Adherence to treatment guidelines improves lung cancer outcomes

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A team of researchers led by Dr Ani John at Roche Diagnostics Information Solutions investigates how the treatment outcomes in lung cancer are affected by adherence to pre-set care guidelines. Using real-world data, their aim is to better understand how pre-treatment diagnostic testing, the subsequent selection of the appropriate treatment, and its success are correlated in a broad spectrum of treatments. Their findings underline the significance of practising timely access to biomarker testing and individualised treatment for patients.
Lung cancer, also known as lung carcinoma, is a malignant lung tumour characterised by uncontrolled cell growth. Lung cancer is the leading cause of cancer death globally. Many causes of lung cancer have been identified, including cigarette smoking.

Lung carcinomas are divided into two groups based on how their cells look: small cell lung cancer (SCLC) and the more common non-small cell lung cancer (NSCLC). There are three main types of NSCLC: the adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. NSCLC usually forms from cells that line the alveoli (the small air sacs in the lungs) and make mucus.

Once lung cancer has been diagnosed, doctors will work to determine the stage of the cancer using biopsies and various radiological imaging methods. This is followed by careful analysis of the patient’s cancer cells in order to reveal the type of cancer they have. These tests help to inform the appropriate treatment for each patient.


Surgery, chemotherapy, and radiotherapy (high-powered energy beams from sources such as X-rays and protons to kill cancer cells) are some of the traditionally available treatment options. However, to personalise therapy and to improve precision, targeted drug treatments that focus on specific molecular abnormalities within cancer cells, and immunotherapies (the treatment of disease by activating or suppressing the immune system) are two of the most recent and novel treatment choices, especially for advanced NSCLC. These treatments are tailored for the individual according to the results of the diagnostic work up, including sophisticated specific biomarker tests that can identify specific expression of genes associated with the disease.

“The goal for all patients with cancer is precision medicine − care that is personalised, targeting the right treatments for the right patients at the right time.”

Dr Ani John, Dr Baiyu Yang, and Roma Shah at Roche Diagnostics Information Solutions have been studying the results of these biomarker-driven treatments. Specifically, they explored whether adherence to the testing and treatment guidelines set by NCCN (National Comprehensive Cancer Network) influences patient outcomes and treatment success. Importantly, their study included the analysis of multiple biomarkers instead of the usual pattern of studying just one at a time. Their holistic approach adds great clinical significance to their results.

Staging system

The American Joint Committee on Cancer (AJCC) is the organisation that sets the standards for staging lung cancer. The stages of NSCLC range from stage 0 to stage 4. Stage 0 is when cancer cells have formed in the airways but haven’t grown into the lung tissue. Stage 1 (I), stage 2 (II), and stage 3 (III) cancers have grown into lung tissue, and some have potentially spread to nearby lymph nodes. These cancers have not spread to body parts far from the lung tumour. In stage 4 (IV), the cancer has already spread to distant organs by the time of diagnosis. Lung cancer tends to spread to the brain and adrenal gland, and from one lung to the other lung. Unfortunately, most lung cancers are stage III or IV when diagnosed, resulting in a poor prognosis.

The team explored whether adherence to testing and treatment guidelines influences patient outcomes and treatment success. Saiful52/

The study methods
This was a retrospective cohort study of 28,784 adult patients diagnosed with a stage III or IV NSCLC over a period of eight years (2011–2019). The researchers used a real-world dataset: Flatiron Health database, a demographically and geographically diverse database derived from US electronic health records. Data included information on diagnosis, laboratory values, medication given, and patients’ demographic characteristics. At first, adherence to NCCN recommendations for biomarker testing and overall survival were assessed. Next, the team investigated the patient’s adherence to NCCN-recommended, biomarker-driven therapy and their ability to remain on treatment. Their aim was to explore any differences between the guideline adherent versus non-adherent group of patients.

Adherence to biomarker-testing guidelines reduces mortality risk

Two thirds of patients had evidence of guideline-adherent biomarker testing. Adherence to testing guidelines was associated with a 11% reduced risk of mortality for patients with advanced diagnosis, while in a subset of patients with stage IV cancer at initial diagnosis, the risk of mortality was reduced by 20% compared to non-adherent patients.

Microscopic view of lung adenocarcinoma, a type of non-small cell carcinoma (NSCLC). David A Litman/

Several previous studies have demonstrated improved survival outcomes in patients adherent to NCCN guidelines, focusing on a single biomarker. Notably, however, John and her team assessed the clinical impact of adherence to the guidelines in a more holistic way by studying multiple biomarkers at the same time and outcomes.

Success of biomarker driven treatment

70% of the patients had treatments that adhered to NCCN guidelines. This means that after recommended biomarker testing, their treatment was tailored to the results of their tests. Adherent patients had a 40% lower risk of treatment discontinuation versus non-adherent patients, and their treatment duration was significantly longer (3.45 versus 2.40 months).

“The goal for all patients with cancer is precision medicine − care that is personalised, targeting the right treatments for the right patients at the right time.”

This was a large study, and inevitably there was significant variety in the types of treatment for both groups. It was also observed that the risk of discontinuation of treatment and its total length differed by the type of treatment; immunotherapy and targeted therapy treatments were less likely to discontinue compared to chemotherapy alone. However, it was evident across all treatment groups that the patients with treatments that adhered to guidelines were less likely to discontinue their treatment than non-adherent patients.

John assessed the clinical impact of adherence to guidelines in a holistic way by studying multiple biomarkers. Korawat photo shoot/

In essence, adhering to the biomarker-testing guidelines was associated with a significant benefit for patient survival, while patients adhering to treatment guidelines were found to be more likely to remain on their treatment. Importantly, the findings from this study show that even among a large, heterogeneous population across the US, where testing and medicine availability may differ, testing guidelines and appropriate treatment decisions can lead to better clinical outcomes.

This study further underscores the importance of supporting the practice of precision medicine in oncology, and the value of biomarker testing. Testing lung cancer patients for specific biomarkers in a timely manner should be an essential element of routine oncology practice. Evidently, guidelines built on the results of these tests are a practical tool for clinicians, helping them to tailor sophisticated treatments for cancer patients and therefore improve their quality of care.

Testing lung cancer patients for specific biomarkers in a timely manner should be an essential part of routine oncology practice. Arif biswas/
What is next for your research?
We are looking to better understand if certain sequences of treatments show improvements in outcomes for patients.What can be changed in everyday oncology practice to help support cancer patients and their treatments?
It’s likely that healthcare providers and their patients are not intentionally non-adherent, but could be a result of many factors, including healthcare systems, policy, and payer. If we all can collaborate to provide access to timely biomarker testing that leads to effective treatment we can help patients to improve their outcomes.



  • John, A, et al, (2021) Clinical Impact of Adherence to NCCN Guidelines for Biomarker Testing and First-Line Treatment in Advanced Non-Small Cell Lung Cancer (aNSCLC) Using Real-World Electronic Health Record Data. Advances in Therapy, 38, 1552–1566. doi:10.1007/s12325-020-01617-2
  • California Health Benefits Review Program (CHBRP), 2021 Analysis of California Senate Bill 535 Biomarker Testing. Berkeley, CA.

Research Objectives

This study aimed to comprehensively assess the association between guideline-adherence to biomarker testing and first-line therapies in non-small cell lung cancer patients, and patient outcomes using real-world data.


Roche Information Solutions, Santa Clara, California


Ani John is a Senior Principal Clinical Research Scientist at Roche Diagnostics Information Solutions group, where she leads activities to support the use of real-world data for regulatory purposes across several therapeutic areas. She has over 20 years of real-world and clinical trial research experience in diagnostics and pharma resulting in over 65 publications. She has also led a number of collaborations with external registries, academic institutions, patient and professional societies. Ani has a BS in nursing and psychology, MPH and PhD in epidemiology.

Baiyu Yang is a Principal Quantitative Scientist at Roche Diagnostics, where she leads real-world data studies to support the value of diagnostics and digital health products. Baiyu has a Bachelor’s degree in Medicine and a PhD in Cancer Epidemiology. She has six years of working experience in observational study design and analysis, with over 30 publications in this field.

Roma Shah is a Principal Data Scientist within the Roche Diagnostics Information Solutions group, with over 10 years of experience in a publication-driven space. With substantial knowledge of R and SAS, along with a strong understanding of statistical analytical methods, she conducts real-world studies employing manipulation of large-scale datasets to support the value of digital healthcare products.

Roche Information Solutions
2881 Scott Blvd, Santa Clara, CA 95050

T: 6504914374
W: – Ani John

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