Interobserver agreement of qualitative analysis and tumor delineation of 18F-fluoromisonidazole and 3'-deoxy-3'-18F-fluorothymidine PET images in lung cancer.

UNLABELLED: As the preparation phase of a multicenter clinical trial using (18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG), (18)F-fluoromisonidazole ((18)F-FMISO), and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in non-small cell lung cancer (NSCLC) patients, we investigated whether 18 nuclear medicine centers would score tracer uptake intensity similarly and define hypoxic and proliferative volumes for 1 patient and we compared different segmentation methods. METHODS: Ten (18)F-FDG, ten (18)F-FMISO, and ten (18)F-FLT PET/CT examinations were performed before and during curative-intent radiotherapy in 5 patients with NSCLC. The gold standards for uptake intensity and volume delineation were defined by experts. The between-center agreement (18 nuclear medicine departments connected with a dedicated network, SFMN-net [French Society of Nuclear Medicine]) in the scoring of uptake intensity (5-level scale, then divided into 2 levels: 0, normal; 1, abnormal) was quantified by κ-coefficients (κ). The volumes defined by different physicians were compared by overlap and κ. The uptake areas were delineated with 22 different methods of segmentation, based on fixed or adaptive thresholds of standardized uptake value (SUV). RESULTS: For uptake intensity, the κ values between centers were, respectively, 0.59 for (18)F-FDG, 0.43 for (18)F-FMISO, and 0.44 for (18)F-FLT using the 5-level scale; the values were 0.81 for (18)F-FDG and 0.77 for both (18)F-FMISO and (18)F-FLT using the 2-level scale. The mean overlap and mean κ between observers were 0.13 and 0.19, respectively, for (18)F-FMISO and 0.2 and 0.3, respectively, for (18)F-FLT. The segmentation methods yielded significantly different volumes for (18)F-FMISO and (18)F-FLT (P < 0.001). In comparison with physicians, the best method found was 1.5 × maximum SUV (SUVmax) of the aorta for (18)F-FMISO and 1.3 × SUVmax of the muscle for (18)F-FLT. The methods using the SUV of 1.4 and the method using 1.5 × the SUVmax of the aorta could be used for (18)F-FMISO and (18)F-FLT. Moreover, for (18)F-FLT, 2 other methods (adaptive threshold based on 1.5 or 1.6 × muscle SUVmax) could be used. CONCLUSION: The reproducibility of the visual analyses of (18)F-FMISO and (18)F-FLT PET/CT images was demonstrated using a 2-level scale across 18 centers, but the interobserver agreement was low for the (18)F-FMISO and (18)F-FLT volume measurements. Our data support the use of a fixed threshold (1.4) or an adaptive threshold using the aorta background to delineate the volume of increased (18)F-FMISO or (18)F-FLT uptake. With respect to the low tumor-on-background ratio of these tracers, we suggest the use of a fixed threshold (1.4).

The predictive value of treatment response using FDG PET performed on day 21 of chemoradiotherapy in patients with oesophageal squamous cell carcinoma. A prospective, multicentre study (RTEP3).

PURPOSE: FDG PET has been suggested to have predictive value in the prognosis of oesophageal carcinoma. However, the retrospective studies reported in the literature have shown discordant results. Additionally, only four studies have evaluated FDG PET during chemoradiotherapy (CRT) in patients with different histological lesions. The purpose of this study was to investigate the predictive value of FDG PET performed early during CRT (on day 21) in a population of patients with oesophageal squamous cell carcinoma. METHODS: Included in this prospective study were 57 patients with a histological diagnosis of squamous cell carcinoma of the oesophagus. Of these 57 patients, 48 (84%) were evaluated (aged 63 ± 11 years; 44 men, 4 women). Each patient underwent FDG PET (4.5 MBq/kg) before CRT, according to the Herskovic protocol (t0; PET1) and on day 21 ± 3 from the start of CRT (d21; PET2). The response assessment included a clinical examination, CT scan or FDG PET and histological analysis 3 months and 1 year after PET1. The patients were classified as showing a complete response (CR) or a noncomplete response. A quantitative analysis was carried out for PET1 and PET2 using the following parameters: SUVmax, SUVmean (with SUVmean40 as the 3-D volume at an SUVmax threshold of 40% and SUVmeanp as that defined by a physician), tumour volume (TV, with TV40 defined as the TV at 40% of SUVmax, and TVp as that defined by a physician); and the total lesion glycolysis (TLG, SUVmean × TV, with TLG40 defined as the TLG at 40% of SUVmax, and TLGp as that defined by a physician). The differences in responses at 3 months and 1 year between PET1 (t0) and PET2 (d21) were assessed in terms of variations in SUV, TV and TLG using a repeated measures of variance (ANOVA). RESULTS: SUVmax, SUVmean and TLG decreased significantly between PET1 (t0) and PET2 (d21; p < 0.0001). The TV significantly decreased only when assessed as TVp (p = 0.02); TV40 did not decrease significantly. With respect to the predictive value of PET1, only TV40_1 and TVp_1 values, and therefore TLG40_1 and TLGp_1, but not the SUV values, were significantly lower in patients with CR at 3 months. SUVmax1, TVp_1 and TLGp_1 were significantly lower in patients with CR at 1 year. With respect to the predictive value of PET2, only TV40_2 and TVp_2 values, and therefore TLG40_2 and TLGp_2, but not the SUV values, were significantly lower in patients with CR at 3 months. None of the PET2 parameters had significant value in predicting patient outcome at 1 year. The changes in SUVmax, TV40, TVp, TLG40 and TLGp between PET1 and PET2 had no relationship to patient outcome at 3 months or 1 year. CONCLUSION: This prospective, multicentre study performed in a selected population of patients with oesophageal squamous cell cancer demonstrates that the parameters derived from baseline PET1 are good predictors of response to CRT. Specifically, a high TV and TLG are associated with a poor response to CRT at 3 months and 1 year, and a high SUVmax is associated with a poor response to CRT at 1 year. FDG PET performed during CRT on day 21 appears to have less clinical relevance. However, patients with a large functional TV on day 21 of CRT have a poor clinical outcome (ClinicalTrials.gov NCT 00934505).

Thoracic 131I uptake after previous pneumonectomy in patients treated for differentiated thyroid cancer.

In patients treated for differentiated thyroid cancer with radioiodine (131I), abnormal uptake on post-therapeutic whole-body scan may lead to repeated administration of 131I. Uptake not linked to thyroid cancer but to other conditions should be recognized so that patients are not overtreated. We describe 3 cases of unilateral thoracic 131I uptake in patients previously treated by pneumonectomy for lung cancer, without evidence of persistent lung cancer.

Strategies of radioiodine ablation in patients with low-risk thyroid cancer.

BACKGROUND: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS: In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS: There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS: The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).

Laparoscopic sentinel lymph node (SLN) versus extensive pelvic dissection for clinically localized prostate carcinoma.

PURPOSE: Lymph node metastasis is an important prognostic factor in prostate cancer (PC). The aim of this prospective study was to evaluate the accuracy of sentinel lymph node (SLN) biopsy by laparoscopy in staging locoregional patients with clinically localized PC. METHODS: A transrectal ultrasound-guided injection of 0.3 ml/100 MBq (99m)Tc-sulphur rhenium colloid in each prostatic lobe was performed the day before surgery. Detection was performed intraoperatively with a laparoscopic probe (Gamma Sup CLERAD) followed by extensive resection. SLN counts were performed in vivo and confirmed ex vivo. Histological analysis was performed by haematoxylin-phloxine-saffron staining, followed by immunohistochemistry (IHC) if the SLN was free of metastasis. RESULTS: The study included 93 patients with PC at intermediate or high risk of lymph node metastases. The intraoperative detection rate was 93.5% (87/93). Nineteen patients had lymph node metastases, nine only in SLN. The false-negative rate was 10.5% (2/19). The internal iliac region was the primary metastatic site (43.3%). Metastatic sentinel nodes in the common iliac region beyond the ureteral junction were present in 13.3%. Limited or standard lymph node resection would have ignored 73.2 and 56.6% of lymph node metastases, respectively. CONCLUSION: Laparoscopy is suitable for broad identification of SLN metastasis, and targeted resection of these lymph nodes significantly limits the risk of extended surgical resection whilst maintaining the accuracy of the information.

FDG PET evaluation of early axillary lymph node response to neoadjuvant chemotherapy in stage II and III breast cancer patients.

PURPOSE: Regional axillary lymph node status has remained the single most independent variable to predict prognosis both in terms of disease recurrence and survival. This study aimed to prospectively assess sequential [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) findings as early predictors of axillary lymph node response to neoadjuvant chemotherapy in stage II and III breast cancer patients. METHODS: Images were acquired with a PET/CT scanner in 52 patients after administration of FDG (5 MBq/kg) at baseline and after the first, second, third and sixth course of chemotherapy before surgery. Clinical examination and ultrasound (US) were used to assess the size of axillary nodes. Decrease in the standardized uptake value (SUV) with PET corrected or not for partial volume effects was compared to the pathological response. RESULTS: The sensitivity, specificity and accuracy of axillary node staging was higher with PET (75, 87 and 80%) than with US (50, 83 and 65%), and even more so when PET images were corrected for partial volume effects (86, 83 and 84%). While FDG uptake did not vary much in non-responders, as confirmed by histopathological analysis, it markedly decreased to baseline levels in responders (p < 10(-5)). Fifty per cent of baseline SUV was considered the best cutoff value to distinguish responders from non-responders. The sensitivity, specificity, negative predictive value and accuracy of FDG PET after one course of chemotherapy were, respectively, 96, 75, 95 and 84%. CONCLUSION: The pathological status of regional axillary lymph nodes in stage II and III breast cancer patients could be accurately predicted after one course of neoadjuvant chemotherapy based on FDG PET images.

Clinical and survival impact of FDG PET in patients with suspicion of recurrent cervical carcinoma.

PURPOSE: The aim of this retrospective study was to evaluate the contribution of (18)F-FDG PET to the clinical management and survival outcome of patients suspected of recurrent cervical carcinoma and in line with the hypothesis that early diagnosis of recurrent cervical cancer may improve overall survival. METHODS: A total of 40 patients underwent conventional imaging (CI) and FDG PET/CT for suspected cervical cancer. Clinical management decisions were recorded with CI and additional PET/CT. Discordances and concordances between CI and PET/CT results were compared to the final diagnosis as based on histopathology analysis or follow-up considered as the gold standard. RESULTS: The final diagnosis was established pathologically (n = 25) or by median clinical follow-up for 48 months after the PET (n = 15). The PET/CT was positive in 76% (20/26) of patients compared to 19% (6/26) with CI. Globally PET/CT modified the treatment plan in 55% (22/40) of patients and in 75% (18/24) when the CI was negative prior to PET/CT. These changes led to the use of previously unplanned therapeutic procedures in 37.5% (15/40). When FDG PET was positive for recurrence (> 3 foci), the median overall survival was 12 months (2-70) compared to patients with PET findings with < or = 1 focus for which the median survival was not attained (p = 0.007). A multivariate analysis of prognostic factors demonstrated that abnormal FDG uptake (> 3 foci) was the most significant factor (p < 0.03) for death from cervical cancer. CONCLUSION: FDG PET is a valuable tool in the case of suspected recurrence of cervical cancer on account of its impact on treatment planning and especially in predicting patient outcome.

Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient management in patients with head and neck squamous cell carcinoma: a multicenter prospective study.

PURPOSE To address the impact of positron emission tomography with [(18)F]fluorodeoxyglucose (PET-FDG) on the initial staging and management of patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS This multicenter, prospective study included 233 patients with newly diagnosed and untreated HNSCC. TNM stage and therapeutic decision were first determined based on the conventional work-up (including physical examination, computed tomography [CT]/magnetic resonance imaging of the head and neck region, and thoracic CT) and sealed in envelope 1. Whole-body PET-FDG was then performed, and subsequent TNM stage and therapeutic decision were written in envelope 2. Changes in TNM stages and in patient management as a result of PET-FDG imaging were recorded. Clinical outcome and histopathology were used as gold standards to validate the TNM stage. Conventional and PET stages were compared using the McNemar test. Results Conventional and PET stage were discordant in 100 (43%) of 233 patients. PET proved to be accurate in 47 patients and inaccurate in 13 patients. TNM status was left unconfirmed in 40 patients because no therapeutic change was expected from the stage difference. Conventional + PET TNM classification (envelope 2) was significantly more accurate than conventional classification (envelope 1; P < .0001, McNemar test). PET-FDG altered the therapeutic plan in 32 (13.7%) of 233 patients. CONCLUSION Adding whole-body PET-FDG to the pretherapeutic conventional staging of HNSCC improved the TNM classification of the disease and altered the management of 13.7% of patients. These findings support the implementation of PET-FDG in the routine imaging work-up of HNSCC.

Prospective preoperative mediastinal lymph node staging by integrated positron emission tomography-computerised tomography in patients with non-small-cell lung cancer.

OBJECTIVE: Mediastinal lymph node staging determines the treatment strategy for non-small-cell lung cancer. This study aims to evaluate prospectively the accuracy of preoperative integrated 18-fluoro-2-deoxy-D-glucose positron emission tomography-computerised tomography ((18)FDG PET-CT) for mediastinal lymph node staging. METHODS: Preoperative integrated (18)FDG PET-CT was used to analyse mediastinal lymph nodes in patients with non-small-cell lung cancer. Nodal stations were identified according to the American Thoracic Society mapping system. Lymph nodes with a standardised uptake value (SUVmax) >3 were considered to be positive. The mediastinal lymph nodes were harvested during lung resection and the results of integrated (18)FDG PET-CT were compared to the mediastinal lymph node histology results. RESULTS: A total of 51 patients were enrolled in this study. The mean interval between integrated (18)FDG PET-CT and surgery was 31+/-15.8 days (range: 2-78 days). The mean mediastinal lymph node harvested and station number per patient during surgery were 11.8+/-5.6 (range: 2-27) and 3.8+/-1 (range: 2-6), respectively. The incidence of N2 pathological disease was 19.6%. The integrated (18)FDG PET-CT sensitivity and specificity were 40+/-30% and 85+/-11%, respectively. The positive and negative predictive values were 40+/-30% and 85+/-11%, respectively. False-positive results (six patients) were mainly due to inflammatory lymph nodes. False-negative results (six patients) were mainly due to infra-centimetrical, malignant lymph node invasion. CONCLUSION: The sensitivity of integrated (18)FDG PET-CT for mediastinal lymph node staging in patients selected for surgery is low. When positive mediastinal lymph nodes are detected, invasive mediastinal staging must be performed. On the other hand, the specificity is high: patients with negative integrated (18)FDG PET-CT can be operated upon without invasive mediastinal staging.

Therapeutic impact of 18FDG-PET/CT in the management of iodine-negative recurrence of differentiated thyroid carcinoma.

BACKGROUND: 18-F-fluoro-2-deoxyglucose positron emission tomography ((18)FDG-PET) is useful in the detection of iodine-negative differentiated thyroid carcinoma (DTC). The aim of this prospective study was to assess therapeutic impact of (18)FDG-PET imaging using a PET/computed tomography (CT) system in patients with iodine-negative recurrence of DTC. METHODS: From 2002 to 2006, patients with recurrence of DTC diagnosed by elevated thyroglobulin level and negative 131-I whole-body scan were included. RESULTS: Forty-five patients (31 women, 14 men), with a mean age of 55 years, with 36 papillary, 5 follicular, and 4 Hürthle carcinomas, were studied. All patients had previously undergone total thyroidectomy and postoperative thyroid remnant ablation with 131-I. The findings of (18)FDG-PET/CT were positive in 31 patients (68.8%) and negative in 14 (32.2%). Results were true positive in 24 of 31 patients. The sensitivity, positive predictive value, and accuracy of (18)FDG-PET/CT were 63%, 77%, and 53%, respectively. Twenty patients were operated on, 19 had neck surgery with mediastinal lymph node dissection (1 case) and lung resection (1 case), and 1 underwent lung resection. Seven patients had a stimulated thyroglobulin level <1 ng/mL. CONCLUSION: (18)FDG-PET/CT is able to select patients who can benefit from surgery. Normalization of thyroglobulin is observed in one third of operated patients.

Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F]fluorodeoxyglucose positron emission tomography.

PURPOSE: This study aimed to assess prospectively the efficacy of sequential [18F]fluorodeoxyglucose positron emission tomography (FDG PET) to evaluate early response to neoadjuvant chemotherapy in stage II and III breast cancer patients. PATIENTS AND METHODS: Images were acquired with a PET/computed tomography scanner in 64 patients after administration of FDG (5 MBq/kg) at baseline and after the first, second, third, and sixth course of chemotherapy. Ultrasound and mammography were used to assess tumor size. Decrease in the standardized uptake value (SUV) with PET was compared with the pathologic response. RESULTS: Surgery was performed after six courses of chemotherapy and pathologic analysis revealed gross residual disease in 28 patients and minimal residual disease in 36 patients. Although SUV data did not vary much in nonresponders (based on pathology findings), they decreased markedly to background levels in 94% (34 of 36) of responders. When using 60% of SUV at baseline as the cutoff value, the sensitivity, specificity, and negative predictive value of FDG PET were 61%, 96%, and 68% after one course of chemotherapy, 89%, 95%, and 85% after two courses, and 88%, 73%, and 83% after three courses, respectively. The same parameters with ultrasound (US) and mammography were 64%, 43%, and 55%, and 31%, 56%, and 45%, respectively. Assessment of tumor response with US or mammography was never significant whatever the cutoff. CONCLUSION: Pathologic response to neoadjuvant chemotherapy in stage II and III breast cancer can be predicted accurately by FDG PET after two courses of chemotherapy.

Feasibility and benefit of fluorine 18-fluoro-2-deoxyglucose-guided surgery in the management of radioiodine-negative differentiated thyroid carcinoma metastases.

BACKGROUND: Fluorine 18-fluoro-2-deoxyglucose (FDG) positron emission tomography ((18)F-FDG PET) can be used to visualize metastases in patients with differentiated thyroid carcinoma that does not take up radioiodine ((131)I). This study was aimed at evaluating the feasibility of (18)F-FDG radio-guided surgery in patients with radioiodine-negative differentiated thyroid cancer. METHODS: Ten patients received a mean activity of 265 MBq of (18)F-FDG 30 minutes before operation. Radioactivity uptake (counts per second [cps], with a pretime of 10 seconds) in tumor and normal tissues was measured before and after resection. RESULTS: Patients with 1 to 5 foci detected by FDG-PET were included in the study. Six of these patients were injected with recombinant human thyroid-stimulating hormone (TSH) preoperatively. Abnormal findings detected by preoperative (18)F-FDG PET were also detected with the gamma probe in all patients. The mean tumor activity in vivo was 3,272 cps, and tumor-to-neck and tumor-to-shoulder ratios were, respectively, 1.40 and 1.73. Tumor resection was incomplete in 3 patients. When resection was complete, mean radioactivity at the tumor site was decreased by 22%. The ex vivo mean tumor-to-normal tissue ratio was 2.4. All positive tissues detected with the probe were confirmed histologically to be differentiated thyroid cancer. The surgeon's hands were exposed to 90 to 270 microSv. CONCLUSIONS: These results show the feasibility and benefit of (18)F-FDG radio-guided surgery with a gamma probe in the management of differentiated thyroid cancer patients with radioiodine-negative recurrence.

[Radiation therapy with 131I-MIBG is still relevant for metastatic carcinoid tumors]. / Tumeur carcinoïde au stade métastatique: intérêt toujours d'actualité de la thérapie à la mIBG-I131.

We report different treatment options (currently used and on trial) for a patient with a gastrointestinal carcinoid tumor and metastases in the liver, and discuss the advantages of using internal radiotherapy with 131I-MIBG rather than other treatments. According to the literature, this pathology has a poor prognosis, and considering the significant efficacy of this radiopharmaceutical treatment on symptoms, tumor reduction, and biochemical parameters, it seems to be under used. There are currently no standard treatment options. We present a management strategy for gastrointestinal carcinoid tumors with 131I-MIBG.