Staging

Treatment by Stage For early stage lung cancers, surgery or radiation alone For larger tumors (>4 cm) and N+, chemotherapy should be added as well For metastatic disease, chemotherapy and palliative radiation is used

Surgery Resection remains the preferred local tx modality For smokers, encourage quitting and waiting 4 weeks smoke-free before surgery

Surgery for Early Stage Sleeve lobectomy is preferred Sublobar resection: Segmentectomy is preferred over wedge resection for pts with poor pulm reserve, small nodules of AIS, > 50% ground glass appearance, or long radiological doubling time Goal of >2 cm margins, and should sample N1/N2 LN stations if possible

VATS vs open thoracotomy In centers with high volumes of VATS, there are improved early outcomes: Reduced pain Shortened hospital stay Faster recovery Fewer complications Similar rates of tumor control

Radiation in Early Stage Stereotactic Body Radiotherapy (SBRT) delivers a high, tumor-ablative dose to the target while minimizing normal tissue dose In Stage I NSCLC, SBRT shows rates of local tumor control (90-98%) and overall survival 30-80%) comparable to lobectomy

Stage III Controversies Historically Stage IIIA/B have been considered unresectable and definitive chemotherapy and radiation (concurrently or sequentially) is the tx of choice Two randomized studies have failed to show an OS benefit in adding surgical resection to chemo and RT, but NCCN guidelines still include it as an option to consider Breaks from neoadjuvant tx for surgical evaluation should be < 1 week

Resection of Stage IIIA (N2) In addition to N1/N2 dissection, ipsilateral mediastinal LN dissection should be done Complete resxn (R0) = free margins, systemic LN sampling or dissections, and the highest mediastinal node taken should be negative for tumor Incomplete: positive margins, unremoved positive LN’s, or positive pleural or pericardial effusion (R1 if microscopic, R2 if gross residual tumor)

Chemotherapy Multiple randomized trials show the benefit of chemotherapy in Stage II and III NSCLC (maybe even Stage IB with tumor > 4cm) Platinum-based doublet: Cisplatin/etoposide Cisplatin/vinblastine Carboplatin/paclitaxel Pemetrexed for nonsquamous histology, gemcitabine for squamous

M1b, Solitary Site For solitary brain metastasis: resection + WBI, or SBI + SRS, or SRS alone For adrenal metastasis: resection or RT (SBRT) to metastasis Then tx the lung per it’s stage without the metastasis

Advanced or Metastatic Disease EGFR and ALK testing for non-squamous histologies Bevacizumab + chemotherapy in pts with good performance status Erlotinib is first line therapy in pts with EGFR mutation Crizotinib is first line therapy in pts who are ALK positive

Targeted Therapies Bevacizumab (Avastin) – VEGF Erlotinib (Tarceva) – EGFR Gefitinib (Iressa) – EGFR Crizotinib – ALK These targets are mainly applicable in adenocarcinomas, with most SQCC lacking EGFR mutation and ALK rearrangement Cetuximab has shown activity in SQCC’s with high EGFR expression (FLEX)

Future Targets for SQCC In squamous cell NSCLC’s genomic profiling shows potential targets in PI3K pathway, FGFR1 amplifications and DDR2 mutations ECLIPSE: Phase III trial of carboplatin/gemcitabine =/- iniparib (a PARP inhibitor) is underway Phase III trial of carboplatin/paclitaxel +/- ipilimumab (targets the inhibition of cytotoxic T cells)

Follow Up Physical exam and CT scan every 6 months for 2 years Exam and CT scan every year after that