Cancer of the Lung
Non–Small Cell Lung Cancer and Small Cell Lung Cancer
Leora Horn, Rosana Eisenberg, David Gius, Katherine N. Kimmelshue, Pierre P. Massion, Joe Bill Putnam, Clifford G. Robinson and David P. Carbone
Summary of Key Points
Non–Small Cell Lung Cancer
Incidence and Epidemiology
• Constitutes 80% to 85% of new cases of lung cancer in North America.
• Most frequent histologies: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.
• Leading cause of cancer-related death in the United States for both men and women; represents one of the most preventable forms of cancer death.
Staging Evaluation
• History and physical examination, routine hematologic and biochemical testing.
CT scan (with contrast) evaluating lungs, mediastinum, liver, and adrenals
Positron emission tomography (PET) scan
If patient has locally advanced or metastatic disease, add magnetic resonance imaging (MRI) of brain
• Bronchoscopy and/or CT-guided and/or ultrasound-guided biopsy.
• If disease is clinically more advanced, use the least invasive biopsy procedure and sample to confirm advanced disease.
Primary Therapy
Postoperative chemotherapy useful in resected IIIA in patients with a good performance status.
Concurrent chemotherapy combined with radiation therapy in patients with a good performance status.
Concurrent chemotherapy combined with radiation is superior to radiation alone; increased toxicity limits this approach in frail patients.
Clinical trials of new approaches should be a high priority.
Primary chemotherapy with platinum-based doublet improves the quality and quantity of life.
All tumors should be sent for molecular testing.
No advantage for triplet therapy.
Non–platinum-based therapy is appropriate in selected patients.
Single-agent therapy reserved for select populations.
There is a clear need for more clinical trials at this stage.
Small Cell Lung Cancer
Staging Evaluation
• History and physical examination, routine histologic and biochemical testing.
CT scan (with contrast) evaluating lungs, mediastinum, liver, and adrenals.
PET useful with clinically early stage disease.
Brain evaluation (MRI preferred).
If there are signs or symptoms of bone involvement, a bone scan or PET scan is recommended.
Mediastinal node evaluation is not required unless as a convenient site for biopsy.
Therapy
Concurrent etoposide plus cisplatin and radiation to the intrathoracic disease.
Prophylactic cranial irradiation in complete (or near complete) responders.
Etoposide (or irinotecan) plus cisplatin or carboplatin.
No evidence a third agent or dose intensification improves outcome.
Research studies are a clear priority given the lack of progress in this arena.
Prophylactic cranial irradiation in complete (or near complete) responders.
Consider consolidative radiotherapy (RT) to primary in complete responders.
Second-line therapy useful mainly in patents who have experienced a longer treatment-free interval and a good performance status.
Topotecan FDA-approved; however, any of several chemotherapy agents offer short-term benefit.
Research protocols are a preferred choice for patients with disease recurrence.
1. A 56-year-old never-smoker presents to her primary care physician with dyspnea and cough. A chest x-ray identifies multiple pulmonary masses and a new pleural effusion. Further imaging, including a CT scan of her chest/abdomen, confirms multiple lung nodules, a pleural effusion, and lesions in her bones and liver. A biopsy is positive for adenocarcinoma with the epidermal growth factor receptor (EGFR) mutation deletion 19. You recommend treatment with:
2. A 66-year-old woman with a 30 pack-year smoking history who quit smoking last year when her brother was diagnosed with lung cancer comes to your clinic for assessment. She is concerned about developing lung cancer and would like to be screened. You recommend:
3. You are evaluating a 70-year-old former smoker in your clinic who has been diagnosed with squamous cell lung cancer after biopsy of a right upper lobe lung mass. His workup included a PET scan that showed a fluorodeoxyglucose (FDG) 5.4-cm right upper lobe mass and FDG-avid mediastinal adenopathy at level 4R. He is seen for surgical evaluation. You recommend:
A No surgery, because he has N2 disease on imaging
B Endobronchial ultrasound (EBUS) or mediastinoscopy for sampling of lymph nodes
4. A 50-year-old never-smoking patient with stage IV non–small cell lung cancer adenocarcinoma histology who has progressed after multiple lines of chemotherapy presents to your clinic for a second opinion. He has a repeat biopsy and his tumor is positive for the ALK fusion. You recommend treatment with:
1. Answer: B. Patients with EGFR mutant tumors treated with an EGFR tyrosine kinase inhibitor (erlotinib, gefitinib, or afatinib) have a longer progression-free survival than those who receive chemotherapy. (Maemondo et al, 2010; Mitsudomi et al, 2010; Mok et al, 2009; Yang et al, 2012; Zhou et al, 2011.)
2. Answer: C. The National Lung Cancer Screening Trial demonstrated a relative reduction in lung cancer mortality of 20% for patients at high risk for lung cancer (age 55 to 74 years; smoking history of at least 30 pack-years; and if former smoker, who quit within the previous 15 years) who were screened by low-dose CT scans annually for 3 years compared with single-view anteroposterior chest x-ray (Aberle et al, 2012).
3. Answer: B. A trial comparing EBUS and transbronchial needle aspirate (TBNA) with mediastinoscopy found excellent agreement between procedures (Yasufuku et al, 2011). Diagnostic yield of EBUS or endoscopic ultrasonography TBNA is better in high-volume hospitals (Ost et al, 2011).
4. Answer: A. Patients with tumors that are positive for the ALK fusion have a response rate of approximately 57% and progression-free survival of 9.7 months when treated with crizotinib (Shaw et al, 2010).
