RESUMEN
Predictive biomarkers are necessary for the identification of immunotherapy-responsive patients. Tumor mutation burden (TMB), as determined by next-generation sequencing (NGS), and PD-L1 expression, as evaluated by Immunohistochemistry (IHC), are the biomarkers most frequently employed in clinical practice. In addition, microsatellite instability (MSI) was the first biomarker to demonstrate immunotherapy efficacy irrespective of the type of tumor and possesses a high predictive value. However, its limited use across most tumor types limits its therapeutic potential. This report describes two cancer patients with positive TMB and PD-L1 expression. The molecular profile of the tumor indicated that the first patient was responsive to Immune checkpoint inhibitors (ICI), while the second patient was resistant. These case studies demonstrate that tumor molecular analysis in combination with immunotherapy predictive biomarkers, such as PD-L1 expression and TMB, can enhance the prediction of response to ICI for specific patients. This methodology enables an individualized and improved approach to the treatment and management of the disease.
RESUMEN
BACKGROUND: Tumor molecular profile analysis by Next Generation Sequencing technology is currently widely applied in clinical practice and has enabled the detection of predictive biomarkers of response to targeted treatment. In parallel with targeted therapies, immunotherapies are also evolving, revolutionizing cancer therapy, with Programmed Death-ligand 1 (PD-L1), Microsatellite instability (MSI), and Tumor Mutational Burden (TMB) analysis being the biomarkers employed most commonly. METHODS: In the present study, tumor molecular profile analysis was performed using a 161 gene NGS panel, containing the majority of clinically significant genes for cancer treatment selection. A variety of tumor types have been analyzed, including aggressive and hard to treat cancers such as pancreatic cancer. Besides, the clinical utility of immunotherapy biomarkers (TMB, MSI, PD-L1), was also studied. RESULTS: Molecular profile analysis was conducted in 610 cancer patients, while in 393 of them a at least one biomarker for immunotherapy response was requested. An actionable alteration was detected in 77.87% of the patients. 54.75% of them received information related to on-label or off-label treatment (Tiers 1A.1, 1A.2, 2B, and 2C.1) and 21.31% received a variant that could be used for clinical trial inclusion. The addition to immunotherapy biomarker to targeted biomarkers' analysis in 191 cases increased the number of patients with an on-label treatment recommendation by 22.92%, while an option for on-label or off-label treatment was provided in 71.35% of the cases. CONCLUSIONS: Tumor molecular profile analysis using NGS is a first-tier method for a variety of tumor types and provides important information for decision making in the treatment of cancer patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to better tumor characterization and offer actionable information in the majority of patients. Furthermore, our data suggest that one in two patients may be eligible for on-label ICI treatment based on biomarker analysis. However, appropriate interpretation of results from such analysis is essential for implementation in clinical practice and accurate refinement of treatment strategy.
Asunto(s)
Inmunoterapia , Inestabilidad de Microsatélites , Adulto , Antígeno B7-H1 , Biomarcadores de Tumor , Humanos , MasculinoRESUMEN
BACKGROUND: Many countries adopt eHealth applications to support patient-centered care. Through information exchange, these eHealth applications may overcome institutional data silos and support holistic and ubiquitous (regional or national) information logistics. Available eHealth indicators mostly describe usage and acceptance of eHealth in a country. The eHealth indicators focusing on the cross-institutional availability of patient-related information for health care professionals, patients, and care givers are rare. OBJECTIVES: This study aims to present eHealth indicators on cross-institutional availability of relevant patient data for health care professionals, as well as for patients and their caregivers across 14 countries (Argentina, Australia, Austria, Finland, Germany, Hong Kong as a special administrative region of China, Israel, Japan, Jordan, Kenya, South Korea, Sweden, Turkey, and the United States) to compare our indicators and the resulting data for the examined countries with other eHealth benchmarks and to extend and explore changes to a comparable survey in 2017. We defined "availability of patient data" as the ability to access data in and to add data to the patient record in the respective country. METHODS: The invited experts from each of the 14 countries provided the indicator data for their country to reflect the situation on August 1, 2019, as date of reference. Overall, 60 items were aggregated to six eHealth indicators. RESULTS: Availability of patient-related information varies strongly by country. Health care professionals can access patients' most relevant cross-institutional health record data fully in only four countries. Patients and their caregivers can access their health record data fully in only two countries. Patients are able to fully add relevant data only in one country. Finland showed the best outcome of all eHealth indicators, followed by South Korea, Japan, and Sweden. CONCLUSION: Advancement in eHealth depends on contextual factors such as health care organization, national health politics, privacy laws, and health care financing. Improvements in eHealth indicators are thus often slow. However, our survey shows that some countries were able to improve on at least some indicators between 2017 and 2019. We anticipate further improvements in the future.
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Benchmarking , Países Desarrollados , Telemedicina , Continuidad de la Atención al Paciente , Salud Global , Intercambio de Información en Salud , Accesibilidad a los Servicios de Salud , Humanos , Atención Dirigida al Paciente , Encuestas y Cuestionarios , Telemedicina/normasRESUMEN
Immune checkpoint inhibitors have revolutionized cancer treatment with patient improved survival, quality of life, and a longer response. However, up to 30% of patients experience paradoxical accelerated tumor progression early after immune-checkpoint blockade therapy. This phenomenon is also known as hyperprogression (HP). Unlike other responses, such as pseudoprogression or natural progression, HP causes worse survival outcomes in patients. Older age, higher metastatic burden, and previous radiation have been independently associated with HP. Even though the exact molecular mechanism underlying HP after immune-checkpoint blockade therapy remains unknown, oncogenic signaling activation including MDM2 amplification or EGFR alterations, the modification of tumor microenvironment by radiotherapy with immune checkpoint inhibitors, and alterations in immune landscape of tumors have been hypothesized as the biological mechanisms behind HP. Patients with HP have been presented with poor prognosis and increased deleterious mutations in cancer genes, along with alterations in the tumor microenvironment. As immune checkpoint inhibitors have been more widely accepted by oncologists, proper assessment of this unique tumor response remains challenging in clinical practice. This work documents the recent findings on epidemiology, biological and clinicopathological factors of HP after immunotherapy.
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Inmunoterapia/métodos , Progresión de la Enfermedad , HumanosRESUMEN
Curcumin is a substance obtained from the root of the turmeric plant, which has the feature of being a yellow or orange pigment. It is also the main component of curry powder commonly used in Asian cuisine. Curcumin, a substance that has had an important place in traditional Indian and Chinese medicines for thousands of years, has been the center of interest for scientific studies especially in the field of cancer treatment for several years. Laboratory studies have presented some favorable results in terms of curcumin's antioxidant, antiinflammatory and anticancer properties in particular. However, since such findings have yet to be confirmed in clinical studies, its effect on humans is not clearly known. Therefore, when its advantages in terms of toxicity, cost and availability as well as the favorable results achieved in laboratory studies are considered, it would not be wrong to say that curcumin is a substance worth being studied. However, for now the most correct approach is to abstain from its use for medical purposes due to lack of adequate reliable evidence obtained from clinical studies, and because of its potential to interfere with other drugs.
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Antineoplásicos Fitogénicos/uso terapéutico , Curcuma/química , Curcumina/uso terapéutico , Extractos Vegetales/uso terapéutico , Animales , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/aislamiento & purificación , Curcumina/efectos adversos , Curcumina/aislamiento & purificación , Humanos , Fitoterapia , Extractos Vegetales/efectos adversos , Extractos Vegetales/aislamiento & purificación , Plantas MedicinalesRESUMEN
Having a long historical past in traditional Chinese medicine, Ganoderma Lucidum (G. Lucidum) is a type of mushroom believed to extend life and promote health. Due to the increasing consumption pattern, it has been cultivated and marketed intensively since the 1970s. It is claimed to be effective in the prevention and treatment of many diseases, and in addition, it exerts anticancer properties. Almost all the data on the benefits of G. Lucidum are based on laboratory and preclinical studies. The few clinical studies conducted are questionable. Nevertheless, when the findings obtained from laboratory studies are considered, it turns that G. Lucidum is likely to have some benefits for cancer patients. What is important at this point is to determine the components that will provide these benefits, and use them in drug development, after testing their reliability. In conclusion, it would be the right approach to abstain from using and incentivizing this product, until its benefits and harms are set out clearly, by considering its potential side effects.
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Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Preparaciones de Plantas/uso terapéutico , Reishi/química , Agaricales/química , Humanos , Medicina Tradicional China/métodosRESUMEN
Derived from the Greek word Panacea that means 'cure for all', Ginseng (Panax) has had an important place in Chinese Medicine for many of years. As the name suggests, it is believed to be a miraculous plant effective in the treatment of many health problems. It is claimed to have many effects such as sedative, hypnotic, aphrodisiac, antidepressant, diuretic, and stimulating effects, and to be effective in the treatment of certain health problems such as diabetes, Alzheimer's disease, erectile dysfunction and infections. In addition, its effects on the prevention and treatment of cancer as well as on the reduction of cancer-related symptoms have been prioritized in recent years. However, the studies that have been done so far do not confirm these effects. Although certain favorable results have been obtained in some studies intended for investigating its effects on acute nasopharyngitis, diabetes, Alzheimer's disease, and erectile dysfunction, it is early to say anything conclusive. And in cancer patients, it has been shown to be effective in reducing weakness due to cancer and its treatment. On the other hand, ginseng may cause important drug interactions, although it is described as a relatively safe product. For now, it seems to be reasonable to use ginseng only for cancer-related weakness in cancer patients at this point. But this should definitely be done within the knowledge and under the control of oncologists.