# Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression

Source: https://onco.cc/key-papers/paper-crane-smad4-progression-pattern-locally-advanced-jco-2011/  
OnCo record `paper-crane-smad4-progression-pattern-locally-advanced-jco-2011` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In 69 people with locally advanced pancreatic cancer, an ordinary Smad4 stain on the diagnostic needle sample predicted whether the cancer would grow locally or spread, the finding that supports using it to decide who gets radiotherapy.

## Summary

Treatment-naive patients with locally advanced pancreatic cancer (n = 69) received gemcitabine and oxaliplatin every two weeks for four doses then radiation (50.4 Gy) with concurrent capecitabine, with cetuximab throughout. Diagnostic cytology specimens were immunostained for Smad4(Dpc4). Median overall survival was 19.2 months with 1-, 2- and 4-year survival of 66.0%, 25.0% and 11.3%; radiographic local progression was 22.8% at one year and 61.0% at two. Smad4(Dpc4) expression correlated with a local rather than distant dominant pattern of disease progression (P = .016); prospective validation of Smad4 in cytology as a predictive biomarker was recommended.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Journal of Clinical Oncology
- Year: 2011
- DOI: 10.1200/JCO.2010.33.8038
- Authors: Crane CH, Varadhachary GR, Yordy JS, et al.
- Findings: Smad4 expression correlated with a local-dominant progression pattern (P = .016).; Median overall survival 19.2 months with chemotherapy then chemoradiation.
- What it means: It carried Iacobuzio-Donahue's autopsy finding into the clinic on a routine stain of the diagnostic sample, the basis for the still-unvalidated idea of choosing radiotherapy by SMAD4 status.
- Caveats: Single-arm phase 2 with cetuximab, which has no role today.; Prospective validation of Smad4 as a predictive marker has not been completed.

## Sources

- Crane et al., J Clin Oncol 2011: Smad4 immunostaining and progression pattern in 69 locally advanced patients: https://doi.org/10.1200/JCO.2010.33.8038
- PubMed: https://pubmed.ncbi.nlm.nih.gov/21709185/

## Connected records

- cancers: [Locally advanced unresectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/locally-advanced-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- targets: [SMAD4](https://onco.cc/targets/smad4/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Cetuximab](https://onco.cc/drugs/cetuximab/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Oxaliplatin](https://onco.cc/drugs/oxaliplatin/)
- institutions: [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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