Prediction Model for Estimating the Survival Benefit of Adjuvant Radiotherapy for Gallbladder Cancer

Portland State University, Portland, Oregon, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 06/2008; 26(13):2112-7. DOI: 10.1200/JCO.2007.14.7934
Source: PubMed


The benefit of adjuvant radiotherapy (RT) for gallbladder cancer remains controversial because most published data are from small, single-institution studies. The purpose of this study was to construct a survival prediction model to enable individualized predictions of the net survival benefit of adjuvant RT for gallbladder cancer patients based on specific tumor and patient characteristics.
A multivariate Cox proportional hazards model was constructed using data from 4,180 patients with resected gallbladder cancer diagnosed from 1988 to 2003 from the Surveillance, Epidemiology, and End Results database. Patient and tumor characteristics were included as covariates and assessed for association with overall survival (OS) with and without adjuvant RT. The model was internally validated for discrimination and calibration using bootstrap resampling.
On multivariate regression analysis, the model showed that age, sex, papillary histology, stage, and adjuvant RT were significant predictors of OS. The survival prediction model demonstrated good calibration and discrimination, with a bootstrap-corrected concordance index of 0.71. The model predicts that adjuvant RT provides a survival benefit in node-positive or >or= T2 disease. A nomogram and a browser-based software tool were built from the model that can calculate individualized estimates of predicted net survival gain attributable to adjuvant RT, given specific input parameters.
In the absence of large, prospective, randomized, clinical trial data, a regression model can be used to make individualized predictions of the expected survival improvement from the addition of adjuvant RT after gallbladder cancer resection.

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Available from: Dean Forrest Sittig, May 30, 2015
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    • "Although there are studies that demonstrate survival benefits of radiotherapy alone or in combination with adjuvant therapies, particularly when used at a dose >40Gy with fluoropyrimidine29303132, there are also studies demonstrating that it does not provide a survival advantage[33]. Wang et al investigated the efficacy of adjuvant radiotherapy alone and chemoradiotherapy in two different studies and similarly reported that >T2 node-positive patients benefited from adjuvant therapies[34,35]. Horgan et al carried out a meta-analysis and compared the group that underwent surgery alone with the group receiving any adjuvant therapy after surgery, but failed to find a significant difference in terms of survival[36]. "

    Preview · Article · Jan 2015 · Journal of Gastroenterology and Hepatology Research
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    • "It was observed an increase in median survival with adjuvant treatment (14 versus 8 months, p < 0.001) for the subgroup of patients presenting with locally advanced disease and lymph node involvement. The second [18], analyzed a sample of 4180 patients (18% received adjuvant radiotherapy) where despite the lack of information about the margin status, surgical technique and/or the use of chemotherapy, the addition of adjuvant RT was associated with a benefit in overall survival, particularly for patients with positive lymph nodes. The third study [19] aimed to define independent prognostic factors influencing overall survival. "
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    ABSTRACT: Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.4 Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%). Surgical margins were negative in 11 patients (48%), narrow in 2 (9%), and microscopically involved in 8 (35%). Eleven patients (55%) had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98). Acute gastrointestinal grade 2 toxicity (RTOG scale) was recorded in 2 patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) and 2 patients (9%) respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung). No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p=0.04). The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p=0.07). Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor location.
    Full-text · Article · Jun 2011 · BMC Cancer
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    • "However the outcomes are still dismal with the pressing need for development of newer therapies.1, 24, 25 "
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    ABSTRACT: Increased epidermal growth factor receptor (EGF receptor) expression has been noted in various cancers and has become a useful target for therapeutic interventions. Small studies from Asia and Australia have demonstrated EGFR over-expression in gallbladder cancer. We sought to evaluate the expression of EGFR in a series of 16 gallbladder cancer patients from North America. Using tumor registry data, we identified 16 patients diagnosed with gall bladder carcinoma at our medical center between the years of 1998 and 2005. We performed a retrospective review of these patients' charts, obtained cell blocks from pathology archives and stained for EGFR and Her2/neu. Fifteen of sixteen patients were noted to over-express EGFR. Three were determined 1+, nine were 2+ and three were 3+. Eight patients had poorly differentiated adenocarcinoma, six had moderately differentiated and two had well-differentiated tumors. In this small series, there was a trend toward shorter survival and more poorly differentiated tumors in patients with greater intensity of EGFR expression. One patient was EGFR negative but 3+ for erb-2/Her 2-neu expression. No patient co-expressed EGFR and Her-2-neu. Median survival of patients in this series was 17 months. In view of our observations confirming the over-expression of EGFR in our patient population in North America, and the recent success of EGFR targeted therapies in other solid tumors that over-express EGFR, it may now be appropriate to evaluate agents targeting this pathway either as single agents or in combination with standard chemotherapy.
    Preview · Article · Feb 2008 · International journal of medical sciences
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