Six country vignettes: Strengthening radiotherapy and theranostics.

BACKGROUND: For cancer patient populations worldwide, the synchronous scale-up of diagnostics and treatments yields meaningful gains in survival and quality of life. Among advanced cancer therapies, radiotherapy (RT) and theranostics are key to achieving practical, high-quality, and personalized precision medicine - targeting disease manifestations of individual patients and broad populations, alike. Aiming to learn from one another across different world regions, the six country vignettes presented here depict both challenges and victories in de novo establishment or improvement of RT and theranostics infrastructure. METHODS: The International Atomic Energy Agency (IAEA) convened global RT and theranostics experts from diverse world regions and contexts to identify relevant challenges and report progress in their own six countries: Belgium, Brazil, Costa Rica, Jordan, Mongolia, and South Africa. These accounts are collated, compared, and contrasted herein. RESULTS: Common challenges persist which could be more strategically assessed and addressed. A quantifiable discrepancy entails personnel. The estimated radiation oncologists (ROs), nuclear medicine physicians (NMPs), and medical physicists (MPs for RT and nuclear medicine) per million inhabitants in the six collective countries respectively range between 2.69-38.00 ROs, 1.00-26.00 NMPs, and 0.30-3.45 MPs (Table 1), reflecting country-to-country inequities which largely match World Bank country-income stratifications. CONCLUSION: Established goals for RT and nuclear medicine advancement worldwide have proven elusive. The pace of progress could be hastened by enhanced approaches such as more sustainably phased implementation; better multinational networking to share lessons learned; routine quality and safety audits; as well as capacity building employing innovative, resource-sparing, cutting-edge technologic approaches. Bodies such as ministries of health, professional societies, and the IAEA shall serve critical roles in convening and coordinating more innovative RT and theranostics translational research, including expanding nuanced global database metrics to inform, reach, and potentiate milestones most meaningfully. POLICY SUMMARY: Aligned with WHO 25×25 NCDs target; WHA70.12 and WHA76.5 resolutions.

The Diagnostic and Predictive Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Laryngeal Squamous Cell Carcinoma.

This retrospective study examines the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and neck magnetic resonance imaging (MRI) in detecting nodal metastasis for patients with laryngeal squamous cell carcinoma (LSCC) and assesses the predictive values of metabolic and structural features derived from 18F-FDG PET/CT. By involving 66 patients from 2014 to 2021, the sensitivity and specificity of both modalities were calculated. 18F-FDG PET/CT outperforms neck MRI for nodal disease detection, with 89% sensitivity, 65% specificity, and 77% accuracy for nodal metastasis (p = 0.03). On the other hand, neck MRI had 66% sensitivity, 62% specificity, and 64% accuracy. Approximately 11% of patients witnessed a change in their therapy intent when relying on 18F-FDG PET/CT nodal staging results. Analyzing the cohort for PET-derived metabolic and morphological parameters, a total of 167 lymph nodes (LN) were visualized. Parameters such as the LN maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN size were computed. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Among the 167 identified cervical LNs, 111 were histopathologically confirmed as positive. ROC analysis revealed the highest area under the curve for LN MTV (0.89; p < 0.01), followed by LN size (0.87; p < 0.01). Both MTV and LN size independently predicted LN metastasis through multivariate analysis. In addition, LN MTV can reliably predict false-positive LNs in preoperative staging, offering a promising imaging-based approach for further exploration.

Widespread presentation of brown tumors mimicking multiple myeloma.

Brown tumors or osteitis fibrosa cystica has become a rare presentation of primary hyperparathyroidism in up-to-date clinical practice. Here, we describe a case of longstanding untreated hyperparathyroidism presenting itself with brown tumors in a 65-year-old patient. During the diagnostic work-up of this patient, bone SPECT/CT and 18F-FDG-PET/CT revealed multiple widespread osteolytic lesions. Differentiating from other bone tumors such as multiple myeloma is challenging. In this case, the final diagnosis was made by integrating the medical history, biochemical diagnosis of primary hyperparathyroidism, pathological findings and medical imaging.

Shallow-depth sequencing of cell-free DNA for Hodgkin and diffuse large B-cell lymphoma (differential) diagnosis: a standardized approach with underappreciated potential.

Shallow-depth sequencing of cell-free DNA, a cheap and standardized approach to obtain molecular information on tumors non-invasively, is insufficiently explored for lymphoma diagnosis and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non- HL patients, represented by 81 diffuse large B-cell lymphoma (DLBCL) cases. Following sequencing, copy number alterations and viral read fractions were derived and analyzed. At diagnosis, liquid biopsies showed detectable copy number alterations in 84.2% of HL (88.6% for classical HL) and 74.1% of DLBCL patients. Copy number profiles between liquid-solid pairs were highly concordant within DLBCL (r=0.815±0.043); and, compared to tissue, HL liquid biopsies had abnormalities with higher amplitudes (P=.010), implying that tumor DNA is more abundant in plasma. Additionally, 39.5% of HL and 13.6% of DLBCL cases had a significantly elevated number of plasmatic Epstein-Barr virus DNA fragments, achieving a sensitivity of 100% compared to current standard. Longitudinal analysis determined that, when detectable, copy number patterns were similar across (re)staging moments in refractory/relapsed patients. Moreover, the overall profile anomaly highly correlated with the total metabolic tumor volume (P.

Differentiated thyroid cancer patients potentially benefitting from postoperative I-131 therapy: a review of the literature of the past decade.

BACKGROUND: Since the last major review of literature on the benefit of I-131 therapy, the continued debate on postoperative radioiodine treatment (RIT) in differentiated thyroid carcinoma (DTC) has led to a number of further studies being published on this topic. AIM: The aim of the present paper is to report the results of an updated structured review of the literature pertaining to the prognostic benefits of postoperative RIT in DTC in terms of recurrence-free and disease-specific survival. METHODS: A systematic search of the literature was performed using the Medline and Cochrane Library database. The search period started in August 2007 and ended on December 6, 2017. Search terms used included "differentiated thyroid cancer" and "radioiodine therapy" amended by specific terms for recurrence/disease-free survival or overall and/or cancer-specific survival. Included in the search were systematic reviews, randomized clinical trials, or cohort studies consisting of both patients who underwent postoperative RIT and patients treated by surgery alone. RESULTS: Eleven retrospective cohort studies met the defined inclusion criteria and were included in the present review. Results of the studies were mixed, with some showing a benefit of RIT even in microcarcinoma whereas others showed no benefit at all. CONCLUSION: Literature published in the last decade offers data that support adjuvant postoperative RIT in DTC patients with a tumor diameter exceeding 1 cm. Therefore, at least until randomized prospective studies prove otherwise, the prescription of adjuvant I-131 treatment to all DTC patients with a primary tumor diameter exceeding 1 cm remains a reasonable option.

68Ga-Prostate-Specific Membrane Antigen-11 PET/CT: A New Imaging Option for Recurrent Glioblastoma Multiforme?

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and most aggressive primary tumor of the brain. After initial therapy and total resection of GBM, 80% to 90% of recurrences occur at the surgical margins. Currently, limited data are available in the literature on the possible use of Ga-prostate-specific membrane antigen (PSMA-11) for diagnosis of recurrence in GBM patients. The aim was to assess the feasibility and potential of Ga-PSMA-11 PET/CT as a diagnostic procedure in patients with histologically confirmed of GBM and suspected recurrent disease on MRI. RESULTS: No radiopharmaceutical-related adverse events were noted. Characterization of recurrent disease with MRI included T2-weighted fast spin-echo images, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences, and gadolinium enhanced T1-weighted images. Visual interpretation of PET showed increased accumulation of Ga-PSMA-11 in recurrent lesion detected by T1 contrast enhanced and diffusion-weighted imaging images in all patients with a median SUVmax of the tumor of 6.5 and an SUVmean of 3.5. The median tumor-to-background brain ratio and tumor-to-liver ratio obtained from Ga-PSMA-11 PET/CT were 96.7 and 0.8, respectively. CONCLUSIONS: The extremely low background uptake in normal brain tissue and consequently high tumor-to-brain ratio make Ga-PSMA-11 PET/CT highly promising for diagnosis of recurrent disease in GBM patients. Although PSMA expression in recurrent GBM also opens a potential way for targeted peptide therapy with α/ß-emitters as well as for prediction of treatment with antiangiogenic agents, the low tumor-to-liver ratio observed in the majority of patients in this study suggests a limited role of radiolabeled PSMA ligands for targeted radionuclide therapy of recurrent GBM.

Controversies, Consensus, and Collaboration in the Use of 131I Therapy in Differentiated Thyroid Cancer: A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association.

BACKGROUND: Publication of the 2015 American Thyroid Association (ATA) management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer was met with disagreement by the extended nuclear medicine community with regard to some of the recommendations related to the diagnostic and therapeutic use of radioiodine (131I). Because of these concerns, the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging declined to endorse the ATA guidelines. As a result of these differences in opinion, patients and clinicians risk receiving conflicting advice with regard to several key thyroid cancer management issues. SUMMARY: To address some of the differences in opinion and controversies associated with the therapeutic uses of 131I in differentiated thyroid cancer constructively, the ATA, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association each sent senior leadership and subject-matter experts to a two-day interactive meeting. The goals of this first meeting were to (i) formalize the dialogue and activities between the four societies; (ii) discuss indications for 131I adjuvant treatment; (iii) define the optimal prescribed activity of 131I for adjuvant treatment; and (iv) clarify the definition and classification of 131I-refractory thyroid cancer. CONCLUSION: By fostering an open, productive, and evidence-based discussion, the Martinique meeting restored trust, confidence, and a sense of collegiality between individuals and organizations that are committed to optimal thyroid disease management. The result of this first meeting is a set of nine principles (The Martinique Principles) that (i) describe a commitment to proactive, purposeful, and inclusive interdisciplinary cooperation; (ii) define the goals of 131I therapy as remnant ablation, adjuvant treatment, or treatment of known disease; (iii) describe the importance of evaluating postoperative disease status and multiple other factors beyond clinicopathologic staging in 131I therapy decision making; (iv) recognize that the optimal administered activity of 131I adjuvant treatment cannot be definitely determined from the published literature; and (v) acknowledge that current definitions of 131I-refractory disease are suboptimal and do not represent definitive criteria to mandate whether 131I therapy should be recommended.

Long-term follow-up of 2 patients treated with 90 Y-rituximab radioimmunotherapy for relapse of nodular lymphocyte-predominant Hodgkin lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma (<5% of Hodgkin's lymphomas) predominantly affecting the middle-aged man, with an indolent behavior. Given the rare occurrence of this lymphoma, there are currently no clear guidelines for initial treatment or relapse. In this report, we present the follow-up of 2 patients treated by radioimmunotherapy for first relapse of their NLPHL. Both patients were initially treated with rituximab and relapsed 1 year after the end of their treatment.

Correction to: Dosimetry in clinical radionuclide therapy: the devil is in the detail.

The above article which was published in Volume 44/ Issue 12 has incorrect page numbers. Instead of 1-3, it should have been 2137-2139.

Primary hyperparathyroidism associated to thrombocytopenia: an issue to consider?

Primary hyperparathyroidism (PHPT) is probably the most common endocrine disorder of the parathyroid glands, causing hypercalcemia. It is diagnosed often in persons with elevated serum calcium levels. However, hematological manifestations, such as thrombocytopenia are less known. In this case we describe the possible association of PHPT with reversible thrombocytopenia after parathyroidectomy. This hematological abnormality can be included in the spectrum of possible causes, including seemingly non-specific symptoms, in the decision tree towards surgical assessment.

Tumour targeting and radiation dose of radioimmunotherapy with (90)Y-rituximab in CD20+ B-cell lymphoma as predicted by (89)Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab.

PURPOSE: To compare using immuno-PET/CT the distribution of (89)Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with (90)Y-labelled rituximab in CD20+ B-cell lymphoma. METHODS: Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline (89)Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m(2)) of unlabelled rituximab followed by injection of (89)Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by (90)Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. RESULTS: With a cold rituximab preload, the calculated whole-body dose of (90)Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59% and 87% was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. CONCLUSION: Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the "prerituximab era". Clinical Trial Application: CTA 2011-005474-38 TRIAL REGISTRY: EudraCT.

Radioembolization of the spleen: a revisited approach for the treatment of malignant lymphomatous splenomegaly.

Intraarterial administration of (90)Y microspheres to the spleen in patients with malignant lymphoma was mentioned once in the literature in 1973. This case study illustrates the potential indication of selective internal radiotherapy in a heavily pretreated patient with highly refractory disease with a marginal zone lymphoma in leukemic phase and symptomatic splenomegaly. We describe the clinical course of disease; the biological and clinical response to the treatment after radioembolization; and simulation and dosimetry by multimodal imaging via single-photon emission computed tomography and computed tomography. The advantages of radioembolization for the management of lymphomatous splenomegaly are discussed.

The ESTRO Breur Lecture 2009. From population to voxel-based radiotherapy: exploiting intra-tumour and intra-organ heterogeneity for advanced treatment of non-small cell lung cancer.

Evidence is accumulating that radiotherapy of non-small cell lung cancer patients can be optimized by escalating the tumour dose until the normal tissue tolerances are met. To further improve the therapeutic ratio between tumour control probability and the risk of normal tissue complications, we firstly need to exploit inter patient variation. This variation arises, e.g. from differences in tumour shape and size, lung function and genetic factors. Secondly improvement is achieved by taking into account intra-tumour and intra-organ heterogeneity derived from molecular and functional imaging. Additional radiation dose must be delivered to those parts of the tumour that need it the most, e.g. because of increased radio-resistance or reduced therapeutic drug uptake, and away from regions inside the lung that are most prone to complication. As the delivery of these treatments plans is very sensitive for geometrical uncertainties, probabilistic treatment planning is needed to generate robust treatment plans. The administration of these complicated dose distributions requires a quality assurance procedure that can evaluate the treatment delivery and, if necessary, adapt the treatment plan during radiotherapy.

18F-fluoro-2-deoxy-D-glucose positron emission tomographic imaging: recent developments in head and neck cancer.

PURPOSE OF REVIEW: Positron emission tomography using 18F-fluoro-2-deoxy-D-glucose (18FDG-PET) is well established in clinical routine as a metabolism-based whole-body imaging tool for cancer diagnosis and follow-up. Several reports have appeared indicating the potential and limitations of this technique in head and neck cancer (HNC). This review limits its scope to the recent advances using 18FDG-PET in the clinical management of HNC. RECENT FINDINGS: The combination of 18FDG-PET and sentinel node biopsy has been explored for the surgical treatment planning of oral and oropharyngeal cancer. Recent reports indicate that multimodality imaging combining PET with high-end CT scanning increases the diagnostic accuracy. 18FDG-PET has a potential for use in radiation treatment planning and for the prediction of response and early evaluation of treatment efficacy. SUMMARY: Increasingly 18FDG-PET is used as a clinical imaging modality in the different stages of the management of HNC. In particular, its clinical value in initial staging of neck lymph nodes and in the evaluation of recurrent or residual disease is well established. In these settings 18FDG-PET has been shown to be more accurate than conventional imaging. Recent studies indicate that 18FDG-PET could be of additional value in staging the N0 neck, in radiation treatment planning, and in prediction of treatment efficacy.

Optimal dose of 18F-FDG required for whole-body PET using an LSO PET camera.

Reducing the acquisition time of whole-body fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) (corrected for attenuation) is of major importance in clinical practice. With the introduction of lutetium oxyorthosilicate (LSO), the acquisition time can be dramatically reduced, provided that patients are injected with larger amounts of tracer and/or the system is operated in 3D mode. The aim of this study was to determine the optimal dose of 18F-FDG required in order to achieve good-to-excellent image quality when a "3-min emission, 2-min transmission/bed position" protocol is used for an LSO PET camera. A total of 218 consecutive whole-body 18F-FDG PET studies were evaluated retrospectively. After excluding patients with liver metastases, hyperglycaemia and paravenous injections, the final study population consisted of 186 subjects (112 men, 74 women, age 59 +/- 15 years). Patients were injected with an activity of 18F-FDG ranging from 2.23 to 15.21 MBq/kg. Whole-body images corrected for attenuation (3 min emission, 2 min transmission/bed position) were acquired with an LSO PET camera (Ecat Accel, Siemens) 60 min after tracer administration. Patients were positioned with their arms along the body. Image reconstruction was done iteratively and a post-reconstruction filter was applied. Image quality was scored visually by two independent observers using a five-point scoring scale (poor, reasonable, good, very good, excellent). In addition, the coefficient of variability (COV) was measured in a region of interest over the liver in order to quantify noise. Of the images obtained in 118 patients injected with > or =8 MBq/kg 18F-FDG, 92% and 90% were classified as good, very good or excellent by observer 1 and observer 2, respectively. The COV averaged 10.63% +/- 3.19% for doses > or =8 MBq/kg and 16.46% +/- 5.14% for doses <8 MBq/kg. Administration of an 18F-FDG dose of > or =8 MBq/kg results in images of good to excellent quality in the vast majority of patients when using an LSO PET camera and applying a 3-min emission, 2-min transmission/bed position acquisition protocol. At lower doses, a rapid decline in image quality and increasing noise are observed. Alternative protocols should be adopted in order to compensate for the loss in image quality when doses <8 MBq/kg are used.