Targetable mutations in gastrointestinal malignancies: A comparison of RAS mutant and RAS wild type tumors.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 129-129
Author(s):  
Jamie Randall ◽  
Hongkun Wang ◽  
Sheryl Krevsky Elkin ◽  
Gail Payne ◽  
Sarah Mullaly ◽  
...  
Keyword(s):  
Stage Iv ◽  
Predictive Biomarker ◽  
Tumor Board ◽  
Driver Mutations ◽  
P Value ◽  
Molecular Testing ◽  
Wild Type ◽  
Level Of Evidence ◽  
Gastrointestinal Malignancies ◽  
Molecular Tumor Board

129 Background: KRAS and NRAS (RAS) mutations are considered driver mutations in gastrointestinal malignancies such as colorectal and pancreatic cancer. Our institution obtains broad molecular testing (commercial panels with full exon coverage of at least 300 genes) for all stage IV gastrointestinal malignancies that are reviewed at an internal molecular tumor board (MTB). The MTB subjectively felt there was less benefit from comprehensive molecular testing in RAS mutant tumors and wished to quantify this using standardized analysis according to validated guidelines. Methods: We performed a retrospective cohort study of 209 consecutive genomic sequencing results of advanced gastrointestinal malignancies at our institution dating from March 2016 until December 2019. We compared the number of “targetable” mutations in the RAS mutant and wild type (WT) malignancies, as analyzed by an interpretation service according to the Association of Molecular Pathology (AMP) guidelines. A lower AMP score corresponds to a higher level of evidence as a predictive biomarker. We also compared molecular tumor board specific recommendations for each group (excluding recommendations regarding RAS such as EGFR mAbs). Results: There were 134 RAS mutant and 75 RAS WT cases. Alterations with AMP scores of 1A,1B, and 1C were more commonly seen in the RAS WT population 18/75 and 9/134 respectively (24.0% versus 6.7% p-value=0.0004). 39 of 75 cases in RAS WT and 27/134 in RAS mutant (52.0 versus 20.1%, p-value <0.0001) cohort had at least one alteration that was deemed actionable by our institution’s current MTB criteria. Conclusions: Actionable mutations were significantly less common in the RAS mutant versus RAS WT population, and further studies assessing the value of comprehensive genomic testing in RAS mutant gastrointestinal malignancies may be warranted. [Table: see text]

Impact of molecular tumor board on late-stage gastrointestinal malignancies at a tertiary center.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 483-483
Author(s):  
Timothy Lewis Cannon ◽  
Jo-Ellen Murphy ◽  
Jennifer Carter ◽  
Donald L. Trump ◽  
Sheryl Krevsky Elkin ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Disease Stage ◽  
Tumor Board ◽  
Molecular Testing ◽  
Tier 2 ◽  
Gastrointestinal Malignancies ◽  
Tier 1 ◽  
Molecular Tumor Board ◽  
Recommended Therapy ◽  
Guided Therapy

483 Background: Inova Schar Cancer Institute formed a molecular tumor board in early 2016 to identify treatment options for patients with gastrointestinal malignances based on molecular testing and to track outcomes. Methods: From March 2016 to June 2017, 78 patients with advanced gastrointestinal malignancies were presented at our molecular tumor board. The most common mutations, the percentage of patients who received targeted therapies, responded to targeted therapies, died or went on hospice prior to receiving a recommended therapy, and had an available Association of Molecular Pathology Tier 1 or Tier 2 recommendation available were reviewed retrospectively. We also compared the overall survival of patients who received a new treatment after MTB compared to those who did not. N-of-One, Inc. provided curation of molecular testing and participated in the MTB. Results: 78 patients with gastrointestinal cancers were presented between March 2016 and June 2017. Thirteen (19%) patients received targeted therapy and 31% had partial response, 15% had Stable Disease, and 54% had progression of disease. 12 patients (15%) died or went on hospice before recommendations could start and 11 patients (14%) are waiting to start recommended therapy. 38 (49%) patients did not have a mutation that prompted a MTB recommendation. Median OS of the 33 patients who started a new therapy (including chemotherapy or unrelated clinical trials) after MTB was 15.3 months vs. 11.5 months in 40 patients who continued current therapy (P = 0.016 Wilcoxon). The three most common mutations detected were TP53, KRAS, and APC. The majority of cases had more than one variant. 18% of cases had a variant classified as Tier 1; 74% of cases had a variant with the highest AMP classification of Tier 2. Conclusions: The majority of patients with Gastrointestinal malignancies presented to the Inova MTB had a finding that supported a molecularly-guided therapy, with a small but meaningful number of partial responses. Barriers to the use of molecular guided therapy included molecular testing and presentation at a late disease stage, and alternative chemotherapeutic options.

hSRBC promoter CpG island hypermethylation as resistant predictive biomarker of oxaliplatin based chemotherapy in metastasic colorectal cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14609-e14609
Author(s):  
Catia Moutinho ◽  
Anna Martinez-Cardus ◽  
Cristina Santos ◽  
Valentín Navarro-Perez ◽  
Eva Martinez-Balibrea ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cpg Island ◽  
Methylation Status ◽  
Stage Iv ◽  
Predictive Biomarker ◽  
Promoter Hypermethylation ◽  
Chemotherapeutic Agents ◽  
P Value ◽  
Potential Biomarker

e14609 Background: Resistance acquisition to chemotherapeutic agents is one of the main problems that come up during cancer treatment. hSRBC is a tumor suppressor gene whose inactivation has been associated with malignant tumor progression. In a previous work, we investigated the influence of hSRBC promoter methylation alterations in oxaliplatin (OXA) resistance acquisition by using a CRC “in vitro” model, detecting an hSRBC promoter hypermethylation in OXA–resistant derived cells when compared with the sensitive counterpart. These results were validated by functional analyses in the same model. Taking this into account, our aim in the present work is to determine the role of hSRBC methylation status as a potential biomarker of OXA resistance, in metastatic CRC patients, treated at first line with fluouropirimidines plus OXA based chemotherapy. Methods: hSRBC promoter hypermethylation was analyzed in DNA extracted from paraffin embebbed tissue of 111 metastatic CRC tumors by using Methylation Specific PCR. Methylation data was correlated to overall response (OR) and progression free survival (PFS) by using F-Fisher test and Kaplan-Meyer Survival curves respectively. A multivariate analysis was carried out by Cox regression. p-values under 0.05 were considered statistic significant. Results: Two independent cohorts of stage IV CRC tumors were included. Twenty-two out of 111 patients received radical surgery for metastasis, that became to be a positive prognostic factor (p-value = 0.04). Gene hypermethylation was detected in a 33% of cases. Although OR was not associated with hSRBC methylation, we observed a significant correlation between hypermethylation of gene and a worse PFS in patients without metastasis surgery (Log Rank; p-value = 0.04). Conclusions: Remarkably, hSRBC promoter hypermethylation is associated with worse PFS in metastatic CRC patients. We suggest hSRBC methylation status as a predictive biomarker of OXA-based treatment outcome in metastatic CRC patients. However, further studies are warranted in order to elucidate the clinical application of these findings.

scholarly journals A virtual molecular tumor board to improve efficiency and scalability of delivering precision oncology to physicians and their patients

JAMIA Open ◽  
2019 ◽  
Vol 2 (4) ◽  
pp. 505-515 ◽  
Author(s):  
Michael J Pishvaian ◽  
Edik M Blais ◽  
R Joseph Bender ◽  
Shruti Rao ◽  
Simina M Boca ◽  
...  
Keyword(s):  
Treatment Plan ◽  
Critical Role ◽  
Tumor Board ◽  
Care Process ◽  
Molecular Profile ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Therapy Options ◽  
Scoring Model ◽  
Molecular Tumor Board

Abstract Objectives Scalable informatics solutions that provide molecularly tailored treatment recommendations to clinicians are needed to streamline precision oncology in care settings. Materials and Methods We developed a cloud-based virtual molecular tumor board (VMTB) platform that included a knowledgebase, scoring model, rules engine, an asynchronous virtual chat room and a reporting tool that generated a treatment plan for each of the 1725 patients based on their molecular profile, previous treatment history, structured trial eligibility criteria, clinically relevant cancer gene-variant assertions, biomarker-treatment associations, and current treatment guidelines. The VMTB systematically allows clinician users to combine expert-curated data and structured data from clinical charts along with molecular testing data to develop consensus on treatments, especially those that require off-label and clinical trial considerations. Results The VMTB was used as part of the cancer care process for a focused subset of 1725 patients referred by advocacy organizations wherein resultant personalized reports were successfully delivered to treating oncologists. Median turnaround time from data receipt to report delivery decreased from 14 days to 4 days over 4 years while the volume of cases increased nearly 2-fold each year. Using a novel scoring model for ranking therapy options, oncologists chose to implement the VMTB-derived therapies over others, except when pursuing immunotherapy options without molecular support. Discussion VMTBs will play an increasingly critical role in precision oncology as the compendium of biomarkers and associated therapy options available to a patient continues to expand. Conclusion Further development of such clinical augmentation tools that systematically combine patient-derived molecular data, real-world evidence from electronic health records and expert curated knowledgebases on biomarkers with computational tools for ranking best treatments can support care pathways at point of care.

Implementation and impact of the first two years of a systemwide molecular tumor board at Henry Ford Health System (HFHS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19266-e19266
Author(s):  
Igor I. Rybkin ◽  
Nadia Z Haque ◽  
Kristen Collins ◽  
Louisa Laidlaw ◽  
Tom Mikkelsen
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Performance Status ◽  
Tumor Board ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Ecog Performance Status ◽  
Off Label ◽  
Molecular Tumor Board ◽  
The Impact

e19266 Background: HFHS implemented clinically-oriented Precision Medicine Program (PMP) in 2016. As part of the program, multidisciplinary molecular tumor board (MTB) was created to review complex molecular cases, providing guidance to treating medical oncologist in selecting targeted therapies and clinical trials. In some cases MTB recommended genetic counseling or recommended against/for additional molecular testing. MTB consists of oncologists, molecular pathologists, clinical trial staff, and genetic counselors. MTB was designed as teaching platform engaging hematology-oncology fellows into cases analysis and presentation. Here we present preliminary analysis of the impact of the MTB on the HFHS oncology practice. Methods: From 09/08/2017 to 12/31/2019 MTB reviewed 120 cases, 116 cases were used for this analysis. Data was abstracted using Syapse precision oncology platform, MTB recommendation note, electronic medical record (EMR), and molecular test results. Results: Out of 116 pts 83 (72%) were Caucasian, 25 (22%) African American, 4 (3%) Asian, 1 (1%) American Indian. Fifty-two % (n = 21) had an ECOG performance status of 1. Most common primary disease sites were lung (39%, n = 45) brain (12%, n = 15), and hematologic cancers (9%; n = 10), followed by breast (5%, n = 6), prostate (4%, n = 5), colon (3%, n = 4), and others (28%, n = 31). The most common genetic abnormalities discussed were atypical EGFR (n = 15), non-V600 BRAF (n = 10), KRAS (n = 8), BRCA2 (n = 5), NF2 (n = 4), PTEN (n = 4), CSF3R (n = 3), IDH1 (n = 3), TP53 (n = 3), and 29 less common mutations. Thirty five (30%) pts out of 116 total were recommended clinical trials, although only 3 patients (10% of recommended) were enrolled into trials. 31 pts (27%) were recommended off-label therapy, although trials were preferred. 18% of pts (n = 21) were recommended genetics referral, although only 3 have seen Geneticist, with two undergoing germline testing. One pt was discovered to have a germline RET V804M mutation which was originally detected in the cancer. Conclusions: The first two years of data demonstrate the utility of the MTB and provide a basis for ongoing analysis. Through multidisciplinary approach, MTB encourages care coordination and collaboration. MTB resulted in genetics referrals, clinical trial recommendations, and identification of targeted therapy options, including off label. In many cases, MTB recommendations prevented futile therapies and/or additional molecular testing.

Mutational landscape of metastatic colorectal cancer: Aggregate insights from a molecular tumor board.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 837-837
Author(s):  
Mark Andrew Lewis ◽  
Derrick S. Haslem ◽  
Ramya Thota ◽  
Terence Duane Rhodes ◽  
Tyler Barker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Stage Iv ◽  
Tumor Board ◽  
Primary Tumors ◽  
Multiple Metastases ◽  
Molecular Tumor Board ◽  
Generation Sequencing

837 Background: The mutational landscape of metastatic colorectal cancer (CRC) is being elucidated by next-generation sequencing of both primary tumors and metastatic foci. In this study, we examined the results of all stage IV CRC cases submitted to our molecular tumor board (MTB). Methods: We performed a retrospective analysis of all patients who had next-generation sequencing performed between January 2015 and August 2017 on either their primary tumor and/or metastasis. Cases were presented at a MTB convened twice monthly. For the purposes of this study only pathogenic mutations were notated, not variants of unknown significance (VUS). Results: Eighty-seven unique patients had 97 specimens sequenced (28 primary tumors and 69 metastases). The primaries averaged 3 mutations per specimen (range: 1-6) whereas the metastases averaged 4 (range: 1-14, p=.25). The most common anatomic sites of submitted metastatic tissue were the liver (n=35, average mutations=4), followed by the lungs (n=10, average mutations=3) and the omentum/peritoneum (n=8, average mutations=3). Two patients had both a primary tumor and a metastasis sequenced, with a 33% rate of concordance in inter-specimen mutations. Five patients had multiple metastases sequenced, with a 53% rate of concordance in inter-specimen mutations; in every case of longitudinal sequencing, mutational burden increased in metastases over time. The most common mutation was apc (21% of all mutations), followed by p53 (16%) and then kras (13%). Candidacy for EGFR-directed therapy was found in 8 cases, and mismatch repair defects were detected in 5 cases. Conclusions: In stage IV CRC cases sent to our MTB, tissue from metastases was more commonly submitted for analysis than from the primary tumors. There is not necessarily concordance between mutations in primary tumors and metastases, nor among multiple metastases in the same patient. Sequencing at multiple time points in the disease course may allow observation of clonal evolution and dynamic adaptation of therapeutic targets.

scholarly journals Personalized Clinical Decision Making Through Implementation of a Molecular Tumor Board: A German Single-Center Experience

2018 ◽  
pp. 1-16 ◽  
Author(s):  
Rouven Hoefflin ◽  
Anna-Lena Geißler ◽  
Ralph Fritsch ◽  
Rainer Claus ◽  
Julius Wehrle ◽  
...  
Keyword(s):  
Single Agent ◽  
Treatment Recommendations ◽  
Disease Stage ◽  
Tumor Board ◽  
Comprehensive Cancer Center ◽  
Molecular Diagnostic ◽  
Molecular Testing ◽  
Targeted Drugs ◽  
Off Label ◽  
Molecular Tumor Board

Purpose Dramatic advances in our understanding of the molecular pathophysiology of cancer, along with a rapidly expanding portfolio of molecular targeted drugs, have led to a paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report the 2-year experience of the Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one of the first interdisciplinary molecular tumor conferences established in Europe. The role of the MTB is to recommend personalized therapy for patients with cancer beyond standard-of-care treatment. Methods This retrospective case series includes 198 patients discussed from March 2015 through February 2017. The MTB guided individual molecular diagnostics, assessed evidence of actionability of molecular alterations, and provided therapy recommendations, including approved and off-label treatments as well as available matched clinical trials. Results The majority of patients had metastatic solid tumors (73.7%), mostly progressive (77.3%) after a mean of 2.0 lines of standard treatment. Diagnostic recommendations resulted in 867 molecular diagnostic tests for 172 patients (five per case), including exome analysis in 36 cases (18.2%). With a median turnaround time of 28 days, treatment recommendations were given to 104 patients (52.5%). These included single-agent targeted therapies (42.3%), checkpoint inhibitors (37.5%), and combination therapies (18.3%). Treatment recommendations were implemented in 33 of 104 patients (31.7%), of whom 19 (57.6%) showed stable disease or partial response, including 14 patients (7.1% of the entire population) receiving off-label treatments. Conclusion Personalized extended molecular-guided patient care is effective for a small but clinically meaningful proportion of patients in challenging clinical situations. Limited access to targeted drugs, lack of trials, and submission at late disease stage prevents broader applicability, whereas genome-wide analyses are not a strict requirement for predictive molecular testing.

scholarly journals The Prognostic and Predictive Role of Somatic BRCA Mutations in Ovarian Cancer: Results from a Multicenter Cohort Study

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 565
Author(s):  
Angela Toss ◽  
Claudia Piombino ◽  
Elena Tenedini ◽  
Alessandra Bologna ◽  
Elisa Gasparini ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Positive Impact ◽  
Progression Free Survival ◽  
Molecular Testing ◽  
Wild Type ◽  
Brca Mutations ◽  
Multicenter Cohort Study ◽  
Advanced Stages ◽  
Predictive Role

Previous research involving epithelial ovarian cancer patients showed that, compared to germline BRCA (gBRCA) mutations, somatic BRCA (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of BRCA genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.

scholarly journals Making the Most of Complexity to Create Opportunities: Comprehensive Genomic Profiling and Molecular Tumor Board for Patients with Non-Small Cell Lung Cancer (NSCLC)

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 609
Author(s):  
Caterina Fumagalli ◽  
Elena Guerini-Rocco ◽  
Massimo Barberis
Keyword(s):  
Lung Cancer ◽  
Small Cell ◽  
Tumor Board ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Molecular Alterations ◽  
Comprehensive Genomic Profiling ◽  
Molecular Tumor Board ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Personalized cancer therapy matches the plan of treatment with specific molecular alterations [...]

Planning for End of Life

2021 ◽  
pp. 104990912110141
Author(s):  
Natasha Ansari ◽  
Eric Johnson ◽  
Jennifer A. Sinnott ◽  
Sikandar Ansari
Keyword(s):  
End Of Life ◽  
Treatment Options ◽  
Stage Iv ◽  
P Value ◽  
Life Planning ◽  
Number Of Patients ◽  
End Of Life Planning ◽  
The Difference ◽  
Alternative Medications ◽  
Patient’S Perception

Background: Oncology provider discussions of treatment options, outcomes of treatment, and end of life planning are essential to care for patients with advanced malignancies. Studies have shown that despite this, many patients do not have adequate care planning, including end of life planning. It is thought that the accessibility of information outside of clinical encounters and individual factors and/or beliefs may influence the patient’s perception of disease. Aims: The objective of this study was to evaluate if patient understanding of treatment goals matched the provider and if there were areas of discrepancy. If a discrepancy was found, the survey inquired further into more specific aspects. Methods: A questionnaire-based survey was performed at a cancer hospital outpatient clinic. 100 consecutive and consenting patients who had stage IV non-curable lung, gastrointestinal (GI), or other cancer were included in the study. Patients must have had at least 2 visits with their oncologist. Results: 40 patients reported their disease might be curable and 60 reported their disease was not curable. Patients who reported their disease was not curable were more likely to be 65 years or older (P-value: 0.055). They were more likely to report that their doctor discussed the possibility of their cancer getting worse (78.3% VS 55%; P-value 0.024), that their doctor discussed end of life plans (58.3% VS 30%; P- value: 0.01), and that they had appointed a health care decision-maker (86.7% VS 62.5%; P-value: 0.01). 65% of patients who thought their disease might be curable reported that their doctor said it might be curable, compared with only 6.7% of patients who thought their disease was not curable (p < 0.001). Or, equivalently, 35% of patients who thought their disease might be curable reported that their doctor’s opinion was that it was not curable, compared with 93% of patients who thought their disease was not curable (p < 0.001). Patients who had lung cancer were more likely to believe their cancer was not curable than patients with gastrointestinal or other cancer, though the difference was not statistically significant (p = 0.165). Patients who said their disease might be curable selected as possible reasons that a miracle (50%) or alternative medicine (66.7%) would get rid of the cancer, or said their family wanted them to believe the cancer would go away (16.7%) or that another doctor said it would (4.2%). Patients who said their disease might be curable said they did so due to alternative medications, another doctor, or their family. Restricting to the 70 patients who reported their doctors telling them their disease was not curable, 20% of them still said that they personally felt their disease might be curable. Patients below 65 years of age were more likely to disagree with the doctor in this case (P-value: 0.047). Conclusion: This survey of patients diagnosed with stage IV cancer shows that a significant number of patients had misunderstandings of the treatment and curability of their disease. Findings suggest that a notable proportion kept these beliefs even after being told by treating physicians that their disease is not curable.

Müller-Weiss Disease: The Descriptive Factors of Failure Conservative Treatment

2021 ◽  
pp. 107110072110028
Author(s):  
Thos Harnroongroj ◽  
Theerawoot Tharmviboonsri ◽  
Bavornrit Chuckpaiwong
Keyword(s):  
Regression Analysis ◽  
Conservative Treatment ◽  
Demographic Characteristics ◽  
Classification Systems ◽  
Clinical Severity ◽  
P Value ◽  
Level Of Evidence ◽  
Factors Associated ◽  
Radiographic Parameters ◽  
Significant Difference

Background: Conservative treatment is the first-line approach for Müller-Weiss disease (MWD). However, factors associated with the failure of conservative treatment have never been reported. Our objectives were to compare the differences in demographic and radiographic parameters between “successful” and “failure” conservative treatment in patients with MWD and identify descriptive factors associated with failure conservative treatment. Methods: We retrospectively reviewed 68 patients with MWD divided into 29 “failure” and 39 “successful” conservative treatment groups. Demographic characteristics, Foot and Ankle Outcome Score (FAOS), visual analog scale (VAS) scores for pain and walking disability, and radiographic parameters such as calcaneal pitch, lateral Meary, anteroposterior (AP) Meary angle, and talonavicular-naviculocuneiform arthritis were compared. Logistic regression analysis was performed to identify descriptive factors of failure conservative treatment. A P value <.05 was considered a statistically significant difference. Results: We found more severe VAS pain and walking disability scores and FAOS for the pain, activities of daily living, and quality of life subscales in the failure group ( P < .05). Regression analysis demonstrated 2 significant descriptive factors associated with failure conservative treatment: abducted AP Meary angle >13.0 degrees and radiographic talonavicular arthritis. No demographic characteristics were found to be associated with failure conservative treatment. Conclusion: Midfoot abduction (AP Meary angle, >13 degrees) and radiographic talonavicular arthritis were factors associated with failure conservative treatment in MWD and should be determined concurrently with the clinical severity. Classification systems for MWD should include these factors. Level of evidence: Level III, retrospective comparative study.

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