Dataset Information

Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials.

ABSTRACT:

Background

The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice.

Methods

CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012-2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes.

Results

The median age of the patients was 64 years (range: 13-88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer-related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%).

Conclusion

CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with "pan-negative" lung AD who may benefit from enrollment in mechanism-driven clinical trials.

Implications for practice

National Comprehensive Cancer Network guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma (AD) without GAs. Of patients with NSCLC, 71% harbored at least one GA to a gene listed in the guidelines or KRAS; 273 cancer-related genes were altered in at least 0.1% of the AD cases. Although logistical and administrative hurdles limit the widespread use of next-generation sequencing, the data confirm the feasibility and potential utility of comprehensive genomic profiling in clinical practice.

SUBMITTER: Suh JH

PROVIDER: S-EPMC4912374 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials.

Suh James H JH Johnson Adrienne A Albacker Lee L Wang Kai K Chmielecki Juliann J Frampton Garrett G Gay Laurie L Elvin Julia A JA Vergilio Jo-Anne JA Ali Siraj S Miller Vincent A VA Stephens Philip J PJ Ross Jeffrey S JS

The oncologist 20160505 6

<h4>Background</h4>The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice.<h4>Methods</h4>CGP was performed to a mean coverage depth of 576× on ...[more]

PMID: 27151654

Similar Datasets

Project description:Background:Despite recent international efforts to develop resource-stratified clinical practice guidelines for cancer, there has been little research to evaluate the best strategies for dissemination and implementation in low- and middle-income countries (LMICs). Guideline publication alone is insufficient. Extensive research has shown that structured, multifaceted implementation strategies that target barriers to guideline use are most likely to improve adherence; however, most of this research has been conducted in high-income countries. There is a pressing need to develop and evaluate guideline implementation strategies for cancer management in LMICs in order to address stark disparities in cancer outcomes. Methods:In preparation for the launch of Tanzania's first National Cancer Treatment Guidelines, we developed a theory-driven implementation strategy for guideline-based practice at Ocean Road Cancer Institute (ORCI). Here, we use the Intervention Mapping framework to provide a detailed stepwise description of our process. First, we conducted a needs assessment to identify barriers and facilitators to guideline-based practice at ORCI. Second, we defined both proximal and performance objectives for our implementation strategy. Third, we used the Capability, Opportunity, Motivation and Behavior/Behavior Change Wheel (COM-B/BCW) framework to categorize the barriers and facilitators, choose behavior change techniques most likely to overcome targeted barriers and leverage facilitators, and select a feasible mode of delivery for each technique. Fourth, we organized these modes of delivery into a phased implementation strategy. Fifth, we operationalized each component of the strategy. Sixth, we identified the indicators of the process, outcome, and impact of our intervention and developed an evaluation plan to measure them using a mixed methods approach. Discussion:We developed a robust, multifaceted guideline implementation strategy derived from a prominent behavior change theory for use in Tanzania. The barriers and strategies we generated are consistent with those well established in the literature, enhancing the validity and generalizability of our process and results. Through our rigorous evaluation plan and systematic account of modifications and adaptations, we will characterize the transferability of "proven" guideline implementation strategies to LMICs. We hope that by describing our process in detail, others may endeavor to replicate it, meeting a widespread need for dedicated efforts to implement cancer guidelines in LMICs.

Project description:ObjectiveTo evaluate the implementation of National Institute for Health and Care Excellence antenatal hypertension guidelines, to identify strategies to reduce incidences of severe hypertension and associated maternal and perinatal morbidity and mortality in pregnant women with chronic hypertension.MethodsWe used a multiple method multisite approach to establish implementation of guidelines and the associated barriers and facilitators. We used a national survey of healthcare professionals (n=97), case notes review (n=55) and structured observations (n=42) to assess implementation. The barriers and facilitators to implementation were identified from semistructured qualitative interviews with healthcare professionals (n=13) and pregnant women (n=18) using inductive thematic analysis. The findings were integrated and evaluated using the Consolidated Framework for Implementation Research.Setting and participantsPregnant women with chronic hypertension and their principal carers (obstetricians, midwives and physicians), at three National Health Service hospital trusts with different models of care.ResultsWe found severe hypertension to be prevalent (46% of case notes reviewed) and target blood pressure practices to be suboptimal (56% of women had an antenatal blood pressure target documented). Women were infrequently given information (52%) or offered choice (19%) regarding antihypertensives. Women (14/18) reported internal conflict in taking antihypertensives and non-adherence was prevalent (8/18). Women who were concordant with treatment recommendations described having mutual trust with professionals mediated through appropriate information, side effect management and involvement in decision making. Professionals reported needing updates and tools for target blood pressure setting and shared decision making underpinned by antihypertensive safety and effectiveness research.ConclusionsWomen's non-adherence to antihypertensives is higher than anticipated. Suboptimal information provision around treatment, choice of antihypertensives and target setting practices by healthcare professionals may be contributory. Understanding the reasons for non-adherence will inform education and decision-making strategies needed to address both clinician and women's behaviour. Further research into the effectiveness and long-term safety of common antihypertensives is also required.

Project description:Purpose The National Comprehensive Cancer Network (NCCN) clinical guidelines influence medical practice, payor coverage, and standards of care. The levels of evidence underlying radiation therapy recommendations in NCCN have not been systematically explored. Herein, we aim to systematically investigate the NCCN recommendations pertaining to the categories of consensus and evidence (CE) for radiation therapy. Methods and Materials We evaluated the distribution of CE underlying current treatment recommendations for the 20 most prevalent cancers in the United States with at least 10 radiation therapy recommendations in the NCCN clinical guidelines. For context, the distribution of evidence in the radiation therapy guidelines was compared with that of systemic therapy using a χ2 test. The proportion of category I CE between radiation and systemic therapy was compared using a 2-proportion, 2-tailed z-test in total and for each disease site. A P value of < .05 was considered significant. Results Among all radiation therapy recommendations, the proportions of category I, IIA, IIB, and III CE were 9.7%, 80.6%, 8.4%, and 1.3%, respectively. When analyzed by disease site, cervix and breast cancer had the highest portion of category I CE (33% and 31%, respectively). There was no radiation therapy category I CE for hepatobiliary, bone, pancreatic, melanoma, and uterine cancers. There was a significant difference in the distribution of CE between the systemic therapy recommendations and the radiation therapy recommendations (χ2 statistic 64.16, P < .001). Overall, there was a significantly higher proportion of category I CE in the systemic therapy recommendations compared with the radiation therapy recommendations (12.3% vs 9.7%, P = .043). Conclusions Only 9.7% of radiation therapy recommendations in NCCN guidelines are category I CE. The highest levels of evidence for radiation therapy are in breast and cervical cancers. Despite major advances in the field, these data underline that the majority of NCCN radiation therapy recommendations are based on uniform expert opinion and not on higher level evidence.

Project description:PURPOSE:Engaging in positive health behaviors post-treatment is important for cancer survivors' health. However, little is known about whether survivors are practicing health promoting behaviors. We aimed to explore whether survivors are meeting the recent health behavior guidelines set forth by the National Comprehensive Cancer Network (NCCN) and to examine associations between health behaviors and distress. METHODS:Sixty-six survivors completed a cross-sectional questionnaire assessing health behaviors prior to an initial appointment at a survivorship care clinic. Information about sociodemographic, clinical, and psychosocial variables and six health behavior recommendations, including physical activity, sunscreen use, tobacco use, alcohol consumption, weight management, and annual primary care provider visits, was collected. FINDINGS:Only 7.6% of survivors met all six NCCN health behavior guidelines. One in ten (10.6%) survivors had smoked a cigarette in the previous 30 days, and half did not use sunscreen regularly (50%), had an unhealthy body mass index (53%), and did not engage in >10 MET-h/week of physical activity (50%). Approximately 1 in 6 (15.1%) survivors reported drinking beyond the recommended limit, and a similar proportion had not seen a PCP in the previous year (27.3%). Clinically significant levels of distress (>5; range 0-10) on the NCCN distress scale were reported by 64.6% of survivors. Participants with clinical levels of distress were less likely to adhere to health behavior guidelines than those who were not distressed (p = .002). CONCLUSIONS:Overall, survivors engaged at a survivorship clinic did not meet the NCCN recommended health behavior guidelines. Implications for Psychosocial Providers or Policy: Survivors' health behaviors and distress should be assessed and intervened upon during survivorship care. Survivorship clinics may provide a unique forum in which to provide ongoing behavioral health counseling and psychosocial support for these patients.

Project description:OBJECTIVE:To evaluate the association of sociodemographic and hospital characteristics with adherence to National Comprehensive Cancer Network treatment guidelines for stage IB-IIA cervical cancer and to analyze the relationship between adherent care and survival. METHODS:This is a retrospective population-based cohort study of patients with stage IB-IIA invasive cervical cancer reported to the California Cancer Registry from January 1, 1995, through December 31, 2009. Adherence to National Comprehensive Cancer Network guideline care was defined by year- and stage-appropriate surgical procedures, radiation, and chemotherapy. Multivariate logistic regression, Kaplan-Meier estimate, and Cox proportional hazard models were used to examine associations between patient, tumor, and treatment characteristics and National Comprehensive Cancer Network guideline adherence and cervical cancer-specific 5-year survival. RESULTS:A total of 6,063 patients were identified. Forty-seven percent received National Comprehensive Cancer Network guideline-adherent care, and 18.8% were treated in high-volume centers (20 or more patients/year). On multivariate analysis, lowest socioeconomic status (adjusted odds ratio [OR] 0.69, 95% CI 0.57-0.84), low-middle socioeconomic status (adjusted OR 0.76, 95% CI 0.64-0.92), and Charlson-Deyo comorbidity score 1 or higher (adjusted OR 0.78, 95% CI 0.69-0.89) were patient characteristics associated with receipt of nonguideline care. Receiving adherent care was less common in low-volume centers (45.9%) than in high-volume centers (50.9%) (effect size 0.90, 95% CI 0.84-0.96). Death from cervical cancer was more common in the nonadherent group (13.3%) than in the adherent group (8.6%) (effect size 1.55, 95% CI 1.34-1.80). Black race (adjusted hazard ratio 1.56, 95% CI 1.08-2.27), Medicaid payer status (adjusted hazard ratio 1.47, 95% CI 1.15-1.87), and Charlson-Deyo comorbidity score 1 or higher (adjusted hazard ratio 2.07, 95% CI 1.68-2.56) were all associated with increased risk of dying from cervical cancer. CONCLUSION:Among patients with early-stage cervical cancer, National Comprehensive Cancer Network guideline-nonadherent care was independently associated with increased cervical cancer-specific mortality along with black race and Medicaid payer status. Nonadherence was more prevalent in patients with older age, lower socioeconomic status, and receipt of care in low-volume centers. Attention should be paid to increase guideline adherence.

Project description:This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Significantly new data have been published on laryngeal cancer management since the last edition of the guidelines. This paper discusses the evidence base pertaining to the management of laryngeal cancer and provides updated recommendations on management for this group of patients receiving cancer care. Recommendations • Radiotherapy (RT) and transoral laser microsurgery (TLM) are accepted treatment options for T1a-T2a glottic carcinoma. (R) • Open partial surgery may have a role in the management of selected tumours. (R) • Radiotherapy, TLM and transoral robotic surgery are reasonable treatment options for T1-T2 supraglottic carcinoma. (R) • Supraglottic laryngectomy may have a role in the management of selected tumours. (R) • Most patients with T2b-T3 glottic cancers are suitable for non-surgical larynx preservation therapies. (R) • Concurrent chemoradiotherapy should be regarded as the standard of care for non-surgical management. (R) • Subject to the availability of appropriate surgical expertise and multi-disciplinary rehabilitation services, TLM or open partial surgical procedures ± post-operative RT, may be also be appropriate in selected cases. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to at least lymph node levels II, III and IV bilaterally. In node positive disease, it is recommended that lymph node levels II-V should be treated on the involved side. If level II nodes are involved, then elective irradiation of ipsilateral level Ib nodes may be considered. (R) • Most patients with T3 supraglottic cancers are suitable for non-surgical larynx preservation therapies. (R) • Concurrent chemoradiotherapy should be regarded as the standard of care for non-surgical management. (R) • Subject to the availability of appropriate surgical expertise and multi-disciplinary rehabilitation services, TLM or open partial surgical procedures ± post-operative RT, may also be appropriate in selected cases. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to at least lymph node levels II, III and IV bilaterally. In node positive disease, lymph node levels II-V should be treated on the involved side. (R) • As per the PET-Neck clinical trial, patients with N2 or N3 neck disease who undergo treatment with chemoradiotherapy to their laryngeal primary and experience a complete response with a subsequent negative post-treatment positron emission tomography combined with computed tomography (PET-CT) scan do not require an elective neck dissection. In contrast, patients who have a partial response to treatment or have increased uptake on a post-treatment PET-CT scan should have a neck dissection. (R) • Larynx preservation with concurrent chemoradiotherapy should be considered for T4 tumours, unless there is tumour invasion through cartilage into the soft tissues of the neck, in which case total laryngectomy yields better outcomes. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to bilateral lymph node levels II, III, IV, V and VI. (R).

Dataset Information

Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials.

Background

Methods

Results

Conclusion

Implications for practice

Publications

Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure