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abstract
22 NOV 2016
BACKGROUND
Ovarian
metastases from colorectal cancer (OM-CRC) often are unresponsive to
chemotherapy and are associated with poor survival. To the authors'
knowledge, the clinicopathologic and genomic predictors of OM-CRC are
poorly characterized and optimal clinical management remains unclear.
METHODS
Women
with a histopathological diagnosis of OM-CRC who were treated at
Memorial Sloan Kettering Cancer Center from 1999 to 2015 were
identified. Next-generation somatic mutation profiling (Memorial Sloan
Kettering-Integrated Mutation Profiling of Actionable Cancer Targets
[MSK-IMPACT]) was performed on 38 OM-CRC cases, including 21 matched
tumor pairs/trios. Regression models were used to analyze variables
associated with progression-free survival and overall survival (OS).
RESULTS
Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), SMAD family member 4 (SMAD4), and neurotrophic receptor tyrosine kinase 1 (NTRK1) mutations were more frequent in cases of OM-CRC than in instances of CRC occurring without OM. SMAD4 and lysine methyltransferase 2D (KMT2D)
mutations were associated with reduced OS. Matched multisite tumor
sequencing did not identify OM-specific genomic alterations. Of the 195
patients who underwent oophorectomy for OM-CRC (median age, 49 years
with a progression-free survival of 9.4 months and an OS of 23 months
from oophorectomy), 76% had extraovarian metastasis (EOM). In
multivariable analysis, residual disease after surgery (R2 resection)
was associated with worse survival. Patients with EOM were less likely
to achieve R0/R1 surgical resection status (complete macroscopic
resection without clinical/radiological evidence of disease) (48% vs
94%). However, if R0/R1 resection status was achieved, both patients
with (35.9 months vs 12 months) and without (43.2 months vs 14.5 months)
EOM were found to have better OS. Among 114 patients with R0/R1
resection status, 23 (20%) had no disease recurrence, including 10
patients (9%) with > 3 years of follow-up.
CONCLUSIONS
Loss-of-function alterations in SMAD4
are frequent and predictive of worse survival in patients with OM-CRC.
Similar to oligometastatic CRC to the lung or liver, surgical resection
of OM-CRC is associated with a better outcome only if all macroscopic
metastatic disease is resected.
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