Medical imaging and nuclear medicine: a Lancet Oncology Commission.

The diagnosis and treatment of patients with cancer requires access to imaging to ensure accurate management decisions and optimal outcomes. Our global assessment of imaging and nuclear medicine resources identified substantial shortages in equipment and workforce, particularly in low-income and middle-income countries (LMICs). A microsimulation model of 11 cancers showed that the scale-up of imaging would avert 3·2% (2·46 million) of all 76·0 million deaths caused by the modelled cancers worldwide between 2020 and 2030, saving 54·92 million life-years. A comprehensive scale-up of imaging, treatment, and care quality would avert 9·55 million (12·5%) of all cancer deaths caused by the modelled cancers worldwide, saving 232·30 million life-years. Scale-up of imaging would cost US$6·84 billion in 2020-30 but yield lifetime productivity gains of $1·23 trillion worldwide, a net return of $179·19 per $1 invested. Combining the scale-up of imaging, treatment, and quality of care would provide a net benefit of $2·66 trillion and a net return of $12·43 per $1 invested. With the use of a conservative approach regarding human capital, the scale-up of imaging alone would provide a net benefit of $209·46 billion and net return of $31·61 per $1 invested. With comprehensive scale-up, the worldwide net benefit using the human capital approach is $340·42 billion and the return per dollar invested is $2·46. These improved health and economic outcomes hold true across all geographical regions. We propose actions and investments that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programmes in LMICs, to produce massive health and economic benefits and reduce the burden of cancer globally.

Economics of New Molecular Targeted Personalized Radiopharmaceuticals.

Nuclear medicine has come a long way since 2007 when Adrian Nunn pointed out the approval of radiopharmaceuticals was at an all-time low with all the major radiopharmaceutical agents in use having been approved over 10 years ago. Challenges being the prohibitively high cost of drug development and the large number of drugs failing in clinical trials. Proceed to today where molecular imaging is fast-tracking the drug discovery process by reducing both the time and cost to screen candidates by quantitating the drugs effect on the target and toxicity to normal tissues. Nuclear medicine is now leading medical practice in personalized medicine using the theragnostic approach. Theragnostics is defined as the use of molecular diagnostic techniques in real time to stratify patients to guide treatment decisions such as the choice of drug, the dose of administration, and the timing of drug delivery for a given patient. Enabling visualization and quantitation of in vivo function of the whole body and thus patient heterogeneity and variability informs the physician on how to treat an individual patient. Recent successes such as the Food and Drug Administration approval of Lutathera and NETSPOT have resulted in an increasing number of pharmaceutical companies pursing theragnostics further heightened by the purchase of Advanced Accelerator Applications for 3.9 billion by Novartis and Endocyte, Inc for 2.1 billion. Theragnostics are further aiding drug development by showing which agents are most viable and reducing the overall cost of bringing a drug to clinical trials and regulatory approval. This is indeed a renaissance for nuclear medicine in which the acceptance of imaging to inform and monitor therapy has been embraced and even required by the Food and Drug Administration for the clinical evaluation of targeted therapeutic radiopharmaceuticals showing there is indeed a viable business model for targeted theragnostic radiopharmaceuticals and personalized medicine.

Nuclear Medicine and Wall Street: An Evolving Relationship.

Until recently, it has been challenging to engage Wall Street and large pharmaceutical companies in radiopharmaceutical opportunities. The modest economic prospects of most diagnostic radiopharmaceuticals have not attracted keen interest from the broader business community, despite the rapid advancement of diagnostic imaging capabilities and their increasingly crucial role in the therapeutic process. Similarly, compelling science supporting select radiopharmaceutical therapies in oncology has been overshadowed by the unique challenges posed by this class of drugs and historical commercial failures that serve as sobering reminders of risk. Fortunately, a few notable successes in the targeted radioligand therapeutic space are changing this dynamic, fueling a new flow of investor capital into these technologies and inciting increased merger and acquisition activity that has yielded significant value creation for investors. If the nuclear medicine industry is able to continue to effectively manage historical challenges, then there is significant opportunity for a new and promising wave of radioligand therapies to significantly change the oncology treatment paradigm and elevate the profile of the entire nuclear medicine sector.

Three Nuclear Medicine diagnostic procedures and breast cancer mortality in women. A population-analysis in Taiwan based upon National Health Insurance database.

OBJECTIVE: To investigate the correlation between the utilization of nuclear medicine diagnostic procedures and the mortality of women with breast cancer. SUBJECTS AND METHODS: Based on the National Health Insurance Research Database (NHIRD), we studied female breast cancer patients in 2012 who underwent whole-body bone scan, lymphoscintigraphy, or fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for possibly managing breast cancer metastases. The mortality of breast cancer was then followed up in 2017. Multiple linear regression analysis was applied to analyze the correlation between the use of any of these three nuclear medicine procedures and the mortality of breast cancer. RESULTS: For patients with early-stage breast cancer, single lymphoscintigraphy was the most frequently performed nuclear medicine procedure, accounting for 36.4% of all three nuclear medicine procedures. For patients with late-stage breast cancer, single whole-body bone scan was the most frequently performed nuclear medicine procedure, accounting for 67.2% of all three nuclear medicine procedures. Mortality of breast cancer significantly increased with the prevalence of late-stage breast cancer (b=2.87, P=0.001) and significantly decreased in cases in which whole-body bone scan was used (b=-4.28, P=0.003). CONCLUSION: The mortality of women with late-stage breast cancer was negatively related to the utilization of whole-body bone scan but not to the utilization of lymphoscintigraphy or the 18F-FDG PET/CT scan. In women with early-stage breast cancer, no significant correlation existed between breast cancer mortality and the utilization of the above three nuclear medicine procedures.

The Medical Imaging & Technology Alliance conference on research endpoints appropriate for medicare coverage of new PET radiopharmaceuticals.

The outcomes of a 2011 Medical Imaging & Technology Alliance (MITA) conference helped shape considerations about what might be the most appropriate pathways for the regulatory and payment considerations of new PET radiopharmaceuticals. As follow-up to that conference, MITA convened a second conference of stakeholders to advise payers on what might be acceptable endpoints for clinical trials to support the coverage of novel PET agents. The conference involved experts on imaging and clinical research, providers of PET services, as well as representatives of interested medical societies, the PET industry, and the regulatory and payer communities. The principal outcome of their deliberations was that it was unrealistic to expect trials of new PET radiopharmaceuticals to directly demonstrate a health benefit. Rather, intermediate outcomes, such as a positive change in patient management, would be more efficient and appropriate.

The IAEA technical cooperation programme and nuclear medicine in the developing world: objectives, trends, and contributions.

The International Atomic Energy Agency's technical cooperation (TC) programme helps Member States in the developing world with limited infrastructure and human resource capacity to harness the potential of nuclear technologies in meeting socioeconomic development challenges. As a part of its human health TC initiatives, the Agency, through the TC mechanism, has the unique role of promoting nuclear medicine applications of fellowships, scientific visits, and training courses, via technology procurement, and in the past decade has contributed nearly $54 million through 180 projects in supporting technology procurement and human resource capacity development among Member States from the developing world (low- and middle-income countries). There has been a growing demand in nuclear medicine TC, particularly in Africa and ex-Soviet Union States where limited infrastructure presently exists, based on cancer and cardiovascular disease management projects. African Member States received the greatest allocation of TC funds in the past 10 years dedicated to building new or rehabilitating obsolete nuclear medicine infrastructure through procurement support of single-photon emission computed tomography machines. Agency support in Asia and Latin America has emphasized human resource capacity building, as Member States in these regions have already acquired positron emission tomography and hybrid modalities (positron emission tomography/computed tomography and single-photon emission computed tomography/computed tomography) in their health systems. The strengthening of national nuclear medicine capacities among Member States across different regions has enabled stronger regional cooperation among developing countries who through the Agency's support and within the framework of regional cooperative agreements are sharing expertise and fostering the sustainability and productive integration of nuclear medicine within their health systems.

Nuclear medicine at a crossroads.

The growth of molecular imaging heightens the promise of clinical nuclear medicine as a tool for individualization of patient care and for improvement of health-care outcomes. Together with greater use of integrated structure-function imaging, clinical nuclear medicine reaches beyond traditional specialty borders into diagnostic radiology and oncology. Yet, there are concerns about the future of nuclear medicine, including progressively declining reimbursement, the competitive advantages of diagnostic radiology, limited translation of research accomplishments to clinical diagnostic imaging and patient care, and an insufficient pool of incoming highly qualified nuclear medicine clinicians. Thus, nuclear medicine views itself as being at a critical crossroads. What will be important is for nuclear medicine to be positioned as the quintessential molecular imaging modality more centrally within medical imaging and for the integration of nuclear medicine with primary care specialties to be driven more by patient needs than by specialty needs. In this way, the full potential of nuclear medicine as an effective and efficient tool for improving patient outcomes can be realized.

A 2009 survey of the Australasian clinical medical physics and biomedical engineering workforce.

A survey of the Australasian clinical medical physics and biomedical engineering workforce was carried out in 2009 following on from a similar survey in 2006. 621 positions (equivalent to 575 equivalent full time (EFT) positions) were captured by the survey. Of these 330 EFT were in radiation oncology physics, 45 EFT were in radiology physics, 42 EFT were in nuclear medicine physics, 159 EFT were in biomedical engineering and 29 EFT were attributed to other activities. The survey reviewed the experience profile, the salary levels and the number of vacant positions in the workforce for the different disciplines in each Australian state and in New Zealand. Analysis of the data shows the changes to the workforce over the preceding 3 years and identifies shortfalls in the workforce.

Economic scale of utilization of radiation in medicine in Japan.

Economic scale of radioisotopes (RI) in Japan is studied in the field of medicine, agriculture and a part of industry. (1) RI is used during medical examination with economic scale by 1.7M$ (million dollars) in 1997 and 0.4M$ in 2005. (2) Economic scale of RI utilization in agriculture is 4M$ for R&D, 127M$ for environmental protection and 1M$ for chronology. RI usage in agriculture is increased five times due to needs at environmental technology lasted after the Kyoto protocol. (3) Indirect economic scale of RI ((85)Kr, (147)Pm, (90)Cr) usage in paper fabrication field in Japan for 2006 is 8432M$.

Manhattan transfer: lethal radiation, bone marrow transplantation, and the birth of stem cell biology, ca. 1942-1961.

This study investigates how, in the late 1940s and 1950s, fears of nuclear accidents and nuclear warfare shaped postwar radiobiology. The new and intense forms of radiation generated by nuclear reactor technology, and which would be released in the event of a nuclear war, created concerns about a public-health hazard unprecedented in form and scale. Fears of inadvertent exposure to acute and potentially lethal radiation launched a search for anti-radiation therapies, out of which emerged the new technique of bone marrow transplantation (BMT). This study analyzes the use of BMT first as a research tool to explore the biological effects of ionizing radiation, and then as an adjunct to radiotherapy for the treatment of cancer. In highlighting how BMT became the province of different research and clinical constituencies, this study develops an understanding of the forces and contingencies that shaped its development. Exploring the emergence of BMT and the uses to which it was put, it reveals that BMT remained a technique in the making -- unstable and far from standardized, even as it became both a widely used research tool and rapidly made its way into the clinic. More broadly, it casts new light on one route through which the Manhattan Project influenced postwar radiobiology; it also affords new insights into one means by which radiobiology came to serve the interests of the Cold War state. In its focus on BMT this paper provides a new perspective on the evolving relationship between radiobiology and biomedicine in the postwar period.

Trends in the utilization of medical procedures that use ionizing radiation.

Medical procedures that use ionizing radiation have grown rapidly in volume over the last two decades and constitute a substantial portion of the collective radiation doses to the U.S. population. The purpose of this study is to describe the components of this growth. Summarized claims data from Medicare are used to describe trends for the period 1986-2005; supplemental data from other payers and surveys are used for verification and to describe age distributions of those who have these procedures. A notable trend is the rapid growth of CT and nuclear medicine, with CT volume per fee-for-service Medicare enrollee growing, on average, at 8% per y and nuclear medicine at 7% per y during the period 1986-2005. Cardiac procedures-nuclear medicine and interventional radiology-grew at over 15% per y per fee-for-service enrollee during the same period. The share of nuclear medicine procedures performed in physician offices increased from 10% in 1986 to 55% in 2005; the share of CT in the emergency room increased from 3% in 1992 to 17% in 2005. With this expansion in imaging volumes across practice settings, there is an increased need for radiation safety education of ordering physicians, imaging physicians, and patients, so that adequate consideration is given to radiation risk when determining the appropriateness of a prescribed procedure.

Economic evaluation studies in nuclear medicine: the need for standardization.

The guidelines for publishing economic evaluations require a statement of the economic importance of the analysis and the viewpoint from which it has been carried out, as well as specification of at least two alternative programmes or interventions, the form of economic evaluation, the outcome measure, the method of costing, the time horizon and adjustment for timing of costs and benefits (e.g. by a discount factor), and the allowance for uncertainties (e.g. by implementation of a sensitivity analysis). The decision analysis can be based on clinical trial data, on retrospective or administrative databases, or on modelling. The choice of outcome measures is the key issue in an economic evaluation. In cost-effectiveness analysis, benefits are usually measured in natural units. This is the form of economic evaluation most frequently used in nuclear medicine. Endpoints of effectiveness applied in studies in this field have been procedures avoided, procedures initiated, cardiac events, survival probability, morbidity, quality of life and protracted or failed surgical procedures. In other instances, surrogate endpoints have been used such as metastases detected, staging, viability or tumour response. This, however, limits comparability of cost-effectiveness considerably, as proof of a change in the health outcome cannot be obtained. Measures of utility such as QALYs (quality-adjusted life years) have so far only been applied for decision tree analysis. Useful examples of economic evaluation studies in nuclear medicine are presented here for fluorodeoxyglucose positron emission tomography (FDG-PET) in the preoperative staging of non-small cell lung cancer, for FDG-PET in differentiating indeterminate solitary pulmonary nodules, for somatostatin receptor scintigraphy in detecting metastases of carcinoid tumours, for routine preoperative scintigraphy with sestamibi in patients with parathyroid adenoma, for periodic measurement of thyroid-stimulating hormone in detecting mild thyroid failure, for diagnostic algorithms including a lung scan in patients with suspected pulmonary embolism, for myocardial perfusion imaging as an incremental prognostic factor in patients with coronary artery disease, and for the use of radioiodine as first-line therapy of Graves' hyperthyroidism and of toxic nodular goitres. Further evaluations of effectiveness or utility should be carried out within a multidisciplinary framework to ensure that nuclear medical procedures are included in the general management guidelines.

[Quality criteria for cost-benefit analysis in oncologic nuclear medicine and state of its realization]. / Qualitätskriterien für Kosten-Nutzen-Analysen in der onkologischen Nuklearmedizin und Stand ihrer Realisierung.

Additional or expensive diagnostic imaging had to prove prospectively their diagnostic efficacy, their therapeutic efficacy, or their patient-outcome efficacy. The adherence to methodologic standards in the cost-effectiveness literature is required. Based on the bone scintigraphy in oncologic patients with a low prevalence of bone metastases, the cost-effectiveness is questionable. The economic role of 99m-Tc MIBI mammoscintigraphy and of the imaging for carcinomas of unknown origin is discussed controversially. Based on the reimbursement of the positron emission tomography (PET) in the USA and in Switzerland, cost-effectiveness literature and decision trees for cost-utility analyses are reviewed. PET imaging was cost-effective in non-small-cell lung cancer, in solitary pulmonary nodules, in recurrent colorectal cancer, in metastatic melanoma and in recurrent head and neck cancer with reduced costs of management. The German health insurance calls for PET-data based on the national reimbursement.