High FDG Uptake Research Articles

18F-FDG-PET/CT and Osteolytic Bone Disease in Multiple Myeloma

Introduction: FDG-PET/CT is a promising methodology for staging, prognostication, and response evaluation in multiple myeloma (MM). The number of focal FDG lesions and the intensity of FDG uptake (standard uptake value, SUV) at diagnosis are informative of disease aggressiveness. Osteolytic bone disease is a hallmark of MM. Hypothetically; increased focal metabolic activity will precede, induce and correlate to osteolytic lesions. We aimed to elucidate the association between focal FDG positive lesions and osteolytic bone disease in MM patients.Methods: Twenty-two newly diagnosed MM patients, 16 males and 6 females aged 53-81years, were prospectively enrolled and studied with a standardized baseline FDG-PET/CT at diagnosis. A nuclear medicine and a radiology specialist evaluated the PET and CT parts separately and independently. Focal FDG positive lesions were assessed by dedicated software (ROVER™, ABX, Germany) to yield volume and SUV measures. All osteolytic lesions identified on CT were noted by size and localization.Results: FDG-PET and CT together identified a total of 390 lesions. We found more osteolytic lesions on CT (335) than FDG-positive lesions (169); the concordance between the modalities was 30%. 34% (114/335) of lytic lesions were FDG-positive, whereas ⅔ (114/169) of focal FDG-PET positive lesions were lytic according to CT. We found a significant correlation between higher FDG uptake measured as SUVpeak and osteolytic lesions >10 mm, and focal lesions with high FDG uptake had more pronounced osteolysis than focal lesions with less FDG uptake. Still sparse follow-up data did not allow analysis of the predictive value of focal PET positivity and the risk of development of future osteolysis. More compulsive data will be presented at the meeting.Conclusion: FDG-PET/CT offers dual information including metabolic activity (FDG-avidity) and degree of lytic bone disease (low dose whole body CT) in MM. About ⅔ (221/335) of osteolytic lesions were FDG-negative, whereas ⅔ (114/169) of FDG-positive lesions had a lytic component. DisclosuresPlesner:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

An Unusual Presentation of Adenocarcinoma of the Lung

SESSION TITLE: Global Case Report Poster - Lung Cancer SESSION TYPE: Global Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Lung cancer is the most common type of cancer. Adenocarcinoma occupies approximately %50 in all lung cancer. Adenocarcinomas present as peripheral nodules or masses often with pleural involment. They can present radiologically as a single mass or a diffuse, multi-nodular lesion. It is rare for the non-small cell carcinoma (adenocarcinoma) of the lung to present as miliary mottling (1). Miliary tuberculosis, sarcoidosis, silicosis, pneumoconiosis, varicella infection, histoplasmosis, hemosiderosis demonstrate miliary mottling on chest radiography (2,3). Milliary mottling is seen most frequently in adenocarcinoma (4). CASE PRESENTATION: A 80-year-old female patient, with diabetes mellitus, hypertension, cholelithiasis, coronary artery disease, presented with a history of cough, sputum, weight of-loss, dyspnea, weakness of 1 month duration. Physical examination and laboratory tests were normal. Her chest radiograph demonstrated miliary mottling. In the preliminary diagnosis, miliary tuberculosis was thaught, because tuberculosis incidence is very high in Turkey. Three samples of sputum for AFB and PPD test showed negative results,3 cm nodular lesion at left lower lobe and bilateral multipl nodules were seen in thorax CT. There was no endobronchial lesion in fiberoptic bronchoscopy. Transthoracic biopsy was performed and the histopathological examination revealed Adenocarcinoma. PET/CT was done for disease staging. In PET/CT, multiple intracranial metastases, 20x18mm nodule with high FDG uptake (SUVmax:6.53) at the lower lobe of left lung and multiple nodular lesions maximum size of 1 cm (SUVmax:3.04) in both lungs were seen. Then the patients was considered as T1N3M1B stage 4 disease. 6MV photon cranial radiotherapy was applied for intracranial metastasis. Test for EGFR-ALK mutation was performed; EGFR mutation gene sequencing identified a deletion in exon 19 and ALK was negative. Erlotinib treatment was given. Total survey of the patient was 6 months. DISCUSSION: Milier nodules are oval or round shaped 0.1-1cm nodules and are seen in chest rediography when they reach to the size of 2-3mm (3,4). Miliary mottling on chest radiography is seen in miliary tuberculosis, sarcoidodosis, silicosis, pneumoconiosis, varicella infection, histoplasmosis and hemosiderosis. Adenocarcinomas with miliary mottling consists of %1 of all lung cancers and are seen mostly in non smoking patients (3). In differential diagnosis, sputum AFB should be done as tuberculosis is highly seen in our country. TTFNAB and FOB tests are used in the diagnosis. Chemotherapy and radiotherapy are used in the treatment and EGRF-ALK mutation tests are done for evaluation of treatment choice in such patients(5). CONCLUSIONS: Miliary mottling in lung can be a sign of many diseases and differential diagnosis is very important for treatment decision. Reference #1: 1. Rabia Ergelen, Nuri Cagatay Cimsit Akciğer Tümörleri Marmara Universitesi Pendik Eğitim ve Arastirma Hastanesi, Radyoloji Anabilim Dali, Istanbul, Türkiye 2. Jayaram Subhashchandra B1, Ismailkhan M, Chikkaveeraiah Shashidhar K, Gopalakrishna Narahari M. A rare case of non-small cell carcinoma of lung presenting as military mottling Iran J Med Sci. 2013 Mar;38(1):65-8 Reference #2: 3. Nay Min Tun, MD* and Vijay Mattoo, MD Miliary Mottling on Chest X-ray: An Unusual Presentation of Adenocarcinoma of the Lung The American Journal of medical sciences Volume 34, Issue 4, April 2015, pages e4 4. Saleem A1, Thomas EC, Wilkinson A, Azher M, Saleem N Bilateral miliary shadowing on chest X-ray J Coll Physicians Surg Pak. 2013 Dec;23(12):902-3. doi: 12.2013/JCPSP.902903 Reference #3: 5. Schaller A1, Beau-Faller M2, Mennecier B1, Renaud-Picard B1, Weingertner N3, Massard G4, Quoix E1 Lung Adenocarcinoma with Pulmonary Miliary Metastases and Complex Somatic Heterozygous EGFR Mutation Case Rep Oncol. 2014 Nov 19;7(3):769-73. doi: 10.1159/000369526 DISCLOSURE: The following authors have nothing to disclose: Filiz Cimen No Product/Research Disclosure Information

Application of PET/CT in treatment response evaluation and recurrence prediction in patients with newly-diagnosed multiple myeloma.

Multiple myeloma (MM) causes osteolytic lesions which can be detected by 18F-fluorodeoxyglucose positron emission tomography/Computed tomography (18F-FDG PET/CT). We prospectively involve 96 Newly diagnosed MM to take PET/CT scan at scheduled treatment time (figure 1), and 18F-FDG uptake of lesion was measured by SUVmax and T/Mmax. All MM patients took bortezomib based chemotherapy as induction and received ASCT and maintenance. All clinical features were analyzed with the PET/CT image changes, and some relationships between treatment response and FDG uptakes changes were found: Osteolytic lesions of MM uptakes higher FDG than healthy volunteers, and this trend is more obvious in extramedullary lesions. Compared to X-ray, PET/CT was more sensitive both in discoering bone as well as extramedullary lesions. In newly diagnosed MM, several adverse clinical factors were related to high FDG uptakes of bone lesions. Bone lesion FDG uptakes of MM with P53 mutation or with hypodiploidy and complex karyotype were also higher than those without such changes. In treatment response, PET/CT showed higher sensitivity in detecting tumor residual disease than immunofixation electrophoresis. But in relapse prediction, it might show false positive disease recurrences and the imaging changes might be influenced by infections and hemoglobulin levels. Conclusion: PET/CT is sensitive in discovering meduallary and extrameduallary lesions of MM, and the 18F-FDG uptake of lesions are related with clinical indictors and biological features of plasma cells. In evaluating treatment response and survival, PET/CT showed its superiority. But in predicting relapse or refractory, it may show false positive results.

Impact of pre- and early per-treatment FDG-PET based dose-escalation on local tumour control in fractionated irradiated FaDu xenograft tumours

ObjectiveTo investigate local tumour control after dose-escalation based on [18F]2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) obtained before and early during fractionated irradiation. Materials and methods85 mice bearing FaDu xenografts underwent FDG-PET twice: first immediately prior to the first 2-Gy fraction of irradiation (PET1_0) and second after 18°Gy (PET2_18). After these 9 fractions, animals were randomly allocated to: (1) continuation of 2-Gy fractions (cumulative dose of 60°Gy; n=31), (2) dose-escalation with 3-Gy fractions (cumulative EQD2-dose 86.25°Gy [α/β-value: 10]; n=25), or (3) with 4-Gy fractions (cumulative EQD2-dose 116°Gy; n=29). The effects of SUVmax0°Gy, SUVmax18°Gy, and dose on local tumour control were analysed in two ways. First, the Cox proportional hazards model was used with two covariates: continuous SUVmax values and dose. Second, the Kaplan–Meier method was used, with tumours classified according to SUVmax greater than or less than (1) median maximum standardized uptake value (SUVmax) at PET1_0 and PET2_18, or (2) the cut-off value 2.5. ResultsThe multivariate Cox analysis revealed a significant negative association between higher SUVmax determined before start of treatment and local control (HR=1.59, [95% CI 1.04, 2.42], p=0.031), whereas higher dose had a significant positive effect (HR=0.95, [0.93, 0.98], p<0.001). In contrast, FDG uptake at 18Gy did not correlate with local control (HR=1.14, [0.53, 2.45], p=0.73). Neither FDG uptake prior to irradiation nor at 18Gy correlated with local control irrespective of the delivered dose (log-rank test) when using the median SUVmax values for stratification (SUVmax0Gy: 60Gy: p=0.25, 86.25Gy: p=0.47, 116Gy: p=0.88 and SUVmax18Gy: 60Gy: p=0.42, 86.25Gy: p=0.34, 116Gy: p=0.99). By contrast, stratifying the animals by the cut-off 2.5 at PET1_0 reveals a significant difference in local control for the 60Gy group (p=0.034), but not for the other dose groups. At PET2_18, no significant effect for any dose group was detected. ConclusionsThe multivariate Cox analysis revealed a significantly higher hazard of recurrence for mice with higher SUVmax determined before start of treatment. These results support the hypothesis that patients with high pre-therapeutic FDG uptake should be considered at increased risk of local failure and therefore as possible candidates for dose escalation strategies.

Analysis of 18F-FDG PET/CT imaging characteristics in 36 patients with autoimmune pancreatitis

Objective To investigate the imaging characteristics and the clinical value of 18F-FDG PET/CT imaging in autoimmune pancreatitis (AIP). Methods The 18F-FDG PET/CT imaging characteristics of 36 patients (33 males, 3 females; average age 60 years) with AIP proved by histopathology or clinical follow-up from August 2010 to March 2014 were retrospectively analyzed. The morphologic and metabolic abnormalities of pancreatic and extra-pancreatic lesions were analyzed. The early SUVmax and delayed SUVmax were compared by paired t test in 32 patients who underwent dual time point 18F-FDG PET/CT imaging. Results (1)18F-FDG PET/CT showed diffuse uptake of FDG by the pancreas in 17 patients (47.2%, 17/36), localized uptake in 10 patients (27.8%, 10/36), mixed uptake in 7 patients (19.4%, 7/36), and multifocal uptake in 2 patients (5.6%, 2/36). A total of 33 patients (91.7%) had intense FDG uptake in the pancreas with SUVmax of 5.32±1.83, while the others showed mild FDG uptake with SUVmax of 2.13±0.15. Delayed SUVmax was significantly different from early SUVmax (6.11±2.68 vs 5.08±2.03, t=-7.305, P<0.01) in the 32 patients undergoing delayed scan. The average retention index (RI) in those patients were (18.0±16.1)%. (2) Capsule-like rim surrounding the pancreas was found in 10 patients and abnormality of the main pancreatic duct was found in 9 patients. (3) Thirty-four (94.4%, 34/36) patients had extra-pancreatic lesions, including mediastinal and pulmonary hilar lymph nodes, salivary glands, cervical and submandibular lymph nodes, and foci with the invertedVshaped high FDG uptake in the prostate, which were found in 21 of 33 (63.6%) male patients. (4) The case-times of extra-pancreatic organs involved were 4.17±2.15 in the whole pancreas involved group (diffuse uptake + mixed uptake), and 2.64±1.63 in the partial pancreas involved group (localized uptake + multifocal uptake), which were significantly different (t=2.10, P<0.05). Conclusions Various intense uptake of FDG, which is higher on delayed scan, can be shown in the pancreas in patients with AIP. 18F-FDG PET/CT is an effective modality to detect extra-pancreatic lesions, and it could contribute to the diagnosis and evaluation of AIP. Key words: Autoimmune diseases; Pancreatitis; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose

Rebuttal from Dr. Decaluwé and Dr. Dooms.

We congratulate Drs. Obiols and Call for their excellent argumentations to consider a preoperative exploration of the mediastinal lymph nodes in order to avoid futile anatomical lung resections. As they rightly pointed out, preoperative invasive mediastinal nodal staging is not routinely indicated in clinical stage IA non-small cell lung cancer (cStage-IA NSCLC). Nevertheless, the authors suggested specific indications in which preoperative invasive mediastinal nodal staging might be indicated for cStage-IA NSCLC: centrally located tumor; adenocarcinoma histology; high FDG-uptake on PET; tumor size (≤2 cm vs . 2.1–3.0 cm); or a combination of these factors.

A pulmonary lesion with high FDG uptake and without morphologiacal change on PET/CT images

A pulmonary lesion with high FDG uptake and without morphologiacal change on PET/CT images

Abstract P5-01-03: Stratifying triple-negative breast cancer prognosis using 18F-FDG-PET/CT imaging

Abstract Introduction: Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and may benefit from molecular-targeted therapies. This study aims to stratify prognosis of TNBC patients using pre-treatment 18F-FDG PET/CT, alone and with correlation to immunohistochemistry biomarkers. Method: 200 consecutive TNBC breast cancer patients treated between 2008 and 2012 who received lumpectomy or mastectomy as primary treatment were retrieved. Among the full cohort, 79 patients had pre-treatment 18F FDG PET/CT scans. Immunostaining status (percentage and intensity) of basal biomarkers (EGFR, CK5/6), Ki-67, P53, and other clinicopathological variables (age, tumor size, pathological T/N stage, nuclear grade, and lymph node metastasis) were obtained. Three PET image features were evaluated: maximum uptake values (SUVmax), mean uptake (SUVmean) and target volume (SUVvol) defined by SUV&amp;gt;2.5. The relationships among tumor metabolic activities and clinicopathological factors were evaluated. All variables were analyzed versus disease-free survival (DFS) using univariate and multivariate Cox analysis, Kaplan-Meier curves and log-rank tests. The optimal cutoff points of variables were estimated using time-dependent survival receiver operating characteristic (ROC) analysis. Results: All PET features significantly correlated with proliferation marker Ki-67 (all p&amp;lt;0.010). SUVmax stratified the prognosis of TNBC patients with optimal cutoff derived by ROC analysis (≤3.5 vs &amp;gt;3.5, AUC=0.654, p=0.006). Basal biomarkers EGFR and CK5/6 and image features SUVmax, SUVmean, SUVvol were significant associated with DFS in univariate Cox analysis, whereas SUVmax (p=0.001) and EGFR (p=0.001) were also significant in multivariate Cox analysis. To integrate prognosis of biological and imaging markers, patients were first stratified by EGFR into low (≤15%) and high (&amp;gt;15%) risk groups. Further, SUVmax was used as a variable to stratify the two EGFR groups. In the high EGFR group, patients with high FDG uptake (SUVmax&amp;gt;3.5) had worse survival outcome (median DFS=7.6 months) than those patients with low FDG uptake (SUVmax≤3.5, median DFS=11.6 months). In the low EGFR group, high SUVmax also indicated worse survival outcome (17.2 months) than low SUVmax (22.8 months). The risk stratification with integrative EGFR and PET was statistically significant with log-rank p&amp;lt;&amp;lt;0.001. Multivariate Cox analysis for disease-free survivalVariablesHR (95% CI)p-valuePathology, T stage, ≤ 3 vs &amp;gt;32.337(0.428-7.384)0.148EGFR, ≤15% vs &amp;gt; 15%9.109(1.997-41.55)0.004CK5/6, ≤ 50% vs &amp;gt; 50%1.471(0.598-3.614)0.401SUVmax, ≤3.5 vs &amp;gt; 3.53.883(1.13-13.32)0.031 TNBC patient risk groups stratified by EGFR and SUVmax (with the median values of variables)Risk groups (EGFR&amp;gt;15, SUVmax&amp;gt;3.5)patient#DFS monthsEGFR %SUVmaxSUVmeanSUVvolKi-67%1 (-, -)1222.852.00.60.2342 (-, +)1517.258.94.37.2673 (+, -)1311.6502.72.60.9354 (+, +)377.66011.35.210.960 Conclusions: Pre-treatment 18F-FDG PET/CT imaging has significant prognostic value for predicting survival outcome of TNBC patients. Integrated with basal-biomarker EGFR, PET imaging can further stratify patient risks in the pre-treatment stage, and help select appropriate treatment strategies for individual patients. Citation Format: Yue Y, Cui X, Bose S, Audeh W, Zhang X, Fraass B. Stratifying triple-negative breast cancer prognosis using 18F-FDG-PET/CT imaging. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-01-03.

Use of registration-based contour propagation in texture analysis for esophageal cancer pathologic response prediction

Change in PET-based textural features has shown promise in predicting cancer response to treatment. However, contouring tumour volumes on longitudinal scans is time-consuming. This study investigated the usefulness of contour propagation in texture analysis for the purpose of pathologic response prediction in esophageal cancer.Forty-five esophageal cancer patients underwent PET/CT scans before and after chemo-radiotherapy. Patients were classified into responders and non-responders after the surgery. Physician-defined tumour ROIs on pre-treatment PET were propagated onto the post-treatment PET using rigid and ten deformable registration algorithms. PET images were converted into 256 discrete values. Co-occurrence, run-length, and size zone matrix textures were computed within all ROIs. The relative difference of each texture at different treatment time-points was used to predict the pathologic responders. Their predictive value was assessed using the area under the receiver-operating-characteristic curve (AUC). Propagated ROIs from different algorithms were compared using Dice similarity index (DSI).Contours propagated by the fast-demons, fast-free-form and rigid algorithms did not fully capture the high FDG uptake regions of tumours. Fast-demons propagated ROIs had the least agreement with other contours (DSI = 58%). Moderate to substantial overlap were found in the ROIs propagated by all other algorithms (DSI = 69%–79%). Rigidly propagated ROIs with co-occurrence texture failed to significantly differentiate between responders and non-responders (AUC = 0.58, q-value = 0.33), while the differentiation was significant with other textures (AUC = 0.71‒0.73, p < 0.009). Among the deformable algorithms, fast-demons (AUC = 0.68‒0.70, q-value < 0.03) and fast-free-form (AUC = 0.69‒0.74, q-value < 0.04) were the least predictive. ROIs propagated by all other deformable algorithms with any texture significantly predicted pathologic responders (AUC = 0.72‒0.78, q-value < 0.01).Propagated ROIs using deformable registration for all textures can lead to accurate prediction of pathologic response, potentially expediting the temporal texture analysis process. However, fast-demons, fast-free-form, and rigid algorithms should be applied with care due to their inferior performance compared to other algorithms.

Adrenal Histoplasmosis in Immunocompetent Patients Presenting as Adrenal Insufficiency.

Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum, endemic in central and eastern states of United States, South America and Africa. India is considered to be non-endemic area for histoplasmosis. Disseminated histoplasmosis may affect almost all systems. Disseminated histoplasmosis with asymptomatic adrenal involvement has been described in immunocompromised patients; whereas isolated adrenal involvement with adrenal insufficiency as the presenting manifestation of the disease is rare. Twelve patients from a non-endemic area with adrenal histoplasmosis, who were immunocompetent and diagnosed as adrenal histoplasmosis by cytology/histopathology between January 2012 to December 2014 were studied. 18F-FDG PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) was used to assess the extent of involvement. There were a total of 12 immunocompetent males (mean age: 56.9 years). Ten patients had bilateral adrenal involvement and two had a unilateral left adrenal mass. All the patients had histopathologically/cytologically proven adrenal histoplasmosis. Two patients had simultaneous histoplasmosis of other sites, one in the epiglottis and the other in the alveolus. 18F-FDG PET/CT was performed in 10 patients showing high FDG uptake in the adrenals. All these patients received Amphotericin B and/or Itraconazole treatment that led to symptomatic improvement. A diagnosis of invasive fungal infection requires a high index of suspicion, especially in immunocompetent patients who present with nonspecific symptoms, clinical signs, laboratory and radiological features that can resemble adrenal neoplasms. Clinical specimens must be sent for cytopathology/histopathology together with fungal culture for a definite diagnosis and appropriate management.

Correlation of Ki-67 proliferation index and 18-fluorodeoxyglucose uptake in colorectal incidental lesions detected by positron emission tomography-computed tomography.

To investigate whether focal high maximum standardized uptake value (SUVmax) determined by 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) imaging is correlated with proliferation index in the colorectal region. SUVmax values of 31 colorectal neoplasms that were incidentally detected during PET-CT examination were compared to dysplasia degree, histopathologic diagnosis, and immunohistochemical expression of the Ki-67 proliferation marker. Statistically significant correlations were found between SUVmax and Ki-67 proliferation index, dysplasia degree, and histopathologic diagnosis. Median SUVmax value was found to be significantly higher in high-risk lesions than low-risk lesions. The Ki-67 proliferation index is an indicator of SUVmax in colorectal tract. SUVmax values can predict malignancy and prognosis in this region. Colonoscopy and biopsy should always be performed whenever a focal high FDG uptake is determined incidentally in a patient.

Atypical Carcinoid Tumor of the Larynx: A Challenging Diagnostic Case

Background: Atypical carcinoids are rare neuroendocrine tumors, but they are the most common type of nonsquamous cell laryngeal neoplasms. Recent literature addresses the importance of adequate diagnosis, but lacks consensus in treatment strategy. Case report: A 69-year-old man presented with dysphagia. Diagnosis of supraglottic hemangioma was based on fiberoptic examination. After treatment with CO2 laser excision histopathological diagnosis stated paraganglioma. Dysphagia recurred after 6 months. (18)F-FDG PET/CT-scan revealed high FDG-uptake at the right aryepiglottic fold. After CO2 laser excision histopathology showed atypical carcinoid. Total laryngectomy and neck dissection was performed to secure tumor-free margins, followed by adjuvant radiotherapy due to lymph node metastases. A month after termination of radiotherapy no lesions were determined by somatostatin receptor scintigraphy. Conclusion: Personalized management should be based mainly on mitotic rate and locoregional extension. Surgical treatment and lifelong multidisciplinary follow-up is mandatory, while the role of adjuvant therapy remains debatable.

FDG-PET/CT for detecting relapse in patients with acute lymphoblastic leukemia.

A 16-year-old girl was presented with a mass in the medial side of the left eye with normal visual inspection. She was diagnosed as having precursor b-cell acute lymphoblastic leukemia (B-ALL) 9 years ago by bone marrow biopsy and her treatment was planned as allogeneic transplantation over chemotherapy. Complete remission was achieved by allogeneic bone marrow transplant from her sister. FDG PET/CT imaging was performed for determining extramedullary relapse and a slightly hyperdense, oval shaped 16 × 18 × 16 mmmass (red arrows) was located in the soft tissue between the left eyeball and the left nasal process of the maxilla on unenhanced axial CT image (Fig. 1). Corresponding axial (Fig. 2) PET and fused (Fig. 3) images showed high FDG uptake (SUVmax = 7.70) (red arrows) in the mass. Maximum intensity projection PET images with anterior view (Fig. 4) showed that there was no additional site of relapse. The extramedullary B-ALL relapse was confirmed by an incisional biopsy. The patient underwent bone marrow biopsy and there was no relapse in the bone marrow, compatible with FDG PET/CT findings. Figure 1.

Preclinical Assessment of Efficacy of Radiation Dose Painting Based on Intratumoral FDG-PET Uptake.

We tested therapeutic efficacy of two dose painting strategies of applying higher radiation dose to tumor subvolumes with high FDG uptake (biologic target volume, BTV): dose escalation and dose redistribution. We also investigated whether tumor response was determined by the highest dose in BTV or the lowest dose in gross tumor volume (GTV). FDG uptake was evaluated in rat rhabdomyosarcomas prior to irradiation. BTV was defined as 30% of GTV with the highest (BTVhot) or lowest (BTVcold) uptake. To test efficacy of dose escalation, tumor response (time to reach two times starting tumor volume, TGTV2) to Hot Boost irradiation (40% higher dose to BTVhot) was compared with Cold Boost (40% higher dose to BTVcold), while mean dose to GTV remained 12 Gy. To test efficacy of dose redistribution, TGTV2 after Hot Boost was compared with uniform irradiation with the same mean dose (8 or 12 Gy). TGTV2 after 12 Gy delivered heterogeneously (Hot and Cold Boost) or uniformly were not significantly different: 20.2, 19.5, and 20.6 days, respectively. Dose redistribution (Hot Boost) with 8 Gy resulted in faster tumor regrowth as compared with uniform irradiation (13.3 vs. 17.1 days; P = 0.026). Further increase in dose gradient to 60% led to a more pronounced decrease in TGTV2 (10.9 days; P < 0.0001). Dose escalation effect was independent of FDG uptake in target tumor volume, while dose redistribution was detrimental in this tumor model for dose levels applied here. Our data are consistent with the hypothesis that tumor response depends on the minimum intratumoral dose.

Highlights of This Issue

Immunotherapy with ipilimumab improves the survival of only around 20% of patients with metastatic melanoma. To explore reliable markers for the prediction of clinical outcome, Gebhardt and colleagues analyzed myeloid cells and related inflammatory factors in the peripheral blood of treated patients. Response to the therapy was associated with an early increase in eosinophil count, whereas nonresponders showed elevated amounts and function of circulating monocytic myeloid-derived suppressor cells as well as increased serum levels of S100A8/A9 and HMGB1. These novel complex predictive markers could help to identify metastatic melanoma patients who benefit from the ipilimumab therapy.The identification of biomarkers that early predicts the chemosensitivity of triple-negative breast cancers (TNBC) to standard neoadjuvant chemotherapy (NAC) is an important issue. Indeed, poorly responding women may be good candidates for emerging targeted therapy. Humbert and colleagues studied the predictive value of 18FDG-PET compared with clinicobiologic markers of TNBC. The authors demonstrated that combining positive EGFR status and a low 18FDG-PET tumor response after the first cycle of NAC can predict residual invasive carcinoma at the end of treatment. Multicenter trials using PET-guided treatment strategies are now necessary to evaluate the benefit of early therapeutic changes in poorly responding women.Clinical studies have demonstrated that tumor relapse after radiotherapy occurs preferentially in tumor areas with high 18F-fluorodeoxyglucose (FDG) uptake. To test the therapeutic gain from radiation dose escalation to the potentially radioresistant tumor subvolumes with high FDG, Trani and colleagues employed dose painting approaches in rat rhabdomyosarcoma: targeted dose escalation and dose redistribution. Although dose escalation to high FDG uptake was not superior to the same dose increase in low FDG uptake subvolumes, dose redistribution was even detrimental, consistent with the hypothesis that tumor response depends on the minimum intratumoral dose. These findings provide important information for the design of clinical trials.In HER2/ERBB2-amplified gastrointestinal tumors, concomitant HER2 targeting by trastuzumab antibody and the reversible inhibitor lapatinib is more effective than either agent alone. The mechanisms of this cooperation are unknown. Leto and colleagues found that trastuzumab and lapatinib complement each other to induce sustained neutralization of HER2 and its signaling partners HER3 and EGFR. This durable inhibition, which accounts for massive tumor shrinkage, is recapitulated by monotherapy with the HER2 irreversible inhibitor afatinib. These results provide functional evidence for the collaborative activity of trastuzumab and lapatinib and propose afatinib treatment as a means to diversify therapeutic opportunities in HER2-amplified gastrointestinal carcinomas.

Prognostic value of pretreatment FDG PET in pediatric neuroblastoma

PurposeThis study aimed to evaluate the prognostic value of pretreatment 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in pediatric neuroblastoma patients. MethodsThe study included 50 pediatric neuroblastoma patients who underwent diagnostic work-up FDG PET before any treatment. The maximum standardized uptake value (SUVmax) of the primary tumor lesion (Pmax), the SUVmax of all the tumor lesions, including the primary tumor lesion and metastatic lesions (Tmax), and the uptake ratio of Tmax to mean SUV of normal liver tissue (Tmax/Lmean) were calculated and tested as prognostic factors. ResultsOf the 50 patients, 15 (30.0%) experienced disease progression and 21 (42.0%) died during the follow-up period. On univariate analysis, the histopathology, tumor stage, bone marrow involvement, serum levels of lactate dehydrogenase (LDH), neuron-specific enolase, and ferritin, primary tumor size, Pmax, Tmax, and Tmax/Lmean were significant prognostic factors for disease progression-free survival (PFS), whereas the tumor stage, serum level of LDH, Tmax, and Tmax/Lmean were determined to be significant for predicting overall survival (OS). On multivariate analysis, the histopathology and serum level of LDH were independent prognostic factors for PFS, and only the Tmax/Lmean was an independent prognostic factor for OS. The 2-year PFS and OS rates were over 80.0% in patients with low FDG uptake, meanwhile, patients with high FDG uptake showed the 2-year PFS of less than 30.0% and OS of less than 55.0%. ConclusionFDG PET was an independent prognostic factor for OS in neuroblastoma patients. FDG PET can provide effective information on the prognosis for neuroblastoma patients.

The Diagnostic Performance of FDG PET/CT for Recurrent Gastric Cancer Is Significantly Affected by Primary Tumor FDG Uptake Level

Introduction: The outcome of advanced gastric cancer remains poor, and early detection of recurrence is important. FDG PET/CT is known to be useful in detection of recurrent gastric cancer, but the specific indication for surveillance with PET/CT in gastric cancer following curative resection remains unclarified to date. In this study, we evaluated the relation between FDG uptake of primary tumor and the patterns of recurrent disease in advanced gastric cancer. And we investigated whether FDG-avid primary tumors are associated with improved performance of surveillance PET/CT for detecting recurrent gastric cancer. Methods: Subjects were 372 patients (mean age 57.3 ± 11.5 y, male 254) with advanced gastric cancer who underwent curative surgery. All subjects had FDG PET/CT for initial staging and for recurrence surveillance after surgery. Primary tumors were classified as FDG-avid if they displayed focal uptake with SUVmax ≥ 4, or were otherwise classified as non-FDG-avid. Follow up FDG PET/CT were evaluated for recurrence. The presence of recurrence was determined by medical records with > 11 mo of follow-up. Results: Of the 372 subjects, 240 had FDG-avid primary tumors (64.5%; 59.7 y, male 175), whereas 132 had non-FDG-avid primary tumors (35.5%; 52.9 y, male 79). During follow-up, 72 patients (19.6%) were diagnosed to have recurrence. Among 63 cases with eligible follow-up PET/CT, 42 (3 at anastomosis site only) had FDG-avid primary tumors and 21 (2 at anastomosis site only) had non-FDG-avid tumors. For all recurrences, PET/CT sensitivity was 34/42 (81.0%) for the FDG-avid group and 11/21 (52.4%) for the non-FDG-avid group (P = 0.018). For recurrences outside the anastomosis site, PET/CT sensitivity was 41/58 (70.7%) for all subjects, 32/39 (82.1%) for the FDG-avid group, and 9/19 (47.4%) for the non-FDG-avid group (P = 0.006). PET/CT specificity for recurrence was 97.3%, 97.1%, and 97.5% for respective groups (P = n.s.). Conclusion: The result of our study showed that the detection sensitivity of recurrent gastric cancer by FDG PET/CT was superior in patients with FDG avid primary tumors than patients with FDG non-avid tumors. Hence, follow-up FDG PET/CT appears to have greater value for recurrence surveillance in patients with high tumor FDG uptake on initial PET/CT.

A Case of Extranodal Testicular Involvement in Non-Hodgkin's Lymphoma Detected through 18F-FDG PET-CT.

A 69 year-old patient was admitted for constipation and with a three days history of left lumbar pain radiating into the left iliac fossa. Contrast enhanced abdominal CT (not illustrated) demonstrated a large retroperitoneal conglomerate (7 × 10 cm) of lymph nodes developing around the abdominal aorta from the level of the renal hilum to the iliac arteries bifurcation. Additional chest CT (not illustrated) confirmed another large conglomerate of enlarged lymph nodes in the superior mediastinum. Smaller nodes were also found in the cervical thoracic angles. The definite diagnosis of diffuse large B cell non Hodgkin lymphoma suggested by CT was confirmed by surgical biopsy of a cervical node. Complementary 18F-FDG PET-CT not only confirmed the typical high FDG uptake of the cervical, mediastinal (black arrows on Fig. A) and retroperitoneal (white arrow on Figs. A & B) of lymph nodes but unexpectedly revealed a high FDG uptake of the right testis (black arrow Fig. B) suggesting associated extranodal testicular extension. Colour Doppler Ultrasound of the moderately enlarged but clinically painless right testis revealed a typical hypoechogenicity of the organ (white star on Fig. C) with massive hypervascularity. Associated swelling and hypervascularity of the epididymis (black star on Fig. C) and vas deferens (grey arrow on Fig. C) were found. The patient is actually treated with classical CHOP chemotherapy regimen and drastic reduction of testi cular hypervascularity was already found after 3 courses of chemotherapy (not illustrated)

Stratifying triple-negative breast cancer prognosis using 18F-FDG-PET/CT imaging.

This study aims to stratify prognosis of triple-negative breast cancer (TNBC) patients using pre-treatment 18F-FDG-PET/CT, alone and with correlation to immunohistochemistry biomarkers. 200 consecutive TNBC breast cancer patients treated between 2008 and 2012 were retrieved. Among the full cohort, 79 patients had pre-treatment 18F-FDG-PET/CT scans. Immunostaining status of basal biomarkers (EGFR, CK5/6) and other clinicopathological variables were obtained. Three PET image features were evaluated: maximum uptake values (SUVmax), mean uptake (SUVmean), and metabolic volume (SUVvol) defined by SUV > 2.5. All variables were analyzed versus disease-free survival (DFS) using univariate and multivariate Cox analysis, Kaplan-Meier curves, and log-rank tests. The optimal cutoff points of variables were estimated using time-dependent survival receiver operating characteristic (ROC) analysis. All PET features significantly correlated with proliferation marker Ki-67 (all p < 0.010). SUVmax stratified the prognosis of TNBC patients with optimal cutoff derived by ROC analysis (≤3.5 vs. >3.5, AUC = 0.654, p = 0.006). SUVmax and EGFR were significant prognostic factors in univariate and multivariate Cox analyses. To integrate prognosis of biological and imaging markers, patients were first stratified by EGFR into low (≤15 %) and high (>15 %) risk groups. Further, SUVmax was used as a variable to stratify the two EGFR groups. In the high EGFR group, patients with high FDG uptake (SUVmax > 3.5) had worse survival outcome (median DFS = 7.6 months) than those patients with low FDG uptake (SUVmax ≤ 3.5, median DFS = 11.6 months). In the low EGFR group, high SUVmax also indicated worse survival outcome (17.2 months) than low SUVmax (22.8 months). The risk stratification with integrative EGFR and PET was statistically significant with log-rank p ≪ 0.001. Pre-treatment 18F-FDG-PET/CT imaging has significant prognostic value for predicting survival outcome of TNBC patients. Integrated with basal-biomarker EGFR, PET imaging can further stratify patient risks in the pre-treatment stage and help select appropriate treatment strategies for individual patients.

Influence of Kidney Histology on Prognosis in Multiple Myeloma

was 39.1% in stage I, 41.4% in II, and 18.4% in III. Patients with standard and high cytogenetic risk were 57.5% and 37.9%. More than a half of patients (59.8%) were treated with thalidomide induction. Patients with low and high BM FDG uptake were 69 and 18. High cytogenetic risk (RR 8.20, P1⁄40.018), anemia (RR 5.07, P1⁄40.056), BM plasma cells more than 30% (HR 3.68, P1⁄40.050) and extramedullary disease (EMD; RR 7.72, P1⁄40.017) were associated with high uptake. Three year progression free survival rate was 52.8% in low group and 31.8% in high group (P1⁄40.3916). Overall survival (OS) rate for 5 years in low group was 54.7%, while it was 45.4% (HR 1.976, 95% CI 0.26-0.75, P1⁄40.0538) in high group. To enhance homogeneity of the study population, we run subgroup analyses of patients with thalidomide based induction regimen (n1⁄448). Patients with low and high uptake were 34 and 14, respectively. Five year OS in high group was 48.5% (HR 2.41, 95% CI 0.1762-0.7395, P1⁄40.043), while it was 61.0% in low group. ECOG 2 (HR 2.78, P1⁄40.045), BM plasma cells 30% (HR 3.98, P1⁄40.005), ISS stage III (HR 4.18, P1⁄40.013), elevated LDH (HR 1.33, P1⁄40.004) and 2 microglobulin (HR 4.43, P1⁄40.019). Autologous hematopoietic stem cell transplantation (HR 0.23, P1⁄40.020) and the absence of EMD (HR 0.36, P1⁄40.049) were related with better prognosis. Conclusion: Initial high BM FDG uptake by direct visual assessment in MM showed correlations with poor prognosis and more aggressive disease. This finding could make possible simple and fast prediction of prognosis in MM.