Comparison of CT,MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: Is there a benefit in using functional imaging?

The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and ¹⁸F-FDG-PET (n=23) before and 2–4 weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60±14%) was significantly higher than in nonresponders (37±31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.     

Diagnostic performance and prognostic impact of FDG-PET in suspected recurrence of surgically treated non-small cell lung cancer

Purpose The differentiation of recurrent lung cancer and post-therapeutic changes remains a problem for radiological imaging, but FDG-PET allows biological characterisation of tissues by visualising glucose metabolism. We evaluated the diagnostic performance and prognostic impact of FDG-PET in cases of suspected relapse of lung cancer.Methods In 62 consecutive patients, 73 FDG-PET scans were performed for suspected recurrence after surgical therapy of lung cancer. FDG uptake by lesions was measured as the standardised uptake value (SUV). PET results were compared with the final diagnosis established by biopsy or imaging follow-up. SUV and clinical parameters were analysed as prognostic factors with respect to survival.Results FDG-PET correctly identified 51 of 55 relapses and gave true negative results in 16 of 18 remissions (sensitivity, specificity, accuracy: 93%, 89%, 92%). SUV in recurrent tumour was higher than in benign post-therapeutic changes (10.6±5.1 vs 2.1±0.6, p<0.001). Median survival was longer for patients with lower FDG uptake in recurrent tumour (SUV<11: 18 months, SUV11: 9 months, p<0.01). Long-term survival was observed mainly after surgical re-treatment (3-year survival rate 38%), even if no difference in median survival for surgical or non-surgical re-treatment was detected (11 vs 12 months, p=0.0627). For patients subsequently treated by surgery, lower FDG uptake predicted longer median survival (SUV<11: 46 months, SUV11: 3 months, p<0.001). SUV in recurrent tumour was identified as an independent prognostic factor (p<0.05).Conclusion FDG-PET accurately detects recurrent lung cancer. SUV in recurrent tumour is an independent prognostic factor. FDG-PET helps in the selection of patients who will benefit from surgical re-treatment.     

PET imaging with [<Superscript>18</Superscript>F]3′-deoxy-3′-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer

Purpose Positron emission tomography (PET) using ¹⁸F-labelled 3′-deoxy-3′-fluorothymidine (FLT) was assessed for therapy monitoring in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy. Methods Ten patients with locally advanced rectal cancer were included and underwent long-course preoperative chemoradiotherapy (total dose 45 Gy, 1.8 Gy/day, concomitant 250 mg/m² 5-fluorouracil) followed by surgery. FLT-PET was performed prior to chemoradiotherapy, 2 weeks after initiation of chemoradiotherapy and preoperatively (3–4 weeks post chemoradiotherapy). FLT uptake was correlated with histopathological tumour regression and changes in T stage. Results Mean tumour FLT uptake was 4.2±1.0 SUV before therapy and decreased significantly to 2.9 ± 0.6 SUV 14 days after initiation of chemoradiotherapy (−28.6% ± 10.7%, p = 0.005). The preoperative scan showed a further decrease to 1.9 ± 0.4 SUV (−54.7% ± 7.6%, p = 0.005). However, the degree of change in FLT uptake 2 weeks after initiation and after completion of neoadjuvant therapy did not correlate with histopathological tumour regression. Conclusion FLT-PET did not seem to be a promising method for assessment of tumour response in the studied chemoradiotherapy regimen in patients with rectal cancer.     

Mean and maximum standardized uptake values in [<Superscript>18</Superscript>F]FDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy

Purpose  To evaluate the potential of [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the assessment of histopathological response and survival after neoadjuvant radiochemotherapy in patients with oesophageal cancer. Patients and methods  In 2005 and 2006, 55 patients (43 men, 12 women; median age 60 years) with locally advanced oesophageal cancer (cT3-4 Nx M0; 24 with squamous cell carcinoma, 31 with adenocarcinoma) underwent transthoracic en bloc oesophagectomy after completion of treatment with cisplatin, 5-fluorouracil, and radiotherapy ad 36 Gy in a prospective clinical trial. Of the 55 patients, 21 (38%) were classified as histopathological responders (<10% vital residual tumour cells) and 34 (62%) as nonresponders. FDG-PET was performed before (PET 1) and 3–4 weeks after the end (PET 2) of radiochemotherapy with assessment of maximum and average standardized uptake values (SUV) for correlation with histopathological response and survival. Results  Histopathological responders had a slightly higher baseline SUV than nonresponders (p<0.0001 between PET 1 and PET 2 for responders and nonresponders) and the decrease was more prominent in responders. Except for SUVmax in patients with squamous cell carcinoma neither baseline nor preoperative SUV nor percent SUV reduction correlated significantly with histopathological response. Histopathological responders had a 2-year overall survival of 91 ± 9% and nonresponders a survival of 53 ± 10% (p = 0.007). Conclusion  Our study does not support recent reports that FDG-PET predicts histopathological response and survival in patients with locally advanced oesophageal cancer treated by neoadjuvant radiochemotherapy. An erratum to this article can be found at     

Sequential FDG-PET/CT reliably predicts response of locally advanced rectal cancer to neo-adjuvant chemo-radiation therapy

PURPOSE: Prediction of rectal cancer response to preoperative, neo-adjuvant chemo-radiation therapy (CRT) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches. Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up, but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT, when restaging the patient before surgery. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising tool for monitoring the effect of anti-tumour therapy. The aim of this study was to prospectively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT. METHODS: Forty-four consecutive patients with locally advanced (cT3-4) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospective study. Treatment consisted of external beam intensified radiotherapy (50 Gy to the posterior pelvis, 56 Gy to the tumour), chemotherapy (in most cases PVI 5-FU at 300 mg/m(2) per day) and, 8-10 weeks later, surgery with curative intent. All patients underwent FDG-PET/CT both before CRT and 5-6 weeks after completing CRT. One patient died before surgery because of acute myocardial infarction, and was therefore excluded from further analysis. Semi-quantitative measurements of FDG uptake (SUV(max)), absolute difference (DeltaSUV(max)) and percent SUV(max) difference (Response Index, RI) between pre- and post-CRT PET scans were considered. Results were correlated with pathological response, assessed both by histopathological staging of the surgical specimens (pTNM) and by the tumour regression grade (TRG) according to Mandard's criteria (patients with TRG1-2 being defined as responders and patients with TRG3-5 as non-responders). RESULTS: Following neo-adjuvant CRT, of the 45 patients submitted to surgery, 23 (51.1%) were classified as responders according to Mandard's criteria (8 TRG1 and 15 TRG2), while the remaining 22 (48.9%) were non-responders (9 TRG3 and 13 TRG4-5). Considering all patients, the mean pre-CRT SUV(max) was 15.6, significantly higher than the mean value of 5.4 post CRT (p < 0.001). Nevertheless, when stratifying patients according to response to CRT (using Mandard's criteria), the mean RI was significantly higher in responders than in non-responders (75.9% versus 46.9%,p = 0.0015). Using a 66.2% SUV(max) decrease as the cut-off value (identified by ROC analysis) for defining response to therapy, the following parameters were obtained: 79.2% specificity, 81.2% sensitivity, 77% positive predictive value, 89% negative predictive value and 80% overall accuracy. CONCLUSION: The results suggest the potential utility of FDG-PET as a complementary diagnostic and prognostic procedure in the assessment of neo-adjuvant CRT response of locally advanced rectal cancer. DeltaSUV(max) and RI seem the best predictors of CRT response.     

Association between [18F]fluorodeoxyglucose uptake and postoperative histopathology, hormone receptor status, thymidine labelling index and p53 in primary breast cancer: a preliminary observation

To investigate the possible role of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in the prognostic evaluation of primary breast cancer, we studied 86 patients with T1–3 (TNM classification) breast tumours before surgery and compared the tumour FDG uptake, calculated as a standardized uptake value (SUV), with postoperative histopathological findings, steroid hormone receptor status of the tumour, thymidine labelling index (LI) and tissular expression of p53. SUV was significantly higher in infiltrating ductal carcinomas (n = 68; median SUV = 5.6) than in lobular ones (n = 18; median SUV = 3.8), and in grade 3 carcinomas (n = 26; median SUV = 6.2) than in grade 1–2 ones (n = 60; median SUV = 4.9). Moreover, SUV was significantly higher in carcinomas with high levels of p53 (n = 12; median SUV = 9.5) than in those with low levels (n = 48; median SUV = 4.25). By contrast, there was no significant correlation between SUV and the steroid hormone receptor status or LI of tumours. Our data demonstrate that FDG uptake, expressed as SUV, is associated with certain prognostic factors in breast cancer, such as histopathological grading and p53 expression, which can be assessed only by means of postoperative in vitro examinations. Hence, the information provided by FDG-PET is to some extent related to relevant information on tumour biology. The clinical value of these data will have to be confirmed by analysis of the independence of SUV from other prognostic factors by means of a multivariate analysis performed on a larger series of patients with adequate follow-up. If SUV is confirmed as an independent variable, FDG-PET could assume an important role in the determination of appropriate therapeutic strategies for primary breast cancer. Received 10 January and in revised form 29 May 1998     

90Y microsphere treatment of unresectable liver metastases: changes in 18F-FDG uptake and tumour size on PET/CT

Purpose The intra-arterial administration of ⁹⁰Y microspheres is a new palliative treatment option for unresectable liver metastases. The aim of this study was to quantitatively assess changes in FDG uptake and tumour size following ⁹⁰Y microsphere treatment (SIR-Spheres) using ¹⁸F-fluorodeoxyglucose (FDG) PET/CT imaging.Methods Five patients with unresectable liver metastases who had failed multiple prior chemotherapy regimens received seven ⁹⁰Y microsphere treatments to a single liver lobe. All patients underwent a baseline PET/CT scan prior to treatment, as well as up to four follow-up PET/CT scans. The tumour area of 30 liver metastases was measured on CT and the FDG uptake was semiquantitatively assessed by calculation of standardised uptake values (SUVs). A total of 18 FDG-PET/CT scans were performed.Results The SUVs in the 30 treated liver metastases decreased from 6.5±2.3 at baseline to 4.2±1.8 after the first follow-up PET/CT scan (p=0.001). In contrast, the SUVs of untreated metastases increased slightly from 7.2±2.3 to 8.0±0.8. There was no difference in FDG uptake in treated versus untreated normal liver tissue. Using a previously defined threshold of 20% decrease in SUV from baseline to determine response, 20 out of 30 liver metastases were considered to have responded at the first follow-up PET/CT scan approximately 1 month after treatment. In these metastases, the SUV decreased by 47±12%, compared with a slight increase by 5.9±19% in ten non-responding metastases (p=0.0001). The changes in tumour size did not correlate with changes in FDG uptake. On the first follow-up PET/CT scan, the tumour area on CT increased by 3.1±57% in treated metastases compared with 23.3±32% in untreated metastases. A wide range of post-treatment changes of target lesions was observed on CT, including an increase in the size of hypodense lesions, necrotic features and complete resolution of CT abnormalities.Conclusion The metabolic information obtained from FDG-PET/CT seems to provide a more accurate and earlier assessment of therapy response following ⁹⁰Y microsphere treatment than does the anatomical CT information.     

Mean and maximum standardized uptake values in [<Superscript>18</Superscript>F]FDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy

Purpose

To evaluate the potential of [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the assessment of histopathological response and survival after neoadjuvant radiochemotherapy in patients with oesophageal cancer.

Patients and methods

In 2005 and 2006, 55 patients (43 men, 12 women; median age 60 years) with locally advanced oesophageal cancer (cT3-4 Nx M0; 24 with squamous cell carcinoma, 31 with adenocarcinoma) underwent transthoracic en bloc oesophagectomy after completion of treatment with cisplatin, 5-fluorouracil, and radiotherapy ad 36 Gy in a prospective clinical trial. Of the 55 patients, 21 (38%) were classified as histopathological responders (<10% vital residual tumour cells) and 34 (62%) as nonresponders. FDG-PET was performed before (PET 1) and 3–4 weeks after the end (PET 2) of radiochemotherapy with assessment of maximum and average standardized uptake values (SUV) for correlation with histopathological response and survival.

Results

Histopathological responders had a slightly higher baseline SUV than nonresponders (p<0.0001 between PET 1 and PET 2 for responders and nonresponders) and the decrease was more prominent in responders. Except for SUVmax in patients with squamous cell carcinoma neither baseline nor preoperative SUV nor percent SUV reduction correlated significantly with histopathological response. Histopathological responders had a 2-year overall survival of 91?±?9% and nonresponders a survival of 53?±?10% (p?=?0.007).

Conclusion

Our study does not support recent reports that FDG-PET predicts histopathological response and survival in patients with locally advanced oesophageal cancer treated by neoadjuvant radiochemotherapy.

     

18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer

Purpose The aim of this study was to evaluate FDG-PET for assessment of therapy response and for prediction of patient outcome after neo-adjuvant radio-chemotherapy (NARCT) of advanced non-small cell lung cancer (NSCLC). Methods Seventy patients with histologically proven stage III NSCLC underwent FDG-PET investigations before and after NARCT. Changes in FDG uptake and PET findings after completion of NARCT were compared with (1) the histology of tumour samples obtained at surgery or repeat mediastinoscopy, and (2) treatment results in terms of achieved operability and long-term survival. Results The mean average FDG uptake of the primary tumours in the patient group decreased significantly during NARCT (p = 0.004). Sensitivity, specificity and overall accuracy of FDG-PET were 94.5%, 80% and 91%, respectively, for the detection of residual viable primary tumour, and 77%, 68% and 73%, respectively, for the presence of lymph node metastases. A negative PET scan or a reduction in the standardised uptake value (SUV) of more than 80% was the best predictive factor for a favourable outcome of further treatment. Progressive disease according to PET (new tumour manifestations or increasing SUV) was significantly correlated with an unfavourable outcome (p = 0.005). In this subgroup, survival of patients who underwent surgery was not significantly different from survival among those who did not undergo surgery, whereas for the whole patient group, complete tumour resection had a significant influence on outcome. Conclusion FDG-PET is suitable to assess response to NARCT in patients with stage III NSCLC accurately. It was highly predictive for treatment outcome and patient survival. PET may be helpful in improving restaging after NARCT by allowing reliable assessment of residual tumour viability.     

Pilot study of serial FLT and FDG-PET/CT imaging to monitor response to neoadjuvant chemoradiotherapy of esophageal adenocarcinoma: correlation with histopathologic response

Objective

The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy.

Methods

Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al. criteria, categorizing patients as pathologic responders and non-responders. Participants underwent PET/CT imaging 1 h after intravenous administration of FDG and of FLT on two separate days within 48 h of each other. Each patient underwent a total of 3 scan “pairs”: (1) pre-treatment, (2) during treatment, and (3) post-treatment. Image-based response to therapy was measured in terms of changes in SUVmax (ΔSUV) between pre- and post-therapeutic FLT- and FDG-PET scans. The PET imaging findings were correlated with the pathology results after surgery.

Results

All tumors were FDG and FLT avid at baseline. Lesion FLT uptake was lower than with FDG. Neoadjuvant chemoradiation resulted in a reduction of tumor uptake of both radiotracers in pathological responders (n?=?3) and non-responders (n?=?2). While the difference in the reduction in mean tumor FLT uptake during Tx between responders (ΔSUV = ??55%) and non-responders (ΔSUV = ??29%) was significant (P?=?0.007), for FDG it was not, [responders had a mean ΔSUV = ??39 vs. ??31% for non-responders (P?=?0.74)]. The difference in the reduction in tumor FLT uptake at the end of treatment between responders (ΔSUV = ??62%) and non-responders (ΔSUV = ??57%) was not significant (P?=?0.54), while for FDG there was a trend toward significance [ΔSUV of responders = ??74 vs. ??52% in non-responders (P?=?0.06)].

Conclusion

The results of this prospective pilot study suggest that early changes in tumor FLT uptake may be better than FDG in predicting response of esophageal adenocarcinomas to neoadjuvant chemoradiation. These preliminary results support the need to corroborate the value of FLT-PET/CT in a larger cohort.

     

Dual-phase 18F-fluoro-2-deoxy-d-glucose positron emission tomography as a prognostic parameter in patients with pancreatic cancer

Purpose Recently, dual-phase ¹⁸F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) was shown to be useful in the differentiation between malignant and benign pancreatic lesions. The aim of this prospective study was to evaluate the value of dual-phase FDG-PET as a prognostic parameter in patients with pancreatic cancer.Methods Sixty-five consecutive patients with pancreatic cancer underwent dual-phase FDG-PET. Standardised uptake values at 1 h (SUV1) and 2 h (SUV2) following the injection of FDG were determined, and the retention index (RI) was calculated by dividing the difference between SUV2 and SUV1 by SUV1. The prognostic value of SUV1, SUV2 and RI was analysed, along with the various clinical and biochemical parameters.Results Multivariate analysis showed that only three factors had an independent association with longer patient survival: female gender (p<0.01), TNM stage I–III (p<0.05) and RI>10% (p<0.01). Neither SUV1 nor SUV2 showed any prognostic significance. Combination of tumour stage and RI allowed more accurate prognostic evaluation. Patients at stage I–III with RI>10% survived longer than did patients at the same stage with RI<10% (15.3 vs 11.5 months, p<0.01). Patients at stage IV with RI>10% had an intermediate prognosis, with a median survival of 9.5 months; patients at stage IV with RI<10% showed the worst prognosis, with a median survival of 4.9 months (p<0.05).Conclusion RI calculated with dual-phase FDG-PET can be used not only as a tool for initial diagnosis and staging of pancreatic cancer but also as a strong independent prognostic parameter that can allow accurate identification of those patients who will benefit from intensive anticancer treatment at different stages of the disease.     

Added value of MRI to endoscopic and endosonographic response assessment after neoadjuvant chemoradiotherapy in oesophageal cancer

In order to select oesophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) for organ-preserving treatment instead of surgery, a high diagnostic accuracy is required. The aim of this study was to evaluate whether MRI had additional value to gastroscopy with biopsies and endosonographic ultrasound (EUS) with fine needle aspiration (FNA) for the detection of residual tumour after nCRT. Twenty-two patients with oesophageal cancer eligible for nCRT followed by oesophagectomy were prospectively included. All patients underwent (T2- and diffusion-weighted) MRI and gastroscopy+EUS before and after nCRT. Histopathology after oesophagectomy was the reference standard with pathological complete response (pCR) defined as ypT0N0. Diagnostic performance regarding the detection of residual tumour was calculated for gastroscopic biopsies and for EUS-FNA without and with MRI. Nineteen of the 22 patients (86%) did not achieve pCR after nCRT (7 ypT+N+, 11 ypT+N0, 1 ypT0N+). Biopsies detected residual tumour in 6 of 18 ypT+ patients. After adding MRI, 16 of 18 residual tumours were assessed correctly. EUS-FNA detected 3 out of 8 ypN+ patients, while MRI did not improve detection. Overall, adding MRI improved sensitivity for detection of residual tumour to 89% (17 of 19) from 47% (9 of 19) with endoscopic biopsies and EUS-FNA only. In this small study, the detection of residual tumour after nCRT in oesophageal cancer patients was improved by the addition of MRI to gastroscopy and EUS. • In this small study, the detection of residual tumour after neoadjuvant chemoradiotherapy in oesophageal cancer patients was improved by adding MRI including diffusion-weighted images to gastroscopy and endosonographic ultrasound. • With the addition of MRI assessment to gastroscopy and endosonographic ultrasound, the considerable risk of missing residual tumours decreased from 53 to 11%, while the pitfall was overstaging in one out of three complete responders.     

The value of 18F-FDG PET/CT for assessing the response to neoadjuvant therapy in locally advanced rectal cancer

Purpose

Neoadjuvant radiochemotherapy (RCT) is an accepted treatment for locally advanced rectal cancer (LARC) that improves surgical outcomes. If a pathological complete response is achieved, conservative surgery can be considered. The objective of our study was to assess the reliability of ¹⁸F-FDG PET/CT for evaluating the response to neoadjuvant RCT in LARC.

Methods

We prospectively studied 41 patients diagnosed with LARC and candidates for neoadjuvant RCT. PET/CT was performed before RCT and again 7?weeks later. A visual and semiquantitative analysis was carried out. The pathological response was classified according to the Mandard tumour regression grade (TRG). We analysed: (a) the relationship between TRG and the result of the posttreatment PET/CT scan, and (b) the correlation between the percentage of pathological response and the percentage decrease in SUVmax according to the response index (RI).

Results

The mean SUVmax of the rectal lesions at diagnosis was 13.6 and after RCT 3.96. The mean RI was 65.32?%. Sensitivity was 88.88?%, specificity 92.86?%, positive predictive value 96?%, negative predictive value 81?%. Of the 41 patients, 8 had TRG I (all negative PET/CT); 6 had TRG II (5 negative, 1 positive PET/CT); 16 had TRG III (13 positive, 3 negative PET/CT); 9 had TRG IV (all positive PET/CT); 2 had TRG V (all positive PET/CT). Of the 14 patients classified as responders (TRG I, II), 13 (92.86?%) had negative PET/CT. Of the 27 patients classified as nonresponders (TRG III?CV), 24 (88.88?%) had positive PET/CT. Differences were statistically significant (p?<?0.0001). The RI in responders was 79.9?% and in nonresponders was 60.3?%. Differences were statistically significant (p?<?0.037).

Conclusion

PET/CT is a reliable technique for assessing response to neoadjuvant RCT in LARC, with a view to considering more conservative surgical treatment. The combination of the visual and semiquantitative analysis increases the diagnostic validity of PET/CT.     

Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer

AIM: To assess the clinical diagnostic value of functional imaging, combining quantitative parameters of apparent diffusion coefficient (ADC) and standardized uptake value (SUV)max, before and after chemo-radiation therapy, in prediction of tumor response of patients with rectal cancer, related to tumor regression grade at histology.METHODS: A total of 31 patients with biopsy proven diagnosis of rectal carcinoma were enrolled in our study. All patients underwent a whole body ¹⁸FDG positron emission tomography (PET)/computed tomography (CT) scan and a pelvic magnetic resonance (MR) examination including diffusion weighted (DW) imaging for staging (PET1, RM1) and after completion (6.6 wk) of neoadjuvant treatment (PET2, RM2). Subsequently all patients underwent total mesorectal excision and the histological results were compared with imaging findings. The MR scanning, performed on 1.5 T magnet (Philips, Achieva), included T2-weighted multiplanar imaging and in addition DW images with b-value of 0 and 1000 mm²/s. On PET/CT the SUVmax of the rectal lesion were calculated in PET1 and PET2. The percentage decrease of SUVmax (ΔSUV) and ADC (ΔADC) values from baseline to presurgical scan were assessed and correlated with pathologic response classified as tumor regression grade (Mandard’s criteria; TRG1 = complete regression, TRG5 = no regression).RESULTS: After completion of therapy, all the patients were submitted to surgery. According to the Mandard’s criteria, 22 tumors showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders; 9 tumors were classified as non responders (TRG3, 4 and 5). Considering all patients the mean values of SUVmax in PET 1 was higher than the mean value of SUVmax in PET 2 (P < 0.001), whereas the mean ADC values was lower in RM1 than RM2 (P < 0.001), with a ΔSUV and ΔADC respectively of 60.2% and 66.8%. The best predictors for TRG response were SUV2 (threshold of 4.4) and ADC2 (1.29 × 10^-3 mm²/s) with high sensitivity and specificity. Combining in a single analysis both the obtained median value, the positive predictive value, in predicting the different group category response in related to TRG system, presented R² of 0.95.CONCLUSION: The functional imaging combining ADC and SUVmax in a single analysis permits to detect changes in cellular tissue structures useful for the assessment of tumour response after the neoadjuvant therapy in rectal cancer, increasing the sensitivity in correct depiction of treatment response than either method alone.     

Evaluation of chemotherapy response in osteosarcoma with FDG-PET

Objective  The objective of this study is to evaluate the utility of positron emission tomography (PET) with 2-deoxy-[¹⁸F] fl uoro-D-glucose (FDG) in the assessment of the chemotherapy response of osteosarcoma when compared with the degree of necrosis determined histologically. Methods  Whole-body FDG-PET scan was performed on 11 patients with osteosarcoma. All patients received neoadjuvant chemotherapy. The tumor size changes on magnetic resonance imaging; FDG-PET standardized uptake values prior to (SUV₁) and following (SUV₂) chemotherapy were analyzed and correlated with response to chemotherapy as assessed using histopathology in surgically excised tumors. Nine patients underwent FDG-PET scan both prior to and following neoadjuvant chemotherapy. The remaining two patients were examined only prior to surgery. Results  Histologically, five patients had a good histologic response to chemotherapy (≧90% necrosis). The changes in tumor size did not correlate with histologic response (P > 0.05). SUV₂ with good response was significantly lower than that with poor response (1.93 ± 0.50, 5.86 ± 2.55, respectively). Both the positive and negative predictive values of the SUV₂ of less than 2.5 for a good response were 100%. Patients with good response showed a significantly higher ratio of SUV2 to SUV1 (SUV_2:1) than patients with poor response (0.74 ± 0.11, 0.26 ± 0.39, respectively, P < 0.05). The positive and negative predictive values of SUV_2:1 ≤ 0.5 for good and poor responses were 80% and 100%, respectively. Conclusions  FDG-PET imaging of osteosarcoma correlates positively with histologic response to neoadjuvant chemotherapy. SUV₂ and SUV_2:1 could be feasible as non-invasive surrogate predictors of response in osteosarcoma patients.     

Response of osteogenic sarcoma to neoadjuvant therapy: evaluated by 18F-FDG-PET

OBJECTIVE: The aim of this study was to evaluate the potential role of F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in assessing the chemotherapy response of osteosarcoma when compared with histologically assessed tumor necrosis. METHODS: Fifteen patients were examined with whole-body FDG-PET prior to and following neoadjuvant therapy. The maximum standard uptake value (SUV max) of tumor and tumor to background ratio (TBR) prior to and following chemotherapy was used for semiquantitative PET imaging analysis. The SUV max of prechemotherapy and post-chemotherapy was recorded as SUV1 and SUV2. TBR1 and TBR2 represented prechemotherapy and post-chemotherapy TBR. TBR was calculated by drawing an identical region of interest over the tumor and the contralateral normal limb or pelvis. Tumor necrosis was classified according to Salzer-Kuntschik's criteria. RESULTS: Eight patients with more than 90% tumor necrosis were classified as showing good responses and seven patients with less than 90% tumor necrosis as showing poor responses. SUV2/SUV1, TBR2/TBR1, and TBR2 were significantly correlated with the tumor necrosis degree (P < 0.01, P < 0.001, P < 0.001). TBR2/TBR1 were below 0.46 in all the patients with favorable responses, and higher than 0.49 in all the patients with unfavorable responses. However, it was difficult to distinguish good responses from poor responses by SUV2/SUV1. CONCLUSIONS: FDG-PET is a promising tool to assess the chemotherapy response of osteosarcoma noninvasively. The TBR was better than SUV max in evaluating the chemotherapy response in this study.     

FDG-PET after radiotherapy is a good prognostic indicator of rectal cancer

In the management of rectal cancer after the combined therapy of the radiation and surgical operation, the evaluation of the prognosis is important. Although fluoro- 18-deoxyglucose positron emission tomography (FDG-PET) is considered as a useful tool for evaluation of therapeutic effect of this cancer as well as the other cancers, however, there are few articles that clearly describe the appropriate procedure of the FDG-PET in order to obtain the best prognostic value. The purpose of the present study is to compare several variations of a semi-quantification method, the Standardized Uptake Values (SUV) and to determine the most appropriate parameter, for the prognostic prediction and to propose the quantitative guideline of the FDG-PET. Especially, the authors focused on the SUV after radiotherapy, which had not been considered as a key quantitative value, as it was rather taken as a mere indicator of the therapeutic (radiotherapeutic) effect, not a direct indicator of the prognosis for the cancer itself. METHODS: Forty patients with rectal cancer in the lower rectal region underwent two series of FDG-PET study before and after pre-operative radiotherapy. Their SUVs were calculated from FDG-PET data and compared with the results of the long-term follow-up of the patients as well as with histopathological outcomes. Results: All 40 patients had high FDG uptake before radiotherapy. The mean value of SUV before radiotherapy (SUV1) was 7.6. After radiotherapy, the mean value of SUV (SUV2) decreased to 4.2. There was a significant difference in SUV2 between the groups with and without recurrence (p < 0.05), however, SUVI or SUV ratio (SUV2/SUV1) displayed no significant difference with the incidence of recurrence. CONCLUSION: SUV2 was considered to be a good prognostic indicator for long-term prognosis of rectal cancer patients. SUV1 nor SUV ratio SUV2/SUV1 did not have the equivalent prognostic usefulness. Subsets of patients with SUV2 greater than 3.2 should be observed closely.     

Use of positron emission tomography for staging,preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour

PURPOSE: To evaluate FDG-PET for staging, grading, preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour (WT). METHODS: In this study, 23 FDG-PET examinations in 12 paediatric patients (female, n = 5; male, n = 7; age, 1-19 years) with WT (primary, n = 9; relapsed, n = 3) were analysed. All patients were examined with conventional imaging methods (CIM) according to the SIOP2001/GPOH trial protocol. Additionally, FDG-PET/PET-CT was performed for staging (n = 12), preoperative response assessment (n = 6) and posttherapeutic evaluation (n = 5). Imaging results of FDG-PET and CIM were analysed regarding the accuracy in tumour visualisation, impact on therapeutic management and preoperative response assessment, with clinical follow-up and histopathology as the standard of reference. RESULTS: FDG-PET and CIM showed concordant results for staging of primary WT, whereas FDG-PET was superior in 1/3 cases with recurrent WT. Concerning histological differentiation, one case with anaplastic WT had an standard uptake value (SUV) of 12.3, which was remarkably higher than the average SUV in the eight cases with intermediate risk histology. No parameter analysed for PET or CIM was reliably predictive for histological regression or clinical outcome. After completion of therapy, FDG-PET was superior to CIM in 2/5 cases in detecting residual disease with therapeutic relevance. CONCLUSION: FDG-PET does not provide additional information to the traditional imaging work-up for staging WT patients, preoperative response assessment and clinical outcome. FDG-PET was advantageous in ruling out residual disease after completion of first line treatment and in pretherapeutic staging of relapse patients. Furthermore, there seems to be a good correlation of initial SUV and histological differentiation.     

Early therapy monitoring with FDG-PET in aggressive non-Hodgkin’s lymphoma and Hodgkin’s lymphoma

This study was designed to determine the value of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the early assessment of therapy response in lymphoma patients. We studied 20 patients with pathologically proven lymphoma, including 17 patients with aggressive non-Hodgkins lymphoma and three patients with Hodgkins lymphoma. All patients underwent whole-body FDG-PET imaging at baseline and after 1–2 cycles of chemotherapy. PET images were analysed visually and quantitatively by calculating the standardised uptake value (SUV). In each patient, we measured the SUV of the tumour demonstrating the highest FDG uptake at baseline study and the SUV of the same tumour after 1–2 cycles of therapy. The achievement of complete response was assessed on the basis of a combination of clinical findings and the results of conventional imaging modalities. Follow-up of progression-free survival (PFS) was obtained for the validation of PET data. Of the 20 patients, ten achieved complete remission at the completion of chemotherapy and the other ten did not respond to chemotherapy. Of the ten responders, four are still in remission (PFS 24–34 months) while the other six have relapsed (PFS 8–16 months). For the prediction of 24-month clinical outcome, visual analysis of PET after 1–2 cycles showed high sensitivity (87.5%) and accuracy (80%) but low specificity (50%). Comparison with the baseline SUVs revealed that the responders showed a significantly greater percent reduction in SUV after 1–2 cycles of therapy as compared with the non-responders (81.2%±9.5% vs 35.0%±20.2%, P<0.001). In addition, using 60% reduction as a cut-off value, the responders were clearly separated from the non-responders, with the exception of one non-responder. In conclusion, when performed early during chemotherapy, FDG-PET may be predictive of clinical outcome and allows differentiation of responders from non-responders in cases of aggressive lymphoma.     

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

Purpose

The objective of this study was to evaluate positron emission tomography (PET) using ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients.

Methods

FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n?=?16; osteosarcoma (OS), n?=?11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik.

Results

FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (?SUV, p?=?0.005; SUV2, p?=?0.011) as well as in the subgroup of OS patients (?SUV, p?=?0.009; SUV2, p?=?0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p?=?0.170) or in both subgroups (EWS, p?=?0.950; OS, p?=?1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS.

Conclusion

FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.