2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

LUNG CANCER IN BRAZIL
Fig. 3. Characteristics of groups mutated
for EGFR, KRAS, BRAF, and TP53. 10
Abbreviations: EGFR, epidermal growth
factor receptor; SCC, squamous cell carcinoma.
Health System in Brazil, its use is usually restricted to
patients with early disease who are candidates for curative
surgery. In the absence of specific symptoms, there is no
indication for the use of brain MRI or bone scans in patients
with stage IV disease. An MRI of the brain, however, is
considered by many oncologists in Brazil in the case of lung
adenocarcinoma, because of the higher risk of brain metastases.
Finally, surgical resection without prior invasive
testing may be an option in patients with a highly suspicious
solitary pulmonary nodule.
In a series of 291 patients with NSCLC treated in an
academic hospital in Sao Paulo, Brazil, clinical staging was
based on clinical and imaging studies. PET scan was not
routinely performed. Pathologic staging differed from clinical
staging in 33% of cases (15% were upstaged and 18%
downstaged). Sensitivity, specificity, positive and negative
predictive values, and accuracy for clinical staging were
78%, 69%, 82%, 64%, and 67%, respectively. 16
In another study performed in Porto Alegre, Brazil, the
authors looked at the indications for MRI studies in patients
with NSCLC. MRI was used mainly for patients with superior
sulcus tumors, suspected spinal cord canal invasion, and
suspected brain metastases. 17
Biomarkers
EGFR exon 19 deletion or exon 21 L858R mutation result
in activation of the tyrosine kinase domain and are predictive
of better sensitivity to EGFR-TKIs. These mutations are
found in approximately 10% to 15% of white and 30% to 40%
of Asian patients with NSCLC. 10,18 As described below,
these results were not confirmed in a recent study performed
by investigators of the Brazilian National Cancer Institute,
in which 25.3% (38 of 150 cases) of patients with NSCLC
showed these mutations. EGFR mutations were more common
in women (60.6%), smokers (51.4%), and in the adeno-
carcinoma subtype (54.5%). These mutations were also
detected in never (15.2%) and previous (27.3%) smokers, as
well as in a significant percentage of patients with the
squamous cell subtype (33.4%). 10
Patients with NSCLC with high ERCC1 expression in the
tumor were shown to have a better overall survival than
those with low ERCC1 expression. High ERCC1 levels were
also associated with resistance to platinum-based chemotherapies.
12,19 KRAS mutation is observed in approximately
25% of adenocarcinomas. It is associated with worse survival
and resistance to platinum-based chemotherapy or EGFR-
TKIs. 12,20 Furthermore, high RRM1 levels are associated
with better survival but poor response to gemcitabine or
carboplatin. 12,21
Treatment
Surgical resection should be attempted in all patients with
stage I or II good performance status NSCLC, as it provides
the best chances of cure. 12 In a study performed in a cancer
hospital in Sao Paulo, Brazil, including 737 patients with
NSCLC, complete tumor resection was performed in 24.6%
of patients. The overall 5-year survival rate was 28%, and
the median survival was 18.9 months. 22
The survival advantage of adjuvant cisplatin-based chemotherapy
for patients with completely resected stage I, II,
or III NSCLC was demonstrated in prospective randomized
trials (IALT, NCIC, and ANITA). Postoperative cisplatinbased
chemotherapy produced an absolute benefit of 5% in
5-year survival, especially in patients with stage II-III
disease with good performance status. Adjuvant chemotherapy
was also beneficial for patients with stage I disease
with � 4-cm tumors. 12,23
Several therapeutic options can be considered for patients
with stage IIIA disease. For unresectable cases of stage IIIA
or IIIB disease, chemoradiation was shown to be superior to
429