Post-therapy Scan Research Articles

Abstract 2867: FDG-PET imaging as a potential biomarker of mitochondrial targeting by CPI-613, a novel inhibitor of mitochondrial metabolism

Abstract CPI-613 is a lipoate analogue that has been shown to inhibit the pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (KGDH) complexes selectively in tumor cells (reviewed in Exp.Rev.Clin.Pharma. 7, 837). These two enzymes control the vast majority of carbon flow into the tricarboxylic acid (TCA) cycle and play a central role in mitochondrial metabolism. PDH converts pyruvate into acetyl-CoA, which in turn can enter the TCA cycle for cellular respiration. Since pyruvate is the final product of glycolysis, PDH serves to link glycolysis to the TCA cycle. Early clinical trials with CPI-613 have demonstrated very promising clinical responses in pancreatic cancer, leukemia, and lymphoma when used in combination with standard chemotherapy. Moreover, apparently homeostatic responses of tumor cells to CPI-613 inhibition of mitochondrial metabolism include compensatory upregulation of glucose uptake. Thus, we hypothesized that we can use 18F-Fludeoxyglucose (FDG)-PET/CT, a translational imaging approach that measures cellular glucose uptake, as a biomarker for CPI-613 cellular delivery and its targeting of mitochondrial metabolism. Therefore, in this work we evaluated the in vitro and in vivo glucose uptake in cancer cells and tumor xenografts after treatment with CPI-613. To measure glucose uptake in vitro we pulsed BxPc3 pancreatic cancer cells with 3H 2-deoxyglucose for 15 or 60 minutes following 2 hours of treatment with CPI-613. We observed a significant upregulation (~100% increase) of cellular 2-deoxyglucose uptake, consistent with a compensatory increase in glucose uptake as a result of successful targeting of mitochondrial metabolism. We therefore examined whether this upregulation occurs in vivo using FDG-PET/CT. Mice bearing BxPc3 flank tumors were treated with 50mg/kg of CPI-613 and underwent FDG-PET/CT scans 4 hours and 24 hours post-CPI-613 treatment. Similar to the in vitro response, tumors treated with CPI-613 exhibited a 75% increase in 18F-FDG uptake compared to untreated controls at 4 hours post therapy. In the 24 hour post-therapy scans, tumor 18F-FDG was significantly decreased, indicating tumor cell killing, which corresponds to previously published data that demonstrated efficacy of CPI-613 against BxPc3 tumor xenografts. These results indicate the potential for using the initial FDG flare seen on PET imaging as a biomarker to detect mitochondrial targeting by CPI-613 immediately after CPI-613 treatment, a strategy that may be used, after further clinical validation, to stratify responders to this novel mitochondrial inhibitor. Citation Format: Kiran Solingapuram Sai, Zuzana Zachar, Frankis Almaguel, Shawn D. Stuart, Michael S. Dahan, Moises Guardado, Stephanie Rideout, Minghui Wang, Anirudh Sattiraju, Paul M. Bingham, Boris Pasche, Akiva Mintz. FDG-PET imaging as a potential biomarker of mitochondrial targeting by CPI-613, a novel inhibitor of mitochondrial metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2867. doi:10.1158/1538-7445.AM2017-2867

Anti-thyroglobulin antibodies do not significantly increase the risk of finding iodine avid metastases on post-radioactive iodine ablation scan in low-risk thyroid cancer patients.

Post-operative thyroglobulin (Tg) levels can predict the likelihood of residual cancer, including distant metastases, thereby influencing postsurgical treatment strategies even in patients with low-risk disease. Circulating anti-thyroglobulin antibodies (anti-Tg Abs) interfere with Tg measurement preventing this clinical use. It is not known if the presence of anti-Tg Abs predicts metastatic disease on post-therapy scan in patients with low-risk disease or if they should influence the use or dose of I-131 therapy. In the present study, we compare post-therapy scans in low-risk patients with and without anti-Tg Abs. This is a single-institution retrospective study. The study population (Group A) included all patients with low-risk differentiated thyroid cancer (DTC) who underwent total thyroidectomy and RAI between 1/1/2006 to 9/11/2015 with intrathyroidal T1-T2, Nx, N0 or N1a (≤5 nodes all measuring, when reported, <2mm) that had anti-thyroglobulin antibodies. Patients were excluded if they had known distant metastases and/or extensive vascular invasion. A second group of patients (Group B) treated during the same period but without anti-Tg antibodies was selected to match group A by propensity core matching with a logistic regression model. Each group included 37 patients. In group A: Median age was 40years, 86% female and 76% PTC. Median tumor size was 2cm (0.2-3.8), 32% had multifocal disease, 16% were N1a and 4% had vascular invasion. Parameters in group B were not statistically different from Group A, as expected based on the selection criteria, except being less likely to have Hashimoto's thyroiditis on pathology (p<0.001). Post-therapy scan results were compared by Chi-square test with 86% negative post therapy scan frequency in group A and 92% in group B without evidence of a difference (p=0.45). In patients with low-risk DTC, anti-Tg Abs did not significantly predict metastatic disease on post-therapy scan. If confirmed, these data suggest that the presence of anti-Tg Abs alone should not influence initial therapy in patients with low-risk DTC.

Tumor interface stability on CT imaging is an early marker of response to cytotoxic therapy in pancreatic ductal adenocarcinoma.

284 Background: There is currently no reliable biomarker for assessing the response to therapy of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated how changes in the tumor/parenchyma interface associate with response. Methods: We reviewed pre- and post-therapy scans of patients who received chemotherapy and/or chemoradiation for both localized and metastatic PDAC. We classified the interface between the PDAC tumor and surrounding pancreas parenchyma as stable (remains or becomes well-defined) or unstable (becomes poorly defined) using a novel visual scoring system and quantified changes in enhancement at this interface (Philips Intellispace Portal, quantitative European Association for the Study of Liver [qEASL]). Results: Three retrospective datasets were used to develop this method with consensus visual scoring performed by 3 radiologists. The first dataset included 99 patients with localized PDAC who received neoadjuvant chemoradiation. Patients who were classified as having a stable interface had significantly higher probability of achieving a complete or near-complete pathologic response (21% vs 0%, p = 0.01) and additionally demonstrated an improved median disease-free survival (DFS, 20.9 vs 7.9 mos., p &lt; 0.01) and overall survival (OS, 47.7 vs 19.1 mos., p &lt; 0.01). These results were validated in a separate dataset of 94 patients receiving protocol-based chemotherapy and chemoradiation (chemoRT cohort) and a cohort of 86 patients with stage IV disease. In both cohorts, a stable interface was associated with a significant improvement in progression free survival (PFS, Hazard Ratio [HR] 0.44, p = 0.01 for chemoRT and HR 0.70, p = 0.16 for stage IV) and OS (HR 0.42, p &lt; 0.01 for chemoRT and HR 0.59, p = 0.05 for stage IV). Multivariate analyses for each cohort showed interface stability to be independently associated with both DFS/PFS and OS. Measurements obtained using qEASL were concordant with the visual scoring results. Conclusions: The interface stability of PDAC is an early readout of response to therapy. Integration of this imaging feature into clinical trials for localized and metastatic PDAC may aid in the future development of adaptive treatment strategies.

Incidental Findings of Intense Radioiodine Uptake in Struma Ovarii and Bilateral Nonlactating Breasts Simultaneously on Postablation 131I SPECT/CT for Papillary Thyroid Cancer.

A 52-year-old woman diagnosed with papillary thyroid carcinoma was referred for 131I therapy following total thyroidectomy. She was given 4,810MBq (130mCi) of 131I following 4weeks of thyroid hormone withdrawal. A posttherapy scan showed intense, focal activity in the pelvis and intense, diffuse activity on both sides of the chest, which was localized to the right ovary and both breasts on SPECT/CT examination. She had bilateral nipple pain and a history of antidopaminergic drugs as combination medication for her rheumatoid arthritis and prokinetics during radioiodine therapy. On a 123I whole-body scan 9months later after stopping the drugs, bilateral breast uptake was not visible; however, right ovarian focal uptake was still visualized. Bilateral salpingo-oophorectomy was performed, and revealed struma ovarii with substantial internal necrosis due to radioiodine therapy. This case is interesting as two rare entities, 131I therapy-related struma ovarii and drug-related breast uptake, were simultaneously visualized.

Radioiodine therapy under rhTSH for follicular thyroid carcinoma with sellar metastasis and non-rising TSH

Metastasis to the pituitary gland/sella turcica is an uncommon complication of thyroid cancer. Treating this condition is a challenge in the setting of pituitary insufficiency due to this lesion, and recombinant human thyroid-stimulating hormone (rhTSH) stimulation becomes critically essential. We present a rare case of an 82-year-old female patient with follicular carcinoma of the thyroid with metastasis to the sella turcica in addition to multiple skeletal and lung metastases. MRI of the brain showed a hypointense suprasellar lesion on T 1 weighted images. The thyroid-stimulating hormone level remained persistently low even 4 weeks after thyroidectomy. A whole-body pertechnetate scan could not localize any abnormal tracer uptake and radioactive iodine uptake was also persistently low. The patient did not have symptoms related to pituitary involvement but TSH and early morning adrenocorticotrophic hormone levels were low. After thorough discussion with the neurosurgeon and radiotherapist, it was decided to start the patient on high-dose radioiodine treatment. Persistently low TSH level was a concern for starting radioiodine therapy. In view of this clinical context, rhTSH stimulation was used to achieve adequate TSH levels prior to radioiodine therapy. Subsequently, the patient was treated with 3.7 GBq (100 mci) of high-dose radioiodine. A post-therapy scan demonstrated radioiodine concentration in the thyroid bed remnant, multiple skeletal lesions and the sellar region. Thus, the use of rhTSH was critical in the management of this patient. It helped in radioiodine treatment by stimulating radioiodine uptake in the remnant and at the metastatic sites.

AMC-085: A Pilot Trial of AVD and Brentuximab Vedotin in the Upfront Treatment of Stage II-IV HIV-Associated Hodgkin Lymphoma. A Trial of the AIDS Malignancy Consortium

Introduction: Patients (pts) infected with HIV have a 6-8 fold increased risk of classic Hodgkin lymphoma (cHL). Incidence may have increased with the implementation of combined anti-retroviral therapy (cART) in the mid 1990s. Frontline therapy for HIV-associated cHL (HIV-cHL) using, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in the pre-cART era showed a 2 year overall survival (OS) of 48%, but outcomes are currently similar to the non-HIV population. Pts with advanced disease have a 30% chance of relapse with ABVD. Brentuximab vedotin (BV), an anti-CD30 an antibody drug conjugate that selectively induces apoptosis of CD30+ cells with a complete response of 34% in patients with relapsed/refractory cHL. An international trial of BV with doxorubicin, vinblastine, and dacarbazine (AVD) vs. ABVD is ongoing. Here we present the phase I portion of the first trial using BV with AVD in the upfront treatment of HIV-cHL. The Phase II portion is actively accruing in both the United States and France as part of an AIDS Malignancy Consortium (AMC)/Lymphoma Study Association (LYSA) collaboration.Methods: The Phase I was a 3+3 dose de-escalation design evaluating 3 dose levels of BV (1.2 mg/kg, 0.9 mg/kg, and 0.6 mg/kg) every 2 weeks combined with standard, fixed doses of doxorubicin 25 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 (AVD) in a 28 day cycle. Eligibility: HIV+ pts diagnosed with untreated cHL stage II-IV with CD4 counts ≥50 cells/mm3 were required to take cART regimens for at least 1 week before treatment. Ritonavir, zidovidine, and cobisistat were excluded. Baseline, cycle 2, and post treatment PET/CT scans were required. Dose limiting toxicities (DLTs) were defined during cycle 1.Results: Sixpts (5 men and 1 woman) were treated in the phase I portion from 3/2013-5/2015. Staging: II (n=1), III (n=1) IV (n=4). Pathology: mixed cellularity (n=2), nodular sclerosis (n=3), and lymphocyte depleted/mixed cellularity (n=1) HIV-cHL. The median CD4 T cell count at lymphoma diagnosis was 499 cells/mm3 (range 86-784) and the median viral load was 44 copies/ml (range 20-77). No cycle 1 DLTs were identified in the first 6 eligible patients and only 3 grade 3 adverse events in later cycles were noted, pneumonia, n=1, and neuropathy n=2, and neutropenia, n=1. In 2 pts, toxicity required delays in therapy of over 3 weeks (after c5d1 and after c6d1) resulting in subject removal from further protocol therapy. One pt had a decrease in the diffusion lung capacity for carbon monoxide (DLCO) to 65% after cycle 2, and BV was withheld while AVD continued as per protocol. Two pts were later deemed ineligible, and excluded from any analysis, due to the concomitant use of ritonavir-based cART at enrollment. Both developed febrile neutropenia and one developed a grade 3 pancreatitis during cycle 1, emphasizing the importance of not treating patients with BV + AVD with concurrent CYP3A4 inhibitors. Five of the 6 pts achieved cycle 2 PET/CT negativity as defined by a Deauville score 1-3. The PET/CT positive patient ultimately had a negative post-therapy scan. The 5 pts who completed therapy achieved CR post-therapy, and one patient has yet to complete treatment. Phase II is enrolling at BV 1.2 mg/kg in combination with AVD.Conclusions: AVD-BV in stage II-IV HIV-cHL was well-tolerated therapy as no DLT were identified. Five of the 6 patients achieved a negative C2 PET/CT and 5/5 of the patients who completed therapy thus far achieved a CR. The recommended Phase II dose is 1.2 mg/kg +AVD every other week. The phase II portion (51 subjects) is actively accruing in both the USA and France, in an AMC/LYSA collaboration, clinicaltrials.gov NCT01771107. DisclosuresNo relevant conflicts of interest to declare.

False-Positive Radioactive Iodine Uptake in Uterine Fibroids

A 46 year old female underwent radioiodine therapy for bilateral multifocal papillary thyroid carcinoma. Post-therapy scan with SPECTCT showed increased uptake in the pelvis that corresponded to uterinefibroids, aspreviously characterized by MRI and US exams.

A new appraisal of iodine refractory thyroid cancer.

Thyroid cancer incidence is increasing all over the world - mostly due to an increase in the detection of small tumors that were previously undetected. A small percentage of these tumors lose the ability to uptake and/or to respond to radioiodine (RAI) therapy, especially in metastatic patients. There are several new therapeutic options that have emerged in the last 5 years to treat RAI refractory thyroid cancer patients, however, it is very important to properly identify RAI refractory patients and to clarify those appropriate for these treatments. In this review, we discuss the RAI refractory definitions and the criteria that have been suggested based on RAI uptake in the post therapy scan, as well as the response after RAI therapy and the possible molecular mechanisms involved in this process. We offer a review of the therapeutic options available at the moment and the therapeutic considerations based on a patient's individualized personal characteristics, primary tumor histology, tumor burden and location and velocity of lesion growth.

A Clinical Trial of Optimal Time Interval Between Ablation and Diagnostic Activity When a Pretherapy RAI Scanning Is Performed on Patients With Differentiated Thyroid Carcinoma

This article investigates the association of the time interval between the diagnostic dose and ablation with the stunning effect, when a 74 MBq 131I pretherapy scanning was performed on patients with differentiated thyroid carcinoma (DTC); the patients who were diagnosed as DTC and would be performed radioiodine (RAI) ablation of thyroid remnants or metastases were recruited during January 2011 and May 2012 in our hospital.Thirty-seven patients with DTC who had the RAI ablation of thyroid remnants or metastases for the first time were recruited. All the patients received a dose of 1850 to 7400 MBq of 131I for ablation and a diagnostic scan was performed 24 hours after the administration of 74 MBq 131I before ablation. A posttherapy scan was performed 2 to 7 days after the ablation. The patients were broken down into 3 groups (G1, G2, and G3) according to the interval time between the diagnostic dose and therapy (1–3, 4–7, and >7 days). The fractional concentrations of 131I in remnants or functional metastases were quantified and expressed as therapeutic/diagnostic (Rx/Dx). The level of significance was set at 0.05.Sixty-seven foci were found both on pretherapy and posttherapy scans, the mean ratio of Rx/Dx was 0.43 ± 0.29, and the ratio of 49 foci (73.13%) was <0.6. The ratios in G1, G2, and G3 were 0.46 ± 0.29, 0.29 ± 0.18, and 0.55 ± 0.33, respectively. The differences between G1 and G2, and G2 and G3 were statistically significant (t = 2.40, P = 0.021 and t = 3.28, P = 0.002), whereas the difference between G1 and G3 was not significant (t = 1.01, P = 0.319).By a diagnostic scan of 74 MBq 131I, stunning prominently occurs with a time of 4 to 7 days between the diagnostic dose and ablation. We recommend that for less stunning effect, RAI ablation should be performed within 3 days or postponed until 1 week after the diagnostic dose administrated.

Prediction of treatment response to ¹³¹I therapy by diffuse hepatic uptake intensity on post-therapy whole-body scan in patients with distant metastases of differentiated thyroid cancer.

A diffuse hepatic uptake (DHU) on radioiodine whole-body scans (WBS) after (131)I therapy is caused by (131)I-labeled iodoproteins, particularly (131)I-labeled thyroglobulin (Tg). We hypothesized that the DHU intensity after (131)I therapy might correlate with subsequent serum Tg reduction, suggesting that DHU reflects destruction of functioning thyroid tissue as measured by serum Tg. We retrospectively reviewed the medical records and (131)I WBSs of 47 patients treated with (131)I therapy for distant metastasis from differentiated thyroid cancer (M:F = 15:32, median age 45 years, range 11-74 years). All patients received post-ablative (131)I scans (PAWBS) at first (131)I ablation after total thyroidectomy and post-therapy (131)I scan (PTWBS) at second (131)I therapy. The DHU intensities of the PAWBS and PTWBS were classified into 3 grades: 1, faint; 2, modest; and 3, intense. Serum thyroid-stimulating hormone-stimulated Tg (sTg) levels were measured at the time of each therapy and 1 year after the second (131)I therapy. One year after the second (131)I therapy, 10 patients (21.3%) were in remission and 37 (78.7%) had persistent disease. The DHU intensity on PAWBS correlated with the percentage sTg reduction at the next follow-up point (σ = 0.466, p = 0.0016). The patients with intense DHU on PTWBS tended to have a higher percentage sTg reduction than the other patients, although statistical significances were marginal (Spearman's rank correlation: σ = 0.304, p = 0.054; Kruskal-Wallis test: p = 0.067). In univariate analysis, the DHU grades on PAWBS and the initial sTg levels were significantly different between patients in remission and those with persistent disease (PAWBS: p = 0.022; initial sTg: p = 0.0059). In multivariate logistic regression analysis, after adjusting for initial sTg levels, a DHU grade of 3 on PAWBS was an independent predictor of remission (PAWBS: p = 0.028; initial sTg <100 ng/ml: p = 0.043). In patients with iodine-avid distant metastases, intensity of DHU on (131)I post-therapy scan correlated with subsequent percentage serum sTg reduction. Also, intense DHU could be one of the predictors of remission in these patients.

Bronchiectasis Masquerading as Lung Metastasis in a Patient with Papillary Carcinoma Thyroid Identified by 131I Whole Body Scintigraphy

Differentiated thyroid carcinoma (DTC), arising from thyroid follicular epithelial cells, accounts for the vast majority of thyroid cancers. Despite being well-differentiated, papillary thyroid cancers may be overtly or minimally invasive. They may invade lymphatics but are less likely to invade blood vessels. Iodine-131 (131I) is routinely used to image patients after thyroidectomy to assess the presence of residual thyroid tissue with or without metastasis. False positive 131I scans, showing the presence of 131I uptake in the absence of residual thyroid tissue or metastases can occur, although they are uncommon. Unless recognized as a false positive, 131I uptake may result in diagnostic error and lead to administration of an unnecessary higher therapeutic dose. We present a 55 year old female, histopathologically proven case of follicular variant of papillary carcinoma that underwent Total Thyroidectomy. Residual thyroid and whole body scan showed moderate residual thyroid tissue with abnormal 131I in right lung masquerading as right lung metastases. SPECTCT (single photon emission computed tomography – computed tomography) was incremental in localizing the site of 131I uptake to bronchiectatic changes. 131I diagnostic and post therapy scans are useful to risk stratify DTC patients’ so that amount of high dose 131I to be administered to patient can be estimated and judiciously used in their treatment.

Watch Out for Unexpected Radioiodine Uptake on Post-therapy Thyroid Cancer Imaging

Unexpected radioiodine distributions may be encountered on post-therapy I-131 thyroid cancer scans due to a range of benign physiological processes, causing diagnostic dilemma and potentially mimicking metastatic disease. We present two cases of intense focal uptake related to concentration of radioiodine activity on wrist-watches by differing mechanisms, which should be confirmed by clinical history and not be mistaken for metastatic disease.

Cardiac blood pool activity on postablation radioiodine imaging.

There are reports on physiologic and pathologic mediastinal uptake on radioiodine imaging in patients with thyroid carcinoma. The most commonly reported physiologic causes of mediastinal uptake are esophageal retention of salivary secretion and uptake by hyperplastic or normal thymus gland. In this study, we evaluated physiologic cardiac blood pool (CBP) activity and its associated findings on radioiodine imaging. Cardiac blood pool activity was evaluated in 186 postablation and 32 posttherapy scans. After oral radioiodine administration, imaging was initiated on day 7. Thyroglobulin, anti-thyroglobulin and TSH blood level determination was carried out in all patients. Whole-body scans were inspected with regard to residual thyroid uptake, esophageal uptake, CBP activity, hepatic activity and metastatic iodine uptake. Uptake in the residual thyroid tissue was graded visually as mild (m), moderate (M) and significant (S). Whenever CBP activity was detected on visual inspection, its intensity was graded as mild (1), moderate (2), and significant (3). Cardiac blood pool activity was detected in 61 postablation scans (33 %). Residual thyroid uptake was observed in all patients with CBP. A significant correlation existed between the intensity of uptake and the presence of CBP (p < 0.05). The mean Tg in patients with CBP was significantly higher than those without CBP (p < 0.05). Cardiac blood pool activity was not observed in any posttherapy scans and in those scans with distant metastases in the postablation group. Linear or irregular activity pattern thought to be due to esophagus was detected in 4 % of postablation scans. The results have revealed CBP to be common on postablation scans. Its presence correlated with the intensity of residual thyroid uptake and had a significant association with increased thyroglobulin levels. Its absence on posttherapy scans despite increased Tg levels suggested that this activity is due to labeled thyroid hormones released by the residual thyroid tissue. Its presence might imply a high level of blood radiation dose.

A systematic review and meta-analysis evaluating completeness and outcomes of robotic thyroidectomy.

Despite immense interest, robotic-assisted thyroidectomy (RT) remains controversial in differentiated thyroid carcinoma (DTC). This systematic review and meta-analysis compared surgical completeness and/or oncological outcomes between RT and open thyroidectomy (OT) in low-risk DTC. Systematic review. A systematic review was performed to identify studies that compared surgical completeness and/or oncological outcomes between RT and OT in DTC. Any study that compared at least one parameter relating to surgical completeness and/or oncological outcome for DTC was considered. Number of central lymph nodes (CLNs) retrieved during central neck dissection (CND), preablation stimulated thyroglobulin (sTg) level, radioiodine uptake on post-therapy scan, and locoregional recurrence (LRR) were examined. Meta-analysis was performed using a fixed or random-effects model depending on heterogeneity between studies. Ten studies were eligible. Of the 2,205 DTCs, 752 (34.1%) had RT, whereas 1,453 (65.9%) had OT. Relative to OT, RT had significantly fewer CLNs retrieved during CND (4.7 ± 3.2 vs. 5.5 ± 3.8, standardized mean difference [SMD] = -0.240, 95% confidence interval [CI]: -0.364 to -0.116, P < .001) and higher preablation sTg level (3.6 ± 6.7 ng/mL vs. 2.0 ± 5.0 ng/mL, SMD = 0.272, 95% CI: 0.022 to 0.522, P = .033). Interestingly, these differences were more evident in the robotic transaxillary approach (RTAA) than the robotic bilateral axillo-breast approach. After a mean follow-up of 17.7 months, no LRR was found in RT, whereas after 18.6 months, one LRR was found in OT. Relative to OT, total thyroidectomy by RTAA was associated with fewer CLNs retrieved and less-complete thyroid resection. However, using RTAA is unlikely to compromise the outcomes of low-risk DTC because of its inherently good prognosis.

Lung texture in serial thoracic CT scans: correlation with radiologist-defined severity of acute changes following radiation therapya

This study examines the correlation between the radiologist-defined severity of normal tissue damage following radiation therapy (RT) for lung cancer treatment and a set of mathematical descriptors of computed tomography (CT) scan texture (‘texture features’). A pre-therapy CT scan and a post-therapy CT scan were retrospectively collected under IRB approval for each of the 25 patients who underwent definitive RT (median dose: 66 Gy). Sixty regions of interest (ROIs) were automatically identified in the non-cancerous lung tissue of each post-therapy scan. A radiologist compared post-therapy scan ROIs with pre-therapy scans and categorized each as containing no abnormality, mild abnormality, moderate abnormality, or severe abnormality. Twenty texture features that characterize gray-level intensity, region morphology, and gray-level distribution were calculated in post-therapy scan ROIs and compared with anatomically matched ROIs in the pre-therapy scan. Linear regression and receiver operating characteristic (ROC) analysis were used to compare the percent feature value change (ΔFV) between ROIs at each category of visible radiation damage. Most ROIs contained no (65%) or mild abnormality (30%). ROIs with moderate (3%) or severe (2%) abnormalities were observed in 9 patients. For 19 of 20 features, ΔFV was significantly different among severity levels. For 12 features, significant differences were observed at every level. Compared with regions with no abnormalities, ΔFV for these 12 features increased, on average, by 1.5%, 12%, and 30%, respectively, for mild, moderate, and severe abnormalitites. Area under the ROC curve was largest when comparing ΔFV in the highest severity level with the remaining three categories (mean AUC across features: 0.84). In conclusion, 19 features that characterized the severity of radiologic changes from pre-therapy scans were identified. These features may be used in future studies to quantify acute normal lung tissue damage following RT.

Variability in Assessing Treatment Response: Metastatic Colorectal Cancer as a Paradigm

The cutoff values currently used to categorize tumor response to therapy are neither biologically based nor tailored for measurement reproducibility with contemporary imaging modalities. Sources and magnitudes of discordance in response assessment in metastatic colorectal cancer (mCRC) are unknown. A subset of patients' CT images of chest, abdomen, and pelvis were randomly chosen from a multicenter clinical trial evaluating insulin-like growth factor receptor type 1-targeted therapy in mCRC. Using Response Evaluation Criteria in Solid Tumors (RECIST), three radiologists selected target lesions and measured "uni" (maximal diameter), "bi" (product of maximal diameter and maximal perpendicular diameter), and "vol" (volume) on baseline and 6-week posttherapy scans in the following ways: (i) each radiologist independently selected and measured target lesions and (ii) one radiologist's target lesions were blindly remeasured by the others. Variability in relative change of tumor measurements was analyzed using linear mixed effects models. Three radiologists independently selected 138, 101, and 146 metastatic target lesions in the liver, lungs, lymph nodes, and other organs (e.g., peritoneal cavity) in 29 patients. Of 198 target lesions total, 33% were selected by all three, 28% by two, and 39% by one radiologist. With independent selection, the variability in relative change of tumor measurements was 11% (uni), 19% (bi), and 22% (vol), respectively. When measuring the same lesions, the corresponding numbers were 8%, 14%, and 12%. The relatively low variability in change of mCRC measurements suggests that response criteria could be modified to allow more accurate and sensitive CT assessment of anticancer therapy efficacy.

Low FDG Metabolic Activity of Loco-Regional Recurrence in Thyroid Cancer Patients; Is Iodine-131 has a Potentiality?

Purpose: To investigate the impact of quantitative FDG-Metabolic activity of non-iodine avid Loco-regional recurrence (LRR; thyroid recurrence and/or cervical node metastasis) on therapy selection in thyroid cancer patients with elevated thyroglobulin (TG). Methods: Forty thyroid cancer (33 papillary and 7 follicular) patients who underwent FDG PET/CT were studied (with TSH>30 mU/L). Those with only LRR were classified according to maxSUV (cut-off level 5) into high and low metabolic activity lesions (HMA L their therapy outcome was compared with histopathologic findings and/or follow-up routine evaluation. Results: Only LRRs was found in 20 patients (17 papillary and 3 follicular) with diagnostic accuracy of FDG PET/CT of 100 %. 14/20 patients belonged to HMA where surgical neck exploration was done while in the remaining 6 patients with LMA empirical high dose of radioactive iodine-131 was given based on the assumption of the presence of a mixture of undifferentiated and differentiated thyroid cancer cells; though their post-therapy scan was negative but declined TG- levels were elicited in their follow-up (base-line 27.7±2.4 and at follow-up 6.8±1.4 ng/ml; P 0.02). Conclusion: Max-SUV based classification of non-iodine avid LRR might improve the diagnostic accuracy FDG PET/CT in a therapeutically relevant way in DTC-patients by precisely localizing them with subsequent surgical guidance in HMA lesions while those with LMA could benefit from further RA-131 therapy.

Do negative 124I pretherapy positron emission tomography scans in patients with elevated serum thyroglobulin levels predict negative 131I posttherapy scans?

The management of patients with differentiated thyroid cancer (DTC) who have elevated serum thyroglobulin (Tg) levels and negative (131)I or (123)I scans is problematic, and the decision regarding whether or not to administer (131)I therapy (a "blind" therapy) is also problematic. While (124)I positron emission tomography (PET) imaging has been shown to detect more foci of residual thyroid tissue and/or metastases secondary to DTC than planar (131)I images, the utility of a negative (124)I PET scan in deciding whether or not to consider performing blind (131)I therapy is unknown. The objective of this study was to determine whether a negative (124)I pretherapy PET scan in patients with elevated serum Tg levels and negative (131)I or (123)I scans predicts a negative (131)I posttherapy scan. Several prospective studies have been performed to compare the radiopharmacokinetics of (124)I PET versus (131)I planar imaging in patients who 1) had histologically proven DTC, 2) were suspected to have metastatic DTC (e.g., elevated Tg, positive recent fine-needle aspiration cytology, suspicious enlarging mass), and 3) had (131)I planar and (124)I PET imaging performed. Using these criteria, we retrospectively identified patients who had an elevated Tg, a negative diagnostic (131)I/(123)I scan, a negative diagnostic (124)I PET scan, therapy with (131)I, a post-therapy (131)I scan, and a prior (131)I therapy with a subsequent positive post-(131)I therapy scan. For each scan, two readers categorized every focus of (131)I and (124)I uptake as positive for thyroid tissue/metastases or physiological. Twelve patients met the above criteria. Ten of these 12 patients (83%) had positive foci on (131)I posttherapy scan. In our selected patient population, (131)I posttherapy scans are frequently positive in patients with elevated serum Tg levels, a negative diagnostic (131)I or (123)I scan, and a negative (124)I PET scan. Thus, for a patient with elevated serum Tg level, negative diagnostic (131)I planar scan, and a prior post-(131)I therapy scan that was positive, a negative (124)I PET scan will have a low predictive value for a negative post-(131)I therapy scan and should not be used to exclude the option of blind (131)I therapy.

Radioiodine ablation with 1,850 MBq in association with rhTSH in patients with differentiated thyroid cancer

The aim of this study was to evaluate the efficacy of post-operative radioiodine ablation with 1,850 MBq after recombinant human thyrotropin (rhTSH) administration in patients with differentiated thyroid carcinoma (DTC). We also aimed to assess the prognostic role of several patient features on the outcome of ablation. We retrospectively analyzed data from a total of 125 patients with DTC who underwent post-operative radioiodine ablation with 1,850 MBq of ¹³¹I after preparation with rhTSH. One injection of 0.9 mg rhTSH was administered on each of two consecutive days; ¹³¹I therapy was delivered 24 h after the last injection, followed by a post-therapy whole-body scan. Successful ablation was assessed 6-12 months later and defined as an rhTSH-stimulated serum thyroglobulin (Tg) level ≤1.0 ng/ml and a normal neck ultrasound. Patients were stratified according to the American Thyroid Association (ATA) Management Guidelines for Differentiated Thyroid Cancer. Successful ablation was achieved in 82.4 % of patients, with an ablation rate of 95.1 % in low-risk patients and 76.2 % in intermediate-risk patients. Analyzing the correlation between ablation outcome and patient characteristics, we found a statistically significant association between failure to ablate and class of risk based on ATA guidelines (p = 0.025) and a stimulated Tg value at ablation of above 5 ng/ml (p < 0.001). The use of 1,850 MBq post-operative radioiodine thyroid remnant ablation in association with rhTSH is effective for low- and intermediate-risk patients. Moreover, in our study, we found a statistical correlation between failure to ablate and class of risk based on ATA guidelines for DTC and a stimulated Tg value at ablation.

Predictive role of nontumoral sodium iodide symporter activity and preoperative thyroid characteristics in remission process of thyroid cancer patients.

The target of radioiodine ablation therapy (RIAT) after complete tumor removal is the nontumoral remnant tissue. We aimed to evaluate sodium iodide symporter (NIS) expression in nontumoral thyroid tissue in differentiated thyroid cancer (DTC) patients who have complete but delayed structural response (DSR) to RIAT after surgery. Preoperative thyroid characteristics such as volume and nontumoral histology were also investigated for both DSR and its control group as potential predictors of insufficient NIS activity in this study. Total of 600 patients with postoperative remnant thyroid tissue and who were in remission after RIAT spontaneously, were included in the study. Patients with positive diagnostic whole body scan (DxWBS) with thyroid bed uptake and stimulated serum Tg level <2 ng/mL at first year visit after initial therapy were defined as DSR group. Immunohistochemical staining of NIS protein was performed on the nontumoral tissue sections from surgery and semi quantified in terms of density and intensity. DSR and its control group were also compared in terms of NIS expression, radioiodine (RAI) uptake on post-therapy scan and preoperative thyroid characteristics. When compared with the control group, the density and intensity of NIS expression as well as the intensity of RAI uptake were significantly lower in DSR group (p = 0.001). There were also significant differences between groups regarding preoperative thyroid characteristics; i.e. preoperative thyroid volumes were significantly higher and the presence of concurrent benign thyroid disease was significantly more common in DSR group (p = 0.035, p = 0.001). Hashimoto thyroiditis was 8.59 times higher (95% CI; 2.31-31.96) and multinodular goiter was 7.50 times higher (95% CI; 1.88-29.91) among DSR group when compared with the control group. Our findings suggest that insufficient NIS activity in nontumoral thyroid tissue associates with DSR in DTC patients who have postoperative remnant tissue. Preoperative thyroid characteristics such as volume and concomitant benign thyroid disease may have an important role in predicting the complete response time to RIAT in these patients.