- Email: [email protected]
MTE 18.01 Treatment for Squamous Cell Carcinoma
November 2017 classifications of lung cancer (7th and 8th edition) suggest that PNETs should be staged similarly to Non-Small Cell Lung Cancer (NSCLC). Surgical indications largely depend on histology and stage. Bronchial carcinoids (BCs) represent about 10% of PNETs. The vast majority are typical carcinoids (TC, well-differentiated neuroendocrine tumors); they are usually located centrally in the lung parenchyma/airways (70%), and they are frequently confined to the lung without evidence of locoregional or distant spread, which occur in about 5-10% of the cases. Atypical carcinoids (AT) share most of the characteristics of typical carcinoids, although they present a higher rate of mytoses and necrosis. They are more aggressive than TCs and they present with lymphnodal metastatic involvement in 30%-50% of the cases. LCNEC are usually diagnosed after resection, since a preoperative characterization on small biopsies is challenging. They are aggressive tumors, and more than 50% of the patients present with an advanced disease at diagnosis, for whom surgery is not indicated. As for SCLC, the vast majority of the patients present at an advanced stage, with hematogenous spread. The role of surgery in the treatment of PNETs is similar to what is currently employed for NSCLC. BCs are often amenable to surgery, due to the early stage at presentation. Anatomical resections (segmentectomy, lobectomy or more extended resections) offer the best outcome, while sublobar wedge resection should be avoided in fit patients, and should be reserved only for patients not amenable to anatomical resections. Parenchymal-sparing techniques (bronchial/vascular sleeve resection) should be employed whenever possible to avoid pneumonectomy in centrally-located tumors. Lymphadenectomy should be carried out according to the current guidelines (IASLC/ESTS), including a minimum of 6 nodes/stations of which 3 mediastinal including the subcarinal one. Endoscopic resection may have a role only in case of lobar/lung atelectasis to restore the bronchial patency before definite surgical resection Endobronchial resection is also employed with palliative intent in unresectable disease. Survival after resection of BCs is excellent, with more than 90% of the patients with typical carcinoids alive at 10 years, and 70% and 50% with atypical carcinoids alive at 5 and 10 years. The role of adjuvant therapy after complete resection of BCs is not fully determined and it is often discussed on an individual basis in a multidisciplinary tumor board setting. LCNEC are poor candidates for surgery, because of the loco-regional and distant spread at presentation. Anatomical resections, including extended resection to neighboring organs are needed in order to achieve a complete resection. Despite this, local recurrence and distant metastases are frequent after surgery. Adjuvant therapy (chemotherapy or chemoradiotherapy) is almost always needed after surgery for the disease control. SCLC has customarily been considered nonsurgical because of the high aggressiveness and the chemosensitivity of this neoplasm. However, in carefully selected patients with limited disease (T1-T2N0) surgery as part of a multidisciplinary protocol (chemoradiotherapy) may be proposed after a careful assessment of loco-regional (including mediastinal) and distant spread. 2, Thymic NETs: Thymic NETs (NETTs) are usually aggressive thymic tumors, very often presenting atypical features (atypical carcinoid). They express somatostatin receptors which may justify the use of Octreotide scintigraphy for the diagnosis and follow-up. About 30-40% have metastases at presentation and in some cases they are associated with endocrinopaties (Cushing syndrome, MEN-1 syndrome, etc). The staging system for NETTs has traditionally been the Masaoka system. The 7th edition of the TNM of thymic tumors included also the NETTs. As for other thymic malignancies, surgery is the treatment of choice for local and loco-regional disease (Stage I/II and selected Stage III). The resectability rate for NETTs is far lower than that of thymoma, ranging between 30% and 100% in most series. Complete (R0) resection is the most important prognostic factor. Median sternotomy and open surgical approaches are the optimal accesses for NETTs. The role of minimally-invasive techniques (MIT) in the treatment of NETT is extremely limited, due to the aggressive nature of the tumor. The role of induction and adjuvant treatments (radiotherapy or chemotherapy) has not been established yet, due to the rarity of the condition. 3, The Collaborative Effort: As for many
Abstracts
S1647
rare diseases, also for NETs a collaborative, multi-Institutional, society-based effort is the single most important factor that can provide a real advancement in the research and management of this condition. The European Society of Thoracic Surgeons (ESTS) launched in 2012 a Neuroendocrine Tumors Working Group with the aim of collecting data from interested Institutions across the world. An amazing database collating more than 2100 patients has been designed which represents a tremendous opportunity for the study of these rare conditions. A number of studies have been published so far which constitute a solid backbone for the management of NETs. Keywords: Surgery, lung, Neuroendocrine tumors
MTE 18.01 Treatment for Squamous Cell Carcinoma P. Paik Thoracic Oncology, Memorial Sloan Kettering Cancer Center, New York, NY/US Squamous cell lung cancers (SQCLC) account for between 15-25% of non-small cell lung cancer (NSCLC) cases. They are, biologically, quite distinct from lung adenocarcinomas, though this remains a fact that has had little positive effect to date in the management of this disease. Indeed, despite the FDA approval of a handful of new drugs for patients with SQCLCs since 2014, progress has been, for most, limited, reflecting the modest gains in survival achieved by these new agents. Navigating the treatment landscape has been, by turns, straight-forward and frustrating. This is most evident in the first-line setting where, apart from patients whose tumors exhibit high expression of PD-L1, a variety of platinumbased chemotherapy options are available, all with more or less equivalent efficacy as shown in Table 1. Second-line therapy is dictated then largely through exclusion. Patients who received pembrolizumab as firstline treatment will cycle through platinum-based chemotherapy. Patients who received platinum-based chemotherapy will, by and large, cycle through any one of a number of FDA-approved PD-1/PD-L1 antibody therapies, all with equivalent efficacy (pembrolizumab, nivolumab, atezolizumab). Docetaxel +/- ramucirumab is thus relegated to the de facto third-line option. There are, arguably, few clinically meaningful therapeutic options beyond this; the data behind these options will be discussed in further detail. Most recently, attempts have been made to target putative oncogenic drivers in this disease, based on larger scale genomic analyses and pre-clinical experiments generated TCGA and others.4-6 Three relatively large-frequency signaling pathways and targets have been tested in early phase trials, including FGFR1 amplification, PI3K pathway alterations, and G1/S checkpoint aberrations both by individual groups and SWOG (LUNG-MAP, S1400). In short, there has been modest to no efficacy in targeted therapy trials to date. These studies are summarized in Table 2. Most of these studies have lacked detailed molecular analyses of patient tumor samples, hampering our ability to determine why these targeted efforts have largely failed. One exception is the study of AZD4547 in FGFR1 amplified SQCLCs, where correlative tests demonstrated that focal amplification of FGFR1 in the 8p11 amplicon does not occur in the majority of cases, commensurate with relatively low mRNA and protein expression of the gene.7 Overall, heterogeneity with regard to aberrations in overlapping signaling pathways and clonal diversity remains a concern. The rationale for and data from other studies will also be discussed, including early data from combination chemotherapy plus PD-1/L1 inhibition trials as well as potential future directions for research. References: 1. Thatcher N, Hirsch F, Luft A, Szczesna A, Ciuleanu T, Szafranski W, et al. A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). J Clin Oncol. 2014:abstr 8008. 2. Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al. Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced NoneSmall-Cell Lung Cancer: Final Results
S1648
Journal of Thoracic Oncology
Vol. 12 No. 11S2
Table 1
ORR (%) Median PFS (mo) Median OS (mo)
cisplatin + gemcitabine + necitumumab1
cisplatin + gemcitabine1
carboplatin + nab-paclitaxel2
carboplatin + paclitaxel2
cisplatin + docetaxel3
31 5.7 11.5
29 5.5 9.9
41 5.6 10.7
24 5.7 9.5
37 11.3
Table 2 Target
Frequency
FGFR1 amplification
Up to 20%
PI3K pathway
Up to 50%
G1/S checkpoint
Up to 50%
Drug
ORR 7
AZD4547 BGJ-3988 Dovitinib9 BKM12010 GDC-0032(ASCO 2017) Abemaciclib11
8% 15% 11.5% 0% 5% 17%
of a Phase III Trial. Journal of Clinical Oncology. 2012;30:2055-62. 3. Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, et al. Phase III Randomized Trial of Docetaxel Plus Cisplatin Versus Vindesine Plus Cisplatin in Patients With Stage IV Non-Small-Cell Lung Cancer: The Japanese Taxotere Lung Cancer Study Group. Journal of Clinical Oncology. 2004;22:254-61. 4. TCGA Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519-25. 5. Paik PK, Shen R, Won H, Rekhtman N, Wang L, Sima CS, et al. Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases. Cancer Discovery. 2015;5:610-21. 6. Kim Y, Hammerman PS, Kim J, Yoon J-a, Lee Y, Sun J-M, et al. Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients. Journal of Clinical Oncology. 2014;32:121-8. 7. Paik PK, Shen R, Berger MF, Ferry D, Soria J-C, Mathewson A, et al. A Phase 1b Open Label Multicentre Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers. Clinical Cancer Research. 2017. 8. Nogova L, Sequist LV, Garcia JMP, Andre F, Delord J-P, Hidalgo M, et al. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, DoseEscalation and Dose-Expansion Study. Journal of Clinical Oncology. 2017;35:157-65. 9. Lim SH, Sun J-M, Choi Y-L, Kim HR, Ahn S-M, Lee JY, et al. Efficacy and Safety of Dovitinib in Pretreated Advanced Squamous Non-small Cell Lung Cancer with FGFR1 Amplification: A Single-arm, Phase II Study. Cancer. 2016. 10. Vansteenkiste JF, Canon J-L, De Braud F, Grossi F, De Pas T, Gray JE, et al. Safety and Efficacy of Buparlisib (BKM120) in Patients With PI3K Pathway-Activated Non-Small Cell Lung Cancer (NSCLC): Results From the Phase II BASALT-1 Study. Journal of Thoracic Oncology. 2015;Publish Ahead of Print. 11. Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, et al. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, NoneSmall Cell Lung Cancer, and Other Solid Tumors. Cancer Discovery. 2016. Keywords: squamous, FGFR1, PI3K
MTE 19.01 Laser Therapy for Airway Obstruction K. Sakata Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, NY/US Malignant central airway obstruction (mCAO) occurs in patients with lung cancer and in patients with pulmonary metastases from other malignancies, including thyroid, breast, renal cell, and colon.1 It is loosely defined as obstruction of >50% of the central airways.2 Malignant CAO
results in dramatic alterations to quality of life (QOL), decreased functional status, bleeding, post-obstructive pneumonia, and a poor prognosis.3,4 The principle goal in the management of mCAO is to restore airway patency, palliate, improve QOL and symptoms, spirometric values, and survival.1,5-7 There are 3 classifications of mCAO: endobronchial, extrinsic, or mixed. Multiple ablative bronchoscopic tools are available to relieve endobronchial or mixed obstructions.8 Ablative techniques include lasers, electrocautery, argon plasma coagulation, photodynamic therapy, microdebriders, and cryotherapy.1 Stents are primarily used to treat patients with mixed and extrinsic airway obstruction.1 Lasers have no role in the management of extrinsic airway obstruction.9 Ost and colleagues1 showed that among 26 physicians from 15 centers, performing over 1,100 procedures, there was significant practice pattern variability. They also report that there was no single best ablative technique with regard the primary goal of improvements in dyspnea or QOL. There are no large clinical trials comparing various ablative modalities head-to-head and thus, superiority of one technique over another remains undefined.3 However, all ablative techniques can be used alone or in combination.8 In order to obtain optimal treatment outcomes, physicians should be competent and versatile in the use of multiple complementary modalities. Herein, we provide a clinical review of lasers, a technique that delivers a non-contact heat energy by light via catheter9,10, in the management of mCAO. The effectiveness of lasers in achieving relief of obstruction and symptomatic improvement from mCAO in very large series established credibility of this modality.11 Although outcome data is limited, laser therapy appears to be effective in providing rapid relief of endobronchial obstruction with symptomatic improvement in 70-80%.9,12-15 One-year survival following treatment was around 30%.9 Local disease recurrence with mCAO is typical unless tumor debulking is followed by adjunctive therapies.16 Several types of lasers exist and each use different media to generate light.10 The details and specific role of each laser is beyond the scope of this discussion. Special focus has been placed on the Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser because it has become the most frequently used nonsurgical technique in the management of malignant and benign endobronchial disorders.12,13,17-19 One significant advantage of the Nd:YAG laser is its balanced properties in its ability to photocoagulate or vaporize tumor and cut stenotic lesions. Its ability to photocoagulate and vaporize before mechanical debulking allows for improved control of hemorrhage in the airway during bronchoscopy.9,10 Dumon et al. and Cavaliere et al were among the first to report their experience of the Nd:YAG laser in benign and mCAO.12,13 Cavaliere and colleagues showed an improvement in airway lumen in 92% of patients with mCAO.12 In a follow up article, the largest series to date, radiographic improvement was noted in 93% of patients with bronchogenic carcinoma, and their overall complication rate was 2.3%(20). A disadvantage of the Nd:YAG laser is the associated considerable set-up, maintenance costs, and its bulky size. The power and distance of the fiber from the lesions as well as the ration of absorption and scattering coefficients of laser determine the tissue effect.10 Lower power or the farther the distance between the laser fiber and the lesion lead to a shallow effect and cause superficial tissue coagulation. Conversely, higher power settings or a shorter distance between the laser and lesion result in deeper penetration causing tissue carbonization and vaporization.10 Safety of Nd:YAG laser in airway procedures has been well established and with appropriate precautions, the safety record of laser therapy is excellent. Protective eyewear is mandatory when the laser beam is activated.17 A “timeout” should be performed to confirm that the fraction of inspired oxygen setting is
Abstracts
S1647
rare diseases, also for NETs a collaborative, multi-Institutional, society-based effort is the single most important factor that can provide a real advancement in the research and management of this condition. The European Society of Thoracic Surgeons (ESTS) launched in 2012 a Neuroendocrine Tumors Working Group with the aim of collecting data from interested Institutions across the world. An amazing database collating more than 2100 patients has been designed which represents a tremendous opportunity for the study of these rare conditions. A number of studies have been published so far which constitute a solid backbone for the management of NETs. Keywords: Surgery, lung, Neuroendocrine tumors
MTE 18.01 Treatment for Squamous Cell Carcinoma P. Paik Thoracic Oncology, Memorial Sloan Kettering Cancer Center, New York, NY/US Squamous cell lung cancers (SQCLC) account for between 15-25% of non-small cell lung cancer (NSCLC) cases. They are, biologically, quite distinct from lung adenocarcinomas, though this remains a fact that has had little positive effect to date in the management of this disease. Indeed, despite the FDA approval of a handful of new drugs for patients with SQCLCs since 2014, progress has been, for most, limited, reflecting the modest gains in survival achieved by these new agents. Navigating the treatment landscape has been, by turns, straight-forward and frustrating. This is most evident in the first-line setting where, apart from patients whose tumors exhibit high expression of PD-L1, a variety of platinumbased chemotherapy options are available, all with more or less equivalent efficacy as shown in Table 1. Second-line therapy is dictated then largely through exclusion. Patients who received pembrolizumab as firstline treatment will cycle through platinum-based chemotherapy. Patients who received platinum-based chemotherapy will, by and large, cycle through any one of a number of FDA-approved PD-1/PD-L1 antibody therapies, all with equivalent efficacy (pembrolizumab, nivolumab, atezolizumab). Docetaxel +/- ramucirumab is thus relegated to the de facto third-line option. There are, arguably, few clinically meaningful therapeutic options beyond this; the data behind these options will be discussed in further detail. Most recently, attempts have been made to target putative oncogenic drivers in this disease, based on larger scale genomic analyses and pre-clinical experiments generated TCGA and others.4-6 Three relatively large-frequency signaling pathways and targets have been tested in early phase trials, including FGFR1 amplification, PI3K pathway alterations, and G1/S checkpoint aberrations both by individual groups and SWOG (LUNG-MAP, S1400). In short, there has been modest to no efficacy in targeted therapy trials to date. These studies are summarized in Table 2. Most of these studies have lacked detailed molecular analyses of patient tumor samples, hampering our ability to determine why these targeted efforts have largely failed. One exception is the study of AZD4547 in FGFR1 amplified SQCLCs, where correlative tests demonstrated that focal amplification of FGFR1 in the 8p11 amplicon does not occur in the majority of cases, commensurate with relatively low mRNA and protein expression of the gene.7 Overall, heterogeneity with regard to aberrations in overlapping signaling pathways and clonal diversity remains a concern. The rationale for and data from other studies will also be discussed, including early data from combination chemotherapy plus PD-1/L1 inhibition trials as well as potential future directions for research. References: 1. Thatcher N, Hirsch F, Luft A, Szczesna A, Ciuleanu T, Szafranski W, et al. A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC). J Clin Oncol. 2014:abstr 8008. 2. Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, et al. Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced NoneSmall-Cell Lung Cancer: Final Results
S1648
Journal of Thoracic Oncology
Vol. 12 No. 11S2
Table 1
ORR (%) Median PFS (mo) Median OS (mo)
cisplatin + gemcitabine + necitumumab1
cisplatin + gemcitabine1
carboplatin + nab-paclitaxel2
carboplatin + paclitaxel2
cisplatin + docetaxel3
31 5.7 11.5
29 5.5 9.9
41 5.6 10.7
24 5.7 9.5
37 11.3
Table 2 Target
Frequency
FGFR1 amplification
Up to 20%
PI3K pathway
Up to 50%
G1/S checkpoint
Up to 50%
Drug
ORR 7
AZD4547 BGJ-3988 Dovitinib9 BKM12010 GDC-0032(ASCO 2017) Abemaciclib11
8% 15% 11.5% 0% 5% 17%
of a Phase III Trial. Journal of Clinical Oncology. 2012;30:2055-62. 3. Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, et al. Phase III Randomized Trial of Docetaxel Plus Cisplatin Versus Vindesine Plus Cisplatin in Patients With Stage IV Non-Small-Cell Lung Cancer: The Japanese Taxotere Lung Cancer Study Group. Journal of Clinical Oncology. 2004;22:254-61. 4. TCGA Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519-25. 5. Paik PK, Shen R, Won H, Rekhtman N, Wang L, Sima CS, et al. Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases. Cancer Discovery. 2015;5:610-21. 6. Kim Y, Hammerman PS, Kim J, Yoon J-a, Lee Y, Sun J-M, et al. Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients. Journal of Clinical Oncology. 2014;32:121-8. 7. Paik PK, Shen R, Berger MF, Ferry D, Soria J-C, Mathewson A, et al. A Phase 1b Open Label Multicentre Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers. Clinical Cancer Research. 2017. 8. Nogova L, Sequist LV, Garcia JMP, Andre F, Delord J-P, Hidalgo M, et al. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, DoseEscalation and Dose-Expansion Study. Journal of Clinical Oncology. 2017;35:157-65. 9. Lim SH, Sun J-M, Choi Y-L, Kim HR, Ahn S-M, Lee JY, et al. Efficacy and Safety of Dovitinib in Pretreated Advanced Squamous Non-small Cell Lung Cancer with FGFR1 Amplification: A Single-arm, Phase II Study. Cancer. 2016. 10. Vansteenkiste JF, Canon J-L, De Braud F, Grossi F, De Pas T, Gray JE, et al. Safety and Efficacy of Buparlisib (BKM120) in Patients With PI3K Pathway-Activated Non-Small Cell Lung Cancer (NSCLC): Results From the Phase II BASALT-1 Study. Journal of Thoracic Oncology. 2015;Publish Ahead of Print. 11. Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, et al. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, NoneSmall Cell Lung Cancer, and Other Solid Tumors. Cancer Discovery. 2016. Keywords: squamous, FGFR1, PI3K
MTE 19.01 Laser Therapy for Airway Obstruction K. Sakata Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, NY/US Malignant central airway obstruction (mCAO) occurs in patients with lung cancer and in patients with pulmonary metastases from other malignancies, including thyroid, breast, renal cell, and colon.1 It is loosely defined as obstruction of >50% of the central airways.2 Malignant CAO
results in dramatic alterations to quality of life (QOL), decreased functional status, bleeding, post-obstructive pneumonia, and a poor prognosis.3,4 The principle goal in the management of mCAO is to restore airway patency, palliate, improve QOL and symptoms, spirometric values, and survival.1,5-7 There are 3 classifications of mCAO: endobronchial, extrinsic, or mixed. Multiple ablative bronchoscopic tools are available to relieve endobronchial or mixed obstructions.8 Ablative techniques include lasers, electrocautery, argon plasma coagulation, photodynamic therapy, microdebriders, and cryotherapy.1 Stents are primarily used to treat patients with mixed and extrinsic airway obstruction.1 Lasers have no role in the management of extrinsic airway obstruction.9 Ost and colleagues1 showed that among 26 physicians from 15 centers, performing over 1,100 procedures, there was significant practice pattern variability. They also report that there was no single best ablative technique with regard the primary goal of improvements in dyspnea or QOL. There are no large clinical trials comparing various ablative modalities head-to-head and thus, superiority of one technique over another remains undefined.3 However, all ablative techniques can be used alone or in combination.8 In order to obtain optimal treatment outcomes, physicians should be competent and versatile in the use of multiple complementary modalities. Herein, we provide a clinical review of lasers, a technique that delivers a non-contact heat energy by light via catheter9,10, in the management of mCAO. The effectiveness of lasers in achieving relief of obstruction and symptomatic improvement from mCAO in very large series established credibility of this modality.11 Although outcome data is limited, laser therapy appears to be effective in providing rapid relief of endobronchial obstruction with symptomatic improvement in 70-80%.9,12-15 One-year survival following treatment was around 30%.9 Local disease recurrence with mCAO is typical unless tumor debulking is followed by adjunctive therapies.16 Several types of lasers exist and each use different media to generate light.10 The details and specific role of each laser is beyond the scope of this discussion. Special focus has been placed on the Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser because it has become the most frequently used nonsurgical technique in the management of malignant and benign endobronchial disorders.12,13,17-19 One significant advantage of the Nd:YAG laser is its balanced properties in its ability to photocoagulate or vaporize tumor and cut stenotic lesions. Its ability to photocoagulate and vaporize before mechanical debulking allows for improved control of hemorrhage in the airway during bronchoscopy.9,10 Dumon et al. and Cavaliere et al were among the first to report their experience of the Nd:YAG laser in benign and mCAO.12,13 Cavaliere and colleagues showed an improvement in airway lumen in 92% of patients with mCAO.12 In a follow up article, the largest series to date, radiographic improvement was noted in 93% of patients with bronchogenic carcinoma, and their overall complication rate was 2.3%(20). A disadvantage of the Nd:YAG laser is the associated considerable set-up, maintenance costs, and its bulky size. The power and distance of the fiber from the lesions as well as the ration of absorption and scattering coefficients of laser determine the tissue effect.10 Lower power or the farther the distance between the laser fiber and the lesion lead to a shallow effect and cause superficial tissue coagulation. Conversely, higher power settings or a shorter distance between the laser and lesion result in deeper penetration causing tissue carbonization and vaporization.10 Safety of Nd:YAG laser in airway procedures has been well established and with appropriate precautions, the safety record of laser therapy is excellent. Protective eyewear is mandatory when the laser beam is activated.17 A “timeout” should be performed to confirm that the fraction of inspired oxygen setting is