What are some Genetic Changes that increase the risk of lung cancer?
Mutation tumor suppressor (p53). BCL-2, EGFR overexpression. K-RAS gene mutation. ALK (anaplastic lymphoma kinase) mutation
What is prevention and early detection like for lung cancer?
Low-dose CT scan-based screening (detected LC at earlier stages, recommended in high-risk (age > 55, former smokers). No established chemoprevention agents yet. NO tumor marker to detect lung CA at early stages
What is Small Cell Lung Cancer (SCLC)?
Oat cell, strongly linking to SMOKING. Most aggressive natural course. Only 14% of lung cancers
What is Non-Small Cell Lung Cancer (NSCLC)?
Adenocarcinoma (incidence rising, most common in non-smokers). Squamous cell (clearly related to smoking). Large cell
What are the characteristics of SCLC?
Rapid doubling time. High rate of metastases. Treatment: highly sensitive to radiation and chemotherapy. High rate of paraneoplastic syndrome (PNS)
What are the characteristics of NSCLC?
Relatively slow growing. Low rate of metastases. Treatment: surgery in Stage I and II; less sensitive to chemotherapy than SCLC. Low rate of PNS
What is Paraneoplastic Syndrome?
Due to tumor secretion of hormone like substances): Weight loss, Cushing’s syndrome (ACTH), Anemia, Hyponatremia (SIADH), Hypercalcemia (PTH), Clubbing
What are the SCLC stages?
Limited disease. Extensive disease
What is Limited disease SCLC?
Tumor confined to hemithorax of origin and/or the mediastinum and supraclavicular nodes. Fits in a radiation field
What is Extensive disease SCLC?
Tumor not confined to hemithorax of origin. Distant metastasis
What are the treatment options for SCLC?
Single or combo modality. Surgery rarely, only in very early stage (if confined to chest w/o nodal invasion). Radiation: very radiosensitive
What is radiation therapy like in SCLC?
Goal = cure in limited disease (concurrent chemotx + radiation). Palliative role in extensive disease (bone pain, symptomatic brain mets, SVC syndrome). PCI (prophylactic cranial irradiation): Eradication of occult, microscopic brain metastasis
What are the combination chemotx choices for SCLC (all stages)?
EP (Etoposide, Cisplatin). EP + Radiation in limited disease. EC (Etoposide + Carboplatin). Cisplatin + Irinotecan
What are the complications of treatment with RT + CT (Etoposide/Cisplatin)?
Mucositis, Esophagitis, Esophageal stricture. Myelosuppression. Skin reactions. N/V, wight loss. Renal dysfunction
What is second line or salvage therapy for SCLC?
Most SCLC will relapse: median survival = only 4-5 months when treated w/ further chemotherapy. Second line chemotx provides palliation
What are the agents used in second line or salvage therapy for SCLC?
Docetaxel. Gemcitabine. Ifosfamide. Irinotecan. Paclitaxel. Topotecan. Temozolamide (if w/ brain mets). Vinorelbine
What is the prognosis and treatment tightly linked to for NSCLC?
Stage and well as patient factors (PS, histology, biomarker, gender, weight loss)
What is Stage I NSCLC?
Tumor of any size, located to lung, no lymph nodes
What is Stage II NSCLC?
Same as stage I, but WITH lymph node involvement
What is Stage IIIa NSCLC?
Tumor in chest wall, main bronchus or mediastinum
What is Stage IIIb NSCLC?
Tumor extending into mediastinal structure
Which stages of NSCLC are unresectable and have the lowest survival?
Stage IIIb, Stage IV
What are the treatment options for Resectable Stages of NSCLC (I, II, IIIa)?
Surgery is tx of choice w/ curative intent. Radiation (Stage I and II): treatment for medically inoperable, positive margins after surgery). Chemotherapy: adjuvant cisplatin-based (II, IIIa)
What is the treatment option for Stage IIIa (N2) - locally advanced, resectable NSCLC?
Standard: combined modality (3). Surgery –> adjuvant CT +/- RT. OR. Induction chemoradiation –> surgery
What is the treatment option for UNresectable Stage IIIa/IIIb NSCLC?
Associated w/ high rate of occult metastases; systemic relapse ~70%. Combined chemoradiation - concurrent better than sequential
What is treatment like for Advanced or Metastatic disease NSCLC?
Systemic chemotx: NSCLC only moderately sensitive. Benefit: good PS (performance status: 0-2), >70% Karnofsky, <10% weight loss. PS 3-4: no benefit from tx. Chemotx alone as palliation for Stage IIIb, IV
What type of NSCLC requires mutation testing?
Adenocarcinoma or Large cell. Not routinely recommended for Squamous NSCLC
What treatment options are there for a patient if EGFR or ALK negative?
Chemotherapy
What treatment options are there for a patient if EGFR positive?
Erlotinib
What treatment options are there for a patient if ALK positive?
Crizotinib
What would you choose for firstline therapy if: Stage IV, heavy former smoker, Adenocarcinoma, female, EGFR mutation is negative?
Systemic chemotx. Carbo/Paclitaxel, Carb/Pem, Carbo/Gem, Cis/Pem. In absence of squamous histology, brain mets, or hemoptysis –> Bevacizumab + Chemo (Carb/Paclitaxel/BV)
What does a Zubrod Scale of 0 or Karnofsky Scale of 90-100% indicated?
Normal
What does a Zubrod Scale of 1 or Karnofsky Scale of 70-80% indicated
Symptomatic without significant decrease in daily activities
What does a Zubrod Scale of 2 or Karnofsky Scale of 50-60% indicated
In bed or chair less than 50% of waking hours
What does a Zubrod Scale of 3 or Karnofsky Scale of 30-40% indicated
In bed or chain more than 50% of waking hours
What does a Zubrod Scale of 4 or Karnofsky Scale of 10-20% indicated
Bedridden (unable to care for self)
What is standard first-line therapy for advanced NSCLC w/ good PS?
Platinum-based doublets. Cisplatin or Carboplatin PLUS: Paclitaxel, Docetaxel, Gemcitabine, Vinorelbine, Pemetrexed
What does EGFR overexpression indicated?
Resistance to therapy, metastatic potential, and poorer Px. 17% of lung cancer. More frequently in women, never smoked, and adenocarcinomas (50% of Asian patients)
What is treatment like for Non-Squamous histology, no hemoptysis?
Carboplatin/Paclitaxel + Bevacizumab
What is treatment like for EGFR-expressing?
EGFR TKI (Erlotinib) or Gefitinib. OR. Cisplatin/Vinorelbine + Cetuximab
What is the overall survival like for Cetuximab +/- Chemotherapy?
Based on acne-like rash. Development during 1st cycle = clinical biomarker predictive of overall survival benefit. Category 2B recommendation
What are the toxicities with Cetuximab +/- Chemotherapy?
Neutropenia (40% grade 4), acne-like rash, infusion reactions, poor tolerance
What are good predictors of response with Erlotinib?
Female. Adenocarcinoma. Non-smoker. Asian. EGFR (+). KRAS (-)
What is maintenance therapy like in advanced NSCLC?
Delivered following 4-6 cycles of chemotx in patients who respond or have stable disease
What are the second and third line therapy options if NSCLC progressed during/after platinum?
Single agent Docetaxel, Pemetrexed, or Erlotinib
What is the treatment summary for Stage IV lung cancer?
Platinum-based combo of 2 drugs for PS 0-1. Single cytotoxic drug for PS 2. Halt chemotx if no response, if dz progresses, or 6 cycles given. Squamous: Pemetrexed less effective. Bevacizumab with Carbo-Paclitaxel
What is first line treatment for Stage IV lung cancer that is ALK positive?
Crizotinib
What is Malignant Pleural Effusion?
Accumulation of fluid in the pleural space. MOA: Impairment of lymphatic drainage from pleural space d/t tumor obstruction
What is the treatment for Malignant Pleural Effusion?
Thoracentesis: chest drainage for fluid evacuation. Pleurodesis: instill sclerosing agent (Talc slurry > 90% effective)