Scientific Program

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    MTE19 - How I Treat Advanced Stage Thymic Malignancy Patients (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Moderators:
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      MTE19.01 - How I Treat Advanced Stage Thymic Malignancy Patients

      07:00 - 08:00  |  Presenting Author(s): Heather A Wakelee

      • Abstract

      Abstract

      Given the rarity of thymic epithelial tumors (thymoma and thymic carcinoma) accumulation of clinical trial data to guide management has been challenging, yet the chemo-sensitivity of these malignancies is clearly established. As with most solid tumors it is important to fully assess for any chance of locally aggressive therapy with surgery or radiation for a curative intent. Thymic malignancies are often very radiation sensitive as well and I am quick to refer to radiation oncology for localized disease progression or any symptomatic areas. The high rates of paraneoplastic syndromes and autoimmunity adds to the complexity of management of this disease, especially thymoma.1I am grateful for the support of neurology colleagues and immunology colleagues to help with myasthenia gravis and immunotherapy/rheumatology management of these complex patients.

      Once the disease has spread extensively in the pleural or metastases have developed, systemic therapy will be essential. I tend to start with a platinum based regimen initially. For young and fit patients the three drug CAP regimen of cyclophosphamide, doxorubicin and cisplatin has a very high response rate.2 Given the cumulative cardiotoxicity of the anthracycline in the regimen, I usually stop at 4 and no more than 6 cycles. Most patients are then able to enjoy a chemotherapy holiday for several months, and even up to a year or longer. I will consider cisplatin/etoposide3if anthracyclines are contraindicated, and especially if any concurrent radiation is under consideration. Carboplatin/paclitaxel was also studied prospectively and remains the most studied regimen for thymic carcinoma.4The response rates with all of these regimens are approximately 50%, somewhat higher with the platinum/anthracycline combinations, though given low numbers in trials the precise response rates are difficult to state with certainty. None of these regimens include a maintenance component, yet the PFS can be 1-2 years. I will also consider giving platinum/pemetrexed as a first line regimen given the improved tolerability, despite limited data. This is primarily focused in thymoma patients, though activity in a limited number of thymic carcinoma patients has been noted despite the usual squamous histology.5

      Once a patient has progressed on first line treatment one may choose between a number of single chemotherapeutic agents with activity including 5-FU and derivatives, gemcitabine, pemetrexed, taxanes and others. I choose between these based on toxicity profiles and prior regimens for the patient and do not have a single standard approach. For younger and fit patients, especially if they have a high disease burden, I will consider combination regimens. There is also growing evidence for activity of agents with mechanisms of action that differ from those of traditional cytotoxic drugs. One of the first of these was octreotide with or without prednisione.6I have used this regimen rarely and in the setting of a positive octreotide scan, or a patient with autoimmune diarrhea where the octreotide was also effective in controlling symptoms of disease.

      More recently I have begun to use the mTOR inhibitor everolimus in my thymic malignancy patients based on a 51 patient trial with the compound.7At 10 mg/day oral dosing the drug had a disease control rate of 88%, which was slightly higher for the thymoma subgroup. There was a complete response in a thymic carcinoma patient and partial responses observed in a minority of both thymoma and thymic carcinoma patients. Median PFS exceeded a year in the thymoma patients. However, significant toxicity was seen with serious drug related adverse events in 14 of the 51 patients including 3 events of fatal pneumonitis. In my practice I have found that most patient do require a dose reduction to 7.5 or 5 mg daily. Pneumonitis remains a risk with this agent, but can be managed if discovered early.

      More specifically for thymic carcinoma emerging data with sunitinib has been very encouraging. In a trial that included 23 evaluable thymic carcinoma patients (as well as 16 with thymoma) the partial response rate was 26% for the thymic carcinoma patients with a further 65% with stable disease. Again toxicity is a concern with 13% rate of cardiac toxicity (reduction in ejection fraction).8

      Detailed molecular analysis of a large group of thymic malignancies was published by the TCGA study group and confirmed GTF2I as the most common mutation in thymoma, as well as revealing 4 distinct categories in the primarily early stage thymoma samples analyzed. Unfortunately no obvious new therapeutic options emerged from this work, but this deeper understanding of the molecular underpinnings of the disease will hopefully allow us to improve our therapeutic options.9The low tumor mutation burden of thymomas was also confirmed in the TCGA effort.

      Thymic malignancies, however, are known to have high PD-L1 expression as shown by multiple groups and that led to the first trials of immunotherapy in thymic malignancy patients. A phase II trial with pembrolizumab, restricted to thymic carcinoma patients without any evidence of autoimmunity, enrolled 41 patients.10 The overall response rate was 22.5% including a complete response, however 15% of patients had severe autoimmune toxicity, which involved grade 4 myocarditis in 2 of the patients and myositis (elevated CPK) in an additional 3 patients. Taken together I am still very cautious in considering PD-(L)1 inhibitors in thymic carcinoma patients as the risk/benefit ratio (23% response and 15% severe autoimmune toxicity) is much closer than we have with many other therapeutic options. The risks in patients with thymoma or any underlying paraneoplastic autoimmunity limits our utility of these drugs at this time.

      Thymic malignancy patients have multiple treatment options and many can have long periods of disease control with the traditional cytotoxic options available and a growing number of targeted therapeutics.

      REFERENCES:

      1. Padda SK J Thorac Oncol13(3):436-446;2017

      2. Loehrer PJJ Clin Oncol 12:1164-1168;1994

      3. Giaccone GJ Clin Oncol 14: 814-820;1996

      4. Lemma GLJ Clin Oncol 29:2060-2065;2011

      5. Liang Y Lung Cancer87(1):34-8;2015

      6. Loehrer PJ J Clin Oncol22:293-299;2004

      7. Zucali PA J Clin Oncol36 (4); 342-349;2018

      8. Thomas A Lancet Oncol16(2):177-186;2015

      9. Radovich M Cancer Cell33:244-258;2018

      10. Giaccone G Lancet Oncol19:347-55;2018

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    MTE20 - Molecular Testing in Small Samples (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Pathology
    • Moderators:
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      MTE20.01 - Molecular Testing in Small Samples

      07:00 - 07:30  |  Presenting Author(s): John W Longshore

      • Abstract

      Abstract

      Recent advances over the past decade in canger genomics allows the rapid identification of patients with driver mutations or immune phenotypes that are eligible for targeted, rather than systemic, therapy. In many centers worldwide, biopsy material obtained from lung cancer patients is limited to core needle biopsy or fine needle aspirate samples. After a histologic diagnosis is rendered on these samples, often a limited amount of tissue remains for biomarker testing. To further complicate matters, the number of biomarkers required to profile patients is increasing with the number of new therapeutics available for treatment. During this educational session, techniques for proper tissue stewardship when working with small biopsy samples as well as utilizing tissue sparing biomarker testing methods will be presented.

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      MTE20.02 - Molecular Testing in Small Samples

      07:30 - 08:00  |  Presenting Author(s): Jin-Haeng Chung

      • Abstract

      Abstract

      Molecular targeted therapies have become a standard treatment for patients with lung cancer. Driver genetic alterations such as EGFR mutations, ALK rearrangements and ROS1 rearrangements are currently used as predictive biomarkers for EGFR tyrosine kinase inhibitors (TKIs), ALK inhibitors, and ROS1 inhibitors, respectively. In addition, antibodies blocking the PD-1 ligand PD-L1 have shown prominent antitumor activities and durable clinical response.

      Molecular analyses of these predictive biomarkers in tumor tissue or cytology specimens are the first prerequisite laboratory tests for the clinical management of lung cancers.

      Despite the increasing number of targets to be tested, most patients harboring non-small cell lung carcinoma (NSCLC) presents with advanced stage at the time of diagnosis, so the amount of tissue that can be acquired is very small.

      Small biopsy and cytology samples obtained from a variety of methods are acceptable for molecular testing, including transbronchial lung biopsy, endobronchial ultrasound– guided transbronchial needle aspiration, bronchial brushing or washing, computed tomography–guided gun biopsy or needle aspiration, and pleural fluid sampling.

      The molecular testing results using cytology samples are highly concordant with those of the corresponding tissue samples, especially with more sensitive methods. Routinely prepared cytology samples such as alcohol-fixed smears or cell block samples are also suitable for mutation testing.

      As targetable genetic alterations are increasingly identified, individual genotyping or molecular test seemed to be relatively inefficient and expensive. Thus, next-generation sequencing (NGS) technology with DNA or RNA is reported to be useful method for multiplexed and deep targeted sequencing.

      In this situation, each pathology laboratory needs to make a strategic approach to use these small samples in considerations of the important priorities for the management of the patients.

      In this MET session, I will introduce our experience of strategic approach to obtain the most useful information while reducing the loss of tissue using a small amount of samples.

      References

      1. Li T, Kung HJ, Mack PC, Gandara DR. Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 2013; 31: 1039-49.

      2. Brahmer JR, Tykodi SS, Chow LQ et al. Safety and Activity of Anti-Pd-L1 Antibody in Patients with Advanced Cancer. N Engl J Med 2012; 366: 2455-2465.

      3. Shim HS, Choi YL, Kim L, et al. Molecular testing of lung cancers J Pathol Trans Med 2017; 51: 242-254..

      4. Sun PL, Jin Y, Kim H, Lee CT, Jheon S, Chung JH. High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas. Cancer Cytopathol 2013; 121: 311-9.

      .

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    MTE21 - Can I Treat Brain Metastasis with Immunotherapy? (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Immunooncology
    • Moderators:
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      MTE21.01 - Can I Treat Brain Metastasis with Immunotherapy?

      07:00 - 07:30  |  Presenting Author(s): Sarah B Goldberg

      • Abstract

      Abstract not provided

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      MTE21.02 - Can I Treat Brain Metastasis with Immunotherapy?

      07:30 - 08:00  |  Presenting Author(s): Caroline Chung

      • Abstract

      Abstract not provided

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    MTE22 - Incorporation of Smoking Cessation in Clinical Care (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Prevention and Tobacco Control
    • Moderators:
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      MTE22.01 - Integration of Cessation and Lung Cancer Screening

      07:00 - 07:30  |  Presenting Author(s): Matthew Allen Steliga

      • Abstract

      Abstract

      Lung cancer screening with low dose computed tomography (LDCT) has been studied extensively and is recommended for individuals who are deemed to be at increased risk, typically with a smoking history of 30 pack-years or more. The National Lung Screening Trial (NLST) demonstrated that with a screening program, there was a 20% reduction in lung cancer mortality. The overall incidence of lung cancer in the NLST was around 2%. Unfortunately, an often overlooked, yet treatable condition in any lung cancer screening program is continued tobacco use. In the NLST, 48% of participants were actively smoking at the time of the screening, and in our institutional program 71% are actively smoking. Cessation in this group may be seen as a challenge, as many of these patients have a much greater than 30 pack-year history and have not quit despite being advised by their primary physician. However, the lung cancer screening program may interact with the patient in a 'teachable moment' and these patients receiving screening may have increased motivation and willingness to quit if given the right resources. External resources such as quitlines or referrals to external tobacco cessation programs require action and increased motivation on the aprt of the patient, while integrating resources in the workflow of the screening program deliver the resources to the patient as a standard part of practice. Furthermore, the lung cancer screening program may be able to interact with the patient over time (through annual follow up at least) and may be an optimal way to deliver cessation resources to these patients. This session will explore different programmatic strategies to deliver cessation resources to patients in the construct of a LDCT Lung Cancer screening program. The coordinator of our screening program is a Advance Practice Registered Nurse (APRN) who sought out training and certification as a certified Tobacco Treatment Specialist (TTS). Referrals to the LDCT screening program are initially contacted by phone for a scheduling phone call, which also includes the initial elements of counseling these patients regarding tobacco cessation. An initial intake phone call determines appropriateness for screening and also can include elements of the 5A framework: ASK, ADVISE, ASSESS, ASSIST, ARRANGE. Then on the day of the scan, the APRN coordinator meets with the patient face-to-face at the point of the scan, and has already established rapport by telephone prior to the visit. The day of the scan, the patient recieves in person counseling as part of their visit, and a cessation strategy or "Quit Plan" is made which may include medications such as nicotine patches and/or gum. After the scan, telephone follow up is conducted to both discuss cessation and discuss scan results with a plan for follow up. Additionally, patients can be enrolled in a state Quitline program as a standard part of the workflow which provides them with ongoing support. Another option for patients is for the screening program to refer them to group counseling sessions. The American Lung Association's Freedom From Smoking is one such structured program. Patients may not independently seek these programs out, but as a lung screening program, developing ties to programs in the community with integrated referrals to group counseling programs can be another way to further the delivery of resources to these patients. As patients return for repeat scans to follow up indeterminate nodules, or return the following year for routine scans, further cessation support is delivered, and if they have quit, abstinence support is provided. Quitlines, group counseling, and nicotine replacement therapy have been shown to be cost effective strategies to help people who smoke to increase chances of quitting. A lung screening program may identify 2% of its participants with lung cancer, but if half (or in our case 71%) are smoking, and integrated cessation resources help those patients to reduce or quit smoking, the benefit of the lung screening program is greatly amplified, and patients can reduce risk for future cancers as well as cardiovascular and non-oncologic respiratory diseases.

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      MTE22.02 - Cessation and Clinical Lung Cancer Care

      07:30 - 08:00  |  Presenting Author(s): Jamie Ostroff

      • Abstract

      Abstract not provided

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    MTE23 - Surgical Considerations Following Induction Therapy for Stage IIIA Disease (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Moderators:
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      MTE23.01 - Surgical Considerations Following Induction Therapy for Stage IIIA Disease

      07:00 - 07:30  |  Presenting Author(s): Eric Vallieres

      • Abstract

      Abstract

      Considerations following Induction Therapy for Stage IIIA Disease

      Surgery after induction therapy can at times be very challenging. From my own observations, this may particularly be an issue when the patient had nodal involvement at presentation and experienced a good response to the induction treatment (induction chemoradiation (CRT) or induction chemotherapy (C) alone) where fibrosis of the responding lymph nodes may make the hilar vascular mobilization more difficult. (Induction immunotherapy as well in limited reported series) The following lines will describe some tips on how to minimize the risks of such resections.

      Preoperatively:

      One should always take advantage of the induction therapy period (12 weeks or more) to achieve absolute smoking cessation in these patients. After induction therapy, one should obtain a fresh set of PFTs including a DCO measurement as both radiation and some of the induction chemotherapy agents may have caused significant pneumonitis with resulting altered lung function. If there is a possibility that a pneumonectomy will be required, prepare yourself. (QVQ, stress echo). Radiation esophagitis may have brought some nutritional issues, consider an alimentary “boost” when a significant weight loss has occurred during the induction phase of therapy. If there may be a risk that the SVC will be clamped, repaired or replaced, discontinue the port-o-cath preoperatively. Finally, make sure to review all imaging, particularly the pre-induction therapy CT: the MTD is a good format for such review in our institution.

      Surgery

      Personally, I approach these cases via open thoracotomy, though some have reported successful resections on MIS platforms. All patients get an epidural catheter preop. If one anticipates, issues with the SVC with a R upper lobar resection, get infra diaphragmatic IV access preop. Emphasize w anesthesia, in the preoperative area, the absolute need to keep these patients dry: an irradiated mediastinum cannot handle excess fluid.

      At entry, I prepare/ harvest the intercostal muscle, without dividing it. (I now keep the omentum for later if needed to manage a complication, and spare the serratus anterior in all cases). If accessible, I usually clear zone 7 first, with frozen section read. (The frozen section information/ feedback during this type of surgery can be very useful to have when one gets into a tough surgical corner…) If one is attempting a lobectomy and anticipates possible difficulties in the hilum, one should consider obtaining early circumferential control of the main veins and main PA (if possible), and do so intrapericardially if needed. Similarly, early division of the azygos vein on the right, may help when one anticipates difficulties accessing the main R PA and surrounding structures.

      One may have to alter their usual sequence of dividing the central structures. With both upper lobes, when bulky fibrotic changes are present in the suprahilar areas, proceeding retrograde, from the fissures up is often very helpful. As well, dividing open the upper lobe bronchi from the back can help access and control the often fibrosed and foreshortened proximal lobar PA upper lobar branches.

      On the left, I will identify the vagus nerve low down, away from the fibrotic field and follow it up into the AP window to minimize the risks of inadvertently injuring the recurrent nerve. During the case, I constantly remind anesthesia to keep these patients dry. For pneumonectomies, we give a steroid bolus before dividing the main PA, similarly we initiate amiodorone prophylaxis by infusion during surgery. In high R pneumonectomies, when we have stapled the bronchial stump and a portion of the tracheal wall, I add an additional non resorbable monofilament stitch to reinforce both ends of the bronchial stapled line. Finally, we cover all of our bronchial stumps after induction CRT, and selectively after induction C alone, with the intercostal muscle flap.

      POSTOP AND DC

      Remember to keep the patient dry. Consider maintaining amiodorone prophylaxis for 72 hours after pneumonectomies or with other patients deemed at elevated risk of going into atrial fibrillation post op.

      Beware of a possible left vocal cord palsy after L pneumonectomy and difficult left upper lobectomy: we keep these patients NPO until we are confident that their cords are OK. If there are any concerns, we get an immediate laryngoscopy. If the left cord is found to be paretic, we immediately get VC medicalization. (not negotiable)

      In addition to having a high Caprini DVT Risk Score by virtue of their diagnosis, age and magnitude of surgery, patients who have received induction C or CRT may potentially be at higher risk of post op TBE as some of the C agents are thrombogenic. Unless contraindicated, we will discharge them home on continued TBE chemical prophylaxis for one month after surgery, longer if the recovery lags.

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      MTE23.02 - Surgical Considerations Following Induction Therapy for Stage IIIA Disease

      07:30 - 08:00  |  Presenting Author(s): Jonathan David Spicer

      • Abstract

      Abstract

      Seeking new solutions through the windows of opportunity offered by induction therapy for locoregional disease.

      The predominant model of care for locally advanced solid organ malignancies involves a shotgun approach. Indeed, the full range of “omic” strategies are currently insufficiently exploited when assigning treatment regimens to patients with IIIA non-small cell lung cancer (NSCLC). Despite the advent of precision oncology, management strategies for stage IIIA NSCLC remain relatively untargeted despite such successes as those described in the PACIFIC trial [1]. Indeed, the workhorses of curative intent therapy for IIIA NSCLC and their various permutations (surgery, radiation and chemotherapy) remain essentially unchanged over the last 25 years since the first trials of induction chemotherapy were performed in the early 1990s [2-3]. The paradigm of multimodality therapy combining local and systemic treatments holds true today and offers the best available oncological outcomes recorded to date.

      After decades of debate, emerging data seem to conclude that induction therapy with chemotherapy alone or concurrent chemoradiation offer essentially identical results when planned prior to surgery [4]. However, these data remain largely retrospective with few randomized head to head comparisons in this most heterogeneous of stage groupings. Hence, not only has stage IIIA remained a highly heterogenous cohort with a wide spectrum of disease burden, but its relative rarity has hampered the execution of innovative randomized trials. Thus, most centers have adopted a preferred institutional approach based on expert readings of the available literature. These variations in care have led to heated debates over what is essentially a game of musical chairs, arranging various permutations of conventional therapeutics for which the outcomes are largely identical.

      In this respect, the old debate of whether to give induction chemotherapy or concurrent chemoradiation misses the point and overlooks a tremendous opportunity for discovery. Years of clinical trials have taught us that approximately 15 to 20% of patients will experience a major pathological response after induction chemotherapy [5] and approximately one third will have a pathological complete response after concurrent chemoradiation [6]. Yet, we are no closer to selecting those patients most likely to benefit most from these conventional therapeutics. The windows of opportunity offered by induction therapy in surgically resectable IIIA NSCLC are numerous and vastly powerful. Properly exploited, these opportunities make IIIA NSCLC the perfect pivot point for discovery that will inform both the metastatic setting and novel approaches to early stage disease.

      As NSCLC patients are offered more therapeutic options, the ability to tailor induction therapeutics based on predictive analyses up-front remains under-exploited in IIIA disease. Current trials exploring the value of checkpoint inhibition prior to surgical resection for locally advanced NSCLC assign patients randomly to the available combinations. This again is a key moment to provide improved selection through the extensive correlative science pipelines offered by these window of opportunity trials [7]. The surrogate measure of major pathological response and its close association with long term survival outcomes provides a powerful incentive to rapidly adopt new regimens into the corpus of available therapeutic options.

      Our program capitalizes on the availability of large tissue samples offered by patients treated with multimodality therapy in surgically resectable IIIA NSCLC, to establish lab-based patient avatars. These living and highly personalized biobanks provide the necessary materials to profile and generate a lab-proven first line therapeutic regimen. While such programs would be highly inefficient in early stage disease where cure rates are much higher, patients with stage IIIA have high rates of recurrence and generally benefit from a sufficiently long disease-free interval. This luxury of time offers yet another window of opportunity where patient-derived xenograft models and organoids are generated from the surgical specimen to create the necessary patient avatar to execute a predictive analysis and establish the optimal next step for the significant number of patients who will experience progressive disease. Moreover, the sensitivity of liquid biopsy protocols is easily tested in this setting where a significant proportion of patients are placed into remission with no radiological evidence of disease [8]. Such opportunities provide the ideal setting to revisit our surveillance strategies which have become so resource intensive, yet offering so little measurable benefit [9].

      Finally, a dedicated research program centred on locally advanced NSCLC provides a desirable clinical entity to rapidly establish predictors of response and failure to conventional and emerging biologicals by leveraging all “omic” platforms, from clinical to radiological and from pathological to deep sequencing, metabolomics, immunoprofiles and beyond. Such research provides the pipeline to generate the true essence of personalized medicine in NSCLC, which can easily be translated to both early and late stage disease.

      References

      Antonia SJ, et al. Durvalumab after chemoradiotherapy in stage III non-small cell lung cancer. N Engl J Med, 2017 377(20): 1919-1929

      Roth JA, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small cell lung cancer. J Natl Cancer Inst, 1994 86(9): 673-80.

      Rosell R, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med, 1994 330(3): 153-8

      Spicer J, et al. Multimodality therapy for N2 Non-small cell lung cancer: An evolving paradigm. Under review at Ann Thorac Surg.

      Hellman MD, et al. Pathological response after neoadjuvant chemotherapy in resectable non-small cell lung cancers: Proposal for the use of major pathological response as a surrogate endpoing. Lancet Oncol, 2014 15(1): e42-50.

      Eberhardt WEE, et al. Phase III study of surgery versus definitive concurrent chemoradiotherapy boost in patients with resectable stage IIIA(N2) and selected IIIB non-small cell lung cancer after induction chemotherapy and concurrent chemoradiotherapy (ESPATUE). J Clin Oncol, 2015 33(35): 4194-4201.

      Forde P, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med, 2018 378(21): 1976-1986.

      Chaudhuri AA, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov, 2017 7(12): 1394-1403.

      Colt HG, et al. Follow-up and surveillance of the patient with lung cancer after curative-intent therapy: Diagnosis and management of lung cancer. Chest, 2013 143(5 Suppl): e437S-e454S.

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    MTE24 - Multiple Lung Nodules; Resect, Radiate or Watch? (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Treatment of Early Stage/Localized Disease
    • Moderators:
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      MTE24.01 - Surgery vs SABR for Early NSCLC

      07:00 - 07:30  |  Presenting Author(s): Thomas A. D'Amico

      • Abstract

      Abstract

      Surgery vs SABR/SBRT for Early Stage NSCLC

      Initially, SBRT was used primarily to treat NSCLC patients deemed inoperable secondary to other medical conditions or poor pulmonary function. SBRT is now also being actively investigated to determine its role in the management of patients who can tolerate surgery, though three separate randomized clinical trials have been terminated early secondary to poor accrual. Retrospective single and multi-institutional studies have shown both comparable and improved results with SBRT when compared to surgery. However, two recent large cohort studies reported decreased survival with SBRT compared to surgical resection, though these studies were not focused to wedge resection and considered larger T2 tumors.

      Three recent studies highlight important advantages of surgery.

      Wedge resection vs SBRT

      Limiting the comparison of SBRT and surgical resection to only surgical wedge resection may be more appropriate than considering all types of surgical resections, considering that both SBRT and wedge resection essentially limit treatment to only the immediate lung parenchyma in the area of a lung cancer. A study was undertaken to test this hypothesis using the National Cancer Date Base to assemble a large cohort of stage IA NSCLC patients who were treated with either wedge resection or SBRT. Of the 6295 patients included, 1778 (28.2%) underwent SBRT, and 4517 (71.8%) underwent wedge resection. SBRT was associated with significantly reduced 5-year survival compared with wedge resection in both unmatched analysis (30.9% vs 55.2%,

      P<.001) and after adjustment for covariates (31.0%vs 49.9%, P<.001). SBRT also was associated with worse overall survival than wedge resection after 2 subgroup analyses of propensity-matched patients (P<.05 for both). Centers that used stereotactic body radiotherapy more often

      as opposed to surgery for patients with cT1N0 patients with tumors <2 cm were more likely to have an observed/expected mortality ratio>1 for 3-year mortality (P= .034).

      Another analysis by Puri and colleagues, also using the NCDB, reported outcomes of 117,618 patients undergoing either surgical resection or SBRT, showing a survival advantage for surgical resection. They also performed a subgroup analysis of patients who underwent sublobar resection compared to SBRT which also showed a survival advantage for resection.

      Role of LN staging

      Clinical lymph node staging for stage I NSCLC remains inaccurate, presenting potential treatment dilemmas for patients treated with SBRT, particularly among patients otherwise fit for surgery. We sought to characterize the rate of nodal upstaging among patients with stage I disease, and the downstream implications of these inaccuracies for patients treated with SBRT.

      Patients diagnosed from 2006-2015 with clinical stage I NSCLC were identified in the

      National Cancer Database. A total of 62,451 patients were identified who underwent lobectomy for clinical stage I NSCLC. A median 9 (IQR: 5, 14) lymph nodes were examined. Nodal upstaging occurred in 11.3% of cases (pN1: 7.2%, pN2: 4.1%). Rates of pathologic nodal upstaging by AJCC T-stage subgroup were as follows: T1a: 179/3949 (4.5%), T1b: 2083/24443 (8.5%), T1c: 2823/21776 (13.0%), and T2a: 1995/12283 (16.2%), p<.001. An additional 773 patients were identified who met inclusion criteria and for whom surgical resection was recommended, but who refused surgery and instead opted for SBRT. Propensity-adjusted survival for these patients compared with a matched cohort treated with lobectomy, demonstrated significantly superior survival for patients treated with surgery (5-year survival 63% [95% CI: 59.9-66.3%) vs. 41.9% (95% CI: 36.7- 47.8%), p<.001).

      Recent Systematic Review and Meta-analysis

      A systematic review of relevant studies was performed through online databases and the most updated studies were selected for meta-analysis according to unmatched and matched patient cohorts. Thirty-two studies were identified in the systematic review, and 23 were selected for quantitative analysis. Surgery was associated with superior overall survival in both unmatched (OR, 2.49; 95% CI, 2.10-2.94; p<0.00001) and matched (OR, 1.71; 95% CI, 1.52-1.93; p<0.00001) cohorts. Subgroup analysis demonstrated superior overall survival for lobectomy and sublobar resection, compared with SBRT. In unmatched and matched cohorts, cancer-specific survival, disease-free survival, and freedom from locoregional recurrence were superior after surgery.

      Summary

      These issues related to observational research highlight the need for a prospective randomized clinical trial, but unfortunately this has not been achievable. The three initial randomized clinical trials comparing SBRT to surgery (STARS, ROSEL, and ACOSOG Z4099/RTOG 1021) have all been terminated secondary to poor patient accrual likely related to the patient difficulty of randomizing between dramatically different treatment modalities. However Chang et al. published the combined results of 58 patients with Stage I NSCLC in the STARS and ROSEL trials reporting a survival advantage with SBRT compared with lobectomy. Even these results though are difficult to interpret though given the different inclusion criteria of both trials. Additionally, the overall survival was significantly different in the STARS trial alone (p=0.0067) but not in the ROSEL trial (p = 0.78). New randomized trials including the STABLEMATES (NCT01622621, formerly ACOSOG Z4099), SABRTooth (ISRCTN13029788), and VALOR (CSP 2005) are now ongoing, but their ability to accrue patients remain to be determined and it is likely to be several years before results are reported.

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      MTE24.02 - Small Lung Tumours: High Risk Lesions and Contraindications to Stereotactic Ablative Body Radiotherapy (SABR)

      07:30 - 08:00  |  Presenting Author(s): David L Ball

      • Abstract

      Abstract

      The development of SABR has revolutionised the non-surgical treatment of small, node negative lung tumors, both primary and metastatic. SABR is a convenient, painless, inexpensive outpatient procedure and there is now randomized evidence that it not only results in better local control than conventionally fractionated radiotherapy in patients with inoperable peripheral stage I non-small cell lung cancer, but increases survival as well. The impressive local control rates of over 80% have tempted some investigators to expand the indications for high dose hypofractionated SABR beyond small peripheral tumors.

      Perhaps the most controversial extended indication is the use of SABR for “central” lung tumours. There is no agreed definition of what constitutes a central tumor, although in the absence of consensus, the “no-fly zone” described by Timmerman is widely used even though it was based on a very small number of events.1 Phase II trials have been interpreted as indicating that SABR of central tumors has acceptable toxicity (RTOG 0813), even though there was a 3% mortality likely resulting from treatment; or conversely as unsafe, with the Nordic HILUS trial reporting around 10% mortality after SABR of tumours close to the main or a lobar bronchus. The European Lung Tech trial should throw more light on the safety of treating central tumors with a “risk-adapted” approach using a more fractionated schedule of 60 Gy in 8 fractions.2

      Many patients referred for SABR have poor respiratory or cardiac function making them unsuitable for surgical resection. Does this make them unsuitable for high dose SABR as well? The available evidence suggests not,3 but extreme caution should be taken in patients who have underlying interstitial lung disease.4 The relationship between SABR and cardiac injury, especially in the era of combined immunotherapy and SABR, remains under investigation. This high risk group of patients are currently eligible for the Stablemates trial, which is comparing sublobar resection with SABR. Eligibility includes FEV1 or DLCO < 50% predicted.

      A patient’s suitability for SABR will also depend on the dose constraints on nearby organs at risk. The chest wall is less concerning than previously, but is it the dose to the neurovascular bundle, rib or the whole musculoskeletal structure that most accurately predicts risk of chest wall pain? The brachial plexus tolerates hypofractionation poorly, and as with other scenarios where there is doubt about the safety of SABR, it is well to recognise that less effective but safer fully fractionated schedules are available.

      Other considerations, not in terms of risk, but of practical delivery of the treatment include synchronous multiple tumors, large tumors (>5 cm), and visibility for image guidance: Well defined? Too small? Image degraded by implanted fiducials?

      1. Timmerman R, McGarry R, Yiannoutsos C, et al. Excessive Toxicity When Treating Central Tumors in a Phase II Study of Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Lung Cancer. J Clin Oncol 2006;24:4833-9.

      2. Adebahr S, Collette S, Shash E, et al. LungTech, an EORTC Phase II trial of stereotactic body radiotherapy for centrally located lung tumours: a clinical perspective. Br J Radiol 2015;88:20150036.

      3. Guckenberger M, Kestin LL, Hope AJ, et al. Is there a lower limit of pretreatment pulmonary function for safe and effective stereotactic body radiotherapy for early-stage non-small cell lung cancer? J Thorac Oncol 2012;7:542-51.

      4. Bahig H, Filion E, Vu T, et al. Severe radiation pneumonitis after lung stereotactic ablative radiation therapy in patients with interstitial lung disease. Pract Radiat Oncol 2016;6:367-74.

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    MTE25 - Enhancing the Care of Your Older Adult Population with Lung Cancer (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Nursing and Allied Professionals
    • Moderators:
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      MTE25.01 - Enhancing the Care of Your Older Adult Population with Lung Cancer

      07:00 - 08:00  |  Presenting Author(s): Martine Puts

      • Abstract

      Abstract

      Lung cancer is the most common cancer around the world and it affects many older adults (1). With older age, the risk of treatment complications may rise. However, there is a lack of evidence on how to best treat older adults with cancer as this population has been severely under-represented in clinical trials. As patients age, their health and function can vary significantly, resulting in an increasingly heterogeneous population

      Lung cancer is the most common cancer around the world and it affects many older adults (1). With older age, the risk of treatment complications may rise. However, there is a lack of evidence on how to best treat older adults with cancer as this population has been severely under-represented in clinical trials. As patients age, their health and function can vary significantly, resulting in an increasingly heterogeneous population (3). Many older adults have other health and functional status impairments that may impact cancer treatment benefits and treatment risks.

      Several professional societies and organizations have recommended that for older adults with cancer for whom treatment is considered (3,4,5), comprehensive geriatric assessment (CGA) (consisting of the domains comorbidity, medication use, functional status, cognition, psychosocial wellbeing, social support, mobility/fall risk) should be conducted to help clinicians with the treatment selection and care during the treatment. Implementing a comprehensive geriatric assessment in the oncology setting can help the oncology team with 1) detecting additional health conditions, 2) the assessment data can be used to predict life expectancy; 3) the assessment data can be used to predict chemotherapy toxicity; 4) the assessment data can result in changing treatment plans; and 5) the assessment data can be used to potentially reducing toxicity (3,4,5). The randomized trial of Dr. Corre and his team showed that treatment selection for older adults with Non Small Cell Lung cancer (NSCLC) based on the CGA was associated with decreased treatment toxicity (6). This assessment should be followed up with a care plan to address the health and functional status issues identified. In this session we will review how to enhance the clinical care for your older adult with lung cancer.

      The learning objectives for this session are:

      1. To review the currently available evidence with regard to comprehensive geriatric assessment and management for your older adult with lung cancer patients including the Corre study.

      2. To review how you can improve the clinical care of your older adult with lung cancer (the who/what/how of CGA including which tools, domains, who does what as well as the top 10 clinical pearls).

      Reference list.

      1. Ferlay, J. et al. GLOBOCAN 2012v1.0, Cancer Incidence and Mortality Worldwide. IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer (2013).

      2. Santoni G, Angleman S, Welmer AK, Mangialasche F, Marengoni A, Fratiglioni L. Age-related variation in health status after age 60. PLoS One 2015;10(3):e0120077.

      3. Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 2014 August 20;32(24):2595-603.

      4. Mohile SG, Dale W, Somerfield MR, Hurria A et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology Summary. J Oncol Pract. 2018 Jun 22:JOP1800180. doi: 10.1200/JOP.18.00180. [Epub ahead of print]

      5. Hurria A, Wildes T, Baumgartner J et al. NCCN Clinical Practice Guidelines in Oncology. Older Adult Oncology. Version 1.2018. NCCN; 2018.

      6. Corre R, Greillier L, Le Caër H, et al. Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study. J Clin Oncol. 2016 May 1;34(13):1476-83.

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    MTE26 - New Paradigms in Symptom Management in Lung Cancer (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Moderators:
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      MTE26.01 - Treatment of Cancer Related Symptoms

      07:00 - 07:30  |  Presenting Author(s): Patricia Rivera

      • Abstract

      Abstract

      The majority of patients with lung cancer are diagnosed with advanced disease where the 5-year survival rate remains low. Improving survival, quality of life (QOL) and control of symptoms are pivotal goals for health care professionals caring for patients with lung cancer. Several studies have shown that symptom burden and distress are higher among patients with lung cancer 1,2. Despite advances in treatment of advanced lung cancer including targeted oral therapies which have resulted in improved survival and QOL3, and early palliative care intervention which results in improvement in symptom control and quality of life4, a recent study showed persistent significant symptom burden, distress and unmet needs in patients with advanced lung cancer5. The most common symptom in lung cancer is fatigue, reported in about 40% of patients, followed by pain (30%)5. Organ specific symptoms and complications include cough and dyspnea (20%), airway obstruction, hemoptysis, pleural effusions and tracheoesophageal fistula5,6. Providers caring for lung cancer patients need to be aware of common symptoms and interventions available, particularly non-drug interventions, and work together in multidisciplinary teams to ensure lung cancer patients are receiving the best therapeutic and non-therapeutic interventions in their cancer care in order to improve survival and QOL.

      Interventions:

      -Fatigue:

      Cancer-related fatigue, sometimes referred as cancer fatigue syndrome may be related to both the disease process and treatments, including surgery, chemotherapy and radiation therapy. Other factors that may contribute to fatigue include anemia, dyspnea, decreased nutrition, decreased exercise, pain, depression, and insomnia.Pulmonary rehabilitation (PH)/physiotherapy, shown to be very effective in patients with COPD, is an underappreciated intervention in patients with lung cancer due to lack of randomized data and low rates of referral (<25%). Although limited, existing, evidence supports PH/physiotherapy in lung cancer patients before and after surgery and that in patients receiving therapy other than surgery, may result in both ability to maintain and improve physical function, muscle strength and quality of life 7,8.

      -Pain:

      Acute and chronic pain in the lung cancer patient may be multifactorial and influenced by physical, psychosocial and spiritual factors6. Pain-assessment tools and targeted imaging as required are as first essential steps in evaluating a patient’s pain symptom6. Healthcare providers should understand the WHO analgesic ladder which recommends use of analgesics (acetaminophen and NSAIDs) for mild pain, addition of weaker opioids (codeine or dihydrocodeine) for mild to moderate pain and stronger opioids (morphine, hydromorphone, oxycodone)for severe pain6. Psychologic factors contribute to increased pain and suffering among cancer patients and non-drug interventions including hypnosis, cognitive behavioral coping mechanisms, meditation and relaxation exercises have been shown to reduce pain in patients and long term survivors9.

      -Dyspnea:

      The symptom of dyspnea is complex , often multifactorial and results in worsening QOL in patients with lung cancer. Dyspnea may be due underlying COPD or cardiac disease, complications of the tumor such as airway obstruction or pleural effusion, and side effects of treatment such as anemia, muscle fatigue, infection, pneumonitis and decreased nutrition. Careful and thorough assessment is paramount in order to manage dyspnea effectively.

      -Airway Obstruction:

      Patients with symptomatic endobronchial and extrinsic airway obstruction can benefit significantly from therapeutic bronchoscopy. Therapeutic bronchoscopic interventions, often used in combination, include debulking of airway tumors mechanically, using laser, electrocautery, cryotherapy, argon plasma coagulation. Balloon dilatation and insertion of silicone or metallic airway stents may be performed to treat extrinsic stenosis or endobronchial strictures due to radiation and covered metallic airway stents are effective in the management of tracheoesophageal fistulas6.

      -Hemoptysis:

      Hemoptysis, occurring in about 7-10% of lung cancer patients, is most commonly due to endobronchial tumor involvement. Rare causes include airway-vascular fistula formation, tumor necrosis with cavity formation, and complications from treatment (bevacizumab). Hemoptysis can be minor or severe/massive, the later defined as more than 200 mL of blood in a 24-hour period and commonly requires intervention. Securing the airway with a single-lumen endotracheal tube is paramount. Bronchoscopy is an excellent tool for both diagnosis and therapeutic intervention when endobronchial disease is found as the cause of the hemoptysis and includes laser, electrocautery, and argon plasma coagulation. External beam radiation therapy may also be used for endobronchial tumors causing hemoptysis6. When hemoptysis is due to parenchymal lesion such cavitary lung lesions due to cancer or due to complications of therapy, external bean radiation therapy or bronchial artery embolization is recommended.

      References:

      1. Cooley ME. Symptoms in adults with lung cancer. A systematic research review. J Pain Symptom Manage 2000;19:137-53

      2. Graves KD, Arnold SM, Love CL, et al. Distress screening in a multidisciplinary lung cancer clinic : prevalence and predictors of clinically significant distress. Lung Cancer 2007; 55:215-24

      3. Rolfo C, Passiglia F, Ostrowski M, et al. Improvement in Lung Cancer Outcomes With Targeted Therapies: An Update for Family Physicians. J Am Board Int Med 2015;28:123-33

      4. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small cell lung cancer. N Engl J Med 2010;363:733-42

      5. Sung MR, Patel MV, Djalalov S, et al. Evolution of Symptom Burden of Advanced Lung Cancer Over a Decade. Clinical Lung Cancer 2017;3:264-80

      6. Simoff MJ, Lally B, Slade MG, et al. Symptom Management in Patients With Lung Cancer. Diagnosis and management of Lung Cancer, 3rded: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2013; 143(5) (Suppl):e455S-e497S

      7. Granger CL. Physiotherapy management of lung cancer. Journal of Physiotherapy 2016; 62:60-67

      8. Holland AE, Wadell K, Spruit MA. How to adapt the pulmonary rehabilitation programme to patients with chronic respiratory disease other than COPD. Eur Respir Rev 2013; 22:405-13

      9.Ayrjla KL, Jensen MP, Mendoza ME, et al. Psychological and Behavioral Approaches to Cancer Pain Management. J Clin Oncol 2014; 32:1703-11

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      MTE26.02 - Symptoms and IO Toxicity Management

      07:30 - 08:00  |  Presenting Author(s): Jarushka Naidoo

      • Abstract

      Abstract not provided

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    MTE27 - Controversies in Radiotherapy for SCLC (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Small Cell Lung Cancer/NET
    • Moderators:
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      MTE27.01 - Radiotherapy in ES-SCLC

      07:00 - 08:00  |  Presenting Author(s): Elizabeth Gore

      • Abstract

      Abstract

      Introduction

      Primary therapy for ED-SCLC is 4-6 cycles of platinum-based chemotherapy followed by PCI in select patients. Although response rates to chemotherapy 60-70%, time-to-progression and median survival are modest (4-6 months and < 10 months, respectively).1 Response and improvement in survival is limited for second-line chemotherapy, particularly if progression is within 30-90 days.2 PCI decreases brain metastases 3 and improve 1-year OS in patients that respond to chemotherapy.4 Consolidative thoracic radiation (TRT) for ED-SCLC has been shown to improve survival and locoregional control in both prospective trials 5,6,7,8 and retrospective reviews.7 Additionally, radiation therapy to extra-thoracic disease as part of primary management changes failure patterns.7 It is difficult to interpret these trials and apply this information on a patient-to-patient basis. The patient population is diverse and patient selection, timing and dose of radiation varies significantly from study-to-study.

      Thoracic Radiation

      The trial published by Jeremic et al in 1999 supported TRT for ED-SLC in patients with at least a PR to locoregional disease and a CR to extrathoracic sites with chemotherapy.6 After chemotherapy patients were randomized to two cycles of carboplatin and etoposide +/- concurrent hyperfractionated RT to the thorax (54Gy/36 fractions). Median Survival (17 months versus 11 months, p=0.041), five-year survival (9.1% versus 3.7%, p=0.041). The CREST trial included 495 patients with ED-SCLC randomly assigned to PCI or PCI and TRT (30Gy/10 fractions) after response to chemotherapy. Two-year OS favored the TRT arm, 13% (95% CI 9–19) versus 3% (95% CI 2–8; p=0.004).5 Additional analysis showed that TRT led to a significant difference in overall and progression-free survival in patients who had residual intrathoracic disease after chemotherapy.9

      NRG 0937 randomized patients with ED-SCLC to radiation versus observation after response to chemotherapy. All patients randomized to treatment had TRT (45 GY in 15 fractions). Patients received consolidative RT to metastatic lesions if they had residual metastases after induction chemotherapy. Patients randomized to radiation had lower rates of local progression.7 Yee et al prospectively evaluated the use of TRT in 32 patients with good response to chemotherapy (40 Gy in 15 fractions) resulting in only 5 thoracic recurrences.8

      Radiation dose, fractionation and timing were different in each of these trials although each has demonstrated the effectiveness of TRT. These trials have not established a standard of care although provide important information for individualizing treatment.

      Failure Patterns

      It is intuitive that the most likely site of failure after chemotherapy for ED-SCLC is in areas of measurable disease at diagnosis, particularly sites without at CR to chemotherapy. In the PCI trial for EDSCLC, 90% of patients had intrathoracic progression in the first year.4 Likewise, patients on 0937 were more likely to fail in in sites of disease present at diagnosis (intrathoracic and metastatic). With proper patient selection and improved systemic therapy to address microscopic metastatic disease, radiation therapy to the chest and oligmetastases is may improve overall survival.

      Prophylactic Cranial Irradiation

      PCI remains controversial for ED-SCLC despite a survival advantage at 1 year demonstrated by Slotman et al4 and advantages of PCI in early trials with subset analysis of patients with extensive disease.10 A Japanese prospective trial did not show a survival benefit with PCI, although demonstrated a decrease in brain failures with PCI.3 Although PCI is generally well tolerated, toxicity remains and concern. Improving the toxicity profile of PCI is being evaluated with use of hippocampal sparing in patients with LD SCLC.

      Conclusion

      Patients with ED-SCLC represent a diverse patient population with a wide range of anticipated outcomes. Radiation is effective for local control and prophylaxis of brain failures although patient selection, timing of radiation, dose and fractionation must be individualized. Patients should enrolled on trials.

      Reference

      1. Hanna N, Bunn PA Jr, Langer C, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patientswith previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. PubMed PMID: 16648503.

      2. Hurwitz JL, McCoy F, Scullin P, et al. New advances in the second-line treatment of small cell lung cancer. Oncologist. 2009 Oct;14(10):986-94. doi:10.1634/theoncologist.2009-0026. PubMed PMID: 19819917.

      3. Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017 May;18(5):663-671. doi: 10.1016/S1470-2045(17)30230-9. PubMed PMID: 28343976.

      4. Slotman B, Faivre-Finn C, Kramer G, et al; EORTC Radiation Oncology Group and Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. PubMed PMID: 17699816.

      5. Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015 Jan 3;385(9962):36-42. doi: 10.1016/S0140-6736(14)61085-0. PubMed PMID: 25230595.

      6. Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: A randomized study. J Clin Oncol. 1999 Jul;17(7):2092-9. PubMed PMID: 10561263.

      7. Gore EM, Hu C, Sun AY, et al. Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937. J Thorac Oncol. 2017Oct;12(10):1561-1570. doi: 10.1016/j.jtho.2017.06.015. PubMedPMID: 28648948; PubMed Central PMCID: PMC5610652

      8. Yee D, Butts C, Reiman A, et al. Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer. Radiother Oncol. 2012 Feb;102(2):234-8. doi: 10.1016/j.radonc.2011.08.042. PubMed PMID: 21930323.Zhu H, Zhou Z, Wang Y, et al. Thoracic radiation therapy improves the overall survival of patients with extensive-stage small cell lung cancer with distant metastasis. Cancer 2011; 117:5423–31.

      9. Slotman BJ, Faivre-Finn C, van Tinteren H, et al. Which patients with ES-SCLC are most likely to benefit from more aggressive radiotherapy: A secondary analysis of the Phase III CREST trial. Lung Cancer. 2017 Jun;108:150-153. doi: 10.1016/j.lungcan.2017.03.007. PubMed PMID: 28625628.

      10. Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999 Aug 12;341(7):476-84. PubMed PMID: 10441603.

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    MTE28 - Lessons from the Past-What I Would Not Do Again in Diagnostic and Therapeutic IP (Ticketed Session)

    • Type: Meet the Expert Session
    • Track: Interventional Diagnostics/Pulmonology
    • Moderators:
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      MTE28.01 - Lessons from the Past-What I Would Not Do Again in Diagnostic and Therapeutic IP

      07:00 - 07:30  |  Presenting Author(s): Navneet Singh  |  Author(s): Inderpaul S Sehgal

      • Abstract

      Abstract

      Lung cancer and pulmonology are inseparable – as lung cancer patients are invariably first seen by pulmonologists, often undergo diagnostic and staging procedures performed by pulmonologists, get evaluated by pulmonologists for fitness for surgical resection (in early stage disease), are treated by pulmonologists at certain geographical regions of the world, undergo follow up with pulmonologists for treatment related complications and/or symptom palliation related to either the disease or associated pulmonary co-morbid conditions. The current focus of this abstract is the role of diagnostic and therapeutic interventional pulmonology (IP) in the context of lung cancer. The growing armamentarium of IP includes several procedures as listed in Table 1 below

      PROCEDURE ROLE
      1. Flexible bronchoscopy
      a) Endobronchial biopsy (EBBx) Diagnosis
      b) Transbronchial lung biopsy (TBLB) Diagnosis
      c) Conventional TBNA (c-TBNA) Diagnosis, Staging
      2. Endobronchial ultrasound (EBUS)
      a) Convex probe EBUS Staging, Diagnosis
      b) Radial probe EBUS Diagnosis
      3. Medical Thoracoscopy
      a) Flexi-rigid Diagnosis, Palliation
      b) Rigid Diagnosis, Palliation
      4. Rigid bronchoscopy
      a) Mechanical coring Palliation, Diagnosis
      b) Stent placement Palliation
      c) Argon plasma coagulation Palliation
      d) Electrocautery Palliation
      e) Laser Palliation
      f) Cryotherapy Palliation

      Endobronchial biopsy (EBBx):

      This is the most frequently performed bronchoscopic procedure for diagnosis of lung cancer. Its relatively safe with a high diagnostic yield (76%-97%). As airway bleeding is one of the commonly encountered problems, the learning points include:

      1)Hot (electrocautery enabled) biopsy from vascular lesions

      2)Avoid biopsy from cavity

      3)Avoid biopsy from an excavating ulcer with vascular supply

      4)Avoid biopsy from tracheal tumor or tumor at the tracheal carina

      Importantly, biopsy with electrocautery enabled forceps does not affect the tissue quality or the diagnostic yield.

      Transbronchial lung biopsy (TBLB):

      In certain situations TBLB is needed for diagnosing diffuse infiltrative lung disease in the setting of lung cancer including but not limited to lymphangitis, drug-induced interstitial lung disease, radiation pneumonitis and secondary infection.

      As pneumothorax, airway bleeding and crush artefacts are the commonly encountered problems, the important learning point is:

      1)Do not use cup forceps for doing TBLB. Alligator forceps is preferred. It is likely that the cup forceps cuts through the blood vessels, whereas the alligator forceps crushes the blood vessels, thus leading to higher bleeding with the former method. In addition, the cup forceps has a smaller diameter (4 mm) compared with the alligator forceps (7 mm) in the open position; thus,it possibly reaches the lung segments more distally compared with the alligator forceps, leading to more pneumothoraces.

      Bronchoscopic staging procedures:

      EBUS-TBNA is an accurate, safe and cost-effective tool for lung cancer staging. It has been shown to have a pooled sensitivity and specificity of 93% and 100% respectively. The subgroup of patients who were selected on the basis of CT or PET positive results had higher pooled sensitivity than those without any selection (94% vs. 76%; p<0.05). EBUS-TBNA and EUS-FNA have been shown to have similar yield but lower complication rates as compared to mediastinoscopy in the initial mediastinal staging of non-small cell lung cancer. These endosonographic procedures are also safe and highly specific (99%) for mediastinal restaging of lung cancer

      The important learning points are:

      1)Use of EBUS-TBNA results in significantly shorter time to treatment decision compared to conventional techniques

      2)Do not use conventional TBNA for staging of lung cancer. EBUS-TBNA is preferred for both diagnosis and staging

      3)Upfront mediastinoscopy for lung cancer staging in untreated patients and for restaging in patients after neoadjuvant chemotherapy (or neoadjuvant chemoradiation) is not needed as endoscopic procedures (EBUS-TBNA, EUS-FNA or their combination) are preferred for both of these

      Medical thoracoscopy:

      Medical thoracoscopy is a very useful procedure for both diagnosis of malignant pleural effusions as well as performing pleurodesis. Most patients present late at our center with extensive pleural adhesions and fibrosis. In such cases, flexi-rigid thoracoscopy has a lower yield in such cases (73% vs. 98%). The important learning point is:

      1)Do not use flexi-rigid thoracoscopy for diagnosis of malignant pleural effusions

      Rigid bronchoscopic procedures:

      These are often undertaken as part of intervention for airway obstruction/stenosis. The important learning points are:

      1)Avoid complex intervention procedures using flexible bronchoscope - prefer doing them using a rigid bronchoscope

      2)Avoid placing stents when the distal airways are involved

      3)When in doubt, place a silicon stent. Silicon stents are easy to extract, work even in malignant disorders, can always be replaced by metallic stents. Sometimes, what appears malignant may not be so and in tuberculosis endemic countries, endobronchial tuberculosis is a great mimicker of malignancy

      4)Never place uncovered metallic stent for malignant disorders

      5)Do not place metallic Y-stents using flexible bronchoscopy as this can be associated with criss-crossing of guidewires, loss of airway control (and immediate conversion to rigid bronchoscopy) and need for fluoroscopic guidance

      6)Do not place silicone stents using flexible bronchoscopy

      In summary, each bronchoscopic procedure has inherent risks and potential for unintended complications. Therefore, each procedure teaches us something. The crux of safety in the context of diagnostic and therapeutic IP in lung cancer is to avoid performing biopsy during flexible bronchoscopy in tracheal tumors associated with airway obstruction, to use EBUS-TBNA for diagnosing/staging lung cancer, performing all complex interventions with a rigid bronchoscope and avoiding stent placements in patients with distal airway involvement. The most important principle for IP and practice of medicine, in general, is Primum non nocere (first do no harm).

      Navneet Singh MD DM

      Email: navneetchd@hotmail.com; singh.navneet@pgimer.edu.in

      [The author is a thoracic medical oncologist-cum-pulmonologist currently working as an Additional Professor of Pulmonary Medicine at PGIMER, Chandigarh, India. He is a member of IASLC’s Staging & Prognostic Factors Committee and is IASLC’s Regent for Indian Subcontinent. Additionally, he is Chair of American Society of Clinical Oncology’s (ASCO) International Development and Education Award (IDEA) Working Group and member of its Thoracic-Cancer Guideline Advisory Group. His detailed profile is accessible at http://www.linkedin.com/in/navneet-singh-160012.]

      Acknowledgement: Dr. Inderpaul Singh Sehgal, Assistant Professor of Pulmonary Medicine, PGIMER, Chandigarh, India

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      MTE28.02 - Lessons from the Past-What I Would Not Do Again in Diagnostic and Therapeutic IP

      07:30 - 08:00  |  Presenting Author(s): Jason S Agulnik

      • Abstract

      Abstract

      Lung cancer is the leading cause of cancer death. The Canadian Cancer Society estimates that there were 28,600 new lung cancer cases diagnosed in 2017 in Canada. It is estimated that there were 21,100 deaths from lung cancer in Canada in 2017. Once a diagnosis of lung cancer is made, proper staging is imperitiive. The lung cancer staging system not only predicts the prognosis but also guides the treatment options. Proper staging requires both imaging tests and biopsies. The mediastinal lymph nodes often need to be sampled to differentiate an early stage lung cancer versus a locally advanced stage III NSCLC. ACCP guidelines for methods for staging NSCLC were last published in 2013 and recommend the following:
      4.4.4.1. In patients with discrete mediastinal lymph node enlargement (and no distant metastases) with or without PET uptake in mediastinal nodes, invasive staging of the mediastinum is recommended over staging by imaging alone (Grade 1C).
      4.4.4.2. In patients with PET activity in a mediastinal lymph node and normal appearing nodes by CT (and no distant metastases), invasive staging of the mediastinum is recommended over staging by imaging alone (Grade 1C).
      4.4.4.3. In patients with high suspicion of N2,3 involvement, either by discrete mediastinal lymph node enlargement or PET uptake (and no distant metastases), a needle technique (EBUS-NA, EUS-NA or combined EBUS/EUS-NA) is recommended over surgical staging as a best first test (Grade 1B).
      4.4.6.1. In patients with an intermediate suspicion of N2,3 involvement, ie, a radiographically normal mediastinum (by CT and PET) and a central tumor or N1 lymph node enlargement (and no distant metastases), invasive staging of the mediastinum is recommended over staging by imaging alone (Grade 1C).
      4.4.6.2. In patients with an intermediate suspicion of N2,3 involvement, ie, a radiographically normal mediastinum (by CT and PET) and a central tumor or N1 lymph node enlargement (and no distant metastases), a needle technique (EBUS-NA, EUS-NA or combined EBUS/EUS-NA) is suggested over surgical staging as a best first test (Grade 2B).
      Mediastinoscopy was a common modality for staging the mediastinum and is considered the gold standard for comparative studies. In 2002, a paper by Herth et al. described for the first time endobronchial ultrasound TBNA for lymph node staging. Non-invasive staging is now recommended as the first procedure to stage the mediastinum. Several papers have demonstrated similar results for EBUS TBNA compared to mediastinoscopy. EBUS TBNA is now commonly used as the first modality for mediastinal staging in lung cancer and is considered an essential tool for the interventional pulmonologist. Despite the advantages of EBUS TBNA, there are still occasions when mediastinoscopy is required. Several cases will be discussed that required mediastinoscopy after nondiagnositic EBUS or EUS biopsies.