Non-small cell lung cancer

Epidemiology
Second most common cancer in both men and women (after prostate and breast respectively)
180-200,000 cases per year
Most common cause of cancer death in both sexes

Risk factors
Smoking
Radon
Asbestos
Prior aerodigestive tract cancers

Pathology
Adenocarcinoma
-Most common subtype
-Tends to be peripheral
-Often seen in female nonsmokers
-Variants include bronchioalveolar carcinoma, large cell cancer

Squamous cell carcinoma
-Relative decrease in incidence over recent years
-Smokers
-Proximal lesion

Nodal stations
1 - supraclavicular
2, 4 - paratracheal
3 - posterior mediastinum
6 - anterior mediastinum
5 - AP window
7 - subcarinal
10 - hilar
11, 12 - lobar, interlobar

Clinical
Screening trials of CT in high risk patients are ongoing
Sputum cytology and serial CXR have been unsuccessfully tried as screening tests

30-40% of patients have metastatic disease
Additional 35-40% are stage III

SVC syndrome: most commonly caused by SCLC, then squamous cell ca
Pancoast tumor: apical sulcus tumor associated with brachial plexopathy, Horner's syndrome (compression of cervical sympathetic ganglion causing miosis, ptosis, anhidrosis), shoulder pain (secondary to chest wall invasion); most tumors are squamous cell

Paraneoplastic syndromes associated with NSCLC: hypercalcemia (PTHrP, bone metastasis), hypertrophic osteoarthropathy, gynecomastia (associated with large cell subtype)

Prognostic factors
Performance status*
Stage
Weight loss (+/-)
Cellular markers: k-ras p 53, erb, Ki-67

Therapy: very early stage tumors (T1-2, N0)
Preferred treatment: anatomic lobectomy
Wedge resection vs. lobectomy was tested in a randomized trial (Lung Cancer Study Group; PMID 7677489)
Increased local recurrence rates were observed in the wedge resection group (17 vs. 6%); trend to higher overall and cancer-specific mortality rates in the wedge resection group as well
FEV1 is a common criteria for determining if a patient is an operative candidate (limits vary, common criteria is greater than 40% of predicted or at least 1.2L)
Conventionally fractionated postage stamp RT leads to poor outcomes
SBRT is associated with 85-90% local control rates in medically inoperable patients
Proximally located tumors were associated with higher rates of toxicity (including grade 5 toxicity) in initial RTOG trials of SBRT; investigation is continuing as to which gentler fractionation regimens may be appropriate for patients with proximal tumors
Use of adjuvant chemotherapy after lobectomy for node negative patients continues to evolve; patients with large tumors will usually be given chemo

Therapy: early T, node positive
T1-2, N1: chemotherapy is indicated
T1-2, N2: consider adding postoperative radiation
PORT meta-analysis (PMID 15846628) - 2232 patients, 10 trials
Postoperative radiation was detrimental to survival in stage I patients
Benefit was seen for N2 patients
Unclear results in stage III
Criticisms: included studies which used outdated (2-D) treatment techniques;

Therapy: stage III tumors (T3-4Nx; TxN2-3)
I ran out of gas on my notes here
Concurrent CRT with radiation dose escalation is generally recommended
Absolute benefit to concurrent vs. sequential treatment is small, but statistically significant
In terms of treatment planning, lung volume irradiated is a strong predictor of developing radiation pneumonitis; V20 is a commonly used criteria

Therapy: superior sulcus tumors
3% of all lung cancers
MRI is more accurate than CT for assessing chest wall, vertebral invasion
SWOG protocol (PMID 17235046):
-T3-4, N0-1 patients
-45Gy + cisplatin/etoposide x 2 cycles was given preoperatively
-92% of patients went on to complete resection
-65% had path CR or minimal residual disease
-5yr OS was 44% for patients and 54% for those with a complete resection
For unresectable superior sulcus tumors, radiation doses ~66Gy + concurrent chemo are associated with reasonable local control but worse OS compared with resected patients

Chemotherapy agents
1) pemetrexed: worse survival in squamous cell histology
2) gefitinib: EGFR inhibitor; benefit only in about 10% of patients who express mutated EGFR
3) erlotinib: another EGFR inhibitor; sensitive patients also EGFR-mutated; tend to be young, female, Asian, non smokers
4) bevacizumab: associated with pulmonary hemorrhage in squamous cell patients