PERCIST Criteria Research Articles

Early detection of disease progression after palliative chemotherapy in NSCLC patients by (18)F-FDG-PET.

We investigated whether 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is capable of detecting renewed disease progression earlier than computed tomography (CT) in patients with inoperable non-small cell lung cancer (NSCLC) who have undergone chemotherapy as part of a palliative treatment plan. 18 patients were studied retrospectively. Three FDG-PET/CT scans for initial and follow-up diagnostic purposes were evaluated. Palliative chemotherapy was administered between the first FDG-PET/CT scan (t0) and the second (t1), followed by a treatment-free interval between the second FDG-PET/CT scan (t1) and the third (t2). Maximum standardized uptake values (SUVmax) and largest diameters of lesions were determined for PET scans and the corresponding CTs. Lesion-based and patient-based assessments were performed, as were assessments according to RECIST/PERCIST. 82 lesions were identified in 18patients. In interval t1-t2, the increase in diameter in the lesion-based evaluation was 5.0% (non-significant), while the patient-based evaluation showed a non-significant reduction of 2.8%. Considering PET, both the lesion-based and patient-based evaluations found a significant increase in SUVmax by a median of 30.4% and 45.8%, respectively. PERCIST criteria at time point t2 identified ten more patients with progression than did RECIST. In patients with NSCLC, renewed progression during the treatment-free interval after palliative chemotherapy can be detected earlier with PET than with CT. Thus, FDG-PET appears to be a useful diagnostic imaging procedure regarding this aspect. Its clinical relevance should be investigated in further studies.

Proposal of a New 18F-FDG PET/CT Predictor of Response in Rectal Cancer Treated by Neoadjuvant Chemoradiation Therapy and Comparison With PERCIST Criteria

The aim of this study was to correlate PERCIST criteria and a new criterion developed in our center that we named PREDIST (PET Residual Disease in Solid Tumor) with tumor regression grade (TRG) classification of pathologic response to neoadjuvant chemoradiotherapy (CRT) in patients affected by rectal cancer. Seventy-three consecutive patients affected by locally advanced rectal cancer (LARC) were retrospectively included. FDG-PET/CT scans were performed at staging time and after the end of CRT (mean time 6.5 weeks). The analysis was performed by PERCIST criteria 1.0 and PREDIST criteria based on a new definition of residual disease. We split the TRG system into responders (TRG1-2) and nonresponders (TRG3-5). Pearson chi-square analysis by cross-tabulations was performed. PREDIST classification was statistically predictive of TRG response (P = 0.004, sensitivity 81.8% and specificity 54.9%). On the contrary, PERCIST criteria was not statistically correlated to TRG (P = 0.128) caused by a very low specificity (9.8%). FDG-PET/CT scan is an accurate tool to predict preoperatively the response to CRT in LARC patients. The novel proposed criterion (PREDIST) seems to be helpful to discriminate responder by nonresponder patients.

Interim FDG PET/CT to predict progression-free survival (PFS) better than clinical and baseline metabolic measurements in Hodgkin lymphoma (cHL).

8555 Background: Previous studies in cHL have demonstrated that conventional methods to risk stratify patients into various prognostic groups and predict PFS may not be sufficient to individualize therapy. Metabolic parameters using FDG-PET may be helpful for developing a prognostic algorithm and predict PFS. Objectives: To determine the best predictor of PFS among various variables of tm metabolic measurements at baseline and at interim PET/CT compared to conventional methods in cHL patients. Methods: Retrospective evaluation of prospectively acquired data in 58 cHL pts, all stages [IIB-IV:41%, >IPS-3:24%, unfavorable (UF):44%]. Eligibility: PET/CT prior to and after 1 cycle (PET1) ABVD therapy, imaging at 60min+15min, follow-up>24 mo. Baseline PET parameters including metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, and SULpeak were determined using gradient method (PETVCAR2, GE Healthcare, WI). Data were also evaluated at PET1 for %ΔMTV, %ΔSUVmax, %ΔTLG, PERCIST criteria and visually with Deauville 5-PS. Variables were correlated with PFS. Results: Median follow-up: 32.2 mo. Of 58 pts 14 relapsed (median PFS:6.5 mo). Results for PFS are displayed in the Table. No baseline conventional (stage, IPS, UF vs F) or PET variable was associated with PFS. The best predictor of PFS was Deauville 5-PS at PET1. PERCIST and %ΔTLG using gradient method trended toward significance. Conclusions: Deauville 5-PS best predicts PFS at PET1 in cHL. Neither baseline PET nor conventional prognostic factors correlated with PFS in this group of cHL pts. Risk-stratification of cHL using tumor metabolic volumetry and PERCIST criteria may require a larger sample size and further assessment of various methodologies. [Table: see text]

Abstract P4-02-02: Comparison of 18F-FDG PET-CT and 11C-MET PET-CT for assessment of response to neoadjuvant chemotherapy in locally advanced breast carcinoma.

Abstract INTRODUCTION: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumor load & it offers an opportunity to evaluate response of primary tumor to chemotherapy. This makes response monitoring crucial in the management of breast carcinoma. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response in breast cancer. AIMS AND OBJECTIVES: To compare FDG PET-CT with MET PET-CT for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma and to correlate it with clinico-pathological response. METHODS: In our prospective study, 20 patients with histology proven locally advanced breast carcinoma were enrolled. All patients underwent clinical assessment and PET-CT imaging using FDG and MET before and after 3 cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for modified radical mastectomy and the resected breast with dissected axillary nodes was sent for histo-pathological analysis. Tumor response to the neoadjuvant chemotherapy was evaluated clinically using WHO criteria and by PET-CT imaging using PERCIST criteria. Responses calculated were compared for statistical significance using paired t- test. RESULTS: Mean SUV in FDG-PET for primary tumor (p < 0.001) and axilla (p = 0.001) were significantly higher than in MET-PET. After three cycles of chemotherapy, clinical size of the primary tumor decreased by 55.76%, mean SUVmax of the primary lesion decreased by 47.21% in FDG-PET (p = 0.16) and by 45.5% in MET-PET (p = 0.167). In axilla, a decrease of 53.39% was seen in mean SUVmax in FDG-PET and 48.37% in MET-PET (p = 0.469) with significant positive correlation (R = 0.53). According to PERCIST criteria, complete response was seen in 5% and 35% patients in FDG-PET and MET-PET respectively, while no patient showed complete response on clinical and histo-pathological assessment. Partial response was seen in 65% patients clinically, 70% in FDG-PET and 55% in MET-PET. In axilla, response was seen in 25% of patients clinically, 75% in FDG-PET and 80% in MET-PET. CONCLUSION: In both FDG-PET and MET-PET, there is a significant decrease in SUVmax of primary breast tumor and axillary metastasis after three cycles of neo-adjuvant chemotherapy correlating with decrease in clinical size. Response evaluation for primary breast tumor by clinical method, FDG-PET and MET-PET was statistically similar and a significant positive correlation was seen. Response evaluation for axillary metastasis by FDG-PET and MET-PET shows higher accuracy than clinical examination. Thus, making PET-CT a valuable monitoring tool for guiding the choice of surgical management of axilla. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-02.

Rôle de la TEP au 18F-FDG dans l’évaluation des volumes cibles chez des patients atteints de CBNPC traités par radiochimiothérapie

Currently 18F-FDG-PET is the gold standard to evaluate tumor response after chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC). PET can also determine the volumes to be treated by radiotherapy, in inoperable patients. The aim of our mixed (prospective and retrospective) study concerned 28 patients with NSCLC, was to quantify the variation of the metabolic activity of lesions and their volumes after chemotherapy. We also studied the impact of change of these volumes on the definition of radiotherapy target volumes. Patients with stage II–IV and inoperable NSCLC were included. Two PET scans were performed: before treatment (PET1), then after two to six courses of chemotherapy (PET2). Of the 28 patients included, we observed complete metabolic response in six patients (21%), partial metabolic response in 13 patients (46%), stable disease in seven patients (25%), and progressive metabolic disease in two patients (7%), according to the PERCIST criteria. We observed significant variation (P<0.001) of metabolic activity (estimated by SULpeak or SUVmax) for primary tumor as well as for overall lesions between the two PET scans. Thus, the target volumes of radiotherapy decreased significantly (P<0.01) in PET2. Our results confirm that 18F-FDG-PET is not only a powerful technique for treatment evaluation but also a useful tool for radiotherapy planning after chemotherapy, in the context of personalized treatments.

FOLFIRI plus bevacizumab (B) as neoadjuvant treatment for potentially resectable colorectal cancer patients (pts) with liver metastasis: A phase II trial.

e14130 Background: Irinotecan-based chemotherapy plus B was shown to be effective and safe in both first- and second-line treatment for metastatic colorectal cancer (mCRC) pts.We designed this trial to assess whether the combination of FOLFIRI + B given to untreated, potentially resectable mCRC pts was feasible and active. Methods: Phase II, single arm trial with 1-year progression-free rate (PFR) as primary end-point. A sample size of 39 pts was calculated to detect a 70% ± 12% 1-year PFR. The treatment was FOLFIRI q2w (irinotecan 180 mg/m2, leucovorin 200 mg/m2, 5FU 2400 mg/m2 iv in 46 hrs) plus B 5mg/kg q2w. Last cycle before surgery was without B. Potentially resectable, untreated mCRC pts, with liver as unique site of metastases, were eligible. Normal organ function and no contraindications to B were required. Pts were reevaluated for surgery after 6 cycles. PET-Scan were performed at baseline and at the second cycle. Results: Overall 39 pts were enrolled. Median age was 58 (range 30-75), male/female were 24/15. Twenty seven pts (69.2%; 95%CI 52.4% – 83.0%) were progression-free at 1-year. Thirty seven pts (94.9%) underwent surgery. One complete and 22 partial responses were observed (response rate 59.0%; 95% CI 42.1% – 74.4%); 5 pts had disease progression (4 resectable and 1 unresectable). Early PET-scan was assessed according PERCIST criteria [Wahl RL, J Nucl Med 2009] in 29 pts and showed metabolic response (SUV-max decrease &gt; 30%) in 17 (58.6%; 95% CI: 38.9%- 76.5%).Severe toxicity includes grade 3 neutropenia (3 pts, 7.7%) and grade 3 diarrhea (1 pt, 2.6%). Other toxicities include grade 1-2 diarrhea (15.4%), grade 2 nausea (7.8%), grade 2 leucopenia (5.1%), grade 2 asthenia (5.1%), grade 1 anemia (2.6%), grade 2 thrombosis (2.6%). Overall, 16 pts out of 37 experienced surgical complications (43.2%; 95%CI 27.1% - 60.5%): biliary leak (11 pts, 29.7%), biliary fistula (1 pt, 2.7%), other complications (4 pts, 10.8%). All complications were reversible. No peri-operative bleeding was observed. Conclusions: The trial yielded its primary aim and shows that FOLFIRI plus B is feasible and active as neo-adjuvant treatment in patients with resectable liver metastases of CRC.

A Phase I Trial of Erlotinib and Concurrent Chemoradiotherapy for Stage III and IV (M0) Squamous Cell Carcinoma of the Head and Neck

Erlotinib, an orally active selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has synergistic activity with radiation and with cisplatin. The EGFR is overexpressed in the majority of head and neck cancers. The primary objective of this phase I study was to determine the maximum-tolerated dose (MTD) of erlotinib in combination with low-dose daily cisplatin and radiotherapy. We also sought evidence of biologic activity of erlotinib alone using serial 18-FDG positron emission tomography (PET) imaging. Oral erlotinib was taken daily starting with a 14-day run-in and continued until radiation therapy (RT) was completed. Low-dose daily cisplatin, 6 mg/m(2) i.v. was given concurrently with standard fractionation RT to a total dose of 66 to 70 Gy. Dose escalation followed a modified Fibonacci dose escalation design. Twenty-two patients were enrolled and 18 patients received therapy on protocol. MTD of the combination of erlotinib, cisplatin, and RT was not reached. The recommended phase II dose of erlotinib is 150 mg per day in combination with cisplatin and RT, the highest dose of erlotinib evaluated in this study. 18F-FDG PET showed evidence for metabolic response to single-agent erlotinib. Per PERCIST criteria, the overall metabolic response rate at day 14 was 38.8% (95% CI: 17.3-64.3). On completion of concurrent chemoradiotherapy, overall response rate derived from tumor measurements based on imaging studies was 83% for all dose levels combined. Erlotinib in combination with low-dose daily cisplatin and RT is well tolerated and shows evidence of clinical efficacy. The combination should be evaluated further.

Evaluation of circulating tumor cells (CTCs) enumeration and 18F-Choline positron emission tomography/computed tomography (FCH PET/CT) as early efficacy response biomarkers in metastatic castration-resistant prostate cancer (CRPC) patients (pts) treated with abiraterone acetate.

63 Background: Circulating tumor cells (CTCs) and FCH PET/CT are both promising tools for treatment monitoring in CRPC pts. In this study, we assessed prostate specific antigen (PSA), CTC and FCH PET/CT for monitoring treatment response in metastatic CRPC pts receiving recently approved abiraterone acetate therapy after chemotherapy. Methods: Twenty nine metastatic CRPC pts progressing after docetaxel chemotherapy received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Pts were evaluated monthly for efficacy and safety. CTCs counts (using the CellSearch assay) and FCH PET/CT were performed at baseline and at 4 weeks (PERCIST criteria and SUV Peak). Results: After one month of treatment, 12 pts (41%) had a PSA rise and 17 pts (59%) had a PSA decline. At baseline, 18 pts had detectable CTCs (at least 5 CTCs), and 6 of them (33%) had a decline from at least 5 to less than 5 CTCs after 4 weeks of treatment. 10 of 29 pts (34%) had a &gt; or = 30% decline in CTCs. Amongst 22 pts who were evaluable by FCH PET/CT, response assessment was as follows: response (n=8), stable disease (n=12), progression (n=1). PSA decline and CTCs levels correlated in 16 of 29 pts (55%), and were discordant in 13 of 29 pts (45%). In all 12/29 pts (41%) with a 50% or more decline in PSA both a CTCs response and a FCH PET/CT response was observed. In patients with a PSA rise while on abiraterone acetate, 8 pts did not have a CTCs increase or a CTC conversion from unfavourable to favorable, and 7 of 8 pts had a PSA decline at 3 months or a FCH PET/CT response. No flare phenomenon on FCH PET/CT was observed. Conclusions: Monitoring pts with CRPC who receive abiraterone using both CTCs and metabolic imaging indicate discrepancy in 45% with response assessment using PSA. Association between CTC drop, early FCH PET/CT response and clinical benefit is currently under study.

A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC).

68 Background: EC is commonly managed with concurrent chemoradiotherapy, with or without surgical resection. The optimal combination and dose of agents is the subject of continued investigation. This study examines chemotherapeutic agents with known efficacy in EC in combination with the EGFR inhibitor panitumumab. Methods: Eligible pts received RT (1.8 Gy qd to 50.4 Gy) combined with concurrent chemotherapy. Dose-level (DL) 1 was cape (625 mg/m2/bid RT days), ox (40 mg/m2 weekly X 6 weeks), and pmab (3.6 mg/kg, weeks 1, 3 and 5). Chemotherapy doses were escalated barring dose limiting toxicity (DLT). The primary endpoint was defining the maximally tolerated dose with this combination. Secondary endpoints included toxicity and radiographic/pathologic response rates. Results: Twenty-nine pts were enrolled. Twenty-five had adenocarcinoma, 24 (83%) were cN+ and 9 (31%) had M1a/b disease. DLT was not encountered in DL 1. Two of 6 patients at DL 2 (cape 825 mg/m2/bid RT days, ox 50 mg/m2 weekly, pmab 4.8 mg/kg, weeks 1, 3 and 5) developed DLT (one hospitalization due to dehydration; one with drug reaction requiring hospitalization). Twenty additional pts were enrolled at DL1. Primary toxicities were EGFR-rash, esophagitis, nausea/vomiting and fatigue. On repeat endoscopy, 16 (55%) had CR, 10 (35%) PR and 2 (7%) SD. Using PERCIST criteria, 12 (41%), 11 (38%), 2 (7%) and 3 (10%) had CR, PR, SD and PD response on restaging PET, respectively. Twenty pts underwent esophagectomy, revealing Gr 0 response (no residual disease) in 9 (45%), Gr 1 (single/microscopic cells) in 3 (15%), Gr 2 (fibrosis &gt; gross disease) in 4 (20%) and Gr 3 (gross residual &gt; fibrosis or no evident response) in 4 (20%). Seven pts (35%) experienced anastomotic leak (2 requiring reoperation and 3 stent placement). Conclusions: Concurrent chemoradiotherapy utilizing capecitabine, oxaliplatin, panitumumab is reasonably well-tolerated and associated with high rates of radiographic, endoscopic and pathologic response. Postoperative anastomotic leak rates were higher than expected. Further study of this regimen in the operative and nonoperative settings is warranted.