Barriers to Mutational Testing in Patients with Gastrointestinal Stromal Tumors (GIST) – A Survey of Life Raft Group Members

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Call, Jennily Eshak, Pete Knox, Maeven Luedke, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-737437/v2 This work is licensed under a CC BY 4.0 License Status: Under Review Version 2 posted 10 You are reading this latest preprint version Show more versions Abstract Background Due to the low mutational testing rate in patients with Gastrointestinal Stromal Tumors (GIST), The Life Raft Group (LRG), a non-profit organization that provides support, advocacy, and conducts research for patients with GIST, analyzed various factors that may have an impact on patients’ ability to receive mutational testing. Methods A survey about mutational testing for patients with GIST, or their caregivers, was conducted in June 2020. The survey, sent to 1004 GIST patients and caregivers through email, was promoted through social media with instructions to contact the LRG to participate. The survey was designed by the LRG Patient Registry Department. Members of the LRG, regardless of Patient Registry status, were eligible to participate. Results A total of 295 patients/caregivers participated in this study (response rate: 29.4%). The percentage of patients who indicated they had received mutational testing was much higher in this survey (80%) than in the general GIST community (26.7%). Several reasons were cited for having a test, including: “My doctor ordered/suggested that I have it done” (54%); “The Life Raft Group advised/suggested I have it done” (25%); “I asked my doctor to have it done” (22%); “I had it done as part of a clinical trial” (5%); “I am not sure” (3%) and “Other” (14%). Mutational testing resulted in a treatment change in 25% of cases. Patients were able to select more than one option when completing this question resulting in a percentage greater than 100. Conclusions The LRG membership is voluntary and proactive; patients who join are more likely to participate in surveys and mutational testing, as well has more likely to have a GIST specialist. Mutational testing can influence understanding a patient’s GIST and the treatment best suited to each case. These are extremely important findings, as it helps ensure that patients are on the proper treatment, which should lead to better outcomes. Gastrointestinal Stomal Tumors GIST Mutational testing Biomarker testing Survey Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Gastrointestinal Stromal Tumors (GIST) are a rare disease, as per the National Organization of Rare Disorders (NORD), that can occur anywhere along the gastrointestinal tract (GI), but most commonly occur in the stomach and small intestines [ 1 ] . When metastases occur, it is usually to the liver or the peritoneum. Approximately half of GISTs are categorized as very low, low, or intermediate risk of recurrence [ 2 ] and surgery is typically the only treatment needed for these GISTs. However, the other half of GISTs are high risk or metastatic at diagnosis and typically require additional treatment with tyrosine kinase inhibitors, TKIs, either before or after surgery and in cases where surgery is not possible [ 3 ] . Approximately 75–80% of GISTs are driven by mutations in various exons (8, 9, 11, 13, 17) of the KIT gene that result in constitutive activation of the KIT receptor [ 4 , 5 ] . Another 7% are driven by mutations in the PDGFRA gene [ 6 ] . Apart from some of the very rare KIT exon 17 mutations, nearly all the primary KIT mutations (exons 8, 9 (may benefit from higher a dose) [ 7 ] , 1 and 13) respond extremely well to imatinib and about 1/3 of the PDGFRA mutations do as well. The other nearly 2/3 of PDGFRA mutations that do not respond to imatinib are D842V mutations that occur in exon 18 of PDGFRA [ 6 ] . These mutations respond to avapritinib, which was approved in 2020 for PDGFRA exon 18 mutations including D842V [ 8 ] . Other subtypes and mutations in GIST include succinate dehydrogenase (SDH)-deficient GIST and driver mutations in BRAF, KRAS, NTRK, FGFR1 fusions and other very rare mutations [ 9 , 10 , 11 , 12 ] . Secondary KIT mutations that confer resistance to imatinib can occur in exons 13, 14, 17 and 18 [ 13 , 14 ] . A total of five different TKIs (imatinib, sunitinib, regorafenib, ripretinib and avapritinib) are currently approved for GIST and they each have different sensitivity profiles against the various mutations [ 15 ] . Despite strong guidelines from organizations such as National Comprehensive Cancer Network (NCCN) and College of American Pathologists (CAP) recommending mutational testing, the testing rate for GIST patients in the United States was only 26.7% for patients diagnosed between 2010 and 2015 [ 16 ] . Various international guidelines also publish studies on the importance of mutational testing in patients’ treatment, such as British Sarcoma Group (BSG) and European Society for Medical Oncology/European Reference on Rare Adult Solid Cancer (ESMO/EURACAN) [ 17 , 18 ] . Mutational testing is important not only for the selection of the appropriate treatment in advanced GIST patients, but the results can also help to prevent ineffective treatments from being used in adjuvant settings. A study from Surveillance, Epidemiology, and End Results (SEER) patients, demonstrated that mutational testing has a substantial impact on overall survival (OS) in GIST patients [ 16 ] . Due to the beneficial factors of mutational testing, we assessed the barriers that may have an impact on patients’ ability to receive mutational testing. Methods The Life Raft Group is an international, internet-based non-profit patient support, advocacy, and research organization. In June 2020, the LRG conducted a survey of its members regarding mutational testing. The survey was sent to 1004 GIST patients and caregivers through email. The purpose of the survey was to analyze the different factors that may have an impact in obtaining a mutational test among GIST patients. The LRG maintains a large registry of GIST patients and both registry participants and LRG members not in the registry were eligible to participate in the survey. Survey questions were developed by the Patient Registry Department. The contact method was via email and the survey was filled out online using the Qualtrics platform. For some questions, more than one answer could be provided. The data was analyzed with descriptive statistics and exploratory analysis. The survey was divided into two phases. Phase I consisted of questions about demographic information, GIST diagnosis, and treatment. Phase II consisted of questions about how, why, and where mutational testing was performed. The survey questions are included as Supplemental Table 1. Characteristics of Participants The majority of survey respondents were patients (n = 274, 93%), with 21 caregivers (7%) also participating on behalf of patients, for a total of 295 respondents (Fig. 1A). The gender distribution of GIST patients was somewhat skewed towards females (Fig. 1B), 61% female (n = 179) and 39% male (n = 116). Age distribution of patients followed a normal GIST distribution (Fig. 1C), with a peak of respondents aged 60 to 74 (44% n = 131). Survey respondents had somewhat higher risk than population-based studies which is typical of LRG members with 25% of respondents reporting metastatic disease at diagnosis. Patients from 27 different countries participated, however the majority of patients (78%) were from the United States (Fig. 1D). The years of diagnosis for patients responding to the survey were: <2005, n = 34 (12%), 2005–2009, n = 38 (13%), 2010–2014, n = 84 (28%) and 2015–2020, n = 139 (47%). Results Demographics The percentage of patients receiving a mutational test was highest for patients living in Europe where 26 of 27 (96.3%) patients reported having a test with other continents varying from 66.7% (South America) to 81.8% (Asia). The patient population in this survey was biased toward proactive patients in two ways. Patients participating in the registry are self-referred/more proactive and patients participating in the survey are further selected for proactive participation. As a result, the percentage of patients reporting having a mutational test in this survey was higher (80% n = 237) than in the LRG registry (57% of living patients). Treatments and Mutational Testing Patients reported receiving their GIST diagnosis more often in a “large hospital or academic institution (teaching hospital with an affiliated medical university” (n = 162, 55%) compared to a “local hospital (small-medium sized hospital” (n = 105, 36%) or a “private local doctor/physician or non-hospital based diagnostic center” (n = 28, 9%) (Table 1). In the Mutational Testing sub-section of the survey (Table 2), patients were asked “What is the name of the institution where your doctor practices?” There were 21 institutions listed by three or more patients comprising a total of 115 patients. The most frequently listed sites were: Memorial Sloan Kettering, Dana Farber, Oregon Health Sciences University, MD Anderson, Sylvester Comprehensive Cancer Center and Red de Salud Christus UC (Chile). These more popular sites had a slightly higher percentage of mutational testing (101 of 115, 88%) compared to sites with two or less patients, with 123 of 160 having a mutational test (77%) and were slightly more likely to explain mutational testing results, 76% versus 69% in the less frequently cited centers. However, there was considerable crossover between larger centers and smaller centers within the treatment and testing centers (questions 22, 25, and 26 from Supplemental Table 1). Many patients maintained a relationship with both a local doctor and a GIST/Sarcoma specialty center, in some cases with more than one expert center. When combined with the low percentage of patients in this survey that did not receive a mutational test, it makes any attempt to correlate mutational testing frequency with center size or GIST expertise difficult. One of the major findings of this survey was that from a patient’s perspective, there were three major reasons why a mutational test was performed in their case: Their doctor ordered/suggested the test (54% n = 129), the LRG advised/suggested the test (25% n = 60) and the patient asked their doctor for the test (22% n = 52). In many cases, more than one of these reasons were selected (Supplemental Table 1-Question 19, Figure 2). Patients diagnosed in the last ten years hold a higher rate of mutational testing offered by physicians (79.4%). As more studies and guidelines show the benefits to mutational testing in GIST treatments, we see an increase in the number of patients being offered mutational testing by a physician than in patients with an earlier diagnosis date (20.6%). Patients with no mutational testing (Supplemental Table 1-Question 27, Figure 3) were asked, “Why was mutational testing not done in your case?” The most common two responses were, “My doctor never mentioned it as part of my treatment” (34%) and “I do not know” (29%). Other reasons included, “Mutational testing did not apply in my case (i.e., low risk, metastatic) (17%), “Not enough tissue” (9%), “Cost/insurance” (9%) and “My doctor mentioned it but said that I did not need it” (7%). Treatment Changes Based on Mutational Testing One of the most important findings in this study was that for 58 of the patients (24.5%), treatment was changed based on the results of the mutational test (Supplemental Table 1-question 20, Figure 4A). These treatment changes included (Figure 4B), stopped treatment (n = 14, 24%), switched treatment (n = 10, 17%), increased dosage of current treatment (n = 6, 10%) and other (n = 28, 48%). A post hoc analysis of the free text answers from the 28 “Other” responses (Figure 4C) found that treatment was started for 7 patients (25%) after test confirmed results, 7 patients (25%) declined TKI treatment due to mutation type, 6 patients (21%) switched treatment, two patients stopped treatment, two opted for TKI versus surgery, two opted for surgery versus TKI, one patient’s treatment did not change and one patient’s diagnosis was changed from GIST to a different sarcoma (also changing treatment). Discussion A key finding of this study was the critical role that doctors play in whether or not a patient receives a mutational test. When asked the reason behind why mutational testing was done in their case, 54% of patients reported it was due to the doctor ordering the test or suggesting it be done (Fig. 2), the response with the greatest percentage. This is important because it suggests that reaching out to doctors may have an effect on increasing rates of mutational testing. This is underscored by “My doctor never mentioned it as part of my treatment” being the leading reason (34%) given for why mutational testing was not performed (Fig. 3). Apart from doctors, the next two leading responses for “Why a mutational testing was done?” was that the Life Raft Group suggested having the test done (25%) or the patient asked the doctor themselves (22%) (Fig. 2). This underscores the need for a multi-level approach; in addition to targeting doctors, reaching out to advocacy groups and patients directly may have a beneficial effect as well. Again, this is confirmed by “I do not know” being the second highest reason (29%) (Fig. 3) given as to why a test was not performed, illustrating that an informed patient and/or advocacy group has the power to get a test done, and that an uninformed patient is less likely to succeed in doing so. While increasing the rate of testing is a worthwhile goal, of more importance is the impact it has on patient outcomes. As mentioned in the previous section, the performance of this test was often quite meaningful in terms of the patient’s treatment. In 25% of the cases, the patient’s treatment was changed based on the results of the mutational testing (Fig. 4A). Even in cases where treatment was not changed, an imatinib-sensitive mutation was often confirmed, offering the GIST patient comfort in an optimized treatment plan. These are both extremely important findings, as it helps ensure that patients are being matched with the proper treatment, which should lead to better outcomes, and in some cases preventing them from taking ineffective treatments, thus avoiding potentially harmful (and unnecessary) side effects. In addition, studies have shown that receiving early mutational testing has a positive economic impact, as it leads to a more specific prognosis by incorporating the right treatment plan and eliminating avoidable expenses [ 19 ] . Mutational testing is a cost-effective approach compared with empirical treatment with imatinib [ 20 ] . This study, like all studies, was of course not without its limitations. The Life Raft Group membership has a higher rate of mutational testing than in the general population, and also tends to be seen in both local centers and in larger institutions. Patients in this survey had a much higher rate of mutational testing than in the general GIST population [ 15 ] , which was 26.7% of patients diagnosed between 2010–2015 in a report of 3888 GIST patients from the Surveillance, Epidemiology, and End Results (SEER) database [ 15 ] . Due to these factors, there is an inherent bias in our study population. Only 20% of the respondents did not receive a mutational test (Fig. 3), which is somewhat unrepresentative of the general population, particularly in the United States (which were 78% of respondents, Fig. 1). In addition, there was extensive crossover of patients between local doctors and larger centers, so it is not possible to determine a difference in how patients are treated by a local oncologist versus a larger center/GIST expert center. Given these limitations, it is reasonable to conclude from this study that both doctors and patients/advocacy groups have a role to play in determining whether a patient receives a mutational test, and if the desire is to increase the rate of testing, then focusing on outreach to these groups could prove beneficial. Also, having looked at responses, it is reasonable to state that mutational testing can have a beneficial role in a patient’s treatment, by either helping reinforce that the selected treatment is the correct one or suggesting a different treatment based on their mutational results, either of which should lead to more favorable patient outcomes. Based on these findings, the recommendation of the authors is to further increase outreach to the aforementioned groups as soon as possible in order to accelerate testing rates and thus allow patients to benefit from these more favorable outcomes. Conclusions In conclusion, mutational testing plays an important role in patients’ treatment. The LRG membership is voluntary and proactive; patients who join are more likely to have an LRG recommended GIST specialist and mutational testing. This shows the role doctors and patient advocacy groups can play in helping increase the rate of mutational testing in GIST patients, which is important because it can positively affect the longevity and quality of life by ensuring that patients are on the proper treatment. Abbreviations CAP College of American Pathologists ESMO European Society for Medical Oncology EURACAN European Reference on Rare Adult Solid Cancer GI Gastrointestinal GIST Gastrointestinal Stromal Tumors LRG The Life Raft Group NCCN National Comprehensive Cancer Network NORD National Organization for Rare Disorders SDH Succinate dehydrogenase SEER Surveillance, Epidemiology, and End Results TKIs Tyrosine kinase inhibitors OS Overall survival Declarations Ethics Approval and Consent to Participate All methods in this analysis were conducted in accordance with all relevant guidelines and regulations. The Institutional review board of Advarra, Inc based in Columbia, MD (Protocol ID #: LRG2013PR112) approved the study and allows us to do research based on the data we obtain. We have informed consent that LRG Registry members have signed. In addition, as a patient advocacy organization that considers the rights of the patient fundamental to its mission, our project, along with all of the other activities of the Life Raft Group, aligns with the Declaration of Helsinki, specifically where it states that the investigator’s duty is solely to the patient, where the subject’s welfare shall always take precedence, especially in areas of ethical consideration, and the analysis is conducted by suitably trained investigators with knowledge of the relevant scientific background and using approved protocols subject to independent ethical review (by our aforementioned IRB). Our IRB is responsible for overall review of our patient registry, from which is the source data for many of our studies. Specific ethics approval is not required for this study, as it is secondary analysis of survey data. Through Advarra, Inc, there is overall ethics approval is in place for the overall research program. Consent for Publication Not applicable. Availability of Data and Materials Contact the corresponding author for the datasets and other materials used in the survey study. Competing Interests No conflict of interest reported by authors. Funding Funding for this study was provided by Pfizer Inc. Distribution of funding went towards the software survey program and staff time in design of survey, collection of survey data, writing, and editing of this paper. Authors' Contributions Conceptualization & Methodology: Denisse Montoya; Formal Analysis: Denisse Montoya, Jerry Call, Jennily Eshak, Maeven Luedke; Data Collection: Denisse Montoya, Jennily Eshak, Sahibjeet Kaur; Data Curation: Denisse Montoya; Writing: Jerry Call, Denisse Montoya, Pete Knox, Maeven Luedke; Review & Editing: all authors; Funding Acquisition: Sara Rothschild. Acknowledgements The authors would like to thank all patients and caregivers who participated in this survey and Pfizer Pharmaceuticals for providing financial support for the study. References 1. 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J Clin Oncol 23, 5357–5364 (2005). 7. National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors (GIST) (Version 1.2021) [Internet]. NCCN. 2020 [cited 2021Oct27]. Available from: https://www.nccn.org/guidelines/category_1 8. George, S. et al. Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least 3 Prior Lines of Therapy. The Oncologist . ( 2021) Jan 16. doi: 10.1002/onco.13674. 9. Settas, N., Faucz, F. R. & Stratakis, C. A. Succinate dehydrogenase (SDH) deficiency, Carney triad and the epigenome. Mol. Cell. Endocrinol. (2017) doi:10.1016/j.mce.2017.07.018. 10. Stratakis, C. A. & Carney, J. A. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med 266, 43–52 (2009). 11. Agaram, N. P. et al. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromosomes Cancer 47, 853–859 (2008). 12. Alkhuziem, M., Burgoyne, A. M., Fanta, P. T., Tang, C.-M. & Sicklick, J. K. The Call of “The Wild”-Type GIST: It’s Time for Domestication. Journal of the National Comprehensive Cancer Network 15, 551–554 (2017). 13. Heinrich, M. C. et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J. Clin. Oncol 24, 4764–4774 (2006). 14. Heinrich, M. C. et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J. Clin. Oncol 26, 5352–5359 (2008). 15. Lostes-Bardaji, M. J., García-Illescas, D., Valverde, C. & Serrano, C. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward. Ther Adv Med Oncol 13, (2021). 16. Florindez, J. & Trent, J. Low Frequency of Mutation Testing in the United States: An Analysis of 3866 GIST Patients. Am. J. Clin. Oncol. 43, 270–278 (2020). 17. Judson I, Bulusu R, Seddon B, Dangoor A, Wong N, Mudan S. UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST). Clinical Sarcoma Research. 2017;7(1). 18. Casali PG, Abecassis N, Bauer S, Biagini R, Bielack S, Bonvalot S, et al. Gastrointestinal stromal tumours: ESMO–EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2018Oct1;29:iv68–iv78. 19. Schöffski P, Wozniak A, Schöffski O, van Eycken L, Debiec-Rychter M. Overcoming cost implications of mutational analysis in patients with gastrointestinal stromal tumors: A pragmatic approach. Oncology Research and Treatment. 2016Dec;39(12):811–6. 20. Banerjee S, Kumar A, Lopez N, Zhao B, Tang C-M, Yebra M, et al. Cost-effectiveness analysis of genetic testing and tailored first-line therapy for patients with metastatic gastrointestinal stromal tumors. JAMA Network Open. 2020;3(9). Tables Table 1 - Facilities where patients received their GIST diagnosis No. % Large hospital or Academic Institution (Teaching hospital with an affiliated medical university) 162 55% Local hospital (small-medium sized hospital) 105 36% Private local doctor/physician or non-hospital based diagnostic center 28 9% Table 2 - Why was mutational testing done? My doctor ordered/suggested I have it done 108 (blank) 58 I asked my doctor to have it done 26 The Life Raft Group advised/suggested I have it done 25 I asked my doctor to have it done, The Life Raft Group advised/suggested I have it done 14 Other 18 The life raft group advised/ suggested I have it done/ Other 7 I had it done as part of a clinical trial 6 My doctor ordered/suggested I have it done, I asked my doctor to have it done 6 My doctor ordered/suggested I have it done, I asked my doctor to have it done, The Life Raft Group advised/suggested I have it done 5 My doctor ordered/suggested I have it done, Other 5 I am not sure 5 My doctor ordered/suggested I have it done, The Life Raft Group advised/suggested I have it done 3 I had it done as part of a clinical trial, My doctor ordered/ suggested I have it done; The Life Raft Group advised / suggested I have it done 2 I had it done as part of a clinical trial, Other 1 The life raft group advised/ suggested I have it done/ I am not sure 1 I had it done as part of a clinical trial, My doctor ordered/suggested I have it done 1 I had it done as part of a clinical trial, The Life Raft Group advised/suggested I have it done 1 I am not sure, Other 1 I asked my doctor to have it done, The Life Raft Group advised/suggested I have it done, Other 1 My doctor ordered/suggested I have it done, The Life Raft Group advised/suggested I have it done, Other 1 Total 295 Additional Declarations No competing interests reported. Supplementary Files SupplementalTable1.docx Cite Share Download PDF Status: Under Review Version 2 posted Editorial decision: Major revision 06 Jul, 2022 Reviews received at journal 05 Jul, 2022 Reviews received at journal 21 Jun, 2022 Reviewers agreed at journal 09 Jun, 2022 Reviewers agreed at journal 09 Jun, 2022 Reviewers invited by journal 09 Jun, 2022 Editor assigned by journal 08 Jun, 2022 Editor invited by journal 27 May, 2022 Submission checks completed at journal 27 May, 2022 First submitted to journal 13 Apr, 2022 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-737437","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[{"code":1,"date":"2021-08-19 18:40:56","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":110923405,"identity":"8945cde9-661e-46f1-bfc7-d54e5e11e2b3","order_by":0,"name":"Denisse Montoya","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYDCCA1Can52x4QOIJk4LCEs2MzbOANE9RGsxOMzASJwWvmuHjz3+UHFY3vgwc2PDxz12Evb8ax8+5t3BIGfevwCrFsnbaekGB84cNtx2mLGxccazZAkeiefGxrxnGIxlbjzAqsXgdo6ZxMG2w4xALe2PeQ4w1/FIHGOT5m1jSJwhcQCvFvvNQO83/zlQL0G0lsQNzEAtDAcOS/Dwt0G18Dfg8kuaxJkz6ckzQH7pOXBcgucGG7Ph3DMSxhISOELsdvIxiYoKa9v+9vaHDT8OVEuw9x9jfPB2h42cBD92h0FBMxJbIoGBgbFBAsLADeqQ2CDDGRugjFEwCkbBKBgFDAwAhtxmAGf3cwsAAAAASUVORK5CYII=","orcid":"","institution":"Life Raft Group","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Denisse","middleName":"","lastName":"Montoya","suffix":""},{"id":110923406,"identity":"c09a2953-6017-4cba-b528-ed5c54f71cb0","order_by":1,"name":"Jerry W. Call","email":"","orcid":"","institution":"Life Raft Group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jerry","middleName":"W.","lastName":"Call","suffix":""},{"id":110923407,"identity":"57b93ab4-8526-41ee-8e24-8bb7f1cab47b","order_by":2,"name":"Jennily Eshak","email":"","orcid":"","institution":"Life Raft Group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jennily","middleName":"","lastName":"Eshak","suffix":""},{"id":110923408,"identity":"2907855b-162d-41f2-b5e4-c412b2d5e179","order_by":3,"name":"Pete Knox","email":"","orcid":"","institution":"Life Raft Group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pete","middleName":"","lastName":"Knox","suffix":""},{"id":110923409,"identity":"5ca9d937-a266-4d2d-9dd1-5d671016d7dc","order_by":4,"name":"Maeven Luedke","email":"","orcid":"","institution":"Life Raft Group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maeven","middleName":"","lastName":"Luedke","suffix":""},{"id":110923410,"identity":"61d375a4-f5ef-460e-bf69-a2726f0d8947","order_by":5,"name":"Sahibjeet Kaur","email":"","orcid":"","institution":"Life Raft Group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sahibjeet","middleName":"","lastName":"Kaur","suffix":""},{"id":110923411,"identity":"5c20bf29-e3c4-4c22-b5e6-63a2466daf9f","order_by":6,"name":"Sara Rothschild","email":"","orcid":"","institution":"Life Raft Group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Rothschild","suffix":""},{"id":110923412,"identity":"143b5850-3aaa-4bf1-a1d7-bd96e0643a4a","order_by":7,"name":"Mary Garland","email":"","orcid":"","institution":"Life Raft Group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mary","middleName":"","lastName":"Garland","suffix":""},{"id":110923413,"identity":"95796c40-70ba-45ac-8fa0-56046c990bce","order_by":8,"name":"Norman J. Scherzer","email":"","orcid":"","institution":"Life Raft Group","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Norman","middleName":"J.","lastName":"Scherzer","suffix":""}],"badges":[],"createdAt":"2021-07-20 20:44:05","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-737437/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-737437/v2","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22237250,"identity":"986bc162-902c-484b-aed0-37c260d68e89","added_by":"auto","created_at":"2022-06-03 18:53:54","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":136811,"visible":true,"origin":"","legend":"\u003cp\u003ePanel A - In 93% of cases, the patient was the respondent. Panel B - Patient gender was somewhat skewed towards females. Panel C - Patient’s age follows a normal distribution for GIST patients. Panel D - The majority of respondents were from the United States (78%), which is typical of LRG membership.\u0026nbsp;\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-737437/v2/a968a84e19ef77302d8c5823.jpg"},{"id":22237249,"identity":"95b628be-eee4-4702-b456-5b9238817d87","added_by":"auto","created_at":"2022-06-03 18:53:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":45337,"visible":true,"origin":"","legend":"\u003cp\u003eReasons mutational test was done\u0026nbsp;\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-737437/v2/770f807a7a3a47f39bde108f.jpg"},{"id":22237253,"identity":"4f495d1e-37e0-42d8-86fc-75fd694bd5ca","added_by":"auto","created_at":"2022-06-03 18:53:56","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":60142,"visible":true,"origin":"","legend":"\u003cp\u003eReasons mutational test not done\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-737437/v2/ba1bbe733d3ca91851f26167.jpg"},{"id":22237252,"identity":"68f06117-ffa8-4e77-a100-6870a531bc34","added_by":"auto","created_at":"2022-06-03 18:53:55","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":130315,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment changes based on mutational testing Panel A – Did treatment change based on mutation test result? Panel B – How did your treatment plan change? Panel C – Post hoc analysis of “Other” responses from panel B\u0026nbsp;\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-737437/v2/8132705d19e478474c1eacc9.jpg"},{"id":22237832,"identity":"9cc0ba6c-45aa-43ca-8e14-3792baf9fe10","added_by":"auto","created_at":"2022-06-03 18:58:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":503108,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-737437/v2/a588c0df-a79d-46e3-849c-45471eaf1f82.pdf"},{"id":22237831,"identity":"0409f9ce-c419-484e-ac29-48aabcdd9fab","added_by":"auto","created_at":"2022-06-03 18:58:54","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19403,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-737437/v2/07dca6858fe4f34018b9ee41.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Barriers to Mutational Testing in Patients with Gastrointestinal Stromal Tumors (GIST) – A Survey of Life Raft Group Members","fulltext":[{"header":"Background","content":"\u003cp\u003eGastrointestinal Stromal Tumors (GIST) are a rare disease, as per the National Organization of Rare Disorders (NORD), that can occur anywhere along the gastrointestinal tract (GI), but most commonly occur in the stomach and small intestines\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. When metastases occur, it is usually to the liver or the peritoneum. Approximately half of GISTs are categorized as very low, low, or intermediate risk of recurrence\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e and surgery is typically the only treatment needed for these GISTs. However, the other half of GISTs are high risk or metastatic at diagnosis and typically require additional treatment with tyrosine kinase inhibitors, TKIs, either before or after surgery and in cases where surgery is not possible\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eApproximately 75\u0026ndash;80% of GISTs are driven by mutations in various exons (8, 9, 11, 13, 17) of the \u003cem\u003eKIT\u003c/em\u003e gene that result in constitutive activation of the KIT receptor\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Another 7% are driven by mutations in the \u003cem\u003ePDGFRA\u003c/em\u003e gene\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Apart from some of the very rare \u003cem\u003eKIT\u003c/em\u003e exon 17 mutations, nearly all the primary \u003cem\u003eKIT\u003c/em\u003e mutations (exons 8, 9 (may benefit from higher a dose)\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e, 1 and 13) respond extremely well to imatinib and about 1/3 of the \u003cem\u003ePDGFRA\u003c/em\u003e mutations do as well. The other nearly 2/3 of \u003cem\u003ePDGFRA\u003c/em\u003e mutations that do not respond to imatinib are D842V mutations that occur in exon 18 of \u003cem\u003ePDGFRA\u003c/em\u003e\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. These mutations respond to avapritinib, which was approved in 2020 for \u003cem\u003ePDGFRA\u003c/em\u003e exon 18 mutations including D842V\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Other subtypes and mutations in GIST include succinate dehydrogenase (SDH)-deficient GIST and driver mutations in \u003cem\u003eBRAF, KRAS, NTRK, FGFR1\u003c/em\u003e fusions and other very rare mutations\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Secondary \u003cem\u003eKIT\u003c/em\u003e mutations that confer resistance to imatinib can occur in exons 13, 14, 17 and 18\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. A total of five different TKIs (imatinib, sunitinib, regorafenib, ripretinib and avapritinib) are currently approved for GIST and they each have different sensitivity profiles against the various mutations\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite strong guidelines from organizations such as National Comprehensive Cancer Network (NCCN) and College of American Pathologists (CAP) recommending mutational testing, the testing rate for GIST patients in the United States was only 26.7% for patients diagnosed between 2010 and 2015\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Various international guidelines also publish studies on the importance of mutational testing in patients\u0026rsquo; treatment, such as British Sarcoma Group (BSG) and European Society for Medical Oncology/European Reference on Rare Adult Solid Cancer (ESMO/EURACAN)\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. Mutational testing is important not only for the selection of the appropriate treatment in advanced GIST patients, but the results can also help to prevent ineffective treatments from being used in adjuvant settings. A study from Surveillance, Epidemiology, and End Results (SEER) patients, demonstrated that mutational testing has a substantial impact on overall survival (OS) in GIST patients\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Due to the beneficial factors of mutational testing, we assessed the barriers that may have an impact on patients\u0026rsquo; ability to receive mutational testing.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe Life Raft Group is an international, internet-based non-profit patient support, advocacy, and research organization. In June 2020, the LRG conducted a survey of its members regarding mutational testing. The survey was sent to 1004 GIST patients and caregivers through email. The purpose of the survey was to analyze the different factors that may have an impact in obtaining a mutational test among GIST patients. The LRG maintains a large registry of GIST patients and both registry participants and LRG members not in the registry were eligible to participate in the survey. Survey questions were developed by the Patient Registry Department. The contact method was via email and the survey was filled out online using the Qualtrics platform. For some questions, more than one answer could be provided. The data was analyzed with descriptive statistics and exploratory analysis.\u003c/p\u003e \u003cp\u003eThe survey was divided into two phases. Phase I consisted of questions about demographic information, GIST diagnosis, and treatment. Phase II consisted of questions about how, why, and where mutational testing was performed. The survey questions are included as Supplemental Table\u0026nbsp;1.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of Participants\u003c/h2\u003e \u003cp\u003eThe majority of survey respondents were patients (n\u0026thinsp;=\u0026thinsp;274, 93%), with 21 caregivers (7%) also participating on behalf of patients, for a total of 295 respondents (Fig.\u0026nbsp;1A). The gender distribution of GIST patients was somewhat skewed towards females (Fig.\u0026nbsp;1B), 61% female (n\u0026thinsp;=\u0026thinsp;179) and 39% male (n\u0026thinsp;=\u0026thinsp;116). Age distribution of patients followed a normal GIST distribution (Fig.\u0026nbsp;1C), with a peak of respondents aged 60 to 74 (44% n\u0026thinsp;=\u0026thinsp;131). Survey respondents had somewhat higher risk than population-based studies which is typical of LRG members with 25% of respondents reporting metastatic disease at diagnosis. Patients from 27 different countries participated, however the majority of patients (78%) were from the United States (Fig.\u0026nbsp;1D).\u003c/p\u003e \u003cp\u003eThe years of diagnosis for patients responding to the survey were: \u0026lt;2005, n\u0026thinsp;=\u0026thinsp;34 (12%), 2005\u0026ndash;2009, n\u0026thinsp;=\u0026thinsp;38 (13%), 2010\u0026ndash;2014, n\u0026thinsp;=\u0026thinsp;84 (28%) and 2015\u0026ndash;2020, n\u0026thinsp;=\u0026thinsp;139 (47%).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eDemographics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe percentage of patients receiving a mutational test was highest for patients living in Europe where 26 of 27 (96.3%) patients reported having a test with other continents varying from 66.7% (South America) to 81.8% (Asia).\u003c/p\u003e\n\u003cp\u003eThe patient population in this survey was biased toward proactive patients in two ways. Patients participating in the registry are self-referred/more proactive and patients participating in the survey are further selected for proactive participation. As a result, the percentage of patients reporting having a mutational test in this survey was higher (80% n = 237) than in the LRG registry (57% of living patients).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatments and Mutational Testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients reported receiving their GIST diagnosis more often in a \u0026ldquo;large hospital or academic institution (teaching hospital with an affiliated medical university\u0026rdquo; (n = 162, 55%) compared to a \u0026ldquo;local hospital (small-medium sized hospital\u0026rdquo; (n = 105, 36%) or a \u0026ldquo;private local doctor/physician or non-hospital based diagnostic center\u0026rdquo; (n = 28, 9%) (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the Mutational Testing sub-section of the survey (Table 2), patients were asked \u0026ldquo;What is the name of the institution where your doctor practices?\u0026rdquo; \u0026nbsp; There were 21 institutions listed by three or more patients comprising a total of 115 patients. The most frequently listed sites were: Memorial Sloan Kettering, Dana Farber, Oregon Health Sciences University, MD Anderson, Sylvester Comprehensive Cancer Center and Red de Salud Christus UC (Chile). These more popular sites had a slightly higher percentage of mutational testing (101 of 115, 88%) compared to sites with two or less patients, with 123 of 160 having a mutational test (77%) and were slightly more likely to explain mutational testing results, 76% versus 69% in the less frequently cited centers.\u003c/p\u003e\n\u003cp\u003eHowever, there was considerable crossover between larger centers and smaller centers within the treatment and testing centers (questions 22, 25, and 26 from Supplemental Table 1). Many patients maintained a relationship with both a local doctor and a GIST/Sarcoma specialty center, in some cases with more than one expert center. When combined with the low percentage of patients in this survey that did not receive a mutational test, it makes any attempt to correlate mutational testing frequency with center size or GIST expertise difficult.\u003c/p\u003e\n\u003cp\u003eOne of the major findings of this survey was that from a patient\u0026rsquo;s perspective, there were three major reasons why a mutational test was performed in their case: Their doctor ordered/suggested the test (54% n = 129), the LRG advised/suggested the test (25% n = 60) and the patient asked their doctor for the test (22% n = 52). In many cases, more than one of these reasons were selected (Supplemental Table 1-Question 19, Figure 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients diagnosed in the last ten years hold a higher rate of mutational testing offered by physicians (79.4%). As more studies and guidelines show the benefits to mutational testing in GIST treatments, we see an increase in the number of patients being offered mutational testing by a physician than in patients with an earlier diagnosis date (20.6%).\u003c/p\u003e\n\u003cp\u003ePatients with no mutational testing (Supplemental Table 1-Question 27, Figure 3) were asked, \u0026ldquo;Why was mutational testing not done in your case?\u0026rdquo; The most common two responses were, \u0026ldquo;My doctor never mentioned it as part of my treatment\u0026rdquo; (34%) and \u0026ldquo;I do not know\u0026rdquo; (29%). Other reasons included, \u0026ldquo;Mutational testing did not apply in my case (i.e., low risk, metastatic) (17%), \u0026ldquo;Not enough tissue\u0026rdquo; (9%), \u0026ldquo;Cost/insurance\u0026rdquo; (9%) and \u0026ldquo;My doctor mentioned it but said that I did not need it\u0026rdquo; (7%).\u003cins cite=\"mailto:Maeven%20Luedke\" datetime=\"2021-10-26T16:28\"\u003e\u0026nbsp;\u003c/ins\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment Changes Based on Mutational Testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; One of the most important findings in this study was that for 58 of the patients (24.5%), treatment was changed based on the results of the mutational test (Supplemental Table 1-question 20, Figure 4A). These treatment changes included (Figure 4B), stopped treatment (n = 14, 24%), switched treatment (n = 10, 17%), increased dosage of current treatment (n = 6, 10%) and other (n = 28, 48%). A post hoc analysis of the free text answers from the 28 \u0026ldquo;Other\u0026rdquo; responses (Figure 4C) \u0026nbsp;found that treatment was started for 7 patients (25%) after test confirmed results, 7 patients (25%) declined TKI treatment due to mutation type, 6 patients (21%) switched treatment, two patients stopped treatment, two opted for TKI versus surgery, two opted for surgery versus TKI, one patient\u0026rsquo;s treatment did not change and one patient\u0026rsquo;s diagnosis was changed from GIST to a different sarcoma (also changing treatment).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eA key finding of this study was the critical role that doctors play in whether or not a patient receives a mutational test. When asked the reason behind why mutational testing was done in their case, 54% of patients reported it was due to the doctor ordering the test or suggesting it be done (Fig.\u0026nbsp;2), the response with the greatest percentage. This is important because it suggests that reaching out to doctors may have an effect on increasing rates of mutational testing. This is underscored by \u0026ldquo;My doctor never mentioned it as part of my treatment\u0026rdquo; being the leading reason (34%) given for why mutational testing was not performed (Fig.\u0026nbsp;3). Apart from doctors, the next two leading responses for \u0026ldquo;Why a mutational testing was done?\u0026rdquo; was that the Life Raft Group suggested having the test done (25%) or the patient asked the doctor themselves (22%) (Fig.\u0026nbsp;2). This underscores the need for a multi-level approach; in addition to targeting doctors, reaching out to advocacy groups and patients directly may have a beneficial effect as well. Again, this is confirmed by \u0026ldquo;I do not know\u0026rdquo; being the second highest reason (29%) (Fig.\u0026nbsp;3) given as to why a test was not performed, illustrating that an informed patient and/or advocacy group has the power to get a test done, and that an uninformed patient is less likely to succeed in doing so.\u003c/p\u003e \u003cp\u003eWhile increasing the rate of testing is a worthwhile goal, of more importance is the impact it has on patient outcomes. As mentioned in the previous section, the performance of this test was often quite meaningful in terms of the patient\u0026rsquo;s treatment. In 25% of the cases, the patient\u0026rsquo;s treatment was changed based on the results of the mutational testing (Fig.\u0026nbsp;4A). Even in cases where treatment was not changed, an imatinib-sensitive mutation was often confirmed, offering the GIST patient comfort in an optimized treatment plan. These are both extremely important findings, as it helps ensure that patients are being matched with the proper treatment, which should lead to better outcomes, and in some cases preventing them from taking ineffective treatments, thus avoiding potentially harmful (and unnecessary) side effects. In addition, studies have shown that receiving early mutational testing has a positive economic impact, as it leads to a more specific prognosis by incorporating the right treatment plan and eliminating avoidable expenses\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Mutational testing is a cost-effective approach compared with empirical treatment with imatinib\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study, like all studies, was of course not without its limitations. The Life Raft Group membership has a higher rate of mutational testing than in the general population, and also tends to be seen in both local centers and in larger institutions. Patients in this survey had a much higher rate of mutational testing than in the general GIST population\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, which was 26.7% of patients diagnosed between 2010\u0026ndash;2015 in a report of 3888 GIST patients from the Surveillance, Epidemiology, and End Results (SEER) database\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Due to these factors, there is an inherent bias in our study population. Only 20% of the respondents did not receive a mutational test (Fig.\u0026nbsp;3), which is somewhat unrepresentative of the general population, particularly in the United States (which were 78% of respondents, Fig.\u0026nbsp;1). In addition, there was extensive crossover of patients between local doctors and larger centers, so it is not possible to determine a difference in how patients are treated by a local oncologist versus a larger center/GIST expert center.\u003c/p\u003e \u003cp\u003eGiven these limitations, it is reasonable to conclude from this study that both doctors and patients/advocacy groups have a role to play in determining whether a patient receives a mutational test, and if the desire is to increase the rate of testing, then focusing on outreach to these groups could prove beneficial. Also, having looked at responses, it is reasonable to state that mutational testing can have a beneficial role in a patient\u0026rsquo;s treatment, by either helping reinforce that the selected treatment is the correct one or suggesting a different treatment based on their mutational results, either of which should lead to more favorable patient outcomes. Based on these findings, the recommendation of the authors is to further increase outreach to the aforementioned groups as soon as possible in order to accelerate testing rates and thus allow patients to benefit from these more favorable outcomes.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, mutational testing plays an important role in patients\u0026rsquo; treatment. The LRG membership is voluntary and proactive; patients who join are more likely to have an LRG recommended GIST specialist and mutational testing. This shows the role doctors and patient advocacy groups can play in helping increase the rate of mutational testing in GIST patients, which is important because it can positively affect the longevity and quality of life by ensuring that patients are on the proper treatment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCAP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCollege of American Pathologists\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eESMO\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Society for Medical Oncology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eEURACAN\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Reference on Rare Adult Solid Cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGIST\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGastrointestinal Stromal Tumors\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eLRG\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThe Life Raft Group\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNCCN\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Comprehensive Cancer Network\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNORD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Organization for Rare Disorders\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSDH\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSuccinate dehydrogenase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSEER\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSurveillance, Epidemiology, and End Results\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTKIs\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTyrosine kinase inhibitors\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eOS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOverall survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll methods in this analysis were conducted in accordance with all relevant guidelines and regulations.\u0026nbsp;The Institutional review board of Advarra, Inc based in Columbia, MD (Protocol ID #: LRG2013PR112) approved the study and allows us to do research based on the data we obtain.\u0026nbsp;We have informed consent that LRG Registry members have signed. In addition, as a patient advocacy organization that considers the rights of the patient fundamental to its mission, our project, along with all of the other activities of the Life Raft Group, aligns with the Declaration of Helsinki, specifically where it states that the investigator\u0026rsquo;s duty is solely to the patient, where the subject\u0026rsquo;s welfare shall always take precedence, especially in areas of ethical consideration, and the analysis is conducted by suitably trained investigators with knowledge of the relevant scientific background and using approved protocols subject to independent ethical review (by our aforementioned IRB). Our IRB is responsible for overall review of our patient registry, from which is the source data for many of our studies. Specific ethics approval is not required for this study, as it is secondary analysis of survey data. Through Advarra, Inc, there is overall ethics approval is in place for the overall research program.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContact the corresponding author for the datasets and other materials used in the survey study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflict of interest reported by authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFunding for this study was provided by Pfizer Inc. \u0026nbsp;Distribution of funding went towards the software survey program and staff time in design of survey, collection of survey data, writing, and editing of this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization \u0026amp; Methodology: Denisse Montoya; Formal Analysis: Denisse Montoya, Jerry Call, Jennily Eshak, Maeven Luedke; Data Collection: Denisse Montoya, Jennily Eshak, Sahibjeet Kaur; Data Curation: Denisse Montoya; Writing: Jerry Call, Denisse Montoya, Pete Knox, Maeven Luedke; Review \u0026amp; Editing: all authors; Funding Acquisition: Sara Rothschild.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all patients and caregivers who participated in this survey and Pfizer Pharmaceuticals for providing financial support for the study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Burkill, G. J. C. et al. Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread . Radiology 226, 527\u0026ndash;532 (2003).\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Nilsson, B. et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden. Cancer 103, 821\u0026ndash;829 (2005).\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Demetri, G. D. et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. New Engl J Med 347, (2002).\u003c/p\u003e\n\u003cp\u003e4.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Brčić I, Argyropoulos A, Liegl-Atzwanger B. Update on Molecular Genetics of Gastrointestinal Stromal Tumors. Diagnostics. 2021 Jan 28;11(2):194.\u003c/p\u003e\n\u003cp\u003e5.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Corless, C. L., Barnett, C. M. \u0026amp; Heinrich, M. C. Gastrointestinal stromal tumours: origin and molecular oncology. Nature Reviews. Cancer (2011) doi:10.1038/nrc3143.\u003c/p\u003e\n\u003cp\u003e6. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Corless, C. L. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to Imatinib. J Clin Oncol 23, 5357\u0026ndash;5364 (2005).\u003c/p\u003e\n\u003cp\u003e7. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;National Comprehensive Cancer Network. Gastrointestinal Stromal Tumors (GIST) (Version 1.2021) [Internet]. NCCN. 2020 [cited 2021Oct27]. Available from: https://www.nccn.org/guidelines/category_1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e8.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;George, S. et al. Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFollowing at Least 3 Prior Lines of Therapy. The Oncologist . ( 2021) Jan 16. doi: 10.1002/onco.13674.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e9.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Settas, N., Faucz, F. R. \u0026amp; Stratakis, C. A. Succinate dehydrogenase (SDH) deficiency, Carney triad and the epigenome. Mol. Cell. Endocrinol. (2017) doi:10.1016/j.mce.2017.07.018.\u003c/p\u003e\n\u003cp\u003e10.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Stratakis, C. A. \u0026amp; Carney, J. A. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med 266, 43\u0026ndash;52 (2009).\u003c/p\u003e\n\u003cp\u003e11.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Agaram, N. P. et al. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromosomes Cancer 47, 853\u0026ndash;859 (2008).\u003c/p\u003e\n\u003cp\u003e12.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Alkhuziem, M., Burgoyne, A. M., Fanta, P. T., Tang, C.-M. \u0026amp; Sicklick, J. K. The Call of \u0026ldquo;The Wild\u0026rdquo;-Type GIST: It\u0026rsquo;s Time for Domestication. Journal of the National Comprehensive Cancer Network 15, 551\u0026ndash;554 (2017).\u003c/p\u003e\n\u003cp\u003e13.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Heinrich, M. C. et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J. Clin. Oncol 24, 4764\u0026ndash;4774 (2006).\u003c/p\u003e\n\u003cp\u003e14.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Heinrich, M. C. et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J. Clin. Oncol 26, 5352\u0026ndash;5359 (2008).\u003c/p\u003e\n\u003cp\u003e15.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Lostes-Bardaji, M. J., Garc\u0026iacute;a-Illescas, D., Valverde, C. \u0026amp; Serrano, C. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward. Ther Adv Med Oncol 13, (2021).\u003c/p\u003e\n\u003cp\u003e16.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Florindez, J. \u0026amp; Trent, J. Low Frequency of Mutation Testing in the United States: An Analysis of 3866 GIST Patients. Am. J. Clin. Oncol. 43, 270\u0026ndash;278 (2020).\u003c/p\u003e\n\u003cp\u003e17. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Judson I, Bulusu R, Seddon B, Dangoor A, Wong N, Mudan S. UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST). Clinical Sarcoma Research. 2017;7(1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e18. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Casali PG, Abecassis N, Bauer S, Biagini R, Bielack S, Bonvalot S, et al. Gastrointestinal stromal tumours: ESMO\u0026ndash;EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2018Oct1;29:iv68\u0026ndash;iv78.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e19.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Sch\u0026ouml;ffski P, Wozniak A, Sch\u0026ouml;ffski O, van Eycken L, Debiec-Rychter M. Overcoming cost implications of mutational analysis in patients with gastrointestinal stromal tumors: A pragmatic approach. Oncology Research and Treatment. 2016Dec;39(12):811\u0026ndash;6.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e20. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Banerjee S, Kumar A, Lopez N, Zhao B, Tang C-M, Yebra M, et al. Cost-effectiveness analysis of genetic testing and tailored first-line therapy for patients with metastatic gastrointestinal stromal tumors. JAMA Network Open. 2020;3(9).\u0026nbsp;\u003c/p\u003e"},{"header":"Tables","content":"\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1 - Facilities where patients received their GIST diagnosis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLarge hospital or Academic Institution (Teaching hospital with an affiliated medical university)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e55%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLocal hospital (small-medium sized hospital)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e36%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrivate local doctor/physician or non-hospital based diagnostic center\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"612\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2 - Why was mutational testing done?\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eMy doctor ordered/suggested I have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003e(blank)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI asked my doctor to have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eThe Life Raft Group advised/suggested I have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI asked my doctor to have it done, The Life Raft Group advised/suggested I have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eThe life raft group advised/ suggested I have it done/ Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI had it done as part of a clinical trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eMy doctor ordered/suggested I have it done, I asked my doctor to have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eMy doctor ordered/suggested I have it done, I asked my doctor to have it done, The Life Raft Group advised/suggested I have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eMy doctor ordered/suggested I have it done, Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI am not sure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eMy doctor ordered/suggested I have it done, The Life Raft Group advised/suggested I have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI had it done as part of a clinical trial, My doctor ordered/ suggested I have it done; The Life Raft Group advised / suggested I have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI had it done as part of a clinical trial, Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eThe life raft group advised/ suggested I have it done/ I am not sure\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI had it done as part of a clinical trial, My doctor ordered/suggested I have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI had it done as part of a clinical trial, The Life Raft Group advised/suggested I have it done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI am not sure, Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eI asked my doctor to have it done, The Life Raft Group advised/suggested I have it done, Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003eMy doctor ordered/suggested I have it done, The Life Raft Group advised/suggested I have it done, Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"91.17647058823529%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.823529411764707%\"\u003e\n \u003cp\u003e\u003cstrong\u003e295\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Gastrointestinal Stomal Tumors, GIST, Mutational testing, Biomarker testing, Survey","lastPublishedDoi":"10.21203/rs.3.rs-737437/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-737437/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e\tDue to the low mutational testing rate in patients with Gastrointestinal Stromal Tumors (GIST), The Life Raft Group (LRG), a non-profit organization that provides support, advocacy, and conducts research for patients with GIST, analyzed various factors that may have an impact on patients’ ability to receive mutational testing. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003e\u003c/p\u003e\u003cp\u003e\tA survey about mutational testing for patients with GIST, or their caregivers, was conducted in June 2020. The survey, sent to 1004 GIST patients and caregivers through email, was promoted through social media with instructions to contact the LRG to participate. The survey was designed by the LRG Patient Registry Department. Members of the LRG, regardless of Patient Registry status, were eligible to participate. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e\tA total of 295 patients/caregivers participated in this study (response rate: 29.4%). The percentage of patients who indicated they had received mutational testing was much higher in this survey (80%) than in the general GIST community (26.7%). \u003c/p\u003e\u003cp\u003eSeveral reasons were cited for having a test, including: “My doctor ordered/suggested that I have it done” (54%); “The Life Raft Group advised/suggested I have it done” (25%); “I asked my doctor to have it done” (22%); “I had it done as part of a clinical trial” (5%); “I am not sure” (3%) and “Other” (14%). Mutational testing resulted in a treatment change in 25% of cases. Patients were able to select more than one option when completing this question resulting in a percentage greater than 100.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e\tThe LRG membership is voluntary and proactive; patients who join are more likely to participate in surveys and mutational testing, as well has more likely to have a GIST specialist. Mutational testing can influence understanding a patient’s GIST and the treatment best suited to each case. These are extremely important findings, as it helps ensure that patients are on the proper treatment, which should lead to better outcomes.\u003c/p\u003e","manuscriptTitle":"Barriers to Mutational Testing in Patients with Gastrointestinal Stromal Tumors (GIST) – A Survey of Life Raft Group Members","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2022-06-03 18:53:48","doi":"10.21203/rs.3.rs-737437/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-07-06T06:26:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-07-05T09:31:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-06-21T18:38:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3137df30-284e-48b6-8fc1-835fd178acc7","date":"2022-06-09T19:28:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3ee6f520-dede-4973-bf19-39752854e137","date":"2022-06-09T17:24:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-06-09T17:12:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-06-08T08:01:21+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-05-27T12:05:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-05-27T12:00:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2022-04-13T20:22:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"33cff1bf-f95d-40e6-950c-6ababcac1be5","owner":[],"postedDate":"June 3rd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-10-20T06:29:08+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-03 18:53:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-737437","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-737437","identity":"rs-737437","version":["v2"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}