Tjeerd S. Aukema

Detection of extra-axillary lymph node involvement with FDG PET/CT in patients with stage II-III breast cancer.

PURPOSE The aim of this prospective study was to assess the incidence of extra-axillary lymph node involvement on baseline FDG PET/CT in patients with stage II-III breast cancer scheduled for neo-adjuvant chemotherapy. METHODS Patients with invasive breast cancer of >3 cm and/or proven axillary lymph node metastasis were included for before neo-adjuvant chemotherapy. Baseline ultrasound of the infra- and supraclavicular regions was performed with fine-needle biopsy as needed. Subsequently FDG PET/CT was performed. All visually FDG-positive nodes were regarded as metastatic based on the previously reported high specificity of the technique. RESULTS Sixty patients were included. In 17 patients (28%) extra-axillary lymph nodes were detected by FDG PET/CT, localised in an intra-mammary node (1 lymph node in 1 patient), mediastinal (2 lymph nodes in 2 patients), internal mammary chain (9 lymph nodes in 8 patients), intra- and interpectoral (6 lymph nodes in 4 patients), infraclavicular (5 lymph nodes in 4 patients) and in the contralateral axilla (3 lymph nodes in 2 patients). Ultrasound-guided cytology had detected extra-axillary lymph node involvement in seven of these patients, but was unable to detect extra-axillary nodes in the other 10 patients with positive extra-axillary lymph nodes on FDG PET/CT. Radiotherapy treatment was altered in 7 patients with extra-axillary involvement (12% of the total group). CONCLUSIONS FDG PET/CT detected extra-axillary lymph node involvement in almost one-third of the patients with stage II-III breast cancer, including regions not evaluable with ultrasound. FDG PET/CT may be useful as an additional imaging tool to assess extra-axillary lymph node metastasis, with an impact on the adjuvant radiotherapy management.

The role of FDG PET/CT in patients with locoregional breast cancer recurrence: a comparison to conventional imaging techniques.

PURPOSE The aim of this study was to evaluate the impact of (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) on clinical management in patients with locoregional breast cancer recurrence amenable for locoregional treatment and to compare the PET/CT results with the conventional imaging data. PATIENTS AND METHODS From January 2006 to August 2008, all patients with locoregional breast cancer recurrence underwent whole-body PET/CT. PET/CT findings were compared with results of the conventional imaging techniques and final pathology. The impact of PET/CT results on clinical management was evaluated based on clinical decisions obtained from patient files. RESULTS 56 patients were included. In 32 patients (57%) PET/CT revealed additional tumour localisations. Distant metastases were detected in 11 patients on conventional imaging and in 23 patients on PET/CT images (p < 0.01). In 25 patients (45%), PET/CT detected additional lesions not visible on conventional imaging. PET/CT had an impact on clinical management in 27 patients (48%) by detecting more extensive locoregional disease or distant metastases. In 20 patients (36%) extensive surgery was prevented and treatment was changed to palliative treatment. The sensitivity, specificity, accuracy, positive and negative predictive values of FDG PET/CT were respectively 97%, 92%, 95%, 94% and 96%. CONCLUSIONS PET/CT, in addition to conventional imaging techniques, plays an important role in staging patients with locoregional breast cancer recurrence since its result changed the clinical management in almost half of the patients. PET/CT could potentially replace conventional staging imaging in patients with a locoregional breast cancer recurrence.

Is 18F-FDG PET/CT Useful for the Early Prediction of Histopathologic Response to Neoadjuvant Erlotinib in Patients with Non–Small Cell Lung Cancer?

Early prediction of treatment response is of value in avoiding the unnecessary toxicity of ineffective treatment. The objective of this study was to prospectively evaluate the role of integrated 18F-FDG PET/CT for the early identification of response to neoadjuvant erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. Methods: From October 2006 to March 2009, 23 patients with non–small cell lung cancer eligible for surgical resection were evaluated for this study. Patients received preoperative erlotinib (150 mg) once daily for 3 wk. 18F-FDG PET/CT was performed before and at 1 wk after the administration of erlotinib. Changes in tumor 18F-FDG uptake during treatment were measured by standardized uptake values and assessed prospectively according to the criteria of the European Organization for Research and Treatment of Cancer. Patients with a decrease in standardized uptake values of 25% or more after 1 wk were classified as “metabolic responders.” The metabolic response was compared with the pathologic response, obtained by histopathologic examination of the resected specimen. Results: Following the 18F-FDG PET/CT criteria of the European Organization for Research and Treatment of Cancer, 6 patients (26%) had a partial response within 1 wk, 16 patients (70%) had stable disease, and 1 patient (4%) had progressive disease. The median percentage of necrosis in the early metabolic responder group was 70% (interquartile range, 30%–91%), and the median percentage of necrosis in the nonresponder group was 40% (interquartile range, 20%–50%; P = 0.09). The κ-agreement between the metabolic and pathologic responders was 0.55 (P = 0.008). Conclusion: The results of this study suggest that early during the course of epidermal growth factor receptor tyrosine kinase inhibitor therapy, 18F-FDG PET/CT can predict response to erlotinib treatment in patients with non–small cell lung cancer.

Prevention of Brown Adipose Tissue Activation in 18F-FDG PET/CT of Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy

18F-FDG uptake in brown adipose tissue (BAT) can complicate interpretation and quantification of PET images, especially in regions of possible lymph node metastases such as the axilla and the mediastinum. The aim of this study was to prospectively evaluate the effect of patient preparation using a single oral dose of diazepam and controlled indoor temperature to prevent 18F-FDG uptake in BAT in breast cancer patients referred for monitoring of therapy response with 18F-FDG PET. Methods: During the fall and winter months, 53 patients referred for 18F-FDG PET/CT of breast cancer were included. A cohort of 25 patients was imaged without an intervention, and a second cohort of 28 patients was prepared according to a new protocol that included 10 mg of diazepam and adequate indoor temperature. The generated images were visually assessed for the presence of 18F-FDG at the location of fat-density tissue on CT images using a 4-point scale. Results: In the cohort without intervention, relevant 18F-FDG uptake in BAT was identified in 4 patients (16%); in the cohort prepared according to the proposed protocol, in only 1 patient (4%). The mean score of BAT 18F-FDG uptake evaluated with the 4-point system was 0.04 in the group treated according to the new protocol and 0.16 in the group treated according to the previous protocol. Conclusion: In the clinically relevant group of breast cancer patients, 18F-FDG uptake in BAT can be reduced by a single oral administration of diazepam combined with controlled room temperature in resting rooms.

Added value of prone position technique for PET-TAC in breast cancer patients

Abstract Aim This study has aimed to assess if the prone position shows significant differences in regards to the supine position in PET/CT studies in breast cancer patients and to determine which modality offers better evaluation of the images. Method A total of 30 patients were included from October 2009 to February 2010 prior to beginning neoadjuvant chemotherapy. An intravenous 18 F-FDG dose ranging from 180 to 240 MBq was administered. Image acquisition was begun 60±10 min after injection. First of all, a thorax scan was performed with the patient in prone position, followed by a whole body study with the patient in supine position. Results Uptake in tumor lesions was observed in all of the patients. Twenty-four patients (80%) had the same number of lesions with both techniques. Five patients (17%) had a different amount of axillary lymph nodes. One patient (3.3%) had a different number of lesions. The prone position lesions had a mean SUVmax 8.89±4.18 compared to 7.67±4.34 in supine position. The areas of the primary breast lesions were higher in the prone position (8.59±7.80 compared with 7.81±7.39). Mean SUVmax of axillary nodes was 5.97±4.02 in prone and 4.41±3.10 in supine. Conclusion The hanging breast technique can achieve higher lesion visualization as well as higher semiquantitative values in comparison with standard procedure. This supports its inclusion in acquisition guidelines of PET/CT imaging in breast cancer patients.

FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC

Over recent years, [18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography (FDG-PET/CT) has proven its role as a staging modality in patients with non-small cell lung cancer (NSCLC). The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC, treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI). All published articles from 1 November 2003 to 1 November 2013 reporting on 18F-FDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected. In total 7 studies, including data of 210 patients were eligible for analyses. Our report shows that FDG-PET/CT response during EGFR-TKI therapy has potential in targeted treatment for NSCLC. FDG-PET/CT response is associated with clinical and radiologic response and with survival. Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment. Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment. If metabolic response does not occur within the first weeks of EGFR-TKI treatment, patients may be spared (further) unnecessary toxicity of ineffective treatment. Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

Evaluation of 18F-FDG PET-CT for Differentiation of Pulmonary Pathology in an Approach of Outpatient Fast Track Assessment

Introduction: The aim of our study was to evaluate the clinical performance/ implementation of integrated 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) for differentiation of pulmonary pathology in an approach of outpatient fast track assessment. Methods: A prospective study was performed in 114 consecutive patients with pulmonary symptoms and/or abnormal chest x-ray were referred for fast track assessment to the Netherlands Cancer Institute from March 2005 to September 2007. The presence of malignancy was evaluated in a multidisciplinary setting, including 18F-fluorodeoxyglucose-PET, diagnostic CT, and bronchoscopy (including biopsy), with histopathological evaluation as the reference standard. Results: In 105 patients (92%), a final diagnosis was achieved. A malignancy was diagnosed in 84% of the patients; non-small cell lung cancer in 67%, small cell lung cancer in 7%, and metastases or other malignancies in 10%. Nonmalignant lesions were found in 16% of the patients. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of positive PET/CT for the presence of malignancy were 97, 56, 90, 92, and 77%, respectively. PET/CT showed unexpected M1 disease (not detected on CT) in 10% of the patients. Almost half of the patients with a malignancy were scheduled for curative treatment, of whom 29 patients for surgery and 14 patients for chemoradiotherapy. Conclusion: In this outpatient fast track setting, PET/CT provides valuable information for diagnosing lung cancer, with a high positive predictive value, and is useful for clinical decision making.

A different role for FDG PET/CT in axillary lymph node staging in breast cancer

Dear Sir, With great interest we read the recently published article by Heusner et al. [1] ”Diagnostic value of full-dose FDG PET/ CT for axillary lymph node staging in breast cancer patients”. The authors conclude that FDG PET/CT cannot replace invasive approaches for axillary staging, but may extend the indication for sentinel lymph node biopsy (SLNB). We believe that the study was conducted well and that the results are correct, but we feel that the clinical implications should be interpreted differently. In line with other studies, the authors determined that the sensitivity of FDG PET/CT in the detection of axillary lymph node metastases is only moderate (58%) and thus cannot replace SNLB and axillary lymph node dissection (ALND) for axillary lymph node staging [2–5]. The authors then propose that the performance of FDG PET/CT could be improved by preselecting patients with a higher a priori chance of nodal metastases, as derived from the size of the primary tumour. Although this approach may indeed improve the sensitivity for specific patient categories, we believe that the role of FDG PET/CT may involve other aspects too. The authors demonstrated a good specificity of 92% for axillary lymph node metastases in their population. Other studies have shown an even higher specificity, ranging from 95% to 100% [2–5]. Given this extremely strong diagnostic value, if a positive axillary lymph node is found on FDG PET/CT one may assume that the lymph node contains tumour cells, at least when there is no apparent alternative benign explanation for activation of the lymph nodes. Consequently, a SNLB is no longer required and ALND can be performed immediately. This impact on clinical decision making is becoming more relevant. Not many institutions apply FDG PET/CT for primary staging of breast cancer, as there is not much supportive evidence for such an approach. But when FDG PET/CT is performed for other reasons, for example as a baseline study for monitoring of response to neoadjuvant chemotherapy, one may encounter unexpected axillary lymph node metastases and take action accordingly. In conclusion, due to the limited sensitivity but superior specificity of FDG PET/CT in the detection of axillary lymph node metastases in patients with breast cancer, in our opinion the technique should not be used to extend the indication for SLNB, but rather to reduce it.

Tumor heterogeneity on 18 F-FDG-PET/CT for response monitoring in non-small cell lung cancer treated with erlotinib

Response monitoring using fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography (FDG-PET/CT) textural features has potential in targeted treatment with erlotinib in non-small cell lung cancer (NSCLC) patients. Patients with substantial decrease of metabolic activity during erlotinib treatment will probably benefit from continued treatment. However, various aspects of the method (quantification tools, cut-off values, etc.) need to be standardized before the software becomes widely available in a similar manner as standardized uptake value (SUV) measurements. Heterogeneity on FDG-PET/CT opened an additional window for innovation but simultaneously a new challenge for molecular hybrid imaging.

91 First Clinical Experience with a Dedicated PET for Hanging Breast Molecular Imaging

AIM Recently, a high-resolution dedicated PET system for hanging breast imaging (MAMMI PET) has been developed to improve primary tumor detection and characterization. The aim of this pilot study was to assess its feasibility for tumor detection and FDG uptake measurements in patients with stage II and III breast cancer. METHODS Thirty-two patients with invasive breast cancer (26 ductal, 4 lobular, 2 other), prior to and/or during neoadjuvant chemotherapy, underwent both conventional PET/CT and MAMMI PET in prone position with hanging breasts. Conventional PET/CT and MAMMI PET were performed 60±10 min and 110±10 min after injection of 180-240 MBq of FDG, respectively. Primary tumor detection was assessed and FDG uptake, expressed as maximum standardized uptake value (SUVmax), was calculated. RESULTS Both MAMMI PET and conventional PET/CT visualized the primary tumor in 31 patients (97%). The mean distance from the tumor to the pectoral muscle was 26.4mm (smallest distance 3.3mm). Agreement in FDG uptake between PET/CT and MAMMI PET was high (r=0.86, 95% CI 0.69-0.94). However, SUVmax as assessed with MAMMI PET was consistently higher than with PET/CT in all patients with an average ratio of 2.7. CONCLUSION The dedicated high-resolution breast PET with hanging breast technique is able to visualize approximately all breast tumors in stage II and III breast cancer patients, including tumors in the vicinity of the thoracic wall. This may enable its sequential use in the assessment of response in breast cancer patients receiving neoadjuvant systemic therapy, although SUVmax values are not directly comparable to standard PET/CT.