Virtual Library

Abstract:
Recent advances in personalized medicine and associated companion diagnostic therapeutics have led to an increased utilization of genetic markers in oncology therapy selection. The rapid acceleration of biomarker driven therapy has been widely accepted into clinical guidelines based upon proven clinical utility and unprecedented patient outcomes. Despite these advances, utilization of molecular testing in community oncology practice has been more limited than in academic settings. The Levine Cancer Institute and Carolinas HealthCare System serve a wide variety of oncology patients in both academic and community settings using a multidisciplinary approach. During this session, a discussion of processes used for tissue acquisition and processing, pre-analytics, biomarker testing, and result reporting will be presented. Strategies that have been used in our system to eliminate common roadblocks in the testing process such as tissue stewardship will be discussed. A special emphasis will be given to the discussing the power and pitfalls of common biomarker testing techniques such as real-time PCR companion diagnostic testing, immunohistochemistry, FISH, and next-generation sequencing panels. During the presentation, a significant amount of time will be dedicated to a question and answer session so audience members can address community testing challenges from their local settings. Working to solve these challenges in the community setting will improve the oncology patient journey by increasing access to high quality biomarker testing.

Abstract:
Lung cancer represents the major causes of cancer death in the industrialized countries. Non-small cell lung cancer (NSCLC) accounts for nearly 80% of all lung cancer cases. While in the early stages I and II surgery has been accepted as the major curative therapy, most of patients with NSCLC and major airway and vascular obstruction have an IIIB disease and rarely can be cured by local treatment modalities like surgery or radiotherapy alone. T4 tumors may include the mediastinal organs such as the vena cava, pulmonary artery, thoracic aorta, left atrium, carina and trachea. However the extend of the disease is usually made by radiological methods as computed tomography (CT), magnetic resonance imaging (MRT) or fusioned positron emission tomography and CT-scan (PET-CT) and the correlation between radiologic and pathologic findings is very low. Combined resection of the lung and major vessels or central airways for lung cancer remains challenging in terms of technical aspects and prognosis, because the local advanced disease comprises different subgroups with distinguishable clinical problems and necessary treatment decisions. In the surgical treatment of lung cancer invading the superior vena cava (SVC), the pattern of invasion was considered to be a significant prognostic factor. Patients who underwent partial SVC resection had a significantly higher probability of survival and there was a trend towards later recurrence in patients who had induction treatment. Also survival of patients with N2 disease was significantly worse than those with localized N0/N1 nodal status (1). For combined resection of thoracic aorta and primary lung cancer only studies with small number of cases are reported. The most patients received an adventitia resection or a patch graft repair of the defect in the aortic wall. For a smaller group total replacement of the descending aorta with an artificial vessel was reported, recent report indicated the placement of endoluminal prosthesis 1-3 weeks before surgery. Operative deaths occur in 0-24%, the 5 year survival ranged between 17% and 50%. Survival was only depended on mediastinal nodal involvement (2). Direct invasion of the left atrium (LA) has generally a significantly worse prognosis than patients with great vessels invasion. Patients who undergo LA resection have higher mortality and morbidity rates compared with those who had pneumonectomy alone. Median survival rate is 10 months, the 5-yearsurvival 14-16%. Palliative incomplete resection of T4 disease has not shown any survival benefit (3). Patients with localized invasion of the carina or/and distal trachea may be able to be completely resected despite their T4 classification. Extraluminal extension of the tumor found in CT-scan was associated with unresectability. In general, patients benefit from surgery, when a radical resection and systematic lymph node dissection can be achieved with low morbidity and mortality (4). For inoperable patients, palliative treatment with laser desobliteration, stent implantation or photodynamic therapy can be added to the standard chemoradiotherapy. Surgery in the treatment of lung cancer invading the great vessels, LA and major airways may improve survival only in selected patients. Induction treatment and new drugs may increase the number of potential candidates for surgery and improve survival. Preoperative every possible effort should be made to achieve an adequate evaluation of N-status. Complete resection is important and patient’s functional status must be compatible with the extent of resection and reconstruction. Literature Suzuki K, Asamura H, Watanabe S et al. Combined resection of superior vena cava for lung carcinoma: prognostic significance of patterns of superior vena cava invasion. Ann Thorac Surg 2004; 78:1184-9 Shiraishi T, Shirakusa T, Miyoshi T, et al. Extended resection of T4 lung cancer with invasion of the aorta; is it justified? Thorac Cardiovasc Surg 2005,53:375-9 Fukuse T, Wada H, Hitomi S. Extended operation for non-small cell lung cancer invading great vessels and left atrium. Eur J Cardiothorac Surg 1997; 11:664-9 Yildizeli B, Dartevelle PG, Fadel E, et al. Results of primary surgery with T4 non-small cell lung cancer during a 25-year period in a single center: the benefit is worth the risk. Ann Thorac Surg 2008, 86:1065-75

Abstract:
The National Lung Screening Trial results provided convincing evidence to the US Preventive services Task Force (USPSTF) to give a B recommendation (same as mammography) to screening high-risk individuals with low-dose CT (LDCT) in 2013.[1,2] In response in 2015 the Center for Medicare and Medicaid services (CMS) determined payment for screening those age 55 to 77 with the same smoking requirements.[3] So how is the medical community supposed to implement screening? At this point it appears easier to come up with the questions than the answers and it is unclear if there will be additional large randomized studies to guide the process. Programs will have similar elements with yet with features reflective of local needs and resources. In the US much of this process is being dictated by CMS and the American College of Radiology (ACR) which will maintain the registry through which reimbursement by CMS has been approved. As of July, this registry has not been set up and reimbursement by CMS is promised but not being done. As the NLST is the only randomized control trial to show benefit, whether international adoption occurs remains to be seen. Policy statements are available to help identify the key components and implementation strategies for a CT screening program.[4,5] A multidisciplinary committee that meets regularly consisting of pulmonology, radiology, primary care, thoracic surgery, interventional radiology, and medical and radiation oncology is important to facilitate LDCT screening, and evaluation and treatment of screening results. The inclusion of each of these disciplines helps to assure the patient has a complete complement of options regarding diagnosis and treatment and also limits the implementation of screening to systems with the needed expertise available. Having dedicated secretarial and administrative support is as important to a program’s success. Who to screen? The simplest answer is to screen those for whom benefit has been shown, namely those fitting the NLST criteria: age 55-74 with a 30 pk-year history of smoking and either current smokers or those who have quit within 15 years.[1] But it should be more complicated that as there are many patients at equivalent or higher risk who don’t fit the NLST criteria. There are several guidelines published and they all differ. USPSTF recommends ages 55 to 80 (and is so mandated within the Affordable Care Act), CMS is reimbursing for those age 55 to 77 (in medicare or medicaid), the National Comprehensive Care Network (NCCN) additionally recommends screening for those age > 50 with a 20 pack-year history and one additional risk factor such as COPD, family history of lung cancer, occupational exposure to carcinogens, and significant radon exposure.[6] Similarly the American Association of Thoracic Surgery recommends screening for those ages 55-79 within the NSLT smoking criteria as well as those > age 50 with a > 20 pk-year history and a cumulative risk of > 5% over 5 years.[7] At present the American Academy of Family Physicians recommends against LDCT screening.[8] Our program is recommending screening based on risk rather than reimbursement and, as a consequence, in additional to those who meet USPSTF criteria, recommends screening to those who have equivalent or higher risk using the PLCO~2012~ model.[9] Exclusion criteria should be similar between programs and based on the NLST.[1] Shared Decision Making. The USPSTF recommendation includes a shared decision making process (not recommended for breast cancer screening); this is also mandated by CMS as an identifiable visit with specific components: eligibility, absence of signs or symptoms of lung cancer, benefits and harms of screening, follow-up diagnostic testing, over-diagnosis, false positive rate, radiation exposure; importance of adherence to annual screening, impact of comorbidities, willingness to undergo treatment; and the importance cigarette smoking abstinence or cessation.[3] We mandate tobacco cessation counseling for current smokers prior to screening in an attempt to make clear that cessation is more lifesaving than screening. In the NLST there were 16 deaths within 60 days of an invasive procedure and only 10 of those had cancer; patients need to know process of screening can be fatal.[1] Radiology, results and Data collection. The ACR and Society of Thoracic Radiology have identified specifications for a LDCT and the registry requires that those technical parameters be met.[10] A structured reporting system is desired yet unfortunately the ACR registry requires that LungRADS be used which is not consistent with evidence based guidelines, is ambiguous, and is not aimed at patient communication. Nodule Evaluation. An optimal nodule evaluation algorhythm is yet to be determined, and since patient preference is to be weighed, no one fit will size all. Doing the CT scan is the easy part; follow-up is imperative - a dedicated registry is mandatory in this regard. Many raise concerns about the false positives of CT screening; within the NLST (positive defined as > 4mm) false positives were 96%. The 4 mm nodule has a likelihood of lung cancer of less than 1%. Should we call it a positive with that probability? The reality is that the vast majority of nodules found by CT screening need no additional evaluation other than CT follow-up – most with the next annual scan. We are recommending PET or biopsy (depending on the circumstances) only for nodules 1cm or greater and that eliminates immediate evaluation for 95% of the participants. But we don’t call a 6 mm nodule negative; it exists and needs follow-up – a key is to provide accurate information to the patient and their provider as to the likelihood of malignancy. Our program is responsible for the evaluation and followup of findings in a desire to favorably the tip the balance of benefit versus harms. People don’t die from false positives, but they can die from their evaluation. Nodule evaluation should be done by those who do it every day; we don’t feel this is appropriate for the primary provider and perhaps why the AAFP rejects LDCT screening. A multidisciplinary tumor/nodule board can help share the decision making, cross fertilize, and facilitate care for those who need treatment. 1. Aberle DR, Adams AM, Berg CD, et al. National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365: 395–409. 2. Moyer VA. Screening for lung cancer: U.S. Preventive services task force recommendation statement. Ann Intern Med 2014;160:330-338. 3. Centers for Medicare & Medicaid Services. Decision memo for screening for lung cancer with low dose computed tomography (ldct) (cag-00439n) 2015. Available from: http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=274&NcaName=Screening+for+Lung+Cancer+with+Low+Dose+Computed+Tomography+(LDCT)&MEDCACId=68&IsPopup=y&bc=AAAAAAAAAgAAAA%3d%3d&. 4. Mazzone P, Powell CA, Arenberg D et al. Components necessary for high-quality lung cancer screening: American College of Chest Physicians and American Thoracic Society Policy Statement. Chest. 2015;147:295-303. 5. Wiener RS, Gould MK, Arenberg D, et al. Official American Thoracic Society / American College of Chest Physicians Policy Statement: Implementation of Lung Cancer Screening Programs with Low-Dose Computed Tomography in Clinical Practice. Am J Respir Crit Care Med. 2015; in press. 6. National Comprehensive Cancer Network. Nccn clinical practice guidelines in oncology (nccn guidelines) - lung cancer screening, version 1.2015. 2014. Available from: http://www.nccn.org/professionals/physician_gls/pdf/lung_screening.pdf. 7. Jaklitsch MT, Jacobson FL, Austin JH, et al. The american association for thoracic surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups. J Thorac Cardiovasc Surg 2012;144:33-38. 8. American Academy of Family Physicians Policy Statement available from: http://www.aafp.org/patient-care/clinical-recommendations/all/lung-cancer.html 9. Kazerooni EA, Austin JH, Black WC, et al. Acr-str practice parameter for the performance and reporting of lung cancer screening thoracic computed tomography (CT): 2014 (resolution 4). J Thorac Imaging 2014;29:310-316. 10. Tammemagi MC, Katki HA, Hocking WG, et al. Selection criteria for lung-cancer screening. N Engl J Med 2013;368:728-736.