Oncology drug development is among the most challenging of any therapeutic area, with first‐in‐human trials expected to deliver information on both safety and activity. Until recently, therapeutic ...approaches in oncology focused on cytotoxic chemotherapy agents, ruling out even the possibility of enrolling normal healthy volunteers (NHVs) in clinical trials due to safety considerations. The emergence of noncytotoxic modalities, including molecularly targeted agents with more favorable safety profiles, however, has led to increasing numbers of clinical pharmacology studies of these agents being conducted in NHVs. Beyond rapid enrollment and cost savings, there are other advantages of conducting specific types of studies in NHVs with the goal of more appropriate dosing decisions in certain subsets of the intended patient populations, allowing for enrollment of such patients in therapeutic trials from which they might otherwise have been excluded. Nevertheless, the decision must be carefully weighed against potential disadvantages, and although the considerations surrounding conduct of clinical trials using NHVs are generally well‐defined in most other therapeutic areas, they are less well‐defined in oncology.
Body composition has gained increasing attention in oncology in recent years due to fact that sarcopenia has been revealed to be a strong prognostic indicator for survival across multiple stages and ...cancer types and a predictive factor for toxicity and surgery complications. Accumulating evidence over the last decade has unraveled the “pharmacology” of sarcopenia. Lean body mass may be more relevant to define drug dosing than the “classical” body surface area or flat-fixed dosing in patients with cancer.
Since sarcopenia has a major impact on patient survival and quality of life, therapeutic interventions aiming at reducing muscle loss have been developed and are being prospectively evaluated in randomized controlled trials. It is now acknowledged that this supportive care dimension of oncological management is essential to ensure the success of any anticancer treatment.
The field of sarcopenia and body composition in cancer is developing quickly, with (i) the newly identified concept of sarcopenic obesity defined as a specific pathophysiological entity, (ii) unsolved issues regarding the best evaluation modalities and cut-off for definition of sarcopenia on imaging, (iii) first results from clinical trials evaluating physical activity, and (iv) emerging body-composition-tailored drug administration schemes.
In this context, we propose a comprehensive review providing a panoramic approach of the clinical, pharmacological and therapeutic implications of sarcopenia and body composition in oncology.
Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell ...lung cancers. Therefore, their use will not be limited anymore to selected hospitals involved in clinical trials. Indeed, they will be routinely prescribed in many cancer centers across the world. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events (irAEs). This new family of dysimmune toxicities remains largely unknown to the broad oncology community. Although severe irAEs remain rare (∼10% of cases under monotherapy), they can become life-threatening if not anticipated and managed appropriately. Over the last 5 years, Gustave Roussy has accumulated a significant experience in the prescription of immune checkpoint blockade (ICB) antibodies and the management of their toxicities. Together with the collaboration of Gustave Roussy's network of organ specialists with expertise in irAEs, we propose here some practical guidelines for the oncologist to help in the clinical care of patients under ICB immunotherapy.
The coronavirus disease 2019 (COVID-19) pandemic has burdened health care resources and disrupted care of patients with cancer. Virtual care (VC) represents a potential solution. However, few ...quantitative data support its rapid implementation and positive associations with service capacity and quality.
To examine the outcomes of a cancer center-wide virtual care program in response to the COVID-19 pandemic.
This cohort study applied a hospitalwide agile service design to map gaps and develop a customized digital solution to enable at-scale VC across a publicly funded comprehensive cancer center. Data were collected from a high-volume cancer center in Ontario, Canada, from March 23 to May 22, 2020.
Outcome measures were care delivery volumes, quality of care, patient and practitioner experiences, and cost savings to patients.
The VC solution was developed and launched 12 days after the declaration of the COVID-19 pandemic. A total of 22 085 VC visits (mean, 514 visits per day) were conducted, comprising 68.4% (range, 18.8%-100%) of daily visits compared with 0.8% before launch (P < .001). Ambulatory clinic volumes recovered a month after deployment (3714-4091 patients per week), whereas chemotherapy and radiotherapy caseloads (1943-2461 patients per week) remained stable throughout. No changes in institutional or provincial quality-of-care indexes were observed. A total of 3791 surveys (3507 patients and 284 practitioners) were completed; 2207 patients (82%) and 92 practitioners (72%) indicated overall satisfaction with VC. The direct cost of this initiative was CAD$ 202 537, and displacement-related cost savings to patients totaled CAD$ 3 155 946.
These findings suggest that implementation of VC at scale at a high-volume cancer center may be feasible. An agile service design approach was able to preserve outpatient caseloads and maintain care quality, while rendering high patient and practitioner satisfaction. These findings may help guide the transformation of telemedicine in the post COVID-19 era.
Structural imaging remains an essential component of diagnosis, staging and response assessment in patients with cancer; however, as clinicians increasingly seek to noninvasively investigate tumour ...phenotypes and evaluate functional and molecular responses to therapy, theranostics - the combination of diagnostic imaging with targeted therapy - is becoming more widely implemented. The field of radiotheranostics, which is the focus of this Review, combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy, which involves the use of small molecules, peptides and/or antibodies as carriers for therapeutic radionuclides, typically those emitting α-, β- or auger-radiation. The exponential, global expansion of radiotheranostics in oncology stems from its potential to target and eliminate tumour cells with minimal adverse effects, owing to a mechanism of action that differs distinctly from that of most other systemic therapies. Currently, an enormous opportunity exists to expand the number of patients who can benefit from this technology, to address the urgent needs of many thousands of patients across the world. In this Review, we describe the clinical experience with established radiotheranostics as well as novel areas of research and various barriers to progress.
Diffusion-weighted imaging (DWI) has been at the forefront of cancer imaging since the early 2000s. Before its application in clinical oncology, this powerful technique had already achieved ...widespread recognition due to its utility in the diagnosis of cerebral infarction. Following this initial success, the ability of DWI to detect inherent tissue contrast began to be exploited in the field of oncology. Although the initial oncologic applications for tumor detection and characterization, assessing treatment response, and predicting survival were primarily in the field of neurooncology, the scope of DWI has since broadened to include oncologic imaging of the prostate gland, breast, and liver. Despite its growing success and application, misconceptions about the underlying physical basis of the DWI signal exist among researchers and clinicians alike. In this review, we provide a detailed explanation of the biophysical basis of diffusion contrast, emphasizing the difference between hindered and restricted diffusion, and elucidating how diffusion parameters in tissue are derived from the measurements via the diffusion model. We describe one advanced DWI modeling technique, called restriction spectrum imaging (RSI). This technique offers a more direct in vivo measure of tumor cells, due to its ability to distinguish separable pools of water within tissue based on their intrinsic diffusion characteristics. Using RSI as an example, we then highlight the ability of advanced DWI techniques to address key clinical challenges in neurooncology, including improved tumor conspicuity, distinguishing actual response to therapy from pseudoresponse, and delineation of white matter tracts in regions of peritumoral edema. We also discuss how RSI, combined with new methods for correction of spatial distortions inherent in diffusion MRI scans, may enable more precise spatial targeting of lesions, with implications for radiation oncology and surgical planning. See all articles in this Cancer Research section, "Physics in Cancer Research."
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