non-small cell carcinoma of the lung (NSCLC)
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Introduction
Any carcinoma of the lung, except small cell carcinoma. Often grouped together, because collectively they behave & are treated differently than small cell carcinoma.
Classification
- lung squamous carcinoma (occurs in predominantly in smokers)
- lung adenocarcinoma (most common, occurs in never smokers)
- lung adenosquamous carcinoma
- lung mucoepidermoid carcinoma
- lung large cell carcinoma
- lung adenoid cystic carcinoma
Etiology
- tobacco smoke
- 15% of 15% of patients are non-smokers or have a minimal smoking history[10]
- see lung carcinoma
Epidemiology
- 85% of lung cancers[45]
- 15% of patients with NSCLC are never-smokers[50]
- incidence of NSCLC among never-smokers increased from 8% in 1990 to 15% in 2013[50]
- increased incidence largely, if not exclusively, due to increased incidence of lung adenocarcinoma in never-smokers
Genetics
- epidermal growth factor receptor (EGFR)-activating mutations in some patients[4] (10%)
- mutation (EGFR T790M) confers resistance to tyrosine kinase inhibitors[27]
- abnormalities in the anaplastic lymphoma kinase (ALK) protein in some patients[4]
- inv(2)(p21:q23) resulting in EML4-ALK fusion gene[14]
- HER2 overexpression, amplification, & point mutations (esp exon 20)[73]
- gene for LRP1B prefentially inactivated
- defects in NAT6, ZMYND10 found in NSCLC cell lines
- amplification of WHSC1L1, PRKCI
- downregulation of INTS6 (frequent)
- mutations in oncogenes c-myc &c-raf & in tumor suppressor genes Rb gene & p53 gene
- other implicated genes NBPF3, TUSC1, DMTF1, INTS6, TRY6, VTCN1
Clinical manifestations
- see lung carcinoma
- Horner's syndrome
- shoulder pain & scapula pain, followed by cough & hemoptysis (case report)[27]
- bone pain & neurologivc signs with metastases
Laboratory
- serum chemistries
- comprehensive metabolic panel
- serum sodium: elevated with SIADH
- serum calcium: elevated with hypercalcemia of malignancy
- serum ALT
- serum ALP
- comprehensive metabolic panel
- complete blood count (see lung cancer)
- microarray or PCR for expression of 5 gene set (DUSP6, MMD, STAT1, ERBB3, LCK) predicts relapse & survival[7]
- EGFR gene mutation [27, NICE]
- indicated for lung adenocarcinoma[10]
- may not be indicated for lung squamous cell carcinoma[10]
- Guardant360 CDx is a companion (to amivantamab) diagnostic test for NSCLC with EGFR exon 20 insertion mutation(s)[81]
- ALK gene rearrangement
- ROS1 gene rearrangement
- RET fusion gene
- HER2 (ERBB2) overexpression, amplification, & point mutations[73]
- HER2 expression by immunohistochemistry commonly used
- fluorescence in situ hybridization (FISH) used experimentally
- VeriStrat testing offered for NSCLC without EGFR mutation
- PDL-1 expression[10][88]
- MET exon 14 skipping, NTRK1/2/3 fusions, RET rearrangements[8]
- BRAF p.V600E mutations[88]
- KRAS G12C mutation
- H-ras, K-ras, & N-ras occur largely in adenocarcinoma (30%)[88]
- sputum cytology:
- centrally located endobronchial squamous cell carcinomas may exfoliate malignant cells into sputum
Diagnostic procedures
- lymph node biopsy if lymphadenopathy
- needle aspiration rather than biopsy of lymph node diagnostic according to ref[10]
- bronchoscopy
- thoracentesis with indwelling pleural catheter if pleural effusion
- pleurodesis as indicated
- mediastinoscopy if indicated by imaging studies (no metastases)
- endobronchial ultrasound-guided mediastinal lymph node biopsy[10][17]
- needle aspiration rather than biopsy of lymph node diagnostic according to ref[10]
- pulmonary function testing
- including FEV1 & DLCO
- prediction of postoperative pulmonary reserve[10]
- many patients with lung cancer have COPD[10]
Radiology
- see lung carcinoma
- may present as pneumonia (case report)[27]
- chest X-ray
- computed tomography (CT) of the chest
- MRI of brain to rule out brain metastases[45]
- also surgical candidates & candidates for chemoradiation[10]
- MRI of spinal cord if spinal cord compression is suspected[88]
- bone scan (scintigraphy) if bone metastases suspected[88]
- positron emission tomographic (PET) for staging[45]
Staging
Complications
- intractable cancer pain associated with metastatic cancer[27]
- radiation therapy relieves pain[10]
- paraneoplastic syndromes
- thoracic radiation therapy for pulmonary airway obstruction, superior vena cava syndrome, or spinal cord metastases (after surgical decompression)[10]
- thoracic radiation therapy palliative in 90% of patients[41]
- unsatifactory antibody response to Omicron variant of Covid-19 after Covid-19 vaccine booster in ~25% of patients with NSCLC[94]
Differential diagnosis
- pneumonia
- tuberculosis
- carcinoid
- granuloma
- abscess
- hamartoma
- small cell lung carcinoma
- metastatic cancer
- superior vena cava syndrome[88]
Management
- palliative care referral for advanced-stage NSCLC[35][37][38]
- concurrent chemotherapy & palliative care can improve quality of life & increase life expectancy 20%[10][35]
- Patient selection:
- neither age nor comorbidities predicts response to therapy, progression-free survival, or disease-specific survival[8]
- comorbidities do predict shorter overall survival[8]
- performance status should be considered while making shared palliative care treatment decisions for advanced NSCLC[77]
- smoking cessation[10]
- continued smoking increases risk of complications associated with treatment & reduces potential benefit of treatment
- continued smoking increases risk of secondary cancers in patients with lung cancer
Stages 1, 2 & some 3a
- stages 1 & 2 -> surgical resection within 12 weeks[79] (lobectomy)
- pre-operative pulmonary function testing to assess pulmonary reserve[10]
- sublobar resection (segmentectomy) may be appropriate for some patients[87]
- stage 1A may be treated with surgery alone
- stage 1B & 2: surgery plus adjuvant chemotherapy*
- stage 3a with minimal N2 involvement
- surgical resection
- complete mediastinal lymph node dissection
- consideration of adjuvant chemotherapy*
- adjuvant cispatin-based chemotherapy 4 cycles is standard[88]
- lobectomy associated with better outcomes than sublobar resection in elderly patients[26]
- overall survival for sublobar resection (segmentectomy) noninferior to lobectomy[87]
- thoracoscopic lobectomy with similar survival, shorter hospital stays, & fewer complications than open thoracotomy[25]
- stereotactic ablative radiotherapy
* cispatin-based chemotherapy, 4-6 cycles without radiation for stage 2 & 3 tumors[10]
* adjuvant platinum-based doublet chemotherapy 4 cycles after surgical resection improves 5 year survival for stage II NSCLC 51% vs 43% for surgery alone[45]
* 1st line nivolumab + ipilimumab for patients with high tumor mutational burden, irrespective of PD-L1 expression[62]
* 1st line pembrolizumab (Keytruda) effective even with minimal PD-L1 expression[64]
postoperative radiation therapy for resected localized lung cancer with positive surgical margins[10]
radiation does not benefit patients with negative surgical margins[10]
proton therapy as effective as conventional radiotherapy but no less toxic[34]
early NSCLC located too close to vital organs for conventional treatment may be amenable to proton beam therapy[46]
Stage 3a, Stage 3b
Stage 3a & some T3 tumors
- bulky mediastinal or hilar lymph node involvement generally considered unresectable & treated with chemoradiation[10]
- unresectable tumors treated with chemoradiation + durvalumab for 1 year if chemoradiation results in a partial or complete response[88]
- tumors with chest wall invasion (T3)
- enblock resection of the tumor with involved chest wall
- consideration of postoperative radiation therapy
- superior sulcus (Pancoast) (T3) tumors
- preoperative radiation therapy (3000-4500 cGy)
- enblock resection of the involved lung & chest wall
- consideration of intraoperative brachytherapy
- consideration of postoperative radiation therapy
- proximal airway involvement (< 2 cm for carina) without mediastinal nodes
- sleeve resection preserving distal normal lung
- pneumonectomy (if sleeve resection not feasible)
Stage 3a, Stage 3b, & clinically evident N2 (with tolerable radiation port)
- curative radiation therapy plus chemotherapy
- radiation therapy alone if performance status is poor
- stage 3a with N2 disease
- combined radiation therapy & chemotherapy* without surgery
- stage 3a with advanced N2 disease
- consider neoadjuvant chemotherapy plus surgical resection
Stage 3b with carinal invasion (T4), but without N2 involvement
- consider pneumonectomy with tracheal sleeve resection with direct reanastomosis to contralateral mainstem bronchus
Stage 3 & more advanced Stage 3b
- radiation therapy to symptomatic local sites
- patients with pleural effusion or pericardial effusion do not benefit from radiation[15]
- chemotherapy for patients with good performance status
- large malignant pleural effusions -> chest tube drainage
- isolated brain or adrenal metastases
- consider resection of primary tumor & metastasis
Metastatic disease (including malignant pleural effusion)
- palliative chemotherapy vs palliative care
- carboplatin + permetrexed + pembrolizumab (Keytruda)[10]
- 1st line pembrolizumab (Keytruda) effective even with minimal PD-L1 expression[64]
- if PD-L1 expression 1-49%, cisplatin-based chemotherapy + pembrolizumab[88]
- if PD-L1 expression > 50%, pembrolizumab alone[88]
- 26 month median survival, 32% 5-year survival pembrolizumab every 3 weeks for 35 cycles (about 2 years)[83]
- nivolumab (Opdivo) for metastatic disease with progression on or after platinum-based chemotherapy[28]
- 1st line nivolumab + ipilimumab for patients with high tumor mutational burden, irrespective of PD-L1 expression[62]
- tislelizumab monotherapy in previously treated advanced NSCLC may extend survival 6 months vs docetaxel regardless of PD-L1 expression[78]
- radiation therapy with curative potential
- selected patients with a single site of metastasis can be treated with surgical resection of the metastatic lesion & aggressive treatment of the primary NSCLC[10]
- adding atezolizumab (Tecentriq) to platinum-based chemotherapy slows tumor progression, but does not improve survival[63]
- glucocorticoids & whole brain radiation therapy for multiple brain metastases
- surgery, sterotactic radiosurgery for single metastasis if feasible
radiation therapy relieves pain from metastatic disease[10]
Chemotherapy for non small-cell lung cancer[2]
- regimens
- cisplatin + gemcitabine (squamous cell carcinoma)[10]
- cisplatin + pemetrexed (adenocarcinoma)[10]
- cisplatin + paclitaxel (histologic type uncertain)[10]
- cisplatin + docetaxel (histologic type uncertain)[10]
- cisplatin + etoposide
- cisplatin + irinotecan
- carboplatin + placitaxel[36]
- addition of bevacizumab of no benefit[39]
- carboplatin + gemcitabine every 21 days for 4 cycles followed by docetaxel every 21 days for 6 cycles[9]
- recommended duration of adjuvant chemotherapy is 1 year[96]
- cisplatin + irinotecan may result in best survival
- adjuvant chemotherapy has become standard of treatment for stage 1B to stage 3[4][5][10][19]
- cisplatin plus etoposide or vinorelbine
- cisplatin plus vinorelbine[5]
- platinum-based chemotherapy + bevacizumab[10]
- durvalumab after chemoradiotherapy[54]
- extends progression-free survival (23.2 vs 14.6 months)
- immunotherapy vs platinum-based chemotherapy[64]
- 1st line nivolumab + ipilimumab or pembrolizumab (Keytruda) may be effective even with minimal PD-L1 expression[62][64]
- immunotherapy (PD-L1 inhibitor) may result in hyper-progression of NSCLC in 9-14% of patients[55]
- advanced disease: pemetrexed (Alimta, Rolazar, Tifolar)
- maintenance therapy with pemetrexed after induction therapy
- standard of care[23]
- pemetrexed 500 mg/m2 IV on day 1 of 21-day cycles
- only switch-maintenance therapy with pemetrexed & erlotinib FDA-approved[45]
- maintenance therapy with pemetrexed not an option for squamous cell carcinoma of lung[45]
- patients with activating EGFR gene mutation
- erlotinib or osimertinib[56]
- osimertinib may be superior to erlotinib[56]
- gefitinib NOT recommended (NICE) [NGC]
- not recommended in early stage NSCLC (assumes complete resection)
- standard chemotherapy superior to EGFR tyrosine kinase inhibitor in patients with wild-type EGFR[24]
- in patients with EGFR gene mutation, stopping erlotinib can worsen disease even if cancer has progressed despite erlotinib therapy[27]
- erlotinib & osimertinib cross blood brain barrier[61]
- amivantamab (Rybrevant) FDA-approved for NSCLC with EGFR exon 20 insertion mutation(s)[81]
- erlotinib or osimertinib[56]
- ALK rene rearrangement
- alectinib is MKSAP19-recommended agent[10]
- alectinib superior to crizotinib with lower toxicity in untreated ALK-positive NSCLC[52]
- crizotinib no longer recommended; not recommended (NICE)
- crizotinib & alectinib cross blood brain barrier[61]
- lorlatinib with longer progression-free survival & higher frequency of intracranial response than crizotinib[75]
- ensartinib with superior efficacy to crizotinib in both systemic & intracranial disease[85]
- ROS1 gene rearrangement
- alectinib is MKSAP19-recommended agent[10]
- crizotinib no longer recommended
- RET gene fusion positive locally advanced or metastatic NSCLC
- selpercatinib is FDA-approved
- BRAF V600E mutation positive metastatic NSCLC
- dabrafenib + trametinib (previously untreated)[68]
- HER2 aberrations
- unlike breast cancer, trastuzumab ineffective as a monotherapy for HER2-overexpressing NSCLC[73]
- HER2 point mutations susceptible to ado-trastuzumab emtansine (Kadcyla)[73]
- fam-trastuzumab deruxtecan-nxki FDA-approved for unresectable or metastatic NSCLS with activating HER2 mutation refractory to prior chemotherapy[95]
- patients with good performance status who have failed one chemotherapy regimen:
- single agent chemotherapy
- patients who have failed platininum-based chemotherapy, erlotinib or crizotinib
- ramucirumab + docetaxel[43]
- nivolumab (FDA-approved regardless of PD-L1 expression)[44]
- pembrolizumab for patients with metastatic NSCLC on or after platinum- containing chemotherapy with PD-L1 expression on at least 50% of tumor cells[42][59]
- 1st line pembrolizumab effective even with minimal PD-L1 expression[64]
- atezolizumab 2-year survival is 24% vs 12% for chemotherapy[44][97]
- durvalumab (Imfinzi) for stage 3 NSCLC without disease progression after concurrent chemoradiation (median overall survival is 47.5 months)[80]
- presence of activating EGFR gene mutation is an exception[80]
- anti-PDCD1 &/or anti-CD274 antibody may induce tumor regression & prolonged stabilization in patients with advanced non-small-cell lung cancer, cutaneous melanoma, or renal cell carcinoma[15]
- immune checkpoint inhibitors nivolumab, pembrolizumab, or atezolizumab 1st line for NSCLC with PD-L1 expression on at least 50% of tumor cells[42][49]
- pembrolizumab may be preferred agent[49][59]
- EGFR/ALK/ROS1 negative[49]
- improves quality of life relative to chemotherapy[47]
- survival gains from immune checkpoint inhibitors may not be generalizable to the elderly[92]
- nivolumab or atezolizumab may be used if PD-L1 expression is negative or unknown[49]
- atezolizumab if patient unable to tolerate platinum-based chemotherapy[89]
- neoadjuvant chemotherapy with nivolumab 4 weeks before surgery may reduce tumor burden[60]
- investigational agents for NSCLC
- lorlatinib for ALK-Positive NSCLC
- sotorasib for NSCLC with KRAS p.G12C mutation
- metformin not indicated in the absence of diabetes mellitus[82]
Avoid: epoetin-alpha
Do NOT treat patients with poor performance status with chemotherapy, regardless of age[10]
Treat patients with poor performance status & advanced NSCLC without a driver mutation with supportive care
Radiation therapy
- does not improve survival & may be harmful to patients with early stage NSCLC[16]
- does not improve survival in locally advanced disease[3]
- hypofractionated image-guided radiation therapy (60 Gy in 15 fractions) is not superior to conventionally fractionated radiotherapy (60 Gy in 30 fractions) for patients with stage II/III NSCLC with poor performance statys ineligible for concurrent chemoradiotherapy[84]
- benefits symptomatic unresectable patients only[3]
- post-operative radiation therapy improves median disease-free survival from 22 months to 31 months, but does not substantially improve overall survival[74]
- radiation doses of 15 Gy to > 10% of left anterior descending coronary artery (LAD) increases risk for major adverse cardiac events & mortality[76]
- treatment of choice for superior vena cava syndrome[41]
- passive scattering proton therapy (PSPT) or intensity-modulated (photon) radiotherapy (IMRT), with concurrent chemotherapy, for inoperable NSCLC
- improvements in either
- no significant difference in radiation pneumonitis
Endobronchial therapy[10]
- photodynamic bronchoscopy
- laser bronchoscopy
- bronchoscopic brachytherapy
- bronchial stent placement
Prognosis
- 5-year survival by stage
- operable
- stage 1A: 77-92%
- stage 1B: 68%
- stage 2A: 60%
- stage 2B: 53%
- stage 3A: 36% --------------------------------
- inoperable
- stage 3B: 26%
- stage 3C: 13%
- stage 4: < 10%[62]
- operable
- mean survival: 10-12 months for patients for non-resectable disease depending on chemotherapy[9]
More general terms
More specific terms
- adenocarcinoma of the lung
- adenoid cystic carcinoma, lung
- adenosquamous carcinoma, lung
- large cell carcinoma, lung
- mucoepidermoid carcinoma, lung
- nonsquamous non-small cell lung cancer
- squamous cell carcinoma, lung
Additional terms
- brachytherapy
- clinical trials, non-small-cell lung cancer
- Pancoast tumor (superior pulmonary sulcus tumor)
- staging of lung cancer
References
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 556
- ↑ 2.0 2.1 Journal Watch 22(4):31, 2002 Schiller JH et al Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11784875
Noda K et al Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346:85, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11784874 Carney DN Lung cancer--time to move on from chemotherapy. N Engl J Med 346:126, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11784881 - ↑ 3.0 3.1 3.2 Journal Watch 22(21):159, 2002 Falk SJ et al Immediate versus delayed palliative thoracic radiotherapy in patients with unresectable locally advanced non-small cell lung cancer and minimal thoracic symptoms: randomised controlled trial. BMJ 325:465, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12202326
- ↑ 4.0 4.1 4.2 4.3 Journal Watch 24(5):40, 2004 Arriagada R et al for the International Adjuvant Lung CAncer Trial Collaborative Group Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 350:351, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14736927
Blum RH Adjuvant chemotherapy for lung cancer--a new standard of care. N Engl J Med 350:351, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14736933 - ↑ 5.0 5.1 5.2 Journal Watch 25(15):122, 2005 Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15972865
- ↑ Noble J et al, Second-line or Subsequent Systemic Therapy for Recurrent or Progressive Non-Small Cell Lung CancerGuideline Program in evidence-based care: Evidence-based Series #7-19: Section 1 Corresponding NGC guideline withdrawn http://www.cancercare.on.ca/pdf/pebc7-19f.pdf
- ↑ 7.0 7.1 Chen H-Y, A five-gene signature and clinical outcome in non-small- cell-lung cancer. N Engl J Med 2007 356:11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17202451
- ↑ 8.0 8.1 8.2 8.3 Asmis TR et al, Age and comorbidity as independent prognostic factors in the treatment of non-small-cell lung cancer. A review of National Cancer Institute of Canada Clinical Trials Group trials. J Clin Oncol 2008, 26:54 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18165640
- ↑ 9.0 9.1 9.2 Fidias PM et al Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 2009 Feb 1; 27:591 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19075278
- ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 10.13 10.14 10.15 10.16 10.17 10.18 10.19 10.20 10.21 10.22 10.23 10.24 10.25 10.26 10.27 10.28 10.29 10.30 10.31 10.32 10.33 10.34 Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Goffin J et al First-line Systemic Chemotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer: Bevacizumab Treatment: Guideline Recommendations http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=45735
- ↑ Davidoff AJ et al. Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 2010 May 1; 28:2191 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20351329
- ↑ ASCO 2010 Report: Lung Cancer GENETIC AND MOLECULAR DRIVERS OF LUNG CANCER Journal Watch: Massachusetts Medical Society http://oncology-hematology.jwatch.org/cgi/content/full/2010/713/5
- ↑ 14.0 14.1 14.2 Soda M et al Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer Nature. 2007 Aug 2;448(7153):561-6 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/17625570 <Internet> http://www.nature.com/nature/journal/v448/n7153/full/nature05945.html
- ↑ 15.0 15.1 15.2 Topalian SL et al Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer N Engl J Med, June 2, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22658127 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1200690
Brahmer JR et al Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer N Engl J Med, June 2, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22658128 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1200694 - ↑ 16.0 16.1 Scott WJ, Howington J, Feigenberg S. Treatment of non-small cell lung cancer stage I and stage II: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007 Sep;132(3 Suppl):234S-242S. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17873171
- ↑ 17.0 17.1 Silvestri GA, Gould MK, Margolis ML et al Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest. 2007 Sep;132(3 Suppl):178S-201S. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17873168
- ↑ Gridelli C, De Marinis F, Di Maio M et al Gefitinib as first-line treatment for patients with advanced non-small-cell lung cancer with activating epidermal growth factor receptor mutation: Review of the evidence. Lung Cancer. 2011 Mar;71(3):249-57 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21216486
- ↑ 19.0 19.1 Sangha R, Price J, Butts CA. Adjuvant therapy in non-small cell lung cancer: current and future directions. Oncologist. 2010;15(8):862-72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20682608
- ↑ Gewanter RM, Rosenzweig KE, Chang JY et al ACR Appropriateness Criteria: nonsurgical treatment for non-small-cell lung cancer: good performance status/definitive intent. Curr Probl Cancer. 2010 May-Jun;34(3):228-49 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20541060
- ↑ Delbaldo C, Michiels S, Syz N et al Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA. 2004 Jul 28;292(4):470-84. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15280345
- ↑ Yang CH, Yu CJ, Shih JY et al Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol. 2008 Jun 1;26(16):2745-53. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18509184
- ↑ 23.0 23.1 Paz-Ares LG et al. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2013 Jul 8 http://jco.ascopubs.org/content/early/2013/07/03/JCO.2012.47.1102
- ↑ 24.0 24.1 Lee JK, Hahn A, Kim DW et al Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors vs Conventional Chemotherapy in Non-Small Cell Lung Cancer Harboring Wild-Type Epidermal Growth Factor Receptor. A Meta-analysis. JAMA. 2014;311(14):1430-1437 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24715074 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1857337
- ↑ 25.0 25.1 Paul S et al. Long term survival with thoracoscopic versus open lobectomy: Propensity matched comparative analysis using SEER-Medicare database. BMJ 2014 Oct 2; 349:g5575 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25277994 <Internet> http://www.bmj.com/content/349/bmj.g5575
- ↑ 26.0 26.1 26.2 Shirvani SM et al. Lobectomy, sublobar resection, and stereotactic ablative radiotherapy for early-stage non-small cell lung cancers in the elderly. JAMA Surg 2014 Dec; 149:1244 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25321323
- ↑ 27.0 27.1 27.2 27.3 27.4 27.5 27.6 Kamdar MM, Doyle KP, Sequist LV et al Case 17-2015 - A 44-Year-Old Woman with Intractable Pain Due to Metastatic Lung Cancer. N Engl J Med 2015; 372:2137-2147. May 28, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26017825 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcpc1404141
- ↑ 28.0 28.1 FDA News Release. March 4, 2015. FDA expands approved use of Opdivo to treat lung cancer. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436534.htm
Chustecka Z Nivolumab in Lung Cancer Shows 'Unprecedented' Survival. Medscape Oncology. May 29, 2015. from the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. http://www.medscape.com/viewarticle/845647?nlid=82185_2202
American Society of Clinical Oncology (ASCO) 2015 Annual Meeting: Abstract LBA109, presented May 30, 2015; abstract 8009, presented May 31, 2015
Brahmer J et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015 May 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26028407 - ↑ Azzoli CG, Baker S Jr, Temin S et al American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 2009 Dec 20;27(36):6251-66 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19917871 guideline update Jan 2015 (NGC)
- ↑ Douillard JY, Rosell R, De Lena M et al Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial. Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):695-701 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18439766
- ↑ Pisters KM, Evans WK, Azzoli CG et al Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-IIIA resectable non small-cell lung cancer guideline. J Clin Oncol. 2007 Dec 1;25(34):5506-18. Epub 2007 Oct 22 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17954710
- ↑ Rosell R, Carcereny E, Gervais R et al Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22285168
- ↑ Soria JC, Mauguen A, Reck M et al Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small- cell lung cancer. Ann Oncol. 2013 Jan;24(1):20-30 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23180113
- ↑ 34.0 34.1 Mulcahy N Finally, RCT Results for Proton Therapy in a Cancer. Medscape. Jun 21, 2016. http://www.medscape.com/viewarticle/865137
- ↑ 35.0 35.1 35.2 Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
- ↑ 36.0 36.1 Quoix E, Zalcman G, Oster JP et al Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21831418
- ↑ 37.0 37.1 Temel JS et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010 Aug 19; 363:733 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20818875
Kelley AS and Meier DE. Palliative care - A shifting paradigm. N Engl J Med 2010 Aug 19; 363:781. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20818881 - ↑ 38.0 38.1 Greer JA et al. Effect of early palliative care on chemotherapy use and end-of-life care in patients with metastatic non-small-cell lung cancer. J Clin Oncol 2012 Feb 1; 30:394 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22203758
- ↑ 39.0 39.1 Zhu J, Sharma DB, Gray SW et al Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA. 2012 Apr 18;307(15):1593-601. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22511687 Free PMC Article
- ↑ Jacobsen J, Jackson V, Dahlin C et al Components of early outpatient palliative care consultation in patients with metastatic nonsmall cell lung cancer. J Palliat Med. 2011 Apr;14(4):459-64. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21417739
- ↑ 41.0 41.1 41.2 NEJM Knowledge+/ Question of the Week. July 26, 2016 http://knowledgeplus.nejm.org/question-of-week/936/
- ↑ 42.0 42.1 42.2 Chustecka Z Earthquake in Lung Cancer: Immunotherapy First-Line. Medscape. Oct 14, 2016. http://www.medscape.com/viewarticle/870289 Pembrolizumab versus Chemotherapy for PD-L1-positive non-Small-Cell Lung Cancer. N Engl J Med. Oct 9, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27718847 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1606774
- ↑ 43.0 43.1 Garon EB, Ciuleanu TE, Arrieta O et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24933332
Perol M, Ciuleanu TE, Arrieta O et al Quality of life results from the phase 3 REVEL randomized clinical trial of ramucirumab-plus-docetaxel versus placebo- plus-docetaxel in advanced/metastatic non-small cell lung cancer patients with progression after platinum-based chemotherapy. Lung Cancer. 2016 Mar;93:95-103. Epub 2016 Jan 19. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26898621 - ↑ 44.0 44.1 44.2 West HJ Should Atezolizumab Be the First-Choice Immunotherapy in Second-Line Non-Small Cell Lung Cancer? Medcape Oncology. Oct 31, 2016 http://www.medscape.com/viewarticle/871119
- ↑ 45.0 45.1 45.2 45.3 45.4 45.5 45.6 Lim MY Non-Small Cell Lung Cancer: 5 Management Challenges. Medscape. Nov 30, 2016 http://reference.medscape.com/features/slideshow/non-small-cell-lung-cancer
- ↑ 46.0 46.1 Susman E Meeting Coverage. RSNA: Protons Destroy Centrally Located Lung Cancer - Early NSCLC close to vital organs found amenable to proton beam approach. MedPage Today. December 03, 2016 http://www.medpagetoday.com/MeetingCoverage/RSNA/61833
- ↑ 47.0 47.1 Davenport L Pembrolizumab 1st-Line in NSCLC Also Boosts Quality of Life. Medscape. Dec 08, 2016. http://www.medscape.com/viewarticle/873079
- ↑ Ettinger DS, Wood DE, Akerley W et al. NCCN Guidelines Insights: non-small cell lung cancer, version 4/2016. J Natl Compr Canc Netw. 2016;14:255-264. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26957612
- ↑ 49.0 49.1 49.2 49.3 49.4 Hanna N, Johnson D, Temin S et al Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer Update. American Society of Clinical Oncology (ASCO). August 14, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28806116 <Internet> http://www.asco.org/practice-guidelines/quality-guidelines/guidelines/lung-cancer
Brooks M ASCO Updates Advice on Drug Therapy for Advanced Lung Cancer Medscape - Aug 16, 2017. http://www.medscape.com/viewarticle/884361 - ↑ 50.0 50.1 50.2 Pelosof L, Ahn C, Gao A et al Proportion of Never-Smoker Non-Small Cell Lung Cancer Patients at Three Diverse Institutions. J Natl Cancer Inst. 2017 Jan 28;109(7). PMID:28132018
- ↑ 51.0 51.1 51.2 Anello J, Feinberg B, Heinegg J et al Stereotactic Body Radiation in NSCLC Guidelines on stereotactic body radiation for early-stage non-small cell lung cancer by the American Society for Radiation Oncology. Medscape: New Guidelines and Recommendations, August 2017. http://reference.medscape.com/viewarticle/884517
- ↑ 52.0 52.1 Peters S, Camidge DR, Shaw AT et al Alectinib versus Crizotinib in Untreated ALK-Positive Non- Small-Cell Lung Cancer. N Engl J Med 2017; 377:829-838. August 31, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28586279 Free full text <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1704795
- ↑ Reck M, Rabe KF. Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2017; 377:849-861. August 31, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28854088 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMra1703413
- ↑ 54.0 54.1 Kris G Durvalumab After Chemoradiotherapy 'Immediately Changes Practice' in Patients With NSCLC. Medscape - Oct 27, 2017. https://www.medscape.com/viewarticle/887419
Antonia SJ, Villegas A, Daniel D et al Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med 2017; 377:1919-1929. November 16, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28885881 Free full text <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1709937 - ↑ 55.0 55.1 Chustecka Z. Lung Cancer May Grow Faster During Immunotherapy, Medscape - Nov 13, 2017. https://www.medscape.com/viewarticle/888525
- ↑ 56.0 56.1 56.2 Soria JC, Ohe Y, Vansteenkiste J et al Osimertinib in Untreated EGFR-Mutated Advanced non-Small-Cell Lung Cancer. N Engl J Med. Nov 18, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29151359 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1713137
- ↑ Liao Z, Lee JJ, Komaki R et al Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 Jan 2:JCO2017740720. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/29293386
- ↑ Pal S. Crizotinib Tx Stakes Claim in ROS1-Positive NSCLC. The TKI boosts outcomes in those with a rare disease -- enough to convince FDA to approve the agent fast and early. MedPage Today. ASCO Reading Room. Feb 9, 2018 https://www.medpagetoday.com/reading-room/asco/lung-cancer/71049
Gainor JF, Tseng D, Yoda S et al Patterns of metastatic spread and mechanisms of resistance to crizotinib in ROS1-positive non-small cell lung cancer. JCO Precision Oncology. Epub 2017 Aug 16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29333528 Free PMC Article - ↑ 59.0 59.1 59.2 Gandhi L, Rodriguez-Abreu D, Gadgeel S et al Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. April 16, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29658856 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1801005
- ↑ 60.0 60.1 Castellino AM Neoadjuvant Nivolumab Shows Benefit in NSCLC Medscape - Apr 17, 2018. https://www.medscape.com/viewarticle/895274
Forde PM, Chaft JE, Smith KN et al Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 Apr 16. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/29658848 Free Articl - ↑ 61.0 61.1 61.2 Bulbul A, Forde PM, Murtuza A et al Systemic Treatment Options for Brain Metastases from Non-Small-Cell Lung Cancer. Oncology (Williston Park). 2018 Apr 15;32(4):156-63. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29684234 Free Article
- ↑ 62.0 62.1 62.2 62.3 62.4 Hellmann MD, Ciuleanu TE, Pluzanski A et al Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 2018; 378:2093-2104. May 31, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29658845 Free full text https://www.nejm.org/doi/full/10.1056/NEJMoa1801946
- ↑ 63.0 63.1 Smith M. Checkpoint Blocker Plus Chemo Slows NSCLC Progress No significant OS improvement in interim analysis of IMpower131 trial. MedPage Today. June 02, 2018 https://www.medpagetoday.com/meetingcoverage/asco/73236
Jotte RM et al IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. American Society of Clinical Oncology (ASCO) 2018: Abstract LBA9000. - ↑ 64.0 64.1 64.2 64.3 64.4 64.5 Davenport L 'End of an Era' for Chemo in Non-Small Cell Lung Cancer. Medscape - Jun 03, 2018. https://www.medscape.com/viewarticle/897538
Lopes G, Wu YL, Kudaba I Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) >= 1%: Open-label, phase 3 KEYNOTE-042 study. ASCO Meeting Library. June 3, 2018 https://meetinglibrary.asco.org/record/165950/abstract - ↑ Tam K, Daly M, Kelly K. Treatment of Locally Advanced Non-Small Cell Lung Cancer. Hematol Oncol Clin North Am. 2017 Feb;31(1):45-57. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27912833 Free Article
- ↑ Ciuleanu T, Brodowicz T, Zielinski C et al Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009 Oct 24;374(9699):1432-40. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19767093
- ↑ Silvestri GA, Gonzalez AV, Jantz MA et al Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):e211S-e250S. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23649440
- ↑ 68.0 68.1 Planchard D, Smit EF, Groen HJM et al Dabrafenib plus trametinib in patients with previously untreated BRAF-V600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1307-1316. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28919011
- ↑ 69.0 69.1 ARUP Consult: Non-Small Cell Lung Cancer - Non-Small Cell Lung Cancer Molecular Markers The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/lung-cancer ARUP Consult: Non-Small Cell Lung Cancer Molecular Markers https://arupconsult.com/ati/non-small-cell-lung-cancer-molecular-markers
- ↑ American Cancer Society Non-Small Cell Lung Cancer Survival Rates, by Stage. https://www.cancer.org/cancer/non-small-cell-lung-cancer/detection-diagnosis-staging/survival-rates.html
- ↑ National Cancer Institute - Non-Small Cell Lung Cancer Treatment http://www.cancer.gov/cancerinfo/pdq/treatment/non-small-cell-lung/healthprofessional/#Section_16
- ↑ Non-Small Cell Lung Cancer (PDQ): Treatment http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/HealthProfessional
- ↑ 73.0 73.1 73.2 73.3 73.4 Pal S Yang Xia, MD, PhD, on HER2 Alterations in NSCLC - Review sheds light on HER2 as a potentially new treatment target in non-small-cell lung cancer.MedPage Today MedPage Today. ASCO Reading Room 07.24.2020 https://www.medpagetoday.com/reading-room/asco/lung-cancer/87729
Phillips JD NSCLC: Understanding the Relevance of HER2 Alterations - New review i s good overview on the potential impact of anti-HER2 therapies. MedPage Today. ASCO Reading Room 07.24.2020 https://www.medpagetoday.com/reading-room/asco/lung-cancer/87725
Zhao J, Xia Y Targeting HER2 Alterations in Non-Small-Cell Lung Cancer: A Comprehensive Review. JCO Precision Oncology - ↑ 74.0 74.1 Kris MG. An Important Negative Study for Post-op RT in Lung Cancer Medscape - Oct 08, 2020 https://www.medscape.com/viewarticle/938455
- ↑ 75.0 75.1 Shaw AT, Bauer TM, de Marinis F et al First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med 2020; 383:2018-2029 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33207094 https://www.nejm.org/doi/full/10.1056/NEJMoa2027187
- ↑ 76.0 76.1 Atkins KM, Chaunzwa TL, Lamba N et al Association of Left Anterior Descending Coronary Artery Radiation Dose With Major Adverse Cardiac Events and Mortality in Patients With Non- Small Cell Lung Cancer. JAMA Oncol. Published online December 17, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33331883 https://jamanetwork.com/journals/jamaoncology/fullarticle/2773837
Bergom C, Rayan D, Brown SA Predicting Radiation-Induced Heart Disease and Survival - Is Location the Key? JAMA Oncol. Published online December 17, 2020 https://jamanetwork.com/journals/jamaoncology/fullarticle/2773835 - ↑ 77.0 77.1 Sehgal K, Gill RR, Widick P et al Association of Performance Status With Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy. JAMA Netw Open. 2021;4(2):e2037120. Feb 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33570575 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776172
- ↑ 78.0 78.1 Bankhead C New Anti-PD1 Drugs Boost Survival in Treated Lung Cancer. Questions about generalizability of results with China-developed therapies. MedPage Today April 14, 2021 https://www.medpagetoday.com/meetingcoverage/aacr/92100
Zhou C et al Results from RATIONALE 303: A global phase III study of tislelizumab vs docetaxel as second- or third-line therapy for patients with locally advanced or metastatic NSCLC. American Association for Cancer Research (AACR) 2021; Abstract CT039 - ↑ 79.0 79.1 Heiden BT, Eaton DB Jr, Engelhardt KE et al Analysis of Delayed Surgical Treatment and Oncologic Outcomes in Clinical Stage I Non-Small Cell Lung Cancer. JAMA Netw Open. 2021;4(5):e2111613.May 27 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34042991 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780403
- ↑ 80.0 80.1 80.2 Pal S Clinical Challenge: Finding the Right Regimen in EGFR-Positive NSCLC. Radiotherapy is certified in treatment paradigm, but driver genes are still an issue. MedPage Today June 18, 2021 https://www.medpagetoday.com/clinical-challenges/asco-nsclc/93168
- ↑ 81.0 81.1 81.2 Mulcahy N FDA OKs First Targeted Therapy for Subset of Patients With NSCLC Medscape - May 21, 2021. https://www.medscape.com/viewarticle/951644
- ↑ 82.0 82.1 Skinner H, Hu C, Tsakiridis T et al Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non-Small Cell Lung CancerThe NRG-LU001 Phase 2 Randomized Clinical Trial. JAMA Oncol. Published online July 29, 2021. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34323922 https://jamanetwork.com/journals/jamaoncology/fullarticle/2782111
Tsakiridis T, Pond GR, Wright J et al Metformin in Combination With Chemoradiotherapy in Locally Advanced Non-Small Cell Lung CancerThe OCOG-ALMERA Randomized Clinical Trial. JAMA Oncol. Published online July 29, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34323924 https://jamanetwork.com/journals/jamaoncology/fullarticle/2782110
Eze C, Belka C, Manapov F. Forging a Path for Metformin Use in Inoperable Locally Advanced Non-Small Cell Lung Cancer. JAMA Oncol. Published online July 29, 2021. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34323949 https://jamanetwork.com/journals/jamaoncology/fullarticle/2782115 - ↑ 83.0 83.1 Phull H 'Exciting But Very Real Possibility of Metastatic NSCLC Becoming a Chronic Illness' Impressive 5-year OS outcomes in this study certainly point to promising forecast. MedPage Today. ACO Reading Room. August 6, 2021 https://www.medpagetoday.com/reading-room/asco/lung-cancer/93925
Pal S Keytruda in Advanced NSCLC -- Still on Target for Upping Long-Term Survival. Clinically meaningful 5-year results from the KEYNOTE-024 trial. MedPage Today. ASCO Reading Room. August 6, 2021 https://www.medpagetoday.com/asco/lung-cancer/93926 - ↑ 84.0 84.1 Bassett M No Survival Boost With Hypofractionated Image-Guided RT for NSCLC. Study still has important lessons for radiation oncologists, say editorialists. MedPage Today August 12, 2021 https://www.medpagetoday.com/oncology/lungcancer/94010
Iyengar P, Zhang-Velten E, Court L et al Radiotherapy for patients with stage II/III non-small cell lung cancer and poor performance status: a randomized clinical trial. JAMA Oncol 2021; Published online August 12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34383006 https://jamanetwork.com/journals/jamaoncology/article-abstract/2783004
Khandekar MJ, Keane FK Radiation dose and fractionation in locally advanced lung cancer: a simple question with a complicated answer. JAMA Oncol 2021; Published online August 12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34383023 https://jamanetwork.com/journals/jamaoncology/article-abstract/2783009 - ↑ 85.0 85.1 Horn L, Wang Z, Wu G et al Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase- Positive Non-Small Cell Lung Cancer. A Randomized Clinical Trial. JAMA Oncol. Published online September 2, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34473194 https://jamanetwork.com/journals/jamaoncology/fullarticle/2783490
Dagogo-Jack I Inserting Ensartinib Into the Starting Lineup for ALK-Rearranged Lung Cancer- A Likely Limited Role on a Deep Bench. JAMA Oncol. Published online September 2, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34473198 https://jamanetwork.com/journals/jamaoncology/fullarticle/2783495 - ↑ 86.0 86.1 Kris MG Early Data Support Neoadjuvant Immunotherapy for NSCLC. Medscape. December 22, 2021 https://www.medscape.com/viewarticle/963745
- ↑ 87.0 87.1 87.2 Saji H et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): A multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet 2022 Apr 23; 399:1607. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35461558 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02333-3/fulltext
- ↑ 88.00 88.01 88.02 88.03 88.04 88.05 88.06 88.07 88.08 88.09 88.10 National Comprehensive Cancer Network. May 31, 2022 Non-Small Cell Lung Cancer Clinical Practice Guidelines (NCCN, 2022). https://reference.medscape.com/viewarticle/974544
Ettinger DS, Wood DE, Aisner DL et al Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. JNCCN 2022. 20(5) https://jnccn.org/view/journals/jnccn/20/5/article-p497.xml
Tan WW, Karim NA Non-Small Cell Lung Cancer (NSCLC). Medscape. May 20, 2022 https://emedicine.medscape.com/article/279960-overview - ↑ 89.0 89.1 Osterweil N Atezolizumab Doubles Survival of Patients With NSCLC and Poor Performance Status. Medscape. Sept 20, 2022 https://www.medscape.com/viewarticle/981097
- ↑ Larkin HD Selpercatinib Receives Regular Approval for Non-Small Cell Lung Cancer. JAMA. 2022;328(17):1679. Nov 1 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36318150 https://jamanetwork.com/journals/jama/fullarticle/2797894
- ↑ Desai AP, Adashek JJ, Reuss JE et al Perioperative Immune Checkpoint Inhibition in Early-Stage Non-Small Cell Lung Cancer. A Review. JAMA Oncol. 2023;9(1):135-142 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36394834 https://jamanetwork.com/journals/jamaoncology/fullarticle/2798846
- ↑ 92.0 92.1 Voruganti T, Soulos PR, Mamtani R et al Association Between Age and Survival Trends in Advanced Non-Small Cell Lung Cancer After Adoption of Immunotherapy. JAMA Oncol. Published online January 26, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36701150 https://jamanetwork.com/journals/jamaoncology/fullarticle/2800947
- ↑ 93.0 93.1 Altorki N, Wang X, Kozono D et al. Lobar or sublobar resection for peripheral stage IA non-small-cell lung cancer. N Engl J Med 2023 Feb 9; 388:489-498. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36780674 https://www.nejm.org/doi/10.1056/NEJMoa2212083
Rusch VW. Initiating the era of "precision" lung cancer surgery. N Engl J Med 2023 Feb 9; 388:557-558. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36780681 https://www.nejm.org/doi/10.1056/NEJMe2215647 - ↑ 94.0 94.1 Valanparambil RM et al Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant. J Clin Oncol. 2022 Nov 20;40(33):3808-3816 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35759727 PMCID: PMC9671759 (available on 2023-11-20)
- ↑ 95.0 95.1 FDA Approved drugs. 2022. August 2022 FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung
- ↑ 96.0 96.1 Duan J, Tan F, Bi N et al Expert consensus on perioperative treatment for non-small cell lung cancer. Transl Lung Cancer Res. 2022 Jul;11(7):1247-1267. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35958323 PMCID: PMC9359944 Free PMC article
- ↑ 97.0 97.1 Lee SM et al. First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum- containing regimen (IPSOS): A phase 3, global, multicentre, open-label, randomised controlled study. Lancet 2023 Aug 5; 402:451. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37423228 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00774-2/fulltext
- ↑ 98.0 98.1 98.2 Worcester S Perioperative Nivolumab Improves EFS in Resectable NSCLC. Meedscape. October 21, 2023 https://www.medscape.com/viewarticle/997604