Ultrasound-Guided Optimization of Preoperative Chemoradiotherapy Using ¹³¹I SPECT/CT for Enhanced Targeting in Differentiated Thyroid Carcinoma.

Surviving Fraction (SF2) and Clonogen Cell Density (CCD) are the Dominant Predictors of Tumor Control Probability (TCP) in High Grade Glioma

Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer

Presently used radiochemotherapy regimens result in moderate local control rates for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Dose escalation (DE) may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT) or proton therapy (IMPT). For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB) in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences <2%) in all models, except for the risk of aspiration, which increased on average by 8 and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence. Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose-response description, e.g., ulcers.

Application of three-dimensional voxel fusion technique to multi-modality fusion of anatomical and functional images

Imagerie hybride (TEMP/TDM, TEP/TDM) et cancer différencié de la thyroïde

Iodine or Not (IoN) for Low-risk Differentiated Thyroid Cancer: The Next UK National Cancer Research Network Randomised Trial following HiLo

The response to radiation therapy is determined by a number of cellular, proliferative and tumor physiological factors. Recent development in molecular and functional imaging provides non‐invasive information about these factors and can potentially be of value in treatment plan optimization. This represents a challenge to the central dogma in radiation therapy as a tailored, inhomogeneous dose is favored in stead of striving for a homogeneous dose to the target volume. One challenge is to develop optimization strategies that take the biological information of the tumortissue adequately into account. A prerequisite for such strategies is detailed knowledge about the dose modifying factor (DMF) associated with the various biological features visualized by different imaging techniques. For most biological factors of relevance for the response to radiation therapy DMF is not well established. The dose modifying effect of tumor hypoxia, i.e. the oxygen enhancement ratio (OER) — has, however, been extensively studied. Moreover, dynamic contrast enhanced MR imaging and PET imaging with Cu‐ATSM or F‐Miso as traces have shown to be promising with respect to imaging of tumor hypoxia. Spatial redistribution of the dose according to hypoxia maps, derived from MRI or PET images, has shown to increase calculated tumor control probability (TCP) significantly compared to a homogeneous dose distribution in canine head and neck tumors. The effect depended on the degree of reoxygenation, with a maximum relative increase in TCP for tumours with poor or no reoxygenation. Also, acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells gave large reductions in TCP. Random errors in positioning were found to give a small decrease in TCP, whereas systematic errors were found to reduce TCP substantially. Molecular and functional imaging provides vast amount of information and the strategies for incorporating this information into treatment plan optimization is still in its infancy.

IntroductionRadiotherapy treatment plans traditionally rely on physical indices like Dose-volume histograms and spatial dose distributions. While these metrics assess dose delivery, they lack consideration for the biological effects on tumors and healthy tissues. To address this, radiobiological models like tumor control probability (TCP) and Normal tissue complications probability (NTCP) are increasingly incorporated to evaluate treatment efficacy and potential complications. This study aimed to assess the predictive power of radiobiological models for TCP in breast cancer radiotherapy and provide insights into the model selection and parameter optimization.MethodsIn this retrospective observational study, two commonly used models, the Linear-Poisson and Equivalent uniform dose (EUD)-based models, were employed to calculate TCP for 30 patients. Different radiobiological parameter sets were investigated, including established sets from literature (G1 and G2) and set with an optimized "a" parameter derived from clinical trial data (a1 and a2). Model predictions were compared with clinical outcomes from the START trials.ResultsThe Linear-Poisson model with es lished parameter sets from the literature demonstrated good agreement with clinical data. The standard EUD-based model (a = -7.2) significantly underestimated TCP. While both models exhibited some level of independence from the specific parameter sets (G1 vs. G2), the EUD-based model was susceptible to the "a" parameter value. Optimization suggests a more accurate "a" value closer to -2.57 and -5.65.ConclusionThis study emphasizes the importance of clinically relevant radiobiological parameters for accurate TCP prediction and optimizing the "a" parameter in the EUD-based model based on clinical data (a1 and a2) improved its predictive accuracy significantly.

Dose Escalation, Not “New Biology,” Can Account for the Efficacy of Stereotactic Body Radiation Therapy With Non-Small Cell Lung Cancer

Background: Differentiated thyroid cancers (DTC) make up 95% of all thyroid cancers. Radioactive iodine therapy (RAI Rx) is an integral part of DTC management. However, 5-15% of DTC and 50% of metastatic DTC become resistant to RAI Rx and carries a 10-year survival of only 10%. One of the newer therapeutic options target “redifferentiation” of the tumor using RAI sensitizers, notably with short-term use of tyrosine kinase inhibitors (TKI). Clinical Case: A 62-year-old women with a 3-year history of Papillary TC s/p surgery (Sx) and 175 mCi RAI presented to establish care and was found to have bulky palpable disease in her left lateral neck. Imaging showed bilateral enlarged lymph nodes in the neck and multiple bilateral pulmonary nodules. Her stimulated thyroglobulin (TG) level was 5341 (1.59 - 50.03 ng/dL) with negative TG antibodies. Bone scan showed no evidence of bone mets. She underwent repeat neck dissection (49 positive lymph nodes) and was BRAF V600E positive. Post-Sx her non-stimulated (NS) TG was 340 ng/dL (0.00 - 41.00 ng/mL) and she received 200mCi RAI Rx with post-Rx whole body scan (WBS) showed uptake only in the thyroid bed. Imaging 6 months later showed stable lung nodules but increase in lymphadenopathy in the neck and her NS-TG was 181 ng/dL. She received 250 mCi of RAI Rx, 10 months after the first dose. Post Rx WBS again showed uptake only in the neck. Her non-stim TG, 9 months later was still high at 130 ng/dL. Given the discordant imaging and TG findings, functional imaging was done which showed multiple avid lesions in bone and lymph nodes confirming the diagnosis of radioiodine-refractory (RAI-R) DTC. Given BRAF V600E positive status, she received Dabrafenib 150 mg PO BID for 6 weeks followed by RAI 300 mCi. Post-RAI WBS showed extensive uptake in base of skull, sternum, cervical spine and right supraclavicular area. Six months post Dabrafenib and RAI, her NS-TG had come down from 130 to 25.7 ng/dL and imaging showed stable structural disease. Her TG levels and imaging have remained stable over the last 18 months indicating both biochemical and structural response to Dabrafenib. Conclusion: The goal of TKIs in redifferentiation of RAI-R DTC is to target specific molecular mechanisms to render the tissue sensitive to RAI. There are several published trials using TKIs for redifferentiation based on the mutation present. Dabrafenib alone and in combination with other TKI’s (Vemurafenib, Trametinib) followed by RAI has shown some response in 60-70% of treated patients with RAI-R tumors. In a study with 10 RAI-R patients with BRAF V600E mutations, dabrafenib used as a radiosensitizer showed RAI uptake in 60%. Three months post Rx, 2 of 6 had a reduction in disease burden while the other 4 had stable disease. Redifferentiation Rx can be successful in slowing disease progression and could be an option in the treatment of RAI-R DTC before initiation of long term TKI Rx.

This review is aimed at summarizing recent advances in functional, anatomical, and hybrid imaging techniques used in the assessment of ischemic complaints in patients with known coronary artery disease (CAD). Cardiovascular imaging has seen significant growth over the last decade in the fields of coronary computed tomography angiography (CCTA), FFR derived from CCTA, cardiac magnetic resonance, radionuclide myocardial perfusion imaging, and hybrid imaging for the purposes of evaluating symptoms concerning for ischemia. This growth stems from refinement of imaging techniques and hardware and software advances that have made current techniques more accurate with less acquisition time. However, every anatomic and functional imaging modality has important technical and patient-specific limitations. This review assesses these issues, guides a patient-centered imaging approach, and identifies important research questions to resolve. Recent advances in non-invasive cardiovascular imaging can provide important information in patients with known CAD beyond traditional imaging techniques; the use of these novel tools refines the clinical management of complex patients with ischemic symptoms and known CAD.

Follow up of patients with differentiated thyroid cancer is based upon anatomical imaging, thyroglobulin assay and functional imaging in the form of iodine uptake scanning. A significant cohort of such patients have rising thyroglobulin levels but negative iodine scans. In this group, 18fluoro-2-deoxyglucose positron emission tomography scans have been commonly employed. The aim of this study was to assess the usefulness of such investigation. The sensitivity of 18fluoro-2-deoxyglucose positron emission tomography for detecting recurrence of differentiated thyroid cancer was calculated from a retrospective review of scan results from patients with iodine scan negative recurrence. Eighteen patients with rising thyroglobulin levels underwent 18fluoro-2-deoxyglucose positron emission tomography scanning. Fourteen patients had negative (and four equivocal) whole body iodine scintigraphy scans. Of these 14, six patients had a positive 18fluoro-2-deoxyglucose positron emission tomography scan, giving a sensitivity of 42.9 per cent. When assessed in the clinical setting and restricted to patients with negative iodine scans, the sensitivity of 18fluoro-2-deoxyglucose positron emission tomography was found to be lower than in previous case series.

The purpose of this work was to investigate how a recently developed MRI-based post-implant dosimetric analysis technique for ultrasound guided transperineal interstitial permanent prostate brachytherapy (TIPPB) compared with the currently accepted CT-based technique. The study was based upon 3-mm MRI and CT scans of 15 patients who had received either 125I or 103Pd implantation. All images were acquired on post-operative day 1 and within 1 hr of each other. Prostate volumes were determined by the same physician. Sources were digitized and calculations performed using an in-house treatment planning system with a nearest neighbor seed sorting routine and AAPM TG43 formalism. Prostate volume, geometric source distribution spread (rcom), dose volume histogram (DVH), and tumor control probability (TCP) calculations were performed from both image sets. Differences in source localization were evaluated by comparing source spread and prescription isodose volumes. Differences in dosimetric analysis were evaluated through prostate-specific DVH and TCP comparisons. Prostate volume as determined from MRI was larger than that of CT by an average of +9.1% (R = 0.70). Calculated rcom was smaller by an average of −0.9 mm (R = 0.81) . Isodose volumes at 80, 90, 100, and 150% of the prescription dose differed by an average of +2.5, +2.9, −2.9, and +4.8%, respectively (R = 0.97, 0.98, 0.98, and 0.91). Percentage volume of the prostate encompassed by 80, 100, and 150% of the prescription dose differed by an average of −0.9, −0.9, and −0.1%, respectively (R = 0.34, 0.35, and 0.35). TCP differed by an average of −0.8% (R = 0.37). The results of this study further support our initial findings that MRI may be used to reliably localize the implanted sources for TIPPB. This study also demonstrated that MRI-based post-implant dosimetric analysis is possible. However, it is evident that differences in prostate localization from MRI to CT can result in significantly different assessments of prostate volume coverage. There is clearly a need to further quantify the differences between these two imaging modalities in this application and address whether greater accuracy in describing the dose-volume relationship based on improvements in visualization of the prostate gland from MRI will translate into improved correlation with treatment outcome. Radiat. Oncol. Invest. 6:90–96, 1998. Published 1998 Wiley-Liss, Inc.

With the increased use of multi‐modality imaging in radiation oncology, dose functional volume histograms (DfVHs) have been introduced as a simple and insightful means of incorporating healthy and diseased tissue functional information in treatment evaluation. The DfVHs themselves may also be used to estimate radiobiological metrics such as the Equivalent Uniform Dose (EUD) or probability of tumor control and normal tissue damage. As the concepts of the DfVH and its utility in computing radiobiological metrics are still in development, the purpose of this work was to investigate the interpretation and sensitivities of DfVH curves and subsequently deduced radiobiological estimates by using mathematically defined and perturbed functional image data sets. Factors such as the signal to noise ratio of the functional image, the relationship between signal intensity of the functional image to the number of functional sub‐units in the voxel, and the extent of mis‐alignment of the functional image to the dose distribution all may affect the shape of the DfVH. As a consequence radiobiological metrics, such as the EUD, are also sensitive to these factors and caution is recommended when using these functions as a predictive measure of outcome. Despite this, the simplicity and relative robustness of the DfVH provides an efficient means of ranking the quality of competing treatment plans. This work was funded through a grant from the MDS‐Nucletron CCO Medical Physics Fund.

Differentiated thyroid cancer (DTC) is one of the fastest growing cancers worldwide. Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, exhibiting a more aggressive behavior. Radioiodine whole-body scintigraphy (WBS) has been used in the detection of DTC. Radioiodine is a sensitive marker for detection of thyroid cancer; however, radioiodine uptake is not specific for thyroid tissue. It can also be seen in healthy tissue as well as in inflammation, or in a variety of benign and malignant non-thyroidal entities. The subject of the present case report is a 52 years old man with brain metastatic DTC who received radioiodine therapy and corticosteroids as palliative therapy. Whole-body scintigraphy revealed bilateral iodine uptake of the femur. Corticosteroid therapy is among the most widely recognized risk factor for osteonecrosis, which at the present case had to be recognized as a false positive (iodine-131) 131I uptake in order to avoid diagnostic error. Post therapeutic whole body scintigraphy revealed no uptake in the thyroid bed as well as pathologic uptake of radioiodine in both femurs. The magnetic resonance imaging (MRI) of the femurs combined with the history of long term exposition on high doses of corticosteroids evidenced diagnosis of steroid-induced osteonecrosis of the femurs. Radioiodine WBS plays an important role in clinical decision making for the evaluation and the management of patients with DTC. Despite its high range of sensitivity and specificity, a variety of reports of false positive whole body scans has demonstrated a diversity of causes. Comprehension of the physiology of iodine uptake and of the pathophysiology of clinical entities which end up giving false positives scans, provides clinicians a useful tool in order to avoid diagnostic and therapeutic errors as far as DTC is concerned.