Response on FDG-PET versus CT imaging according to the RECIST criteria

All patients underwent FDG-PET imaging at day 14, whereas data for day 56 FDG-PET scans were missing for three participants.

Based on FDG-PET imaging at day 14 and according to the EORTC criteria, there were 11 patients (48%) who had PMR, 11 (48%) with SMD, and 1 (4%) with PMD. According to FDG-PET imaging at day 56, we identified 5 patients (25%) with CMR, 7 (35%) with PMR, 5 (25%) with SMD, and 3 (15%) with PMD.

Based on FDG-PET imaging at day 14 and according to the PERCIST criteria, there were 6 patients (26%) who had PMR, 15 (65%) with SMD, and 2 patients (9%) with PMD. According to FDG-PET imaging at day 56, we identified 1 patient (5%) with CMR, 8 patients (40%) with PMR, 7 patients (35%) with SMD, and 4 patients (20%) with PMD.

Based on FDG-PET imaging at day 14 and according to the TLG-S criteria (summing up the five hottest lesions), there were 10 patients (26%) who had PMR, 11 patients (65%) with SMD, and 2 patients (9%) with PMD. According to FDG-PET imaging at day 56, we identified 1 patient (5%)

with CMR, 8 patients (40%) with PMR, 8 patients (35%) with SMD, and 3 patients (20%) with PMD.

Based on CT imaging at day 56 and according to the RECIST criteria, there were 10 patients (26%) who had PR, 5 patients (65%) with SD, and 8 patients (9%) with PD. Two patients classified as having PD and one patient who had PR did not undergo day 56 FDG-PET imaging.

The overall response according to early FDG-PET findings versus the standard CT response is summarized in Table 2.

Four patients who were classified as responders based on CT imaging at day 56 and according to the RECIST criteria were considered as non-responders when the PERCIST criteria were applied on early FDG-PET findings (Figure 2).

The median age at enrollment was 57 years. Most of the study patients (87%) had an ECOG performance status 0 or 1. The median follow-up time in the study cohort was 14 months (range, 1–51 months). At the end of the follow-up period, two patients survived and 21 died. The two patients who survived had a follow-up time of 51 and 39 months, respectively.

The overall response rate (43.5%, 10 out of 23 patients) obtained when the TLG-S system was applied to early FDG-PET results was identical to the overall response rate calculated by applying the RECIST criteria to CT data obtained on day 56. Eight patients with PD according to the RECIST criteria on day 56 were all classified as non-responders when the PERCIST and TLG-S criteria were applied on early FDG-PET findings; however, one of these subjects was classified as a responder based on the EORTC criteria. Taking into account that three patients had missing FDG-PET results, tumor response based on the PERCIST and TLG-S criteria using day 56 FDG-PET data (9 responders and 11 non-responders) was the same as that observed when the RECIST criteria were applied to CT findings (10 responders and 13 non-responders).

Table 1

General characteristics of the study patients [38]

Characteristic Patients,

n

Overall response according to early FDG-PET findings versus standard CT response [38]

Day 56 RECIST criteria

RECIST Response Evaluation Criteria in Solid Tumors version 1.1, EORTC European Organization for Research and Treatment of Cancer, PERCIST PET Response Criteria in Solid Tumors, TLG-S Total Lesion Glycolysis-Systemic approach.

Figure 2

Illustrative images of four non-responders by PERCIST criteria on day 14 PET who had persistent bone uptake due to the bone flare effect during erlotinib treatment (case No. in Figure 2 corresponded to the case No. in Table 3). (a) In case 1, the hottest lesion was identified at the scapula (SUVmax 8.1; arrow) on day 0. On day 14, the hottest lesion was located at the ilium (SUVmax 7.3; hollow arrow). A complete metabolic response was observed on day 56. (b) In case 2, the hottest lesion was identified at mediastinal lymph nodes (SUVmax 15.3; arrow) on day 0. On day 14, the hottest lesion was located at the L3 spine (SUVmax 11.5; hollow arrow). On day 56, a partial metabolic response was observed, with tracer uptake being decreased at the L3 spine (SUVmax 5.3; hollow arrow). (c) In case 3, the hottest lesion was identified at the L5 spine (SUVmax 10.3; arrow) on day 0. On day 14, the hottest lesion was located at the sacroiliac junction (SUVmax 8.2; hollow arrow). On day 56, a decreased activity at the L5 spine (SUVmax 3.2) was observed (arrow) and the lesion located at the sacroiliac junction was not measurable (hollow arrow). (d) In case 4, the hottest lesion was identified at the lumbosacral spine (SUVmax 6.6; arrow) on day 0. On day 14, the hottest lesion was located at the acetabulum (SUVmax 6.2; hollow arrow). On day 56, a partial metabolic response was observed, with tracer uptake being decreased at the acetabulum (SUVmax 3.5; hollow arrow) [38].

3.3 Impact of bone flares on early assessment of treatment response on FDG-PET images using the PERCIST criteria

A total of 13 study patients had bone metastases (Table 3). Bone flares occurred in 4 patients (31%), with the highest tracer uptake in the bone being identified on day 14 FDG-PET. Such flares led to an erroneous classification of these patients as non-responders when PERCIST criteria were applied. All of the bone flares regressed on day 56 FDG-PET images (Figure 2). Notably, all of these four patients were correctly classified as responders according to either the EORTC or TLG-S criteria on day 14 (Figure 3).

All of the four patients identified as non-responders on day 14 according to the PERCIST criteria were classified as responders based on day 56 CT findings (Group A in Table 3). Of the remaining nine patients who did not have bone flares, 3 patients were classified as responders (Group B) and 6 as non-responders (Group C) according to the PERCIST criteria applied to day 14 FDG-PET results and RECIST approach applied to day 56 CT findings (Table 3).

Table 3

Changes of FDG uptake observed in bone lesions and in the hottest single lesions identified during erlotinib treatment among patients with lung cancer and skeletal metastases [38]

Figure 3

Percentage changes of FDG uptake in the four patients with skeletal metastases who were erroneously classified as non-responders according to FDG-PET imaging at day 14 using the PERCIST criteria (a). All of these patients were correctly classified as early responders according to the EORTC criteria (b). The use of a systemic approach that included both primary and metastatic tumors (TLG-S method) was similarly effective in classifying these patients as early responders (c). The cut-off values for defining a reduction of FDG uptake as significant were 25%, 30%, and 45% of baseline values for EORTC, PERCIST, and TLG-S criteria, respectively [38].