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A 59 year old male patient with metastatic non small cell lung cancer. A) Axial CT section (lung window) from a post contrast-enhanced CT scan of the chest and abdomen, shows a 3cm spiculated mass in the upper lobe of the left lung anteriorly with an adjacent small satellite nodule. B) Abdomen image section obtained at the level of the renal hilum from the same post contrast CT chest and abdomen. There are two hypodense lesions in the right liver lobe (segment 6) which show mild contrast enhancement (arrow). (Protocol: 120 kV, 250 mAs, slice thickness 2.5 mm (chest and abdomen), iohexol (omnipaque), 100 ml).
Source publication
We present a case report of a patient with metastatic non-small cell lung cancer (NSCLC) who had a series of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans for assessment of response to treatment. A restaging 18F-FDG PET/CT scan after six cycles showed increased FDG activity in the bone lesion...
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Citations
... Increased FDG uptake was thought to represent osteoblastic activity after an effective therapy [35,36]. This phenomenon had been relatively rare, but recently many cases have been reported, showing that bone flare phenomena are observed on FDG-PET/CT not only for patients with breast cancer, but also for those with non-small cell lung cancer (NSCLC), following the use of anti-VEGF antibodies such as bevacizumab and erlotinib [37][38][39]. The findings of these studies suggest that the addition of immune flare response to monoclonal antibodies on osteoblastic changes may lead to a higher incidence of false positive FDG uptake. ...
Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.
... The development of bone metastases is common in nonsmall cell lung cancer (NSCLC) as about 20-40 percent of patients will be diagnosed with metastatic bone lesions at some point during the course of their disease [1]. In the majority of cases these lesions are osteolytic, but osteoblastic bone metastases in NSCLC have been reported, primarily in adenocarcinoma [2,3]. The finding of new metastatic (bone) lesions will generally prompt a change of treatment. ...
We report the case of a 72-year-old female never-smoker with stage IV endothelial growth factor receptor (EGFR) mutated lung adenocarcinoma. This patient was started on first line tyrosine kinase inhibitor (TKI) and seemingly developed new bone metastases under this treatment. As there was a remarkable discrepancy between the partial response seen in the primary tumor and non-osseous metastatic locations, the possibility of a bone flare phenomenon was considered. In this case report, we demonstrate that new bony lesions are not always synonymous with disease progression.
... In 1999 European Organization for Research and Treatment of Cancer (EORTC) published guidelines for measurement of clinical and subclinical tumor response using FDG-PET [34]. In 2009 a new set of guidelines Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) [29,35] was proposed and even though the acceptance of these criteria have been quite slow, recent publications support the use of PERCIST over the more simple EORTC criteria [36][37][38][39][40][41][42][43][44][45][46][47][48][49]. This study applied, for the first time in a PET/MR setting, PERCIST measurement. ...
... It has been reported that SUV values obtained from tumor areas typically decrease following effectively intervention in solid tumors. However, studies have described a temporary increase in SUV, a flare, shortly after chemotherapy administration due to cell swelling, fibroblasts and macrophage infiltration despite therapeutic effect [13,42,43]. Thus, it is currently a widely hold opinion that differentiating between increased FDG uptake due to flare and true disease progression may not be possible early after chemotherapy. ...
Purpose: With the increasing number of therapy options available for patients with lung cancer, early response evaluation is needed. We performed this pilot study to assess the feasibility of early, repeated Positron emission tomography-magnetic resonance (PET/MR), the impact of timing and the capability for response prediction in lung tumors during chemotherapy. Methods: Patients with stage IV non-small cell lung cancer referred for chemotherapy were prospectively recruited. Fluorine-18-Fluorodeoxyglucose(18F-FDG)-PET/MR scans were performed prior to, during and after the first or second cycle of chemotherapy. Primary tumors were defined on all scans and size, FDG-uptake and apparent diffusion coefficient (ADC) were measured. Early response was described over time and a Standard Linear Mixed Model was applied to analyze changes over time. Results: 45 FDG-PET/MR scans were performed in 11 patients. Whereas the overall changes measured by ADC did not change significantly, there was an overall significant decrease in FDG-uptake from pre to post treatment scans. There was no difference in the FDG-uptake measured 1 or 3 weeks after therapy, but uptake measured 2 weeks after therapy differed from measurements at week 3. Changes measured in patients scanned during the first treatment cycle appeared more pronounced than during the second cycle. Conclusions: This pilot study indicates that response evaluation shortly after initiation of chemotherapy appears concordant with later evaluation and probably more reliable than evaluation midway between cycles. Responses during or after the first cycle of chemotherapy rather than during subsequent cycles are likely to be more readily measured.
... In the present study, bone flares were observed in 31 % of patients with skeletal metastases on FDG-PET scans performed on day 14. However, a case report of the use of FDG-PET for assessing response to erlotinib indicated that disease progression may be misdiagnosed as a bone flare as well [36]. In our study, six non-responders with persistent bone lesions on day 14 had stable disease on day 56. ...
Purpose
In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions.
Methods
We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, diagnostic CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from diagnostic CT imaging was used as the reference standard. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures.
Results
We identified 13 patients with bone metastases. Of these, four (31 %) with persistent bone uptake due to bone flares on day 14 were erroneously classified as non-responders according to the PERCIST criteria, but they were correctly classified as responders according to both the EORTC and TLG-S criteria. Patients who were classified as responders on day 14 based on TLG-S criteria had higher rates of 2-year PFS (26.7 % vs. 0 %, P = 0.007) and OS (40.0 % vs. 7.7 %, P = 0.018). Similar rates were observed in patients who showed a response on day 56 based on CT imaging according to the RECIST criteria. Patients classified as responders on day 14 according to the EORTC criteria on FDG-PET imaging had better rates of 2-year OS than did non-responders (36.4 % vs. 8.3 %, P = 0.015).
Conclusions
TLG-S criteria may be of greater help in predicting survival outcomes than other forms of assessment. Bone flares, which can interfere with the interpretation of treatment response based on PERCIST criteria, are not uncommon in patients with metastatic lung adenocarcinoma treated with erlotinib.
... In NSCLC, different case series on transient increased bone 18F-FDG uptake during chemotherapy [9,10] indicating initial response to anticancer treatment rather than a treatment failure, have been reported. Similar findings have also been described with 18F-FDG-PET/CT [11] and 99mTc-Bone Scintigraphy during EGFR TKIs (Table 1) [12,13]. On the contrary, osteoblastic reaction/response consists in the appearance of either new osteoblastic lesions or of a sclerotic component within or around lytic lesions at CT imaging. ...
... Despite the already known finding of scintigraphic bone flare after treatment in NSCLC (15)(16)(17), the osteoblastic reaction described in our study represented a different phenomenon with structural features found at CT scans performed during periodic tumor assessment. These 2 events are probably related, but the clinical weight of osteoblastic reaction, detectable during routine radiologic disease monitoring, is significantly more relevant than that of early bone flare evidenced by a positron emission tomography or scintigraphy scan. ...
Aims and background:
Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, including the onset of new osteoblastic lesions. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontinuation, changing the disease clinical course. We aim to describe this clinical phenomenon in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene-activating mutations treated with tyrosine kinase inhibitor (TKI).
Methods:
We retrospectively reviewed the computed tomography scans of 43 EGFR-mutated patients with NSCLC treated with EGFR-TKI, analyzing the bone response in terms of increase in the quantity and/or density of lesions, and assessing objective tumor response to treatment.
Results:
Osteoblastic reaction was detected in 10 cases (23%), showing different patterns: dimensional or density increase of known osteosclerotic metastases (pattern A, n = 4); response of previously lytic lesions (pattern B, n = 2); onset of new osteosclerotic lesions (pattern C, n = 4). Seven patients had partial response to TKI treatment, with response rate of 70%, vs 50% of patients with bone metastases without this reaction. No difference in terms of median overall survival or progression-free survival emerged between patients with or without osteoblastic reaction.
Conclusions:
The correct clinico-radiologic interpretation of osteoblastic reaction is crucial to avoid waste of therapeutic lines when TKI treatment has not yet exhausted its potential effectiveness. Clinical implications of ambiguous radiologic findings as described in this study deserve further discussion.
BRAF inhibitors (vemurafenib and dabrafenib) are nowadays commonly prescribed in BRAF-mutant metastatic melanoma and allow improvement of the overall survival and progression-free survival. They are, however, accompanied by many adverse effects which mainly affect the skin. We observed on computed tomographic scans in three different patients after 3 months of treatment, the onset of osteosclerotic lesions. In parallel, the computed tomographic scans showed a significant reduction in all of the previously identified metastases in all patients. The occurrence of such bone modifications under treatment was reported previously in others cancers, such as inoperable non-small-cell lung cancers under epidermal growth factor receptor inhibitors, as the 'osteoblastic bone flare phenomenon'. However, it had never been reported in melanoma patients treated with targeted therapies, and the results of two performed bone biopsies are reported here. This phenomenon is generally believed to indicate a better response under treatment, whereas in our study, the patients experienced, after a short partial response, a severe cerebral relapse leading to death. Finally, although its physiopathological mechanisms are poorly understood, the occurrence of tumor-free osteosclerotic lesions in patients under BRAF inhibitors should not be misinterpreted as a progression of the disease.
Background. Recent technical progress makes sophisticated non-invasive imaging methods available for murine models. For the first time in this study we applied FDG-PET-CT and FDG-PET-MRI to a murine orthotopic model of head and neck cancer immunotherapy. Methods. Tumor growth of floor of mouth tumors was evaluated by multi-modal small-animal imaging using FDG-PET-CT and FDG-PET-MRI. The immunotherapeutic effects of anti-CD137 antibody therapy were examined on body weight, tumor growth, and tumor-infiltrating immune cells in longitudinal imaging studies and immunohistochemical analyses. Results. Imaging revealed aggressive, fast-growing tumors without evidence of local or distant metastases. CD137 immunotherapy decreased tumor take and growth and stabilized body weight over time. A clear case of tumor regression was demonstrated by longitudinal PET-CT. Conclusion. The murine model mimics the characteristics of head and neck cancer in humans and offers excellent opportunities to investigate immunomodulatory anti-cancer drugs. The CD137 antibody showed anti-tumor effects in some therapy-responsive mice. This article is protected by copyright. All rights reserved.
Copyright © 2014 Wiley Periodicals, Inc., A Wiley Company.
We report a case of a patient with lung adenocarcinoma and bone and extraosseus metastases studied with 18F-FDG PET-CT, 99mTc-HMDP and 18F-fluoride PET-CT. It assesses the usefulness of 18F-FDG PET-CT for initial staging of the disease and monitoring response to therapy. For the study of the sclerotic bone metastases it shows the superiority of 99mTc-HMDP bone scintigraphy and 18F-fluoride PET-CT over 18F-FDG PET-CT, and 18F-fluoride PET-CT over bone scintigraphy. It also shows the usefulness of 18F-fluoride PET-CT for monitoring the bone metastases.
We report a case of a patient with lung adenocarcinoma and bone and extraosseus metastases studied with (18)F-FDG PET-CT, (99m)Tc-HMDP and (18)F-fluoride PET-CT. It assesses the usefulness of (18)F-FDG PET-CT for initial staging of the disease and monitoring response to therapy. For the study of the sclerotic bone metastases it shows the superiority of 99mTc-HMDP bone scintigraphy and (18)F-fluoride PET-CT over (18)F-FDG PET-CT, and (18)F-fluoride PET-CT over bone scintigraphy. It also shows the usefulness of (18)F-fluoride PET-CT for monitoring the bone metastases.
Copyright © 2014 Elsevier España, S.L.U. y SEMNIM. All rights reserved.
