Pretherapy Scans Research Articles

Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease

Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α4β7 integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α4β7 integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α4β7 integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α4β7 integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α4β7 integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α4β7 integrin or TNFα expression will benefit of therapy with unlabelled mAb.

ODP463 Assess the Usefulness of Pre–Ablation Diagnostic I-123 Iodine Scans in Patients with Differentiated Thyroid Cancer

Abstract Context: Over the last decade, there have been significant changes in the post-operative management of Differentiated Thyroid cancer. The use of Diagnostic 123-Iodine scans has become controversial as many endocrinology practices now give empiric doses of RAI (Radioactive Iodine) when needed based on risk stratification. Allegheny Health Network (AHN) routinely uses I-123 Pre RAI scans prior to ablative or adjuvant therapy. As per the 2015 ATA (American Thyroid Association) guidelines – Pre therapy scans and/or measurement of thyroid bed uptake may be useful when the extent of the thyroid remnant cannot be accurately ascertained from the surgical report or neck ultrasonography, or when the results would alter either the decision to treat or alter the activity of RAI dose that is administered. ATA recommendation is vague and further studies are needed to identify these patients who need pretreatment scan. Objective The objective of our study is to evaluate the utility of pre-therapy diagnostic 131-I scan for the risk stratification and Radioactive Iodine administration decisions in patients with Differential Thyroid cancer after thyroidectomy. Design: The study is a retrospective blinded chart review of cases at AHN. Setting: The study was conducted at an academic tertiary care center of a large Health Network in Western Pennsylvania. Method: Retrospective chart review of patients at AHN who underwent RAI treatment from 2016-2021 has been completed. 195 patients with Differentiated Thyroid cancer have been included in this study. These patients had a pre-therapy WBI (Whole Body Iodine) scan as per AHN's current clinical practice. Data collection includes demographic information, surgical details including lymph neck dissection performed or not, tumor histopathology, TNM classification, post thyroidectomy labs including TSH (Thyroid Stimulating Hormone), TG (Thyroglobulin) and TGA (Thyroglobulin antibody), pre and post-operative ultrasound, RAI dose, Pre-therapy scan findings and Post therapy RAI scan findings. Intervention: Using clinical and histopathology information a group of blinded endocrinologist are performing risk stratification to determine postoperative management with respect to radioiodine therapy (RAI) planning. The decision to withhold or to administer RAI, and the recommended low, medium or high 123-I activity will be decided by them without having information from the Diagnostic 123-Iodine scans. Main Outcome Measure: Main outcome measures will be difference in risk stratification and management with and without Diagnostic 123-Iodine scans. We plan to compare this empiric management strategy to the actual management strategy that took place based on the Pre-therapy scan. Results This will include percentage of patients where decision to treat or dose of radioactive iodine was different, when information from Diagnostic 123-Iodine scan was not available. This will help streamline Endocrinologist practice for patients with Differentiated Thyroid cancer. Presentation: No date and time listed

Quantification of Tc-99m macroaggregated albumin liver perfusion as a predictor of tumor response to intra-arterial therapy with yttrium 90 spheres

Objectives: It remains unclear whether quantifying the pre-therapy tumor Technetium 99m macro aggregated albumin (Tc 99m MAA) localization can accurately predict the response to Yttrium 90 (Y-90) spheres therapy. Present studies are limited and with contradictory results. The aim of this study is to determine if quantification of Tc-99m MAA in hepatic tumor lesion(s) on pretherapy planning nuclear scan can predict the degree of tumor response after radioembolization using Y-90 Spheres. Material and Methods: We retrospectively included patients with primary liver cancers or metastases who were treated with SirSpheres or TheraSpheres. All patients had a Tc-99m MAA scan with an average dose of 5.0mCi injected aseptically in either the right, left, or common hepatic artery. The patients were subsequently transferred for imaging using planar and single-photon emission computed tomography (SPECT) of the abdomen and planar images of the chest. We calculated geometric mean of radiotracer counts in the largest lesion in the lobe to be treated by placing same size region of interest (ROI) around the largest lesion on the anterior and posterior planar images. Subsequently, an irregular ROI around the liver or lobe to be treated were drawn to calculate the geometric mean of counts in the liver. The percent tracer accumulation in the largest lesion was calculated by dividing the geometric mean of counts in the largest lesion by the geometric mean of counts in the liver or lobe and multiplying by 100%. The size of this largest lesion was obtained on the most recent CT or magnetic resonance imaging (MRI) in cm in 2 directions prior to treatment with Y-90 Spheres. The extent of the response to Y-90 Spheres therapy was re-evaluated with 3 months follow-up MRI or CT by measuring the decrease in the largest lesion size. Comparison of the percent Tc-99 MAA count accumulation in the largest lesion on the pre-therapy scan with the reduction in size using anatomic imaging was performed. Results: A total of 30 patients were included (16 hepatocellular carcinoma, eight colorectal, three breast, one neuroendocrine, one cholangiocarcinoma, and one cervical metastases). There were 14 patients in stable disease or progressive disease group (SD/PD gp) and 16 patients in partial response or complete response group (PR/CR gp). The median lesion size was 3.5 cm in the PD/SD gp versus 2.8 cm in the PR/CR gp (P = 0.31). Additionally, the median delivered Y90 Spheres treatment dose was 51.3 mCi in the PD/SD versus 43.2 mCi in the PR/CR gp (P = 0.22). The percent median largest lesion to liver concentration was 21.9% in the PR/CR gp versus 23.3% in the PR/CR gp (P = 0.74). There was no significant difference in percent Tc-99m MAA distribution in the largest liver lesion between the SD/PD gp and the PR/CR gp. Conclusion: The degree of Tc-99m MAA localization in the largest tumor lesion in the liver compared to the remainder of the liver as quantified from planar images does not predict the response to Y-90 spheres therapy.

124I-PET/CT-Guided Diagnosis and Personalized Treatment of Metastatic Papillary Thyroid Cancer to the Pancreas.

Metastasis to the pancreas from differentiated thyroid carcinoma is rare. A new pancreatic lesion was identified on surveillance imaging of a man with metastatic papillary thyroid carcinoma 7 years after initial diagnosis. Imaging with 124I-PET/CT was performed to noninvasively confirm metastatic thyroid cancer and provide prospective dosimetry to guide selection of a safe and effective administered activity of 131I. This case demonstrates the emerging role of 124I-PET/CT as a useful diagnostic scan, pretherapy scan, and dosimetric tool to deliver personalized therapy for patients with metastatic thyroid cancer.

Early Quantification of Salivary Gland Function after Radioiodine Therapy.

Purpose of the Study:Radioiodine (I-131) is used as an effective noninvasive treatment for thyroid malignancies. Salivary gland is one of the most affected nontarget organs. The present study aims to perform early quantification of salivary gland function after I-131 therapy (RIT) for thyroid cancer considering I-131 down-scatter in the Tc-99m window.Materials and Methods:A total of 20 patients (6 males and 14 females) with differentiated thyroid carcinoma were enrolled in the study. Baseline dynamic salivary scintigraphy was performed in all patients using 185–370 MBq (5–10 mCi) Tc-99m pertechnetate. Posttherapy, salivary scintigraphy was performed 10–25 days after RIT in the range of 1.85–7.4 GBq (50–200 mCi). Time–activity curves obtained from the pre- and posttherapy dynamic salivary scintigraphy were used for semi-quantitative analysis. Uptake ratio (UR), ejection fraction (EF%), and maximum accumulation (MA%) were calculated by drawing regions of interest of individual parotid and submandibular glands over a composite image, after correcting for down-scatter from I-131 in the Tc-99m window. A paired t-test was used for comparison of the parameters obtained.Results:Significant changes were observed in UR and EF% of both parotid and submandibular glands (P < 0.05). No significant changes were found in the value of MA% of left parotid gland and both submandibular glands in the posttherapy scans in comparison to pretherapy scans (P > 0.05). However, significant difference was observed in the MA% of the right parotid gland (P = 0.025).Conclusion:Salivary gland function was found to deteriorate after RIT, with the parotid glands affected more than the submandibular glands.

MON-442 Tall Cell Variant of Papillary Thyroid Carcinoma Presenting Acutely as a Right Thyroid Mass and Thyroiditis - an Unusual Presentation

INTRODUCTIONAggressive malignant thyroid tumors (AMTT) can rarely present with signs and symptoms mimicking that of acute suppurative thyroiditis (AST). In its early course, correct diagnosis may be difficult but a prompt recognition is crucial. We report an interesting case of an aggressive papillary thyroid cancer with presenting acute symptoms masquerading as AST.CLINICAL CASEA 50-year-old Caucasian male was admitted for 2 day history of sore throat, odynophagia, low grade fever with a tender and enlarging right neck swelling, not improving with oral antibiotics. CT neck showed a 5.8 x 4.5cm mass in right thyroid lobe with shallow retropharyngeal effusion. Labs showed elevated WBC 10.7 x 109/L (4–10.5), ESR 20 mm/hr (0–12), CRP 92.93 mg/L (0.2–10), with negative rapid strep and IgM for viruses EBV and CMV. Thyroid function tests were normal. Ultrasound neck showed an ill-defined 6.5 cm hypoechoic mass with cystic component and increased vascularity and calcification, replacing the right thyroid lobe. Due to concern for thyroid abscess he underwent urgent aspiration. Fluid analysis and cultures were negative for bacterial source. FNA (fine needle aspiration) of one specimen was suspicious for follicular neoplasm with predominant hurtle cells and suspicious for thyroid neoplasm with papillary architecture in the other. Core biopsy was suspicious for papillary carcinoma but limited due to scant amount of tissue. Affirma unavailable due to insufficient RNA yield. Flow cytometry was negative for abnormal lymphocyte population. Repeat CT neck 3 weeks later was concerning for metastatic lymphadenopathy. He underwent total thyroidectomy with lymph node (LN) dissection and pathology showed papillary thyroid cancer, tall cell variant, tumor size 6 cm, predominantly hemorrhagic, extending to perithyroidal strap muscles and involving 5/6 LN in right trachea-esophageal groove. It was a stage I, pT3bN1aMx cancer. Subsequently, he underwent thyrogen stimulated I-131 ablation of residual thyroid carcinoma with pretherapy scan showing increased uptake in thyroid bed and a satellite lesion suspicious for LN metastasis. Post-ablative scan showed no other new lesions. He is now on levothyroxine suppressive therapy.CONCLUSIONEarly course of AMTT can rarely present as AST, both being progressive and fatal diseases. Our case had a typical presentation of AST, causing delay in diagnosis of his very aggressive form of thyroid cancer. Gross pathology showed predominantly hemorrhagic areas in the tumor with central necrosis, which was likely the cause of acute mass with systemic signs suspicious for infection. One should consider an alternative diagnosis in suspected cases of AST in the absence of positive cultures or lack of improvement with parenteral antibiotics. It is imperative to make a diagnosis without any delay as prognosis for either condition depends on prompt recognition and treatment.

Management of the neck after definitive chemoradiation in patients with HPV-associated oropharyngeal cancer: An institutional experience.

To investigate the multidisciplinary management of patients with Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and an incomplete nodal response on restaging PET/CT after definitive chemoradiation (CRT). A retrospective chart review was performed of patients diagnosed with node-positive HPV-associated OPSCC from 2012 to 2017, who underwent definitive upfront CRT, and had an incomplete response on post-therapy PET/CT according to NCCN criteria. Post-CRT PET/CT results, management decisions, and clinical outcomes were recorded. Seventy-four patients with node-positive HPV-associated OPSCC were identified; 20 patients with incomplete neck response on PET/CT according to NCCN criteria were included in the final case series. Median follow-up time was 33 months. Patients were managed as follows: 8 underwent observation and surveillance imaging, 6 underwent ultrasound-guided fine needle aspiration (FNA), and 6 had immediate neck dissection. All the observed patients were disease-free at most recent follow-up. None of the patients who underwent immediate neck dissection had residual neck disease on pathological examination; two patients in this group ultimately developed metastatic disease. Among the 6 who underwent FNA, 1 individual had positive pathology, along with residual primary disease, for which the patient underwent salvage surgery. The 5 remaining individuals had negative FNA results, were subsequently observed, and remained free of disease. This institutional experience supports the notion of a high threshold for neck dissection in this low-risk population; only 1 of 20 patients with suspicious PET/CT findings had residual disease in the neck. Moreover, these patients should be managed by a multidisciplinary tumor board (MTB) since current algorithms do not universally include HPV status. Finally, the use of restaging PET/CT to guide management of the neck can be improved with changes in terminology and consideration of FDG-avidity at the primary site and on pre-therapy scans.

Abstract P2-13-05: Prevalence of trastuzumab-induced cardiotoxicity in a real-world setting

Abstract Background: Trastuzumab treatment plus adjuvant or neoadjuvant chemotherapy is the standard of care for women with HER2 positive breast cancer. Despite relative low rates of cardiotoxicity observed in randomized clinical trials, trastuzumab interruption driven by LVEF reduction is a major concern in current clinical practice. Patients and methods: We retrospectively identified women with stage I-III HER2 positive breast cancer who received 12 months of trastuzumab treatment after adjuvant or neoadjuvant chemotherapy at Instituto Nacional de Cancerología (INCan, Mexico City), between 2006 and 2018. Patients were eligible if a pre-therapy MUGA scan and ≥2 subsequent follow-up scans were available. Cardiotoxicity was defined as a ≥10% LVEF reduction to a value &amp;lt; 50%, associated with trastuzumab interruption. Results: 910 patients were included, with a median age at diagnosis of 50 (24-85) years and a median follow up of 7 (2-11 ) years. Among the whole cohort, 10.3% of patients had diabetes, 15.4% had hypertension, 78% were obese/overweight, and 40% had positive estrogen and/or progesterone receptor status. Anthracycline-based therapy was used in 819 (90%) patients, with a median (doxorubicin equivalent) cumulative dose of 200 mg/m2 (IQR 180-240). The median baseline LVEF was 61.8% (50-88.9). In total, 94 (10.3%) patients developed cardiotoxicity, but symptomatic heart failure was observed in only 31 (3.4%) individuals. In univariable analyses, the development of cardiotoxicity was not associated significantly with cardiovascular risk factors. Conclusions: In this large single-center cohort, cardiotoxicity rates remain high, thus, interventions to minimize the risk of cardiotoxicity and trastuzumab treatment interruption should be considered. Citation Format: Calvillo-Argüelles O, Flores-Diaz D, Gonzalez-Serrano J-P, López-Rojas A, Mendoza-Galindo L, Matus-Santos J-A, Reynoso-Noverón N, Cabrera-Galeana P, Bargalló-Rocha E, Arce-Salinas C. Prevalence of trastuzumab-induced cardiotoxicity in a real-world setting [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-13-05.

Pre-therapy CT scan showing peritoneal thickening from metastatic renal pelvis carcinoma patients

We investigated clinical significance of peritoneal thickening from metastatic renal pelvis based on pretherapy computed tomography (CT) scan findings. The criteria for inclusion were as follows: (1) pathology and CT scan confirmed metastatic renal pelvis carcinoma and (2) peritoneal thickening based on pre-therapy CT scan findings. We investigated the route of spread, gastrointestinal (GI) complications, and response to chemotherapy. A total of 68 cases were enrolled in this study, including seven patients with liver metastases and three with abdominal wall invasion. GI complications included obstruction in ten patients and bleeding in three. Response to chemotherapy demonstrated by reduced peritoneal thickening was noted in 24 patients. In conclusion. peritoneal thickening with clinical suspicion of peritoneal involvement can get indirect evidence from route of spread (liver or abdominal wall), GI complications (obstruction or bleeding) or response to chemotherapy (obvious decrease peritoneal thickening) from metastatic renal pelvis carcinoma patients. Pretherapy CT scan with peritoneal thickening should be alert that tumor has spread to the peritoneum.

Computer-based radiological longitudinal evaluation of meningiomas following stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) is a common treatment for intracranial meningiomas. SRS is planned on a pre-therapy gadolinium-enhanced T1-weighted MRI scan (Gd-T1w MRI) in which the meningioma contours have been delineated. Post-SRS therapy serial Gd-T1w MRI scans are then acquired for longitudinal treatment evaluation. Accurate tumor volume change quantification is required for treatment efficacy evaluation and for treatment continuation. We present a new algorithm for the automatic segmentation and volumetric assessment of meningioma in post-therapy Gd-T1w MRI scans. The inputs are the pre- and post-therapy Gd-T1w MRI scans and the meningioma delineation in the pre-therapy scan. The output is the meningioma delineations and volumes in the post-therapy scan. The algorithm uses the pre-therapy scan and its meningioma delineation to initialize an extended Chan-Vese active contour method and as a strong patient-specific intensity and shape prior for the post-therapy scan meningioma segmentation. The algorithm is automatic, obviates the need for independent tumor localization and segmentation initialization, and incorporates the same tumor delineation criteria in both the pre- and post-therapy scans. Our experimental results on retrospective pre- and post-therapy scans with a total of 32 meningiomas with volume ranges 0.4-26.5 cm[Formula: see text] yield a Dice coefficient of [Formula: see text]% with respect to ground-truth delineations in post-therapy scans created by two clinicians. These results indicate a high correspondence to the ground-truth delineations. Our algorithm yields more reliable and accurate tumor volume change measurements than other stand-alone segmentation methods. It may be a useful tool for quantitative meningioma prognosis evaluation after SRS.

Diagnostic whole body scan (pre-therapy scan) in differentiated thyroid cancer: A single center community hospital experience.

Diagnostic whole body scan (pre-therapy scan) with either I-123 or I-131 (radioactive isotopes of iodine) is performed to assess the extent of thyroid cancer especially distant metastasis prior to administering the therapeutic dose of I-131. Our aim of the following study was to determine the utility of the diagnostic pre-therapy scan in the management of differentiated thyroid cancer. It was a case-control study carried out by retrospective chart review, of a randomly selected 100 patients with differentiated thyroid cancer who had followed in our community hospital over the course of 1 year. We collected data on multiple variables in the subjects - including age, gender, pre-operative size of the nodules, diagnosis, stage of the malignancy, size of the tumor, multifocality, lymphovascular invasion, dose of radioiodine used for remnant ablation, recurrence rates and persistence rates. Continuous variables were compared using the independent sample Mann-Whitney U-test whereas the Chi-square test was used for nominal variables. The mean dose of radioactive iodine administered was 97.56 (±27.98) in the pre-therapy scan group and it was 97.23 (±32.40) in the control group. There was no difference between the two groups (P - 0.45). There was also no difference in the recurrence rates between the groups (P = 1.0). There was a trend toward a higher degree of persistent cancer in the group that had the pre-therapy scans (P - 0.086). Pre-therapy scan may not affect the dose of radio-iodine I-131 used for remnant ablation of differentiated thyroid cancer and does not influence the recurrence rates. This was especially true with respect to I-131 remnant ablation for low risk tumors.

Statistical and radiobiological analysis of the so-called thyroid stunning.

BackgroundThe origin of the reduction in thyroid uptake after a low activity iodine scan, so-called stunning effect, is still controversial. Two explanations prevail: an individual cell stunning that reduces its capability to store iodine without altering its viability, and/or a significant cell-killing fraction that reduces the number of cells in the tissue still taking up iodine. Our aim is to analyze whether this last assumption could explain the observed reduction.MethodsThe survival fraction after administration of a small radioiodine activity was computed by two independent methods: the application of the statistical theory underlying tissue control probability on recent clinical studies of thyroid remnant 131I ablation and the use of the radiosensitivities reported in human thyroid cell assays for different radioiodine isotopes.ResultsBoth methods provided survival fractions in line with the uptake reduction observed after a low 131I activity scan. The second method also predicts a similar behavior after a low 123I or 124I activity scan.ConclusionsThis study shows that the cell-killing fraction is sufficient to explain the uptake reduction effect for 131I and 123I after a low activity scan and that even if some still living cells express a stunning effect just after irradiation (as shown in vitro), they will mostly die with time. As the β/α value is very low, this therapy fractionation should not impact the patient outcome in agreement with recent studies. However, in case of huge uptake heterogeneity, pre-therapy scan could specifically kills high-uptake cells and by the way could reduce the cross irradiation to the low-uptake cells during the therapy, resulting in a reduction of the ablation success rate.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0144-9) contains supplementary material, which is available to authorized users.

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.

Effect of deformable registration on the dose calculated in radiation therapy planning CT scans of lung cancer patients.

To characterize the effects of deformable image registration of serial computed tomography (CT) scans on the radiation dose calculated from a treatment planning scan. Eighteen patients who received curative doses (≥ 60 Gy, 2 Gy/fraction) of photon radiation therapy for lung cancer treatment were retrospectively identified. For each patient, a diagnostic-quality pretherapy (4-75 days) CT scan and a treatment planning scan with an associated dose map were collected. To establish correspondence between scan pairs, a researcher manually identified anatomically corresponding landmark point pairs between the two scans. Pretherapy scans then were coregistered with planning scans (and associated dose maps) using the demons deformable registration algorithm and two variants of the Fraunhofer MEVIS algorithm ("Fast" and "EMPIRE10"). Landmark points in each pretherapy scan were automatically mapped to the planning scan using the displacement vector field output from each of the three algorithms. The Euclidean distance between manually and automatically mapped landmark points (dE) and the absolute difference in planned dose (|ΔD|) were calculated. Using regression modeling, |ΔD| was modeled as a function of dE, dose (D), dose standard deviation (SD(dose)) in an eight-pixel neighborhood, and the registration algorithm used. Over 1400 landmark point pairs were identified, with 58-93 (median: 84) points identified per patient. Average |ΔD| across patients was 3.5 Gy (range: 0.9-10.6 Gy). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, with an average dE across patients of 5.2 mm (compared with >7 mm for the other two algorithms). Consequently, average |ΔD| was also lowest using the Fraunhofer MEVIS EMPIRE10 algorithm. |ΔD| increased significantly as a function of dE (0.42 Gy/mm), D (0.05 Gy/Gy), SD(dose) (1.4 Gy/Gy), and the algorithm used (≤ 1 Gy). An average error of <4 Gy in radiation dose was introduced when points were mapped between CT scan pairs using deformable registration, with the majority of points yielding dose-mapping error <2 Gy (approximately 3% of the total prescribed dose). Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm, resulting in the smallest errors in mapped dose. Dose differences following registration increased significantly with increasing spatial registration errors, dose, and dose gradient (i.e., SDdose). This model provides a measurement of the uncertainty in the radiation dose when points are mapped between serial CT scans through deformable registration.

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.

TU‐F‐BRF‐03: Effect of Radiation Therapy Planning Scan Registration On the Dose in Lung Cancer Patient CT Scans

Purpose:To characterize the effect of deformable registration of serial computed tomography (CT) scans on the radiation dose calculated from a treatment planning scan.Methods:Eighteen patients who received curative doses (≥60Gy, 2Gy/fraction) of photon radiation therapy for lung cancer treatment were retrospectively identified. For each patient, a diagnostic‐quality pre‐therapy (4–75 days) CT scan and a treatment planning scan with an associated dose map calculated in Pinnacle were collected. To establish baseline correspondence between scan pairs, a researcher manually identified anatomically corresponding landmark point pairs between the two scans. Pre‐therapy scans were co‐registered with planning scans (and associated dose maps) using the Plastimatch demons and Fraunhofer MEVIS deformable registration algorithms. Landmark points in each pretherapy scan were automatically mapped to the planning scan using the displacement vector field output from both registration algorithms. The absolute difference in planned dose (|ΔD|) between manually and automatically mapped landmark points was calculated. Using regression modeling, |ΔD| was modeled as a function of the distance between manually and automatically matched points (registration error, E), the dose standard deviation (SD_dose) in the eight‐pixel neighborhood, and the registration algorithm used.Results:52–92 landmark point pairs (median: 82) were identified in each patient's scans. Average |ΔD| across patients was 3.66Gy (range: 1.2–7.2Gy). |ΔD| was significantly reduced by 0.53Gy using Plastimatch demons compared with Fraunhofer MEVIS. |ΔD| increased significantly as a function of E (0.39Gy/mm) and SD_dose (2.23Gy/Gy).Conclusion:An average error of &lt;4Gy in radiation dose was introduced when points were mapped between CT scan pairs using deformable registration. Dose differences following registration were significantly increased when the Fraunhofer MEVIS registration algorithm was used, spatial registration errors were larger, and dose gradient was higher (i.e., higher SD_dose). To our knowledge, this is the first study to directly compute dose errors following deformable registration of lung CT scans.

Iodine Radioisotope Diagnostic Scanning With SPECT/CT After Thyroidectomy for Thyroid Cancer: Essential Data or Unnecessary Investigation?

In the clinical management of patients with differentiated thyroid cancer after total thyroidectomy, there is controversy on the utility of postsurgical iodine radioisotope diagnostic imaging (using 131-I or 123-I), with or without single photon emission computed tomography (SPECT)/ computed tomography (CT). Some arguments supporting the use of postsurgical radioactive iodine (RAI) diagnostic scans, with or without SPECT/CT, include beliefs that this procedure may optimize postoperative risk classification by ascertaining disease status/staging, optimize selection of patients with RAI-avid disease for RAI therapy, optimize RAI therapeutic dose activity selection, and identify patients who may benefit from additional surgical therapy (such as debulking of distant metastases or resection of a large thyroid remnant) (1). Theoretical challenges in endorsing routine use of postoperative RAI diagnostic scans, with or without SPECT, may include the lack of controlled trials proving that a strategy of using such scans to guide RAI treatment decisions (including patient selection for treatment or dose activity selection) improves long-term patient outcomes or reduces overall healthcare costs, compared to a strategy of therapeutic decision-making based on clinicopathological stage with additional cross-sectional imaging (such as preor postoperative neck ultrasound). Moreover, there are conflicting data on whether pretherapy 131-I diagnostic scans reduce efficacy of remnant ablation, with some authors reporting an adverse impact (2, 3) and others reporting no significant difference, as compared to empiric 131-I treatment (4). A pretherapy 131-I scan dose activity of 1 mCi (37 MBq) has been reported to be less likely to impair success of remnant ablation, compared to higher dose activities (5). A practical issue in considering the feasibility of postsurgical RAI diagnostic scanning in medical decision-making is the institutional ability/inability to modify preordered therapeutic dose activities of 131-I, in response to data obtained in the days preceding therapy. Clinical practice guideline recommendations on the use of postsurgical RAI diagnostic scanning are variable. The American Thyroid Association has recommended select use of postsurgical RAI diagnostic scanning or uptake measurement if the size of the thyroid remnant cannot be determined by other means or if the results would impact decision-making (on selection for RAI treatment or dose activity selection) (6). A European consensus panel provided a conditional recommendation for the use of postsurgical RAI diagnostic scanning if there is uncertainty about the extent of thyroidectomy (7). The British Thyroid Association suggested that preablation scanning is not routinely indicated but can be performed to assess remnant size if the extent of thyroidectomy is uncertain (8). The Society for Nuclear Medicine has indicated that “routine” preablation scanning “can be useful in guiding 131-I therapy” (9). The European Association for Nuclear Medicine has recommended that 131-I diagnostic scanning or uptakes should be avoided in cases where RAI therapy is clearly necessary because the results would not alter clinical management and the procedure may impair therapeutic efficacy (10). The Latin American Thyroid Association has acknowledged the controversy surrounding this procedure (11). In summary, there is some disagreement internationally on the utility of post-thyroidectomy RAI diagnostic scans.

I-131 MIBG post-therapy scan is more sensitive than I-123 MIBG pretherapy scan in the evaluation of metastatic neuroblastoma

Iodine-123 metaiodobenzylguanidine (I-123 MIBG) scintigraphy is gradually replacing I-131 MIBG scans in the diagnostic workup of neuroblastoma. High-dose I-131 MIBG, however, is commonly used for subsequent therapy in patients with proven MIBG-avid lesions. The objective of this study was to compare the sensitivities of pretherapy I-123 MIBG and post-therapy I-131 MIBG scans for detecting metastatic lesions of neuroblastoma and determine the suitability of post-therapy scans for detecting new metastases. Pretherapy I-123 MIBG scans and post-therapy I-131 MIBG scans of 126 patients with neuroblastoma were analyzed retrospectively and the number of detected lesions was compared. In 70 patients (55.6% cases), the pretherapy and post-therapy scans were concordant, showing similar MIBG-avid foci. In the remaining 56 patients (44.4% cases), the post-therapy I-131 MIBG scans revealed additional lesions (i.e. a total of 716 lesions) compared with pretherapy I-123 MIBG scans (only 532 lesions). All lesions detected on pretherapy I-123 MIBG scans were revisualized on the post-therapy I-131 MIBG scans, the latter also revealing 184 new MIBG-avid lesions. Post-therapy I-131 MIBG scans demonstrate new lesions in almost half of the patients when compared with pretherapy I-123 MIBG scans and therefore are essential to delineate the disease extent.

The Utility of I-123 Pretherapy Scan in I-131 Radioiodine Therapy for Thyroid Cancer

There is a growing belief that a pretherapy scan yields little or no additional information that would impact on radioiodine ablation dosing. In addition, there is some concern regarding on the stunning effect of a pretherapy scan, especially when I-131 radioisotope is used for imaging. We hypothesized that a pretherapy scan provides invaluable information on the amount of thyroid remnant, sometimes indicating the need for two-step I-131 ablation. It may also detect unsuspected local lymph node involvement or distant metastases, indicating the requirement for a higher I-131 dose after thyroidectomy. The aim of this study was to evaluate how effective pretherapy scans are for guiding I-131 therapy planning and augmenting information provided in the pathology reports for thyroidectomy specimens. We reviewed 122 patients who underwent I-123 pretherapy scan and I-131 radioablation at Yale New Haven Hospital between January 2006 and August 2007. The percentage of neck uptake and whole-body images were acquired 24 hours following the administration of 51.8 MBq (1.4 mCi) of I-123 NaI. A 24-hour uptake of >3% was used as the cutoff to determine whether there was a greater than desired quantity of thyroid remnant, which would require a two-step treatment protocol. Furthermore, attention was paid to identifying cervical lymph nodes, which may not have presented themselves in the euthyroid state at the time of thyroidectomy. Additional clinical information provided by pretherapy scans was computed as percentages with 95% confidence intervals by using adjusted Wald intervals. Overall, the pretherapy scans provided additional critical information in 25% of the cases (31/122; 95% CI: 18%-34%). For cases demonstrating >3% uptake with midline lymph nodes, the pretherapy scan provided additional information in 50% of the cases (8/16; 95% CI: 28%-72%). Our study demonstrated that I-123 pretherapy scans provide valuable information with regard to unsuspected lymph nodes or distant metastases, indicating the requirement for a significantly higher I-131 dose, and unexpected large thyroid remnants, suggesting the need for two-step ablation. We should take advantage of stimulated pretherapy scans and adjust the treatment dosing accordingly.

Factors affecting resection rate in patients undergoing neoadjuvant therapy for pancreatic cancer.

e14531 Background: Patients who derive benefit from neoadjuvant therapy in pancreatic cancer is unclear. A subset, borderline resectable (BR) has been defined in whom therapy may be of benefit. We evaluated factors affecting resection, in particular those patients deemed borderline resectable. Methods: This is a retrospective chart review of patients who received neoadjuvant therapy at the University of Oklahoma over a 5 year period. Pre-therapy scans were reviewed and classified as locally advanced (LA) or BR per the AHPRA/SSO/SSAT Consensus Conference. Unless otherwise speicified, p-values are exact calculations from Chi-square tests on the equality of two independent proportions. Results: Among 18 patients studied, 9 underwent surgery. Pathology was available for 8 patients. All underwent R0 (62%) or R1 (38%) resections. Amongst those with LA, 5/6 (83%) underwent surgery, compared with 4/12 (33%) with BR disease (p value Pearson chi-square=0.1312). Kaplan-Meier analysis estimated median survival at 24 months in those with LA and 19 months with BR disease (p from log rank test=0.3475). Seven of 12 (58%) of patients who received only chemotherapy underwent surgery, compared with 2 of 6 (33%) patients who received chemoradiation (exact p=0.6199). High baseline level of Ca19-9 (>100) was not predictive of resectability (exact p=1.0) in the 12 patients whose Ca19-9 expression was unaccompanied by high levels of total bilirubin (>1.4). Among these patients, mean Ca19-9 expression was nonsignificantly higher (exact p from Wilcoxon test=0.5417) among those with BR disease. Two of 7 (29%) patients ≥ 65 y/o underwent surgery, compared with 7 of 11 (64%) younger patients (exact p=0.3348). Outcome did not differ between patients who underwent surgery more than 90 days from start of therapy (8/14 or 57%) vs less than 90 days (1/4 or 25%; exact p=0.5765). Conclusions: A higher percentage of LA patients underwent resection than those with BR. This preliminary data underscores the importance of disease biology in this patient group and the need, in future multivariable analysis on more patients to adjust for factors like age, CA 19-9 levels and pathologic grade that may independently affect surgical candidacy and survival.