In the rapidly evolving field of oncology, staying up to date with the latest advancements and innovations is crucial for physicians while managing their clinical responsibilities.
The discovery of new molecular targets and the development of targeted therapies has significantly improved patient outcomes in certain settings. This has been done through the advancements in diagnostic tools leading to more accurate detection and biological characterization of the malignant tissues, resulting in better treatment decision making and patients benefiting from the most innovative therapies. At the same time, these scientific innovations keep driving cancer research and clinical trials forward, while generating valuable evidence to support the adoption of precision oncology innovations in routine clinical practice across all regions, including low- and mid-income countries, with the aim to make cancer a chronic disease.
Thanks to earlier and more accurate diagnosis as well as more effective treatments, the overall survival has improved for most of the cancers. As exemplified here below, one can see the impact of these innovations on the survival of breast cancer patients from 1975 until 2020 in US (Data from https://seer.cancer.gov/statfacts/html/breast.html).
In this specific case, we can see that because of the advancements we’ve mentioned earlier, as well as increase in social awareness around benefits of preventive screening and regular check-ups, 5-y survival amongst breast cancer patients has increased from 75.8% in 1980 to 92.8% in 2015. This means that out of 100 breast cancer patients, 17 additional patients have been alive 5 years after diagnosis in 2015 when compared to 1980.
It is undeniable that precision oncology space is undergoing a revolution and we are lucky to be part of it. However, I’m wondering how can cancer care workers keep up with this pace of innovation while managing and executing their clinical duties?
Novel molecular methods used for molecular profiling based on next-generation sequencing (NGS) as well as artificial intelligence (AI) in digital pathology and imaging technologies are just some of the new tools that enable assessment of actionable biomarkers and identification of cancerous lesions, providing insights into the degree of aggressiveness of the disease. Jointly, data from these tools help treating physicians to assign cancer patients to a specific therapy, help them stratify affected individuals into specific risk categories, and inform about the probable response to a given therapy.
Importantly and challenging at the same time, most of these tools are available through a variety of commercial and service providers, mainly through non-standardized solutions. The lack of harmonization does not only apply for innovative technologies, but equally applies to some well-established techniques such as assessment of HER2 biomarker using immunohistochemistry (IHC) (1).
Fortunately, many international efforts are ongoing aimed towards standardization of these different methods. With regards to NGS-based testing, some initiatives are focused on setting up frameworks and standards for liquid biopsy testing by groups such as BloodPAC and project around use of ctDNA in the context of monitoring ctMoniTR, led by Friends of Cancer Research. Additionally, external quality assessments schemes are driving important efforts looking into different approaches for somatic variant detection across single genes such as EGFR in cfDNA lead by International Quality Networks for Pathology (IQNPath) in Europe, as well as standardization of detection of novel biomarkers such as TMB and HRD, efforts lead by Friends of Cancer Research in US. Importantly, medical societies such as ASCO, CAP and ESMO are also regularly providing recommendations related to use of these novel methods such as the one related to HER2 assessment by IHC in breast cancer (2), NGS-based testing in metastatic cancer patients by ESMO (3) and ASCO’s provisional clinical opinion related to somatic profiling in advanced or metastatic setting (4).
Surprisingly, parameters such as variant allele frequency (VAFs) which represents the percentage of cells carrying a specific mutation within a specific gene (or locus), has been poorly defined and is currently not standardized across different assays. Many studies have shown that dynamic changes in VAF, especially in the context of ctDNA analysis can be linked to either disease progression (increase in VAF) or decrease in the context of response to treatment. As the authors of this recent manuscript suggest, given the multitude of available assays, frameworks establishing assay-specific cutoffs are urgently needed, realistically in disease-specific settings (5).
This list of standardization efforts is far from complete, but it demonstrates some of the initiatives taking place across cancer community, which will ultimately ensure accuracy, consistency and most probably faster implementation in precision oncology testing.
Medical sectors such radiomics, advanced imaging technologies, liquid biopsy, microfluidics, nanotechnology and many of these in combination with AI are areas which have also undergone huge amount of progress over last ten years, as well as drug development. Pharmaceutical industry with the help of impressive advancements in cancer research and now growing use of AI within drug development pipelines, has led to launch of many new and very effective therapies. Some of them are antibody-drug conjugates (ADCs), immune checkpoint inhibitors (ICIs), Chimeric Antigen Receptor T (CART) cell therapies, radiotherapeutics, mRNA vaccines, epidrugs and more, which has resulted to 115 approvals to biomarker based targeted therapies (6).
In spite of NGS multi-gene panels being now recommended in the patients with advanced and metastatic disease, a recent survey conducted by ESMO (7) has revealed a relatively poor and varied adoption of biomolecular methods throughout Europe. This discrepancy can be attributed to various factors, including insufficient infrastructure, expertise, and/or reimbursement. It underscores the additional challenges associated with integrating precision oncology advancements into healthcare systems, ultimately affecting the practices of oncologists treating patients.
Each day, physicians deal with matters of life and death, often encountering grief more frequently than their counterparts in other medical fields. Balancing the relentless pursuit of optimal patient outcomes and potential cures with the demands of administrative tasks, electronic documentation, extensive working hours, participation in medical conferences, and staying abreast of scientific advancements presents an overwhelming challenge for healthcare professionals. Studies indicate that burnout not only affects the quality of care across all medical disciplines but also carries significant implications for all involved stakeholders (8).
On the other side, the oncology startup scene is experiencing a surge, offering tools that could enhance physicians’ ability to treat patients successfully and efficiently. It’s a bustling and thrilling landscape, one that I’ll delve into in my upcoming article.
Ultimately, the implementation of numerous precision oncology innovations provides not only individual benefits but also significant social and financial advantages for health systems. Should conversations about these topics be limited to the domain of health economists, or should they be disseminated through mainstream channels?
While health economists undoubtedly play a crucial role, there is a need for broader awareness and understanding across various sectors. This ensures that stakeholders beyond the specialized field recognize the holistic benefits and support effective implementation strategies for precision oncology innovations.
Concluding remarks
The development of innovations, as highlighted briefly in this article, is undeniably critical. However, a significant gap exists in the implementation of these advancements within healthcare systems. While it is essential to foster innovation, it is equally important to ensure that these advancements are implemented effectively across health systems to prevent exacerbating existing inequalities.
Strategic planning amongst all stakeholders is necessary to guarantee that innovations are not only realized but also contribute to equitable healthcare access for all.
1. Karakas C, et al. Interobserver and Interantibody Reproducibility of HER2 Immunohistochemical Scoring in an Enriched HER2-Low-Expressing Breast Cancer Cohort. Am J Clin Pathol. 2023 May 2;159(5):484-491.
2. Wolff AC et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018 Jul 10;36(20):2105-2122.
3. Mosele F et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020 Nov;31(11):1491-1505.
4. Debyani Chakravarty et al. Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer: ASCO Provisional Clinical Opinion. JCO 40, 1231-1258(2022).
5. Boscolo Bielo et al. Variant allele frequency: a decision-making tool in precision oncology? Trends Cancer. 2023 Dec;9(12):1058-1068
6. Mateo J et al. Delivering precision oncology to patients with cancer. Nat Med. 2022 Apr;28(4):658-665.
7. Bayle A et al. ESMO study on the availability and accessibility of biomolecular technologies in oncology in Europe. Ann Oncol. 2023 Oct;34(10):934-945.
8. De Hert S. Burnout in Healthcare Workers: Prevalence, Impact and Preventative Strategies. Local Reg Anesth. 2020 Oct 28;13:171-183.
Disclaimer: The information in this blog is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. All content available here is for general information purposes only.
