Response Evaluation Criteria in Solid Tumors

Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a new standardized method to assess chemotherapeutic response metabolically and quantitatively. The aim of this study was to evaluate therapeutic response to neoadjuvant chemotherapy for locally advanced esophageal cancer, comparing PERCIST with the currently widely used response evaluation criteria in solid tumors (RECIST). Fifty-one patients with locally advanced esophageal cancer who received neoadjuvant chemotherapy (5-fluorouracil, adriamycin, and cisplatin), followed by surgery were studied. Chemotherapeutic lesion responses were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST methods. The PET/CT scans were obtained before chemotherapy and about 2 wk after completion of chemotherapy. Associations were statistically analyzed between survival (overall and disease-free survival) and clinicopathologic results (histology [well-, moderately, and poorly differentiated squamous cell carcinoma], lymphatic invasion, venous invasion, clinical stage, pathologic stage, resection level, reduction rate of tumor diameter, reduction rate of tumor uptake, chemotherapeutic responses in RECIST and PERCIST, and pathologic response). There was a significant difference in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P < 0.0001). Univariate analysis showed that lymphatic invasion, venous invasion, resection level, pathologic stage, and PERCIST were significant factors associated with disease-free or overall survival in this study. Although multivariate analysis demonstrated that venous invasion (disease-free survival: hazard ratio [HR] = 4.519, P = 0.002; overall survival: HR = 5.591, P = 0.003) and resection level (disease-free survival: HR = 11.078, P = 0.001) were the significant predictors, PERCIST was also significant in noninvasive therapy response assessment before surgery (disease-free survival: HR = 4.060, P = 0.025; overall survival: HR = 8.953, P = 0.034). RECIST based on the anatomic size reduction rate did not demonstrate the correlation between therapeutic responses and prognosis in patients with esophageal cancer receiving neoadjuvant chemotherapy. However, PERCIST was found to be the strongest independent predictor of outcomes. Given the significance of noninvasive radiologic imaging in formulating clinical treatment strategies, PERCIST might be considered more suitable for evaluation of chemotherapeutic response to esophageal cancer than RECIST.

Neoadjuvant Chemotherapy in Breast Cancer: Prediction of Pathologic Response with PET/CT and Dynamic Contrast-enhanced MR Imaging—Prospective Assessment

To clarify whether fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging performed after two cycles of neoadjuvant chemotherapy (NAC) can be used to predict pathologic response in breast cancer. Institutional human research committee approval and written informed consent were obtained. Accuracy after two cycles of NAC for predicting pathologic complete response (pCR) was examined in 142 women (mean age, 57 years: range, 43-72 years) with histologically proved breast cancer between December 2005 and February 2009. Quantitative PET/CT and DCE MR imaging were performed at baseline and after two cycles of NAC. Parameters of PET/CT and of blood flow and microvascular permeability at DCE MR were compared with pathologic response. Patients were also evaluated after NAC by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on DCE MR measurements and European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Multiple logistic regression analyses were performed to examine continuous variables at PET/CT and DCE MR to predict pCR, and diagnostic accuracies were compared with the McNemar test. Significant decrease from baseline of all parameters at PET/CT and DCE MR was observed after NAC. Therapeutic response was obtained in 24 patients (17%) with pCR and 118 (83%) without pCR. Sensitivity, specificity, and accuracy to predict pCR were 45.5%, 85.5%, and 82.4%, respectively, with RECIST and 70.4%, 95.7%, and 90.8%, respectively, with EORTC and PERCIST. Multiple logistic regression revealed three significant independent predictors of pCR: percentage maximum standardized uptake value (%SUV(max)) (odds ratio [OR], 1.22; 95% confidence interval [CI]: 1.11, 1.34; P < .0001), percentage rate constant (%k(ep)) (OR, 1.07; CI: 1.03, 1.12; P = .002), and percentage area under the time-intensity curve over 90 seconds (%AUC(90)) (OR, 1.04; CI: 1.01, 1.07; P = .048). When diagnostic accuracies are compared, PET/CT is superior to DCE MR for the prediction of pCR (%SUV(max) [90.1%] vs %κ(ep) [83.8%] or %AUC(90) [76.8%]; P < .05). The sensitivities of %SUV(max) (66.7%), %k(ep) (51.7%), and %AUC(90) (50.0%) at (18)F-FDG PET/CT and DCE MR after two cycles of NAC are not acceptable, but the specificities (96.4%, 92.0%, and 95.2%, respectively) are high for stratification of pCR cases in breast cancer.

Phase II study of helical tomotherapy in the multidisciplinary treatment of oligometastatic colorectal cancer

BackgroundComplete metastasectomy provides a real chance for long-term survival in patients with oligometastatic colorectal cancer (CRC). For inoperable patients, we evaluated in this study intensity-modulated and image-guided radiotherapy (IMRT-IGRT) by helical tomotherapy.MethodsTwenty-four CRC patients with ≤ 5 metastases were enrolled, receiving a dose of 50 Gy in fractions of 5 Gy. No limitations concerning dimension or localization of the metastases were imposed. Whole body PET-CT was performed at baseline and 3 months after the initiation of RT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0.ResultsA total of 53 metastases were treated. Seventeen patients (71%) received previously ≥ 1 line of chemotherapy for metastatic disease, displaying residual (n = 7) or progressive (n = 10) metabolic active oligometastatic disease at time of inclusion. Most common sites were the lung, liver and lymphnodes. One patient (4%) experienced grade 3 dysphagia. Twenty-two patients were evaluated by post-treatment PET-CT. Twelve patients achieved a complete (n = 6) or partial (n = 6) metabolic response, resulting in an overall metabolic response rate of 55%. At a median follow-up of 10 months, 7 patients (29%) are in remission, of which 5 received previous chemotherapy with residual oligometastatic disease at time of inclusion. The actuarial 1-year local control, progression-free survival, and overall survival were 54%, 14% and 78%.ConclusionsHelical tomotherapy delivering 10 fractions of 5 Gy resulted in a metabolic response rate of 55%, and appeared to be attractive as consolidation of inoperable oligometastatic disease after effective chemotherapy.Trial registrationEudract 2008-008300-40; NCT00807313

Évaluation de la réponse thérapeutique par tomographie par émission de positons (TEP) au 18fluoro-désoxyglucose (FDG) en oncologie-hématologie

18Fluoro-deoxyglucose (FDG) positron emission tomography (PET) is an imaging technique which studies the cellular glucidic metabolism. It is particularly indicated in oncology, especially for cancer diagnosis (with a potential prognosis interest) or detection of recurrence. Because of its functional approach to the tissues, its use has logically evolved into the evaluation of cancer treatments, both for the individual care of patients for clinical trials of new therapies. Also, it tends to displace conventional imaging in this indication, whose main limitation is not to assess the viability of residual masses, potentially necrotic or fibrous after treatment. However, the use of FDG-PET requires a rigorous methodology for both the exams achievement but also for the quality of their interpretation, including the choice of the comparison tool. Based on an increasing literature on the subject, were published and updated interpretation criteria for both lymphoma and solid cancers. For lymphoma, standardized assessment criteria were proposed in 2007 during an International Harmonize Project (IHP). For solid cancers, Positron Emission tomography Response Criteria In Solid Tumors (PERCIST) recommendations version 1.0 were recently proposed by an American workshop in 2009 in order to clarify and standardize practices.

Phase II study of helical tomotherapy for oligometastatic colorectal cancer

BackgroundTo evaluate the efficacy and toxicity of helical tomotherapy in the treatment of oligometastatic colorectal cancer (CRC) patients who were not amenable for metastasectomy and/or (further) systemic treatment. Patients and methodsCRC patients with five or less metastases were enrolled. No limitations concerning dimension or localization of the metastases were imposed. Patients were treated with intensity-modulated and image-guided radiotherapy using helical tomotherapy, delivering a total dose of 40 Gy in fractions of 4 Gy. Positron emission tomography–computed tomography (PET-CT) was carried out at baseline and 3 months after the initiation of radiotherapy to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0. Side-effects were scored using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI–CTC AE) version 3.0. ResultsTwenty-three patients were enrolled. A total of 52 metastases were treated. One patient (4%) experienced grade 3 vomiting; two patients (9%) grade 2 diarrhea and dysphagia, respectively. Twenty-two patients were evaluated by post-treatment PET-CT. Five (23%) and seven patients (32%) achieved a complete and partial metabolic response, respectively, resulting in an overall metabolic response rate of 55%. The actuarial 1-year local control, progression-free survival, and overall survival were 54%, 25% and 86%, respectively. ConclusionThe use of helical tomotherapy in oligometastatic CRC patients resulted in a promising metabolic response rate of 55%.

Study evaluating different methods of tumor volume estimation on PET-CT in carcinoma lung.

e17528 Background: PET-CT has got a very vital role in present day oncology for diagnosis, staging, radiation planning, and response evaluation of tumors. We have even started talking about PET Response Criteria in Solid Tumors (PERCIST). Unfortunately, target delineation with PET currently remains a largely unaddressed problem. PET is a functional modality and the FDG concentrations within the tumor are variable. PET may either underestimate or overestimate the actual target volume. Various thresholding techniques have been developed where we take a certain percentage of the maximum SUV for edge definition. Many studies take from 15 to 40 % of Maximum SUV. The purpose of this study is to determine the performance of different edge detection methods for tumor volume estimation. Methods: Ten cases of newly diagnosed untreated Non Small cell lung cancer that underwent diagnostic PET, which had a measurable tumor on the images, were enrolled. The PET Images were transferred to the radiotherapy treatment planning system and PET and CT images were co-registered by pixel data matching. Gross Tumor was contoured on CT scan slice by slice manually by an oncologist (GTV-CT). Tumor volume was determined by summation of manually drawn regions of interest. Tumor volume was determined on FDG-PET with a semi automated method. The PET-GTV was delineated automatically by use of various percentages of the SUVmax. GTV-50, GTV-40, GTV-30, GTV-20 and GTV-15, based on the volume covered by respective percentage of maximum SUV were estimated. These volumes were compared with CT-GTV. Results: The mean maximum SUV was 7±3. The average volume of the GTV-CT was 125 cc. A significant impact of PET-derived contours on tumor volume estimation has been shown in 7 of the 10 patients with respect to the CT-GTV. PET defined GTV- 50 and GTV-40, were less than GTV-CT. Whereas GTV-30, GTV-20 and GTV-15 overestimated the GTV volume in majority of the cases. Even though GTV 40 underestimated the GTV, it was the closest match. Conclusions: Whereas the different thresholding methods either overestimated or underestimated the target volume, GTV 40 is the closest method for tumor delineation in NSCLC in our study. Further large studies needed. No significant financial relationships to disclose.

Cancer Response Criteria and Bone Metastases: RECIST 1.1, MDA and PERCIST

Response criteria represent the standard by which the efficacy of therapeutic agents is determined in cancer trials. The most widely used criteria are based on the anatomic measurement of solid tumors. Because bone metastases are typically located in irregularly shaped bones and are difficult to measure with rulers, they have been previously considered unmeasurable disease. New developments in cancer response criteria have increased awareness of the importance of the response of bone metastases to therapy. The recently updated Response Evaluation Criteria in Solid Tumors (RECIST 1.1) now consider bone metastases with soft tissue masses > 10 mm to be measurable disease. Response criteria specific to bone metastases have been developed at The University of Texas MD Anderson Cancer Center (MDA criteria) and can be used to assess therapeutic response in numerous types of bone metastases. Functional imaging criteria, such as the recently developed Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) allow response to be measured in the absence of anatomic change through assessment of metabolic activity. As monitoring tumor response of bone metastases becomes more important in the management of cancer, so does the demand on radiologists and nuclear medicine physicians for accurate interpretation of the behavior of these lesions. This article reviews anatomic, bone, and metabolic response criteria, providing illustrations for the interpretation of therapy-induced change in bone metastases.

From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors

The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with (18)F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0. PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors' experience, draft criteria were formulated for PET tumor response to treatment. Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has limitations in response assessments. For example, despite effective treatment, changes in tumor size can be minimal in tumors such as lymphomas, sarcoma, hepatomas, mesothelioma, and gastrointestinal stromal tumor. CT tumor density, contrast enhancement, or MRI characteristics appear more informative than size but are not yet routinely applied. RECIST criteria may show progression of tumor more slowly than WHO criteria. RECIST 1.1 criteria (assessing a maximum of 5 tumor foci, vs. 10 in RECIST) result in a higher complete response rate than the original RECIST criteria, at least in lymph nodes. Variability appears greater in assessing progression than in assessing response. Qualitative and quantitative approaches to (18)F-FDG PET response assessment have been applied and require a consistent PET methodology to allow quantitative assessments. Statistically significant changes in tumor standardized uptake value (SUV) occur in careful test-retest studies of high-SUV tumors, with a change of 20% in SUV of a region 1 cm or larger in diameter; however, medically relevant beneficial changes are often associated with a 30% or greater decline. The more extensive the therapy, the greater the decline in SUV with most effective treatments. Important components of the proposed PERCIST criteria include assessing normal reference tissue values in a 3-cm-diameter region of interest in the liver, using a consistent PET protocol, using a fixed small region of interest about 1 cm(3) in volume (1.2-cm diameter) in the most active region of metabolically active tumors to minimize statistical variability, assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional) most metabolically active tumor focus as a continuous variable, requiring a 30% decline in SUV for "response," and deferring to RECIST 1.1 in cases that do not have (18)F-FDG avidity or are technically unsuitable. Criteria to define progression of tumor-absent new lesions are uncertain but are proposed. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria have limitations, particularly in assessing the activity of newer cancer therapies that stabilize disease, whereas (18)F-FDG PET appears particularly valuable in such cases. The proposed PERCIST 1.0 criteria should serve as a starting point for use in clinical trials and in structured quantitative clinical reporting. Undoubtedly, subsequent revisions and enhancements will be required as validation studies are undertaken in varying diseases and treatments.

Progression and regression of atherosclerosis

<b>215</b> <h3><b>Objectives:</b></h3> Metastatic colorectal cancer (mCRC) has a poor prognosis, however strong variation of survival exists among patients, at least partially related to the rapid apparition of treatment resistance. ¹⁸F-FDG PET/CT is a sensitive imaging tool for early detection of treatment resistance. Early non-response detection should have a high negative predictive value through the use of a low response threshold to avoid unjustified discontinuation of an effective treatment. This prospective study aimed to assess and validate the 15% response threshold for early metabolic response assessment in large exploratory and validation cohorts of mCRC patients treated respectively with multikinase inhibitors and chemotherapy. <h3><b>Methods:</b></h3> The exploratory cohort was composed of 224 patients with unresectable chemorefractory mCRC enrolled in two prospective Belgian multicenter non-randomized clinical trials investigating new targeted agents: combined sorafenib/capecitabine (EudraCT number: 2010-023695-91) and regorafenib (EudraCT number: 2012-005655-16). The validation cohort included 122 mCRC patients in an Italian prospective monocentric study treated with chemotherapy and bevacizumab. Standardized baseline and early ¹⁸F-FDG PET/CT scans were performed within 2 weeks before treatment and 2-3 weeks after the beginning of the therapy, respectively. After independent quality control, 216 and 102 patients for the exploratory and the validation cohorts, respectively, were considered suitable for analysis. The European Organization for Research and Treatment of Cancer (EORTC) criteria with threshold of 15%, PET Response Criteria in Solid Tumors (PERCIST) 1.0 with thresholds of 15 and 30%, and CONSIST method (non-responder patient identified when at least one target lesion showed no significant decrease of SUVmax (&lt;15%)) were tested. Univariate analyses for overall survival (OS) were performed to assess the predictive values of these different response criteria and multivariate analyses to assess their prognostic independency along with well-known clinical factors (i.e. age, gender, BMI, ECOG performance status, time since diagnosis, previous use of bevacizumab, KRAS mutation, and use of sorafenib vs. regorafenib). <h3><b>Results:</b></h3> In the exploratory cohort, univariate analyses showed that early ¹⁸F-FDG PET/CT response was strongly related to outcome whatever the criteria used (hazard ratio (HR): 1.65, <i>P</i> &lt; 0.001 for CONSIST 15%; HR: 1.48, <i>P</i> = 0.005 for PERCIST with 15% threshold and HR: 1.48, <i>P</i> = 0.006 for PERCIST 30%). Early ¹⁸F-FDG PET/CT response was identified by multivariate analyses as independent predictor of OS along with clinical factors for the different response criteria (HR: 1.62, <i>P</i> = 0.001 for CONSIST 15%; HR: 1.45, <i>P</i> = 0.01 for PERCIST 15%; and, HR: 1.44, <i>P</i> = 0.02 for PERCIST 30%). In the validation cohort, only early ¹⁸F-FDG PET/CT response using the 15% threshold was confirmed to be strongly related to outcome (HR: 2.05, <i>P</i> = 0.002 for CONSIST 15%; HR: 2.08, <i>P</i> = 0.003 for EORTC 15%; and, HR: 2.13, <i>P</i> = 0.002 for PERCIST 15%). PERCIST with 30% threshold was not significantly related to outcome (HR: 1.55, <i>P</i> = 0.055). <h3><b>Conclusions:</b></h3> This prospective study based on two exploratory and one validation cohort validates the strong predictive value of early ¹⁸F-FDG PET/CT response for OS in mCRC patients treated with different treatment modalities (targeted therapy/chemotherapy). A lowered metabolic response threshold of 15% was validated as the most appropriate method for OS prediction in a setting of early metabolic response assessment.