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Positron emission tomography (PET)-computed tomography (CT) images have been widely used in clinical practice for radiotherapy treatment planning of the radiotherapy. Many existing segmentation approaches only work for a single imaging modality, which suffer from the low spatial resolution in PET or low contrast in CT. In this work, we propose a novel method for the co-segmentation of the tumor in both PET and CT images, which makes use of advantages from each modality: the functionality information from PET and the anatomical structure information from CT. The approach formulates the segmentation problem as a minimization problem of a Markov random field model, which encodes the information from both modalities. The optimization is solved using a graph-cut based method. Two sub-graphs are constructed for the segmentation of the PET and the CT images, respectively. To achieve consistent results in two modalities, an adaptive context cost is enforced by adding context arcs between the two sub-graphs. An optimal solution can be obtained by solving a single maximum flow problem, which leads to simultaneous segmentation of the tumor volumes in both modalities. The proposed algorithm was validated in robust delineation of lung tumors on 23 PET-CT datasets and two head-and-neck cancer subjects. Both qualitative and quantitative results show significant improvement compared to the graph cut methods solely using PET or CT. [ABSTRACT FROM PUBLISHER]

Purpose: Radiation therapy (RT) for lung cancer is commonly limited to subtherapeutic doses due to unintended toxicity to normal lung tissue. Reducing the frequency of occurrence and magnitude of normal lung function loss may benefit from treatment plans that incorporate the regional lung and radiation dose information. In this article, the authors propose a method that quantitatively measures the regional changes in lung tissue function following a course of radiation therapy by using 4DCT and image registration techniques. Methods: 4DCT data sets before and after RT from two subjects are used in this study. Nonlinear 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration to estimate the pulmonary function. The Jacobian of the image registration transformation, indicating local lung expansion or contraction, serves as an index of regional pulmonary function. Approximately 120 annotated vascular bifurcation points are used as landmarks to evaluate registration accuracy. The authors compare regional pulmonary function before and after RT to the planned radiation dose at different locations of the lung. Results: In all registration pairs, the average landmark distances after registration are on the order of 1 mm. The pulmonary function change as indicated by the Jacobian change ranges from -0.15 to 0.1 in the contralateral lung and -0.22 to 0.23 in the ipsilateral lung for subject A, and ranges from -0.4 to 0.39 in the contralateral lung and -0.25 to 0.5 in the ipsilateral lung for subject B. Both of the subjects show larger range of the increase in the pulmonary function in the ipsilateral lung than the contralateral lung. For lung tissue regions receiving a radiation dose larger than 24 Gy, a decrease in pulmonary function was observed. For regions receiving a radiation dose smaller than 24 Gy, either an increase or a decrease in pulmonary function was observed. The relationship between the pulmonary function change and the radiation dose varies at different locations. Conclusions: With the use of 4DCT and image registration techniques, the pulmonary function prior to and following a course of radiation therapy can be measured. In the preliminary application of this approach for two subjects, changes in pulmonary function were observed with a weak correlation between the dose and pulmonary function change. In certain sections of the lung, detected locally compromised pulmonary function may have resulted from radiation injury. [ABSTRACT FROM AUTHOR]

In this paper, we study an interesting matrix decomposition problem that seeks to decompose a "complicated" matrix into two "simpler" matrices while minimizing the sum of the horizontal complexity of the first sub-matrix and the vertical complexity of the second sub-matrix. The matrix decomposition problem is crucial for improving the "step-and-shoot" delivery efficiency in Intensity-Modulated Radiation Therapy, which aims to deliver a highly conformal radiation dose to a target tumor while sparing the surrounding normal tissues. Our algorithm is based on a non-trivial graph construction scheme, which enables us to formulate the decomposition problem as computing a minimum s-t cut in a 3-D geometric multi-pillar graph. Experiments on randomly generated intensity map matrices and on clinical data demonstrated the efficacy of our algorithm. [ABSTRACT FROM AUTHOR]

Following on from the 2015 Lancet Oncology Commission on expanding global access to radiotherapy, Radiotherapy and theranostics: a Lancet Oncology Commission was created to assess the access and availability of radiotherapy to date and to address the important issue of access to the promising field of theranostics at a global level. A marked disparity in the availability of radiotherapy machines between high-income countries and low-income and middle-income countries (LMICs) has been identified previously and remains a major problem. The availability of a suitably trained and credentialled workforce has also been highlighted as a major limiting factor to effective implementation of radiotherapy, particularly in LMICs. We investigated initiatives that could mitigate these issues in radiotherapy, such as extended treatment hours, hypofractionation protocols, and new technologies. The broad implementation of hypofractionation techniques compared with conventional radiotherapy in prostate cancer and breast cancer was projected to provide radiotherapy for an additional 2·2 million patients (0·8 million patients with prostate cancer and 1·4 million patients with breast cancer) with existing resources, highlighting the importance of implementing new technologies in LMICs. A global survey undertaken for this Commission revealed that use of radiopharmaceutical therapy—other than 131I—was highly variable in high-income countries and LMICs, with supply chains, workforces, and regulatory issues affecting access and availability. The capacity for radioisotope production was highlighted as a key issue, and training and credentialling of health professionals involved in theranostics is required to ensure equitable access and availability for patient treatment. New initiatives—such as the International Atomic Energy Agency's Rays of Hope programme—and interest by international development banks in investing in radiotherapy should be supported by health-care systems and governments, and extended to accelerate the momentum generated by recognising global disparities in access to radiotherapy. In this Commission, we propose actions and investments that could enhance access to radiotherapy and theranostics worldwide, particularly in LMICs, to realise health and economic benefits and reduce the burden of cancer by accessing these treatments. [ABSTRACT FROM AUTHOR]

NRG Oncology's Developmental Therapeutics and Radiation Therapy Subcommittee assembled an interdisciplinary group of investigators to address barriers to successful early phase clinical trials of novel combination therapies involving radiation. This Policy Review elucidates some of the many challenges associated with study design for early phase trials combining radiotherapy with novel systemic agents, which are distinct from drug–drug combination development and are often overlooked. We also advocate for potential solutions that could mitigate or eliminate some of these barriers, providing examples of specific clinical trial designs that could help facilitate efficient and effective evaluation of novel drug–radiotherapy combinations. [ABSTRACT FROM AUTHOR]

Purpose: The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists. Methods: To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice. Results: Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries. Conclusion: The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics. [ABSTRACT FROM AUTHOR]

This paper is the first of a Series on theranostics that summarises the current landscape of the radiopharmaceutical sciences as they pertain to oncology. In this Series paper, we describe exciting developments in radiochemistry and the production of radionuclides, the development and translation of theranostics, and the application of artificial intelligence to our field. These developments are catalysing growth in the use of radiopharmaceuticals to the benefit of patients worldwide. We also highlight some of the key issues to be addressed in the coming years to realise the full potential of radiopharmaceuticals to treat cancer. [ABSTRACT FROM AUTHOR]

Optical coherence tomography (OCT) has become a key method for diagnosing and staging radiation retinopathy, based mainly on the presence of fluid in the central macula. A robust retinal layer segmentation method is required for identification of the specific layers involved in radiation-induced pathology in individual eyes over time, in order to determine damage driven by radiation injury to the microvessels and to the inner retinal neurons. Here, we utilized OCT, OCT-angiography, visual field testing, and patient-specific dosimetry models to analyze abnormal retinal layer thickening and thinning relative to microvessel density, visual function, radiation dose, and time from radiotherapy in a cross-sectional cohort of uveal melanoma patients treated with 125I-plaque brachytherapy. Within the first 24 months of radiotherapy, we show differential thickening and thinning of the two inner retinal layers, suggestive of microvessel leakage and neurodegeneration, mostly favoring thickening. Four out of 13 eyes showed decreased inner retinal capillary density associated with a corresponding normal inner retinal thickness, indicating early microvascular pathology. Two eyes showed the opposite: significant inner retinal layer thinning and normal capillary density, indicating early neuronal damage preceding a decrease in capillary density. At later time points, inner retinal thinning becomes the dominant pathology and correlates significantly with decreased vascularity, vision loss, and dose to the optic nerve. Stable multiple retinal layer segmentation provided by 3D graph-based methods aids in assessing the microvascular and neuronal response to radiation, information needed to target therapeutics for radiation retinopathy and vision loss. [ABSTRACT FROM AUTHOR]

Intramedullary spinal cord metastasis (ISCM), though rare, represents a potentially debilitating manifestation of systemic cancer. With emerging advances in cancer care, ISCMs are increasingly being encountered in clinical practice. Herein, we describe one of the larger retrospective single institutional case series on ISCMs, analyze survival and treatment outcomes, and review the literature. All surgically evaluated ISCMs at our institution between 2005 and 2023 were retrospectively reviewed. Demographics, tumor features, treatment, and clinical outcome characteristics were collected. Neurological function was quantified via the Frankel grade and the McCormick score (MCS). The pre- and post-operative Karnofsky performance scores (KPS) were used to assess functional status. Descriptive statistics, univariate analysis, log-rank test, and the Kaplan–Meier survival analysis were performed. A total of 9 patients were included (median age 67 years (range, 26–71); 6 were male). Thoracic and cervical spinal segments were most affected (4 patients each). Six patients (75%) underwent surgical management (1 biopsy and 5 resections), and 3 cases underwent chemoradiation only. Post-operatively, 2 patients had an improvement in their neurological exam with one patient becoming ambulatory after surgery; three patients maintained their neurological exam, and 1 had a decline. There was no statistically significant difference in the pre- and post-operative MCS and median KPS scores in surgically treated patients. Median OS after ISCM diagnosis was 7 months. Absence of brain metastasis, tumor histology (renal and melanoma), cervical/thoracic location, and post-op KPS ≥ 70 showed a trend toward improved overall survival. The incidence of ISCM is increasing, and earlier diagnosis and treatment are considered key for the preservation of neurological function. When patient characteristics are favorable, surgical resection of ISCM can be considered in patients with rapidly progressive neurological deficits. Surgical treatment was not associated with an improvement in overall survival in patients with ISCMs. [ABSTRACT FROM AUTHOR]

In August 2022, the Cancer Informatics for Cancer Centers brought together cancer informatics leaders for its biannual symposium, Precision Medicine Applications in Radiation Oncology, co-chaired by Quynh-Thu Le, MD (Stanford University), and Walter J. Curran, MD (GenesisCare). Over the course of 3 days, presenters discussed a range of topics relevant to radiation oncology and the cancer informatics community more broadly, including biomarker development, decision support algorithms, novel imaging tools, theranostics, and artificial intelligence (AI) for the radiotherapy workflow. Since the symposium, there has been an impressive shift in the promise and potential for integration of AI in clinical care, accelerated in large part by major advances in generative AI. AI is now poised more than ever to revolutionize cancer care. Radiation oncology is a field that uses and generates a large amount of digital data and is therefore likely to be one of the first fields to be transformed by AI. As experts in the collection, management, and analysis of these data, the informatics community will take a leading role in ensuring that radiation oncology is prepared to take full advantage of these technological advances. In this report, we provide highlights from the symposium, which took place in Santa Barbara, California, from August 29 to 31, 2022. We discuss lessons learned from the symposium for data acquisition, management, representation, and sharing, and put these themes into context to prepare radiation oncology for the successful and safe integration of AI and informatics technologies. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Scheduling for Radiotherapy Simulation in Children with a Renal Mass," by Heather S. Kaiser, Arnold C. Paulino, and John M. Buatti.

Background: Malignant peripheral nerve sheath tumor (MPNST) is an exceedingly rare and aggressive tumor, with limited literature on its management. Herein, we present our series of surgically managed craniospinal MPNSTs, analyze their outcomes, and review the literature. Methods: We retrospectively reviewed surgically managed primary craniospinal MPNSTs treated at our institution between January 2005 and May 2023. Patient demographics, tumor features, and treatment outcomes were assessed. Neurological function was quantified using the Frankel grade and Karnofsky performance scores. Descriptive statistics, rank-sum tests, and Kaplan–Meier survival analyses were performed. Results: Eight patients satisfied the inclusion criteria (4 male, 4 female). The median age at presentation was 38 years (range 15–67). Most tumors were localized to the spine (75%), and 3 patients had neurofibromatosis type 1. The most common presenting symptoms were paresthesia (50%) and visual changes (13%). The median tumor size was 3 cm, and most tumors were oval-shaped (50%) with well-defined borders (75%). Six tumors were high grade (75%), and gross total resection was achieved in 5 patients, with subtotal resection in the remaining 3 patients. Postoperative radiotherapy and chemotherapy were performed in 6 (75%) and 4 (50%) cases, respectively. Local recurrence occurred in 5 (63%) cases, and distant metastases occurred in 2 (25%). The median overall survival was 26.7 months. Five (63%) patients died due to recurrence. Conclusions: Primary craniospinal MPNSTs are rare and have an aggressive clinical course. Early diagnosis and treatment are essential for managing these tumors. In this single-center study with a small cohort, maximal resection, low-grade pathology, young age (< 30), and adjuvant radiotherapy were associated with improved survival. [ABSTRACT FROM AUTHOR]

Purpose: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly.Methods and Materials: A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA.Results: Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies.Conclusions: Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials. [ABSTRACT FROM AUTHOR]

MR-guided adaptive radiotherapy (MRgART) provides opportunities to benefit patients through enhanced use of advanced imaging during treatment for many patients with various cancer treatment sites. This novel technology presents many new challenges which vary based on anatomic treatment location, technique, and potential changes of both tumor and normal tissue during treatment. When introducing new treatment sites, considerations regarding appropriate patient selection, treatment planning, immobilization, and plan-adaption criteria must be thoroughly explored to ensure adequate treatments are performed. This paper presents an institution's experience in developing a MRgART program for a 1.5T MR-linac for the first 234 patients. The paper suggests practical treatment workflows and considerations for treating with MRgART at different anatomical sites, including imaging guidelines, patient immobilization, adaptive workflows, and utilization of bolus. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this work was to develop and validate a deep convolutional neural network (CNN) approach for the automated pelvis segmentation in computed tomography (CT) scans to enable the quantification of active pelvic bone marrow by means of Fluorothymidine F‐18 (FLT) tracer uptake measurement in positron emission tomography (PET) scans. This quantification is a critical step in calculating bone marrow dose for radiopharmaceutical therapy clinical applications as well as external beam radiation doses. Methods: An approach for the combined localization and segmentation of the pelvis in CT volumes of varying sizes, ranging from full‐body to pelvis CT scans, was developed that utilizes a novel CNN architecture in combination with a random sampling strategy. The method was validated on 34 planning CT scans and 106 full‐body FLT PET‐CT scans using a cross‐validation strategy. Specifically, two different training and CNN application options were studied, quantitatively assessed, and statistically compared. Results: The proposed method was able to successfully locate and segment the pelvis in all test cases. On all data sets, an average Dice coefficient of 0.9396 ±$\pm$ 0.0182 or better was achieved. The relative tracer uptake measurement error ranged between 0.065% and 0.204%. The proposed approach is time‐efficient and shows a reduction in runtime of up to 95% compared to a standard U‐Net‐based approach without a localization component. Conclusions: The proposed method enables the efficient calculation of FLT uptake in the pelvis. Thus, it represents a valuable tool to facilitate bone marrow preserving adaptive radiation therapy and radiopharmaceutical dose calculation. Furthermore, the method can be adapted to process other bone structures as well as organs. [ABSTRACT FROM AUTHOR]

Purpose: To identify prognostic factors, define evolving patterns of care, and the effect of targeted therapies in a larger contemporary cohort of renal cell carcinoma (RCC) patients with new brain metastases (BM).Methods and Materials: A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new BM diagnosed from January 1, 2006, to December 31, 2015, was created. Clinical parameters and treatment were correlated with median survival and time from primary diagnosis to BM. Multivariable analyses were performed.Results: The median survival for the prior/present cohorts was 9.6/12 months, respectively (P < .01). Four prognostic factors (Karnofsky performance status, extracranial metastases, number of BM, and hemoglobin b) were significant for survival after the diagnosis of BM. Of the 6 drug types studied, only cytokine use after BM was associated with improved survival. The use of whole-brain radiation therapy declined from 50% to 22%, and the use of stereotactic radiosurgery alone increased from 46% to 58%. Nonneurologic causes of death were twice as common as neurologic causes.Conclusions: Additional prognostic factors refine prognostication in this larger contemporary cohort. Patterns of care have changed, and survival of RCC patients with BM has improved over time. The reasons for this improvement in survival remain unknown but may relate to more aggressive use of local brain metastasis therapy and a wider array of systemic treatment options for those patients with progressive extracranial tumor. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM).Patients and Methods: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending <60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT.Results: A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in 3 cohorts receiving 112 mg/d over 4 to 6 weeks (n=12), and then 3 additional cohorts receiving 30 or 90 mg/d over 6 to 7 weeks (n=14). A maximum tolerated dose was not reached. One dose-limiting toxicity (grade 3 gastroenteritis and vomiting with hyponatremia) occurred in each of 2 separate cohorts at 112 mg. Nausea/vomiting and facial paresthesia during infusion seemed to be GC4419 dose-related. Severe OM occurred through 60 Gy in 4 of 14 patients (29%) dosed for 6 to 7 weeks, with median duration of only 2.5 days.Conclusions: The safety of GC4419 concurrently with chemoradiation for OCC was acceptable. Toxicities included nausea/vomiting and paresthesia. Doses of 30 and 90 mg/d administered for 7 weeks were selected for further study. In an exploratory analysis, severe OM seemed less frequent and briefer than expected. [ABSTRACT FROM AUTHOR]

Purpose: Quality control plays an increasingly important role in quantitative PET imaging and is typically performed using phantoms. The purpose of this work was to develop and validate a fully automated analysis method for two common PET/CT quality assurance phantoms: the NEMA NU‐2 IQ and SNMMI/CTN oncology phantom. The algorithm was designed to only utilize the PET scan to enable the analysis of phantoms with thin‐walled inserts. Methods: We introduce a model‐based method for automated analysis of phantoms with spherical inserts. Models are first constructed for each type of phantom to be analyzed. A robust insert detection algorithm uses the model to locate all inserts inside the phantom. First, candidates for inserts are detected using a scale‐space detection approach. Second, candidates are given an initial label using a score‐based optimization algorithm. Third, a robust model fitting step aligns the phantom model to the initial labeling and fixes incorrect labels. Finally, the detected insert locations are refined and measurements are taken for each insert and several background regions. In addition, an approach for automated selection of NEMA and CTN phantom models is presented. The method was evaluated on a diverse set of 15 NEMA and 20 CTN phantom PET/CT scans. NEMA phantoms were filled with radioactive tracer solution at 9.7:1 activity ratio over background, and CTN phantoms were filled with 4:1 and 2:1 activity ratio over background. For quantitative evaluation, an independent reference standard was generated by two experts using PET/CT scans of the phantoms. In addition, the automated approach was compared against manual analysis, which represents the current clinical standard approach, of the PET phantom scans by four experts. Results: The automated analysis method successfully detected and measured all inserts in all test phantom scans. It is a deterministic algorithm (zero variability), and the insert detection RMS error (i.e., bias) was 0.97, 1.12, and 1.48 mm for phantom activity ratios 9.7:1, 4:1, and 2:1, respectively. For all phantoms and at all contrast ratios, the average RMS error was found to be significantly lower for the proposed automated method compared to the manual analysis of the phantom scans. The uptake measurements produced by the automated method showed high correlation with the independent reference standard (R2 ≥ 0.9987). In addition, the average computing time for the automated method was 30.6 s and was found to be significantly lower (P ≪ 0.001) compared to manual analysis (mean: 247.8 s). Conclusions: The proposed automated approach was found to have less error when measured against the independent reference than the manual approach. It can be easily adapted to other phantoms with spherical inserts. In addition, it eliminates inter‐ and intraoperator variability in PET phantom analysis and is significantly more time efficient, and therefore, represents a promising approach to facilitate and simplify PET standardization and harmonization efforts. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity.Methods and Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity.Results: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test).Conclusions: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts. [ABSTRACT FROM AUTHOR]

Purpose To evaluate dynamic [ 18 F]-fluorodeoxyglucose (FDG) uptake methodology as a post–radiation therapy (RT) response assessment tool, potentially enabling accurate tumor and therapy-related inflammation differentiation, improving the posttherapy value of FDG–positron emission tomography/computed tomography (FDG-PET/CT). Methods and Materials We prospectively enrolled head-and-neck squamous cell carcinoma patients who completed RT, with scheduled 3-month post-RT FDG-PET/CT. Patients underwent our standard whole-body PET/CT scan at 90 minutes, with the addition of head-and-neck PET/CT scans at 60 and 120 minutes. Maximum standardized uptake values (SUV max ) of regions of interest were measured at 60, 90, and 120 minutes. The SUV max slope between 60 and 120 minutes and change of SUV max slope before and after 90 minutes were calculated. Data were analyzed by primary site and nodal site disease status using the Cox regression model and Wilcoxon rank sum test. Outcomes were based on pathologic and clinical follow-up. Results A total of 84 patients were enrolled, with 79 primary and 43 nodal evaluable sites. Twenty-eight sites were interpreted as positive or equivocal (18 primary, 8 nodal, 2 distant) on 3-month 90-minute FDG-PET/CT. Median follow-up was 13.3 months. All measured SUV endpoints predicted recurrence. Change of SUV max slope after 90 minutes more accurately identified nonrecurrence in positive or equivocal sites than our current standard of SUV max ≥2.5 ( P =.02). Conclusions The positive predictive value of post-RT FDG-PET/CT may significantly improve using novel second derivative analysis of dynamic triphasic FDG-PET/CT SUV max slope, accurately distinguishing tumor from inflammation on positive and equivocal scans. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The kinetics of the bone marrow uptake of 3′-deoxy-3′-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (K FLT) and the Patlak constant (K Patlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, K FLT=0.045±0.016 min−1 and K Patlak=0.039±0.013 min−1. After treatment, these values were SUV=0.74±0.19, K FLT=0.011±0.005 min−1 and K Patlak=0.005±0.002 min−1. Compartmental analysis revealed a significant drop in k 3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT. [Copyright &y& Elsevier]

Purpose: To determine the accuracy and prognostic significance of post-treatment [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in head-and-neck squamous cell carcinoma after radiotherapy (RT). Methods and Materials: This was a retrospective study of 188 patients with head-and-neck squamous cell carcinoma who had undergone FDG-PET within 12 months after completing RT. All living patients had ≥1 year of follow-up after FDG-PET. All patients had undergone intensity-modulated RT, 128 with definitive and 60 with postoperative intensity-modulated RT. Results: For all patients, the median follow-up after RT completion was 32.6 months and after FDG-PET was 29.2 months. For the neck, 171 patients had negative FDG-PET findings. Of these results, two were falsely negative. Seventeen patients had positive FDG-PET findings, of which 12 were true-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET in the assessment of the treatment response in the neck was 86%, 97%, 71%, and 99%, respectively. For the primary site, 151 patients had negative FDG-PET findings, of which two were falsely negative. Thirty-seven patients had positive FDG-PET findings, of which 12 were true-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET in the assessment of the treatment response in the primary site was 86%, 86%, 32.4%, and 98.7%, respectively. Patients with positive post-RT PET findings had significantly worse 3-year overall survival and disease-free survival. Conclusion: The results of our study have shown that the findings of post-RT FDG-PET have a high negative predictive value and are a significant prognostic factor. It can provide guidance for the management of head-and-neck cancer after definitive treatment. [Copyright &y& Elsevier]

Purpose: To determine whether the response of human head and neck cancer xenografts to cisplatin (CIS) could be enhanced with 2-deoxy-D-glucose (2DG); whether 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) uptake correlated with responses to this drug combination; and whether 2DG would enhance CIS-induced radiosensitization.Methods and Materials: Clonogenic survival responses to CIS + 2DG were determined in FaDu and Cal-27 cells and reduced/oxidized glutathione levels were monitored as parameters indicative of oxidative stress. The efficacy of CIS + 2DG was determined in FaDu and Cal-27 xenografts, and FDG uptake was determined by using positron emission tomography.Results: Use of CIS + 2DG enhanced cell killing of FaDu and Cal-27 cells compared with either drug alone while increasing the percentage of oxidized glutathione in vitro. Use of CIS + 2DG inhibited FaDu and Cal-27 tumor growth and increased disease-free survival compared with either drug alone. The Cal-27 tumors showed greater pretreatment FDG uptake and increased disease-free survival when treated with 2DG + CIS relative to FaDu tumors. Treatment with 2DG enhanced CIS-induced radiosensitization in FaDu tumor cells grown in vitro and in vivo and resulted in apparent cures in 50% of tumors.Conclusions: These results show the enhanced therapeutic efficacy of CIS + 2DG in human head and neck cancer cells in vitro and in vivo compared with either drug alone, as well as the potential for FDG uptake to predict tumor sensitivity to 2DG + CIS. These findings provide a strong rationale for evaluating 2DG + CIS in combined-modality head and neck cancer therapy with radiation in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor 5-year survival. Pharmacological ascorbate (P-AscH - , high dose, intravenous, vitamin C) has shown promise as an adjunct to chemotherapy. We hypothesized adding P-AscH - to gemcitabine and nab-paclitaxel would increase survival in patients with metastatic PDAC., Methods: Patients diagnosed with stage IV pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC, control) or to SOC with concomitant P-AscH - , 75 g three times weekly (ASC, investigational). The primary outcome was overall survival with secondary objectives of determining progression-free survival and adverse event incidence. Quality of life and patient reported outcomes for common oncologic symptoms were captured as an exploratory objective. Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023., Results: Intravenous P-AscH - increased serum ascorbate levels from micromolar to millimolar levels. P-AscH - added to the gemcitabine + nab-paclitaxel (ASC) increased overall survival to 16 months compared to 8.3 months with gemcitabine + nab-paclitaxel (SOC) (HR = 0.46; 90 % CI 0.23, 0.92; p = 0.030). Median progression free survival was 6.2 (ASC) vs. 3.9 months (SOC) (HR = 0.43; 90 % CI 0.20, 0.92; p = 0.029). Adding P-AscH - did not negatively impact quality of life or increase the frequency or severity of adverse events., Conclusions: P-AscH - infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to quality of life or added toxicity (ClinicalTrials.gov number NCT02905578)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Following on from the 2015 Lancet Oncology Commission on expanding global access to radiotherapy, Radiotherapy and theranostics: a Lancet Oncology Commission was created to assess the access and availability of radiotherapy to date and to address the important issue of access to the promising field of theranostics at a global level. A marked disparity in the availability of radiotherapy machines between high-income countries and low-income and middle-income countries (LMICs) has been identified previously and remains a major problem. The availability of a suitably trained and credentialled workforce has also been highlighted as a major limiting factor to effective implementation of radiotherapy, particularly in LMICs. We investigated initiatives that could mitigate these issues in radiotherapy, such as extended treatment hours, hypofractionation protocols, and new technologies. The broad implementation of hypofractionation techniques compared with conventional radiotherapy in prostate cancer and breast cancer was projected to provide radiotherapy for an additional 2·2 million patients (0·8 million patients with prostate cancer and 1·4 million patients with breast cancer) with existing resources, highlighting the importance of implementing new technologies in LMICs. A global survey undertaken for this Commission revealed that use of radiopharmaceutical therapy-other than 131 I-was highly variable in high-income countries and LMICs, with supply chains, workforces, and regulatory issues affecting access and availability. The capacity for radioisotope production was highlighted as a key issue, and training and credentialling of health professionals involved in theranostics is required to ensure equitable access and availability for patient treatment. New initiatives-such as the International Atomic Energy Agency's Rays of Hope programme-and interest by international development banks in investing in radiotherapy should be supported by health-care systems and governments, and extended to accelerate the momentum generated by recognising global disparities in access to radiotherapy. In this Commission, we propose actions and investments that could enhance access to radiotherapy and theranostics worldwide, particularly in LMICs, to realise health and economic benefits and reduce the burden of cancer by accessing these treatments., Competing Interests: Declaration of interests HH serves (unpaid) on an external advisory board of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, on the International Advisory Board of the University of Vienna, on the Scientific Committee of the German Cancer Research Center (DKFZ), on the Board of Trustees of the DKFZ, and on the advisory board of The Lancet Oncology; is remunerated for serving on the Board of Directors of Ion Beam Applications; receives stock options for serving on the Board of Directors of iCAD; and reports research funding to their institution (Memorial Sloan-Kettering Center Support Grant/Core Grant P30 CA008748) from the National Institutes of Health (NIH)–National Cancer Institute (NCI). AA reports funding to their institution from the National Institute for Health and Care Research (NIHR) and the NIH. GB reports research funding to their institution from the Science and Technology Facilities Council UK and reports travel support from International Council Expert Corps. MD reports research funding to their institution from Science and Technology Facilities Council UK and reports travel support from International Council Expert Corps. TE reports honoraria from the University of Washington and the Japanese Society for Radiation Oncology (JASTRO) and reports receiving travel support to attend meetings from JASTRO, the Turkish Society for Radiation Oncology, and the American Society for Radiation Oncology (ASTRO). SGr reports receiving grants from the NCI; reports consulting fees from Lumonus and the Sustainable Dialogue on Peaceful Uses; and has stock options in Harbinger Health. KH reports research funding to their institution from Novartis and Sofie Biosciences; reports consulting fees from Advanced Accelerator Applications, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curiun, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien Munchen, Janssen, Merck, Molecular Partners, Nvision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Telix, Theragnostics, and Ymabs; reports honoraria for lectures from PeerVoice; serves on paid advisory boards for Fusion and GE Healthcare; reports travel support from Janssen; and has stock options from Sofie Biosciences, Pharma15, Nvision, Convergent, Aktis Oncology, and AdvanCell. MSH reports research funding to their institution from the Prostate Cancer Foundation, the US Department of Defence, Movember, and the Peter MacCallum Foundation; reports clinical trial funding to their institution from Bayer and Isotopia; reports clinical trial support to their institution from the Australian Nuclear Science and Technology Organisation; reports consulting fees from Merck Sharp & Dohme and Novartis; reports speaker fees from Janssen and AstraZeneca; reports fees to their institution for serving on the advisory board on Novartis; reports unremunerated participation in the Scientific Committee at the Australian Friends of Sheba; and is supported by a National Health and Medical Research Council (NHMRC) Investigator grant. DJ reports royalties from Elekta Oncology System, Precision X-ray System, and Modus Medical; reports license of technology to iRT; reports board membership on Break Through Cancer; reports being an advisor to ACS BrightEdge; and is a founder and stockholder in Nanovista. JK reports participation on a data safety monitoring board and advisory board from Novartis (personal fees) and reports lecture honoraria from Monrol. JSL reports research support from Clarity Pharmaceuticals and Avid Radiopharmaceuticals; has acted as an adviser of Alpha-9 Theranostics, Clarity Pharmaceuticals, Earli, Evergreen Theragnostics, Suba Therapeutics, Inhibrx, Precirix, Solve, Goldman Sachs, TPG Capital, Curie Therapeutics, NextTech Invest, and Telix Pharmaceuticals; is secretary/treasurer of the Society of Nuclear Medicine and Molecular Imaging (SNMMI); holds equity in Curie Therapeutics, Summit Biomedical Imaging, Telix Pharmaceuticals, and Evergreen Theragnostics; and is supported by NIH R35 CA232130. YL reports funding to their institution for the European Society for Radiotherapy and Oncology (ESTRO) Chair on Health Economics in Radiation Oncology (HERO)–Value-Based Radiation Oncology, for a proton beam project from the Research Foundation Flanders (FWO)–Applied Biomedical Research with a Primary Finality, and for the ARCHERY trial; reports unpaid positions on advisory boards for the HALT trial and PROSECCA trial; is a member of the ESTRO Scientific Council and the Belgian Board of Oncology; is co-chair of the ESTRO-HERO project; and is principal investigator of the E2-Radiate trial, a joint project of ESTRO, and the European Organisation for Research and Treatment of Cancer (EORTC). JRP reports being an unpaid chair of the American Association of Physicists in Medicine (AAPM) International Council. AAR received consulting fees from Novartis; received honoraria for lectures from the European Society for Medical Oncology, Sociedade Brasileira de Mastologia, and Instituto Oncoclinicas; received financial support for attending meetings from ASTRO, Congresso Gramado, and Congresso Oncolinicas; reports an unpaid leadership position at the Sociedade Brasileira de Radioterapia; and has stock and stock options in Grupo Oncoclinicas. MMS reports research funding to their institution from Aktis, Point Biopharma, and Telix Pharmaceuticals; reports speaker honoraria from Novartis, Ion Beam Applications, and Johnson and Johnson; and holds positions in the Africa Health Research Institute and Adcock. VV holds positions as editor of the Journal of Clinical Oncology/Global Oncology and Translational Oncology and is a member of the board for City Cancer Challenge. RLW reports research funding to their institution from Siemens Healthineers, White Rabbit AI, Fusion, Perspective Therapeutics, Rayze, and Bayer; provides consulting services to Voximetry, Molecular Targeting Technologies (MTT), Perspective, Siemens, Abdera, and Seno; reports speaker payment from Hamad Health Qatar; reports travel support from Rayze and Hamad Health Qatar; has stock options in Voximetry and MTT; is a stockholder in Clarity Pharmaceuticals; participates on advisory boards for Perspective and Fusion; is a member of the SNMMI Mars Shot Board; and was a past president of SNMMI. JSY reports funding to their institution from the NIH, the IVY Foundation, and the Falk Research Medical Trust; reports honoraria from the University of Maryland and the Dana Farber/Harvard Cancer Center; and holds an unpaid position in the Clinical Advisory Council at the American Brain Tumor Association. AMS reports trial funding to their institution from EMD Serono, ITM, Telix Pharmaceuticals, AVID Radiopharmaceuticals, Fusion Pharmaceuticals, and Cyclotek; reports research funding to their institution from Medimmune, Antengene, Humanigen, and Telix Pharmaceuticals; is on advisory boards of Imagion and ImmunOs; reports unpaid board membership of the Australian and New Zealand Society of Nuclear Medicine and the World Federation of Nuclear Medicine and Biology; and is supported by a NHMRC Investigator grant (number 1177837). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

NRG Oncology's Developmental Therapeutics and Radiation Therapy Subcommittee assembled an interdisciplinary group of investigators to address barriers to successful early phase clinical trials of novel combination therapies involving radiation. This Policy Review elucidates some of the many challenges associated with study design for early phase trials combining radiotherapy with novel systemic agents, which are distinct from drug-drug combination development and are often overlooked. We also advocate for potential solutions that could mitigate or eliminate some of these barriers, providing examples of specific clinical trial designs that could help facilitate efficient and effective evaluation of novel drug-radiotherapy combinations., Competing Interests: Declaration of interests JMB received grants or contracts from the National Institutes of Health (NIH); royalties or licences from UpToDate; and has a leadership or fiduciary role in other board, society, committee, or advocacy group (paid or unpaid) for the American Society for Radiation Oncology (ASTRO) and is on the Board of Directors as Science Council Chair. SEF reports ongoing research with Novartis and Bayer; received consulting fees from Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; payment or honoraria as a speaker for Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; participates on an advisory board at Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; and has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid on the board of chancellors at the American College of Radiology. SKJ received grants or contracts from the National Cancer Institute, Merck, Beigene, Guardant, and Adlai made to their institution; consulting fees from Merck, AstraZeneca, Beigene, Radialogica, Syntactx, and IMX; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from ASTRO; is a senior editor at the International Journal of Radiation Biology Physics; received payment for expert testimony from Dechert; support for attending meetings and travel from ASTRO, AstraZeneca, and Merck; and participation on a data safety monitoring board for Advarra. RJK declares ongoing committee role at ASTRO and ongoing senior editor role at International Journal of Radiation Oncology Biology Physics; received grants or contracts from NIH and Bridge Bio to their institution; received consulting fees from HunaTek and Guidepoint Global; has patents planned, issued, or pending with University of Wisconsin; and has leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid with ASTRO. SHL received grants from Beyond Spring, STCube Pharmaceuticals, and Nektar Therapeutics; consulting fees from XRAD Therapeutics; support for attending meetings and travel from AstraZeneca; participated on an advisory board for AstraZeneca and Creatv Microtech; and has stock or stock options from Seek Diagnostics. AMM received consulting fees from AstraZeneca, Merck, Varian Medical Systems, Kortuc, and Siemens; payment for expert testimony from Arizona Legal Group; support for attending meetings and travel from NRG Oncology; and has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at American Brachytherapy Society. JM declares in the last 36 months grants or contracts from NIH, Merck, BMS, Genentech, Incyte, Trisalus, Transgene, and EMD Serono; consulting fees from GLG and Guidepoint; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Association of Northern California Oncologists; participation on a data safety monitoring board or advisory board at Multiplex Thera; and stock or stock options from Multiplex Thera. SPP received grants or contracts from Amgen, AstraZeneca, MedImmune, A2bio, Bristol Myers Squibb, Eli Lilly, Fate Therapeutics, Gilead, Iovance, Merck, Pfizer, and Roche Genentech; and consulting fees from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Certis, Eli Lilly, Jazz, Genentech, Illumina, Merck, Pfizer, Signatera, and Tempus. SS received grants or contracts from Merck, Regeneron, Exelixis, and Innovio; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Exelixis and Medscape; and participated on a data safety monitoring board or advisory board at Luminos, Eisai, and Naveris. MX-W received grants or contracts from NCI; consulting fees from Eli Lilly and Novocure; and participated on a data safety monitoring board or advisory board for Eli Lilly. ZSZ has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at the American Board of Radiology. KRP and PAT-S are employed by the NIH. TMW declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists., Methods: To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice., Results: Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries., Conclusion: The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics., (© 2024. The Author(s).)