Show 3 more Management of metastatic disease (genotype-driven therapy, other genetic alterations): offer platinum-doublet chemotherapy with or without immune checkpoint inhibitors as first-line therapy in patients with MET amplification, NTRK gene fusion, HER2 mutation, or EGFR exon 20 mutation. B Show 4 more https://web.pathway.md/diseases/recomSJPzaod1SYuA 14/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway Management of metastatic disease (salvage surgery): consider offering lung resection with therapeutic intent or a salvage procedure for a primary or metastatic lesion in case of specific complications treatable with salvage surgery in highly selected patients. C Management of metastatic disease, oligometastatic disease: As per ESTRO/ASTRO 2023 guidelines, ensure a patient-centered multidisciplinary team approach for treatment decision-making in patients with oligometastatic NSCLC. E Show 23 more As per ESMO 2022 guidelines: Recognize that patients with oligometastatic disease at diagnosis may experience long-term progression-free survival following systemic therapy and local ablative therapy, such as high- dose radiotherapy or surgery, B but due to limited evidence, prefer inclusion in clinical trials. Recognize that patients with advanced NSCLC and a driver mutation with oligoprogression while on molecular-targeted therapy may benefit from local ablative therapy (high-dose radiotherapy or surgery), including improved long-term disease-free survival, but due to limited data, prefer inclusion in clinical trials. As per ESMO 2022 guidelines, obtain 18F-FDG-positron emission tomography-CT and brain imaging for staging in patients with oligometastatic NSCLC (synchronous, metachronous, oligoprogressive). B Show 2 more Management of metastatic disease (isolated brain metastasis): consider obtaining invasive mediastinal staging and extrathoracic imaging (either whole-body positron emission tomography or abdominal CT plus bone scan) in patients with isolated brain metastasis from NSCLC planned for curative-intent surgical resection. C Show 3 more Management of metastatic disease (isolated adrenal gland metastasis): consider obtaining invasive mediastinal staging and extrathoracic imaging (head CT/MRI plus either whole-body positron emission tomography or abdominal CT plus bone scan) in patients with isolated adrenal metastasis from NSCLC planned for curative-intent surgical resection. C Show 3 more Management of metastatic disease (elderly patients): offer a two-drug combination of monthly carboplatin and weekly paclitaxel in elderly patients (age 70-79 years) with stage IV NSCLC with good performance status and limited comorbidities. A Show 3 more Management of metastatic disease, palliative care: As per ESMO 2022 guidelines, offer early palliative care interventions in parallel with standard oncological care in patients with metastatic lung cancer. A As per ACCP 2013 guidelines, consider offering early palliative care combined with standard oncology care in patients with stage IV lung cancer and/or a high symptom burden. C Show 2 more https://web.pathway.md/diseases/recomSJPzaod1SYuA 15/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway Landmark trials: Early palliative care for metastatic NSLC In patients with newly diagnosed metastatic non-small cell lung cancer, within 8 weeks after diagnosis, early palliative care was superior to standard oncologic care with respect to a FACT-L quality of life scores at 12 weeks. Temel JS et al. N Engl J Med. 2010 Aug 19. Management of metastatic disease (assessment of response, genotype-driven therapy): Obtain response evaluation after 8-12 weeks of genotype-driven treatment using the same radiographic investigation that initially demonstrated the tumor lesions. B Do not obtain routine follow-up positron emission tomography due to its relatively low specificity despite a high sensitivity. B Follow the RECIST for measurements and response assessment. B Recognize that the clinical relevance of the RECIST in evaluating the response remains debatable as patients can derive benefit from continuing the same TKIs after RECIST v1.1 progression. B Management of metastatic disease (assessment of response, non-genotype-driven therapy): obtain an assessment of treatment response after 2-3 cycles of systemic therapy using the same initial radiographic investigation that demonstrated tumor lesions. B Do not obtain routine follow- up positron emission tomography due to its high sensitivity and relatively low specificity. B Show 2 more Symptomatic management (pain control): obtain a thorough assessment of patients with lung cancer experiencing chronic pain. B Show 9 more Symptomatic management (cough): obtain evaluation for other treatable causes of cough, in addition to cancer-related etiologies, in all patients with lung cancer and troublesome cough. B Show 2 more Symptomatic management, hemoptysis: As per ESMO 2022 guidelines, consider performing an endoscopy (endobronchial or by guiding endovascular embolization) for the diagnosis and treatment of hemoptysis. C Show 2 more As per ACCP 2013 guidelines: Secure the airway with a single-lumen endotracheal tube in patients with lung cancer and large-volume hemoptysis. Perform bronchoscopy to identify the source of bleeding, followed by endobronchial management options such as argon plasma coagulation, Nd-YAG laser, and electrocautery for visible central airway lesions. B Perform bronchoscopy to identify the source of bleeding in patients with lung cancer and non- large-volume hemoptysis. Offer endobronchial management options for visible central airway lesions. Offer EBRT for distal or parenchymal lesions. B Symptomatic management, airway obstruction: https://web.pathway.md/diseases/recomSJPzaod1SYuA 16/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway As per ESMO 2022 guidelines, offer EBRT in patients with hemoptysis and symptomatic airway obstruction. B Show 2 more As per ACCP 2013 guidelines, perform therapeutic bronchoscopy with mechanical debridement, brachytherapy, tumor ablation, or airway stent placement to improve dyspnea, cough, hemoptysis, and overall quality of life in patients with inoperable disease and symptomatic airway obstruction. B Symptomatic management, pleural effusion: As per ESMO 2022 guidelines: Perform talc pleurodesis to improve dyspnea in patients with persisting or recurrent pleural effusions. Consider performing thoracoscopic poudrage over injection of talc slurry in patients with primary lung cancer. B Consider performing placement of an indwelling pleural catheter or talc poudrage for the management of recurrent malignant pleural effusions. C As per ACCP 2013 guidelines, perform tunneled pleural catheter placement or chemical pleurodesis with talc in patients with symptomatic recurrent malignant pleural effusion with documented re-expandable lung. B Show 3 more Symptomatic management (trapped lung): perform indwelling pleural catheter placement or pleuroperitoneal shunting to provide symptomatic relief in patients with a trapped lung by a thickened visceral pleural peel. B Symptomatic management (tracheoesophageal fistulas): perform double stenting of the esophagus and airway or esophageal stenting with self-expanding metallic stents in patients with tracheoesophageal fistulas. B Symptomatic management, superior vena cava syndrome: As per ESMO 2022 guidelines: Consider offering radiotherapy to achieve symptom control in patients with vena cava syndrome. C Consider performing vascular stenting in patients with NSCLC-related superior vena cava compression. C As per ACCP 2013 guidelines, obtain histologic or cytologic methods to confirm the definitive diagnosis of lung cancer before initiating treatment in patients with superior vena cava obstruction from suspected lung cancer. B Show 2 more Symptomatic management, neurologic symptoms: As per ESMO 2022 guidelines, consider offering radiotherapy to achieve symptom control in patients with soft tissue or neural invasion. C As per ACCP 2013 guidelines, administer dexamethasone at 16 mg/day during definitive therapy in patients with symptomatic brain metastases, and taper the dose as allowed by https://web.pathway.md/diseases/recomSJPzaod1SYuA 17/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway neurologic symptoms. B Show 3 more Symptomatic management, spinal cord compression: As per ESMO 2022 guidelines, offer early radiotherapy to relieve neurological symptoms from spinal cord compression. B As per ACCP 2013 guidelines, obtain MRI (sagittal T1-weighted) of the entire spine in patients with new-onset back pain. B Show 2 more Symptomatic management, bone symptoms: As per ESMO 2022 guidelines, consider offering radiotherapy to achieve symptom control in patients with painful chest wall disease and bone metastasis. C As per ACCP 2013 guidelines, offer external radiotherapy for pain relief in patients with pain due to bone metastases. A Show 3 more Symptomatic management (psychological symptoms): obtain a comprehensive biopsychosocial assessment soon after the diagnosis of lung cancer and at key transition points (completion of treatment, disease progression, and new symptom onset) thereafter for the remainder of life. B Show 8 more 6. Nonpharmacologic interventions Smoking cessation: As per ESMO 2017 guidelines, advise smoking cessation in all patients with NSCLC. Offer combined behavior techniques and pharmacotherapy. A As per ACCP 2013 guidelines, offer perioperative cessation pharmacotherapy, ideally initiated in the preoperative period, to improve abstinence rates in patients with lung cancer undergoing surgery. B Consider offering cessation counseling alone if pharmacotherapy is contraindicated or refused. B Initiate counseling and pharmacotherapy at the outset of surgical intervention in patients attempting cessation in conjunction with surgical interventions. B Show 2 more Alternative and complementary therapies: ask all patients with lung cancer about their interest in and usage of complementary therapies. Counsel on the benefits and risks of those therapies should be provided. B Show 8 more 7. Perioperative care Preoperative cardiorespiratory assessment: https://web.pathway.md/diseases/recomSJPzaod1SYuA 18/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway As per ESMO 2017 guidelines, assess the cardiopulmonary fitness of the patient with non- metastatic NSCLC for treatment decision-making. Obtain a precise assessment of cardiac and pulmonary function to estimate the risk of operative morbidity before surgical resection. Use the recalibrated RCRI for cardiac assessment. B Show 4 more As per ACCP 2013 guidelines, obtain an assessment by a multidisciplinary team (including a thoracic surgeon specializing in lung cancer, a medical oncologist, a radiation oncologist, and a pulmonologist) in patients with lung cancer planned for curative surgical resection. Obtain a full evaluation in elderly patients with lung cancer planned for curative surgical resection, regardless of age. B Show 11 more Perioperative thromboprophylaxis (lobectomy/segmentectomy): consider administering parenteral anticoagulation with subcutaneous LMWH or UFH for VTE prevention in patients undergoing lobectomy or segmentectomy. C Consider preferring LMWH over UFH. C Show 7 more Perioperative thromboprophylaxis (pneumonectomy): consider administering parenteral anticoagulation with subcutaneous LMWH or UFH for VTE prevention in patients undergoing pneumonectomy or extended lung resection. C Consider preferring LMWH over UFH. C Show 6 more 8. Specific circumstances Patients with central lung cancer (bronchial intraepithelial neoplasia): consider performing standard white light bronchoscopy to exclude an endobronchial lesion in patients with severe dysplasia or carcinoma in situ in sputum cytology with chest imaging showing no localizing abnormality. C Show 4 more Patients with central lung cancer, early-stage disease: As per ESMO 2017 guidelines, perform a bronchoscopy to obtain a pathological diagnosis of centrally located tumors in stages I-II with a biopsy of any visible lesion. B As per ACCP 2013 guidelines, consider performing sleeve or bronchoplastic resection over pneumonectomy in patients with clinical stages I-II central NSCLC suitable for complete resection. C Patients with central lung cancer, locally advanced disease: As per ESMO 2017 guidelines, perform a bronchoscopy to obtain a pathological diagnosis of centrally located tumors in stage III with a biopsy of any visible lesion. B As per ESMO 2017 guidelines, consider offering concurrent chemoradiotherapy followed by definitive surgery (within 4 weeks after the end of radiotherapy) in highly selected patients with potentially resectable T3 or T4 central tumors in experienced centers. C https://web.pathway.md/diseases/recomSJPzaod1SYuA 19/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway As per ACCP 2013 guidelines, obtain extrathoracic imaging (head CT/MRI plus either whole- body positron emission tomography or abdominal CT plus bone scan) in patients with a clinical T4 N0, 1 M0 NSCLC planned for curative resection. B Show 2 more Patients with central lung cancer (metastatic disease): perform a bronchoscopy for central lesions, which can be combined with bronchial washing, brushing, and bronchial and transbronchial biopsy. B Patients with central lung cancer (follow-up): perform surveillance bronchoscopy at 1, 2, and 3 months and thereafter at 3-month intervals during the first year, then every 6 months until 5 years in patients with early central airway SCC treated by curative-intent photodynamic therapy. B Patients with Pancoast tumor (evaluation): obtain a tissue diagnosis before initiating treatment in patients with a Pancoast tumor. B Show 2 more Patients with Pancoast tumor, neoadjuvant therapy: As per ASCO 2022 guidelines, offer neoadjuvant concurrent chemoradiotherapy in patients with resectable superior sulcus disease. B As per ESMO 2017 guidelines, offer concurrent chemoradiotherapy before definitive surgery in patients with a potentially resectable superior sulcus tumor. B As per ACCP 2013 guidelines, consider offering preoperative concurrent chemoradiotherapy before surgical resection in patients with a potentially resectable Pancoast tumor (and good performance status). C Patients with Pancoast tumor, surgical resection: As per ESMO 2017 guidelines, perform surgery within 4 weeks after the end of induction radiotherapy. B As per ACCP 2013 guidelines: Make every effort to achieve complete resection in patients undergoing resection of a Pancoast tumor. B Consider performing lobectomy (instead of a non-anatomic wedge resection) and resection of chest wall structures in patients undergoing resection of a Pancoast tumor. C Patients with Pancoast tumor (definitive and palliative therapy): Consider offering definitive concurrent chemotherapy and radiotherapy in patients with an unresectable, non-metastatic Pancoast tumor with good performance status. C Consider offering palliative radiotherapy in patients with a Pancoast tumor ineligible for curative- intent treatment. C Patients with tumors invading the chest wall: consider obtaining invasive mediastinal staging and extrathoracic imaging (head CT/MRI plus either whole-body positron emission tomography or abdominal CT plus bone scan) in patients with NSCLC invading the chest wall planned for curative-intent surgical resection. C Show 2 more https://web.pathway.md/diseases/recomSJPzaod1SYuA 20/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway Patients with additional pulmoary nodules (same lobe): do not obtain further diagnostic workup of the additional nodule in patients with suspected or proven lung cancer and an additional (suspected) tumor nodule within the same lobe. D Show 2 more Patients with additional pulmoary nodules (ipsilateral different lobe): exclude the possibility that an ipsilateral different lobe nodule represents a benign lesion or synchronous primary lung cancer in patients with suspected or proven lung cancer, taking into account clinical, radiologic, and tumor cytologic/histologic features (if available). B Show 3 more Patients with additional pulmoary nodules, contralateral lobe: As per ESMO 2022 guidelines, consider regarding solitary lesions in the contralateral lung, in most cases, as synchronous second primary tumors and, if possible, treat with curative-intent therapy. C As per ACCP 2013 guidelines: Consider obtaining an evaluation of extrathoracic metastases (by positron emission tomography and brain MRI/CT) and invasive evaluation to rule out mediastinal node involvement in patients with a contralateral lobe tumor nodule. C Consider performing resection of each lesion in patients with NSCLC and a contralateral lobe tumor nodule (and no mediastinal or distant metastases), provided the patient has an adequate pulmonary reserve. C Patients with multifocal lung cancer (evaluation): Consider classifying multiple lesions at least partially ground glass and suspected to be malignant as multifocal lung cancer. C Avoid obtaining routine distant and mediastinal staging in patients with suspected or proven multifocal lung cancer with a negative clinical evaluation and normal mediastinum by CT. D Patients with multifocal lung cancer, management: As per ESMO 2017 guidelines, perform complete resection in patients with multifocal lung cancer whenever possible. Discuss all cases of multifocal lung cancer in a multidisciplinary tumor board. B As per ACCP 2013 guidelines: Consider offering curative-intent treatment in patients with suspected or proven multifocal lung cancer. C Consider performing sublobar resection of all lesions suspected of being malignant, if feasible, in patients with suspected or proven multifocal lung cancer. C Patients with second primary lung cancer: consider identifying two foci typical of primary lung cancer (either proven or suspected, i.e., solid, spiculated masses) as second primary lung cancers (either synchronous or metachronous) based on the judgment of a multidisciplinary team, taking into account clinical, radiologic, and tumor cytologic/histologic features (if available). C Show 2 more https://web.pathway.md/diseases/recomSJPzaod1SYuA 21/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway 9. Preventative measures Smoking cessation: As per ACCP 2021 guidelines, offer evidence-based tobacco cessation treatment in current smokers undergoing low-dose CT screening. B As per ACCP 2013 guidelines: Provide counseling and offer pharmacotherapy for smoking cessation in current smokers undergoing low-dose CT screening. B Offer intensive cessation interventions in current smokers with demonstrated smoking-related pulmonary disease. B Diet: Consider advising a diet rich in non-starchy vegetables and fruits to reduce the risk of lung cancer in individuals at risk of developing lung cancer. C Consider advising to limit the consumption of large amounts of red meat and processed meat to reduce the risk of lung cancer in individuals at risk of developing lung cancer. C Chemoprevention: Do not use the following agents for primary, secondary, or tertiary prevention of lung cancer in individuals at risk for lung cancer or in patients with a history of lung cancer: -carotene vitamin E retinoids N-acetylcysteine and isotretinoin. D Show 3 more 10. Follow-up and surveillance Surveillance after curative-intent therapy: As per ESMO 2021 guidelines: Monitor for treatment-related complications, detection of treatable relapse, or occurrence of second primary lung cancer in patients with NSCLC treated with radical-intent therapy. Obtain multidisciplinary team assessment for feasibility check for treatment of locoregional relapse. B Obtain surveillance every 6 months for 2 years with a visit including history, physical examination, and contrast-enhanced chest and abdominal CT at least at 12 and 24 months, with optional 18F-FDG-positron emission tomography, if required, and thereafter an annual visit including history, physical examination, and chest/upper abdominal CT to detect second primary tumors. B As per ASCO 2020 guidelines, obtain surveillance imaging for recurrence every 6 months for 2 years after definitive curative-intent therapy. B Obtain surveillance imaging for the detection of new primary lung cancers annually after the first 2 years. B Show 5 more https://web.pathway.md/diseases/recomSJPzaod1SYuA 22/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway As per ACCP 2013 guidelines, involve the original treating physicians in decision-making during the follow-up and surveillance of patients with NSCLC treated with curative-intent therapy. B Show 5 more Surveillance after palliative therapy: As per ESMO 2022 guidelines: Obtain follow-up every 6-12 weeks if there is an option for the next line of therapy. B Obtain follow-up CT every 3-4 months after scheduled immune checkpoint inhibitor therapy without signs of disease progression. Consider increasing this interval in patients off therapy at 5 years. B As per ESMO 2017 guidelines: Obtain follow-up CT every 6 months for 3 years in individual patients suitable for salvage treatment, such as surgery or local ablative therapy. B Consider tailoring the frequency of the follow-up visits to the individual patients unsuitable for salvage treatment. B Obtain FDG- positron emission tomography selectively in patients with a recurrence after stereotactic ablative radiotherapy suspected based on serial spiral chest CT. B Perform a biopsy in patients suitable for salvage therapy, whenever possible, due to a high number of false-positive findings on positron emission tomography. B Clinical findings Patient demographics Symptoms Elderly Arm pain Chest discomfort Past medical history Chest pain Cough AAT deficiency Fatigue Adrenal metastasis Hemoptysis Bone metastasis Hoarseness Brain metastasis Loss of appetite COPD Malaise Dermatomyositis Pleuritic chest pain Human immunodeficiency virus infection Shortness of breath Shoulder pain Liver metastasis Weight loss Polymyositis Radiation therapy to the chest area Social history Superficial thrombophlebitis Exposure to air pollution Superior vena cava syndrome Exposure to asbestos Thrombotic microangiopathy Exposure to diesel exhaust VTE Exposure to radon Exposure to silica dust https://web.pathway.md/diseases/recomSJPzaod1SYuA 23/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway Tobacco use Respiratory exam Integument exam Stridor Wheezing Digital clubbing Lab findings Hematological findings serum calcium Anemia DIC Imaging findings WBC count Apical pleural cap blood eosinophils Hilar lymphadenopathy blood platelet count Lung mass Genetic testing Lung nodule Mediastinal lymphadenopathy Alk gene rearrangement Mediastinal mass Braf gene V600E mutation Pleural effusion Egfr gene mutation Her2 gene mutation Kras gene G12C mutation Met exon 14 skipping mutation Ntrk gene rearrangement Ret gene rearrangement Ros1 gene rearrangement Studies 2023 ADAURA In adult patients with postsurgical stage IB, II, or IIIA non-small cell lung cancer who had centrally confirmed epidermal growth factor receptor mutation, osimertinib was superior to placebo with respect to overall survival at 5 years, among patients with stage II to IIIA disease. Masahiro Tsuboi et al. N Engl J Med. 2023 Jun 4. Online ahead of print. 2023 CodeBreak 200 In adult patients with KRASG12C-mutated advanced non-small cell lung cancer, who progressed after previous platinum-based chemotherapy and a programmed cell death protein-1 or programmed cell death-ligand 1 inhibitor, sotorasib was superior to docetaxel with respect to median progression-free survival. Adrianus Johannes de Langen et al. Lancet. 2023 Mar 4. Show 15 more References https://web.pathway.md/diseases/recomSJPzaod1SYuA 24/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway 1. Postmus PE, Kerr KM, Oudkerk M et al. Early and locally advanced non-small-cell lung cancer NSCLC ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv1-iv21. Open 2. Frank C Detterbeck, Sandra Zelman Lewis, Rebecca Diekemper et al. 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G Kasymjanova, N MacDonald, J S Agulnik et al. The predictive value of pre-treatment inflammatory markers in advanced non-small-cell lung cancer. Curr Oncol. 2010 Aug;17 4 52 8. Open 25. Melissa L Johnson, Byoung Chul Cho, Alexander Luft et al. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2022 Nov 3;JCO2200975. Open 26. Matthew D Hellmann, Luis Paz-Ares, Reyes Bernabe Caro et al. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Nov 21;381 21 2020 2031. Open 27. Jean-Charles Soria, Yuichiro Ohe, Johan Vansteenkiste et al. Osimertinib in Untreated EGFR Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378 2 113 125. Open 28. Solange Peters, D Ross Camidge, Alice T Shaw et al. Alectinib versus Crizotinib in Untreated ALK Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug 31;377 9 829 838. Open 29. Adrianus Johannes de Langen, Melissa L Johnson, Julien Mazieres et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial. Lancet. 2023 Mar 4;401 10378 733 746. Open 30. Gregory P Kalemkerian, Navneet Narula, Erin B Kennedy et al. Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International https://web.pathway.md/diseases/recomSJPzaod1SYuA 26/27 6/30/23, 1:18 AM Non-small cell lung cancer Pathway Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol. 2018 Mar 20;36 9 911 919. Open 31. Masahiro Tsuboi, Roy S Herbst, Thomas John et al. Overall Survival with Osimertinib in Resected EGFR Mutated NSCLC. N Engl J Med. 2023 Jun 4. Online ahead of print. 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