KRAS mutations as a prognostic factor after metastasectomy in colorectal cancer patients
M. Domenech ViñolasCristina SantosJavier PérezMar VarelaM. Martínez VillacampaÀlex TeuléJ.C. Ruffinelli RodriguezN. Mulet MargalefG. SolerÁngel OrtegaM. BergaminoXavier SanjuánJoan TorrásEmilio RamosRamón Salazar
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Patients with metastatic colorectal cancer have a 5-year overall survival of less than 10%. Approximately 45% of patients with metastatic colorectal cancer harbor
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The RAS gene family is among the most studied and best characterized of the known cancer-related genes. Of the three human ras isoforms, KRAS is the most frequently altered gene, with mutations occurring in 17%–25% of all cancers. In particular, approximately 30%–40% of colon cancers harbor a KRAS mutation. KRAS mutations in colon cancers have been associated with poorer survival and increased tumor aggressiveness. Additionally, KRAS mutations in colorectal cancer lead to resistance to select treatment strategies. In this review we examine the history of KRAS, its prognostic value in patients with colorectal cancer, and evidence supporting its predictive value in determining appropriate therapies for patients with colorectal cancer.
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e19324 Background: KRAS G12C mutations are present in 15% of non-small cell lung cancer (NSCLC) and have recently been shown to confer sensitivity to KRAS(G12C) inhibitors. This study aims to assess the clinical features and outcomes with KRAS G12C mutant NSCLC in a real-world setting. Methods: Patients enrolled in an Australian prospective cohort study, Thoracic Malignancies Cohort (TMC), between July 2012 to October 2019 with metastatic or recurrent non-squamous NSCLC, with available KRAS test results, and without EGFR, ALK, or ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival was compared for KRAS wildtype ( KRAS WT ) and KRAS mutated ( KRAS mut ) patients, and between KRAS G12C ( KRAS G12C ) and other ( KRAS other ) mutations. Results: Of 1386 patients with non squamous NSCLC, 1040 were excluded for: non metastatic or recurrent (526); KRAS not tested (356); ALK, EGFR or ROS1 positive (154); duplicate (4). Of 346 patients analysed, 202 (58%) were KRAS WT and 144 (42%) were KRAS mut , of whom 65 (45%) were KRAS G12C . 100% of pts with KRAS G12C were smokers, compared to 92% of KRAS other and 83% of KRAS WT . The prevalence of brain metastases over entire follow-up period was similar between KRAS mut and KRAS WT (33% vs 40%, p = 0.17), and KRAS G12C and KRAS other (40% vs 41%, p = 0.74). Likewise, there was no difference in the proportion of patients receiving one or multiple lines of systemic therapy. Overall survival (OS) was also similar between KRAS mut and KRAS WT (p = 0.54), and KRAS G12C and KRAS other (p = 0.39). Conclusions: In this real-world prospective cohort, patients had comparable clinical features regardless of having a KRAS mut , KRAS G12C or KRAS other mutation, or being KRAS WT . Treatment and survival were also similar between groups. While not prognostic, KRAS G12C may be an important predictive biomarker as promising KRAS G12C covalent inhibitors continue to be developed.
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The first, and perhaps most famous, planned pulmonary
metastasectomy in the United States was performed in 1933 by Barney
and Churchill for metastatic renal cell carcinoma. During the
nineteenth century there were sporadic reports of lung resections for
metastatic tumors reported in the European literature. The first one of
these reports was in 1855, by the French surgeon Sedillot, who removed
a chest wall tumor and excised disease extending into the lung.
Almost 30 years later, in 1882, Weinlechner was credited for the
first resection of a true pulmonary metastases.It was not for another 40
years that metastasectomy was performed as a separate procedure by
Divis in Europe. This was followed soon after by similar reports in
the American literature by Torek and Tudor Edwards in the early
twentieth century. These early reports, and others like them, paved the way toward
general acceptance of pulmonary metastasectomy. In 1947 Alexander
and Haight reported the first series of pulmonary metastasectomies.
By the 1950s there were numerous case series with similar accounts.
Today the indications for resection of secondary pulmonary
malignancies have been broadened to include patients not only with
recurrent disease, but those with multiple metastases, bilateral lesions,
and essentially all histologies.
AIMS AND OBJECTIVES :
1. To assess the long term results of pulmonary metastasectomy.
2. To assess prognostic factors which are likely to influence long term outcomes.
3. To find out a favourable subset of prognostic group who may
benefit from pulmonary metastasectomy
METHOD :
Between January 1997 to December 2006 , all patients who
underwent pulmonary metastasectomy were included in this analysis.
Individual patient data were obtained from the case records in the
MMTR which also serves as a HBTR for Cancer Institute (WIA). A total
of 53 patient records were obtained , of that only 42 cases were taken
analysis. Patients who underwent planned sequential or staged
metastasectomies were considered to have single metastasectomy and
redo surgery. Analysis was done using SPSS 11.0.1 statistical package.
Following variables were tested : DFI ,unilateral or bilateral
presentation, number of metastases, histological type and site of primary
tumor, margin status, size of metastases, mediastinal nodes. Survival was
calculated from the time of first metastasectomy to the last date of follow
up by means of Kaplan – Meier estimate.
CONCLUSION :
Pulmonary metastasectomy is a potentially curative treatment that
can be done safely with low mortality or morbidity.
Good prognostic variables like increasing DFI (> 1 year), ability
to do R0 resection, solitary metastasis, size of the lesion less than
1 cm, and absence of mediastinal nodal positivity showed a trend
towards improved survival. Good prognostic group selected on the
basis of the risk factors like completely resected lesions, DFI and
number of metastases show a difference in survival between good
risk and poor risk groups ( 88% and 65% at 36 months). Although
these were not found to be significant in univariate or multivariate
analysis using Cox regression analysis.
There is a need for larger multicenteric analysis of data with larger
duration of follow up, from specialized centres who practice
pulmonary metastasectomy, to arrive at definite conclusions.
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Purpose . To identify prognostic factors for metastatic osteosarcoma patients and establish indication for repeat metastasectomy. Methods . Data from 37 patients with pulmonary metastasis from osteosarcoma who underwent metastasectomy in our institute from 1979 to 2013 were retrospectively reviewed. Results . Prognostic factors analyzed were age, sex, maximal diameter of the tumor at first pulmonary metastasectomy, total number of resected pulmonary metastases at first metastasectomy, number of surgeries, and disease free interval. In our analysis, characteristics associated with an increased overall survival were age > 15 years and fewer metastases (≤3). Of the 37 patients, 13 underwent repeat metastasectomy after the first metastasectomy. Of the 7 patients that underwent only two metastasectomies, three remained disease-free. In contrast, all six patients that underwent three or more metastasectomies died of relapse. Patients who had five or less lesions at second metastasectomy showed better survival compared to those who had six or more lesions. Conclusion . Age > 15 years and number of metastases at first metastasectomy were independent prognostic factors. Metastasectomy may provide curative treatment even in cases requiring repeat surgery. The number of metastases at second metastasectomy may be a potential predictor of the need for repeat surgery.
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