Survey for molecular reports in practicing oncologists in India

INTRODUCTION

Molecular oncology is rapidly emerging as a promising approach in cancer treatment.^[1,2] For the promise of precision oncology to be realized, oncologists will need to understand its benefits, risks, and limitations before consenting to treatment. Yet, integration of matched tumor and germline sequencing into clinical care presenting significant challenges for doctors education. Only a few studies have explored physician perspectives in the context of this precision oncology.^[3,4]

Applications of molecular diagnostics to oncology have been slow to make their way to the clinical laboratory. While numerous genes and mutation spectra have been found to be involved in tumorigenesis, it is only recently that these findings begin to become useful in a clinical setting. Building on the technical knowledge obtained from molecular infectious disease testing, new instruments and assays have been developed to answer similar questions regarding qualitative, quantitative, and genotyping issues. Molecular assessment has been advocated as a way to provide detailed evaluation of the health status. Although recommended by the National Comprehensive Cancer Network and the American Society of Clinical Oncology (ASCO), molecular assessment is not routinely implemented in oncology practice as it is perceived to be time and resource consuming.^[3,4] Although the time commitment and burden on patients and caregivers are concerns, recently developed cancer-specific molecular assessment tools can gather a wealth of information in a relatively short amount of time.^[5,6]

To date, there is limited information on Indian oncologists’ views and experiences of molecular oncology.

This study aimed to explore the views of Indian oncologists regarding the perception of and barriers to the incorporation of molecular technology in routine clinical practice.

MATERIAL AND METHODS

This was an anonymized cross-sectional survey. The online survey, based on a literature review and expert opinion, comprised 14 questions covering [Table 1]:

1. Respondent characteristics, clinical practice environment, and patient population.

2. Challenges and treatment decision-making factors in the prescription, interpretation, authenticity, follow-up, and application of molecular reports.

3. Benefits of and barriers to the implementation of molecular oncology and tumor boards.

The questionnaire was intentionally straightforward so that it could be filled in quickly; we, therefore, did not collect respondents’ characteristics (age, gender, and type of practice). A selection bias could not be avoided, as the medical oncologists most highly motivated in molecular oncology may have been the ones who responded to the survey. We attempted to draft a simplified questionnaire that could be completed in 5–10 min, so as to capture as much participation as possible, albeit at the expense of other relevant information. The Google Forms was case sensitive; as a result, the survey could not be completed twice by the same person.

Electronic responses were automatically captured in a Google spreadsheet that was linked to the online form, and responses collected on the PDF version were manually entered into the same sheet. The survey was designed on Google Forms (Google, Mountain View, and CA).

Qualitative variables were reported as numbers (N) and percentages.

RESULTS

Among the respondents, 90.5% were interested in the molecular testing to be available in the hospital of their practice. Among those who received the reports, 86.5% wanted these to be confidential and all of them wanted to be delivered from an accredited laboratory. However, 27% of the prescribing oncologists were not aware of the agencies for the accreditation for these molecular reports. Among those who have responded, more than 77% were interested in the references and list of mentioned potential therapeutics and drug report form attached. About 50% of the prescribing oncologists were not interested in the remuneration associated in prescribing molecular tests. About 68.9% of the prescribing oncologist did not have the provision of molecular tumor board in the hospital. The factors deciding the preferences for selection of the target molecular profile are enlisted in the Figure 1 based on cost, experience, turnaround time, availability of liquid biopsy, cost, coverage, and targetable mutation. Among the molecular reports, quality of DNA, allele frequency, depth of coverage, platform performed and validation of report, and the physician choice of preferences are illustrated in Figure 2.

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Figure 1:

Preferences of the oncologists for the factors affecting the choice of the panel.

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Figure 2:

Preferences of molecular reporting in medical oncologists.

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DISCUSSION

This longitudinal survey is one of the first and largest studies to examine oncologist understanding and expectations regarding the use of next-generation sequencing in their own cancer treatment. Perhaps, our most notable finding was an apparent mismatch between physician pre-test expectations of direct benefits from cancer genome sequencing and their actual realization of such benefits. Physicians reported expecting a wide range of potential benefits from study participation, including greater understanding of underlying causes of their cancer, genomic information of relevance to their family members’ health, and the ability to enroll more of their patients in the revolution of molecular oncology. Although our study highlighted areas for improvement in oncologists education, it should be noted that participants in the study showed good knowledge of many basic facts about molecular oncology and sequencing.

1. Our findings should be interpreted in light of several study limitations. The study sample of oncologists was disproportionate to those who are prescribing in real-life limiting generalizability of study results. Future research in this area should attempt to enroll oncologists with greater diversity in terms of geography, institution of practice (academic/private), and accessibility to molecular laboratory. Another study limitation was that some key measures had either not been formally validated (e.g., international guidelines or policies) or were not administered in their entirety (e.g., decisional regret), which may have introduced some measurement error into the assessment of key outcomes. The authors agree that tissue availability is a valid concern, but note that there have been significant advances in tumor DNA extraction from low-purity samples and with the advent of blood- based NGS testing. These allow for either the extraction of tumor DNA from as little as 5% tumor purity samples or from the isolation of circulating cell-free DNA if tissue biopsies are not available. While blood-based NGS assays have their distinct limitations, there remains a significant benefit to analyze circulating tumor DNA for routine clinical care of cancer patients. Hand in hand with the issue of tissue scarcity is the perception that NGS-based tumor testing rarely identifies mutations with clinical significance or improves clinical outcomes. The most widespread argument against NGS testing is the additional cost to both patients and payers with little clinical benefit to justify the cost. Recent FDA approvals and Centers for Medicare and Medicaid Services (CMS) coverage guidelines demonstrate the emerging clinical utility of NGS-based tests. A 2017 review of both clinical and cost-effectiveness of NGS testing concluded that NGS-based testing is effective in identifying actionable mutations in cancer and aided in matching 37% of the patients to targeted therapies. Access to molecular tumor boards, limited discussion of supplementary reports, discussion on variance of unknown origin, and adequacy of material were reported as other barriers.

In addition, some commentators have noted that surveys such as ours that demonstrate participant desires for hope that research participation will improve their own personal care while recognizing that such clinical benefits are not the primary purpose of a given study.

CONCLUSION

These challenges, together with perceived funding shortfalls, should inspire educational, training, and other interventions to ensure that developments in molecular oncology can result in optimal cancer care. To disseminate the use of a molecular assessment and the various available screening tools, education of oncologists and molecular oncologists tools that are validated, efficient, and predictive of outcomes is needed. In short, molecular oncology in our country has only just begun – humbly, yet unstoppably.