Edward Christopher Dee1, Morgan E Freret2, Nora Horick3, Ann C Raldow4, Lipika Goyal5, Andrew X Zhu5, Aparna R Parikh5, David P Ryan5, Jeffrey W Clark5, Jill N Allen5, Cristina R Ferrone6, Carlos Fernandez-Del Castillo6, Kenneth K Tanabe7, Lorraine C Drapek8, Theodore S Hong8, Motaz Qadan6, Jennifer Y Wo9. 1. Harvard Medical School, Boston, MA, USA. 2. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA. 4. Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA. 5. Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 6. Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 7. Department of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 8. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 9. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. jwo@mgh.harvard.edu.
Abstract
BACKGROUND: This study assessed patterns of failure and rates of subsequent biliary intervention among patients with resected biliary tract cancers (BTCs) including gallbladder carcinoma (GBC) and extra- and intrahepatic cholangiocarcinoma (eCCA and iCCA) treated with adjuvant chemoradiation therapy (CRT). METHODS: In this single-institution retrospective analysis of 80 patients who had GBC (n = 29), eCCA (n = 43), or iCCA (n = 8) treated with curative-intent resection and adjuvant CRT from 2007 to 2017, the median radiation dose was 50.4 Gy (range 36-65 Gy) with concurrent 5-fluorouracil (5-FU) chemotherapy. All but two of the patients received adjuvant chemotherapy. The 2-year locoregional failure (LRF), 2-year recurrence-free survival (RFS), and 2-year overall survival (OS), and univariate predictors of LRF, RFS, and OS were calculated for the entire cohort and for a subgroup excluding patients with iCCA (n = 72). The predictors of biliary interventions also were assessed. RESULTS: Of the 80 patients (median follow-up period, 30.5 months; median OS, 33.9 months), 54.4% had American Joint Committee on Cancer (AJCC) stage 1 or 2 disease, 57.1% were lymph node-positive, and 66.3% underwent margin-negative resection. For the entire cohort, 2-year LRF was 23.8%, 2-year RFS was 43.7%, and 2-year OS was 62.1%. When patients with iCCA were excluded, the 2-year LRF was 22.6%, the 2-year RFS was 43.9%, and the 2-year OS was 59.2%. In the overall and subgroup univariate analyses, lymph node positivity was associated with greater LRF, whereas resection margin was not. Biliary intervention was required for 12 (63.2%) of the 19 patients with LRF versus 11 (18%) of the 61 patients without LRF (P < 0.001). Of the 12 patients with LRF who required biliary intervention, 4 died of biliary complications. CONCLUSIONS: The LRF rates remained significant despite adjuvant CRT. Lymph node positivity may be associated with increased risk of LRF. Positive margins were not associated with greater LRF, suggesting that CRT may mitigate LRF risk for this group. An association between LRF and higher rates of subsequent biliary interventions was observed, which may yield significant morbidity. Novel strategies to decrease the rates of LRF should be considered.
BACKGROUND: This study assessed patterns of failure and rates of subsequent biliary intervention among patients with resected biliary tract cancers (BTCs) including gallbladder carcinoma (GBC) and extra- and intrahepatic cholangiocarcinoma (eCCA and iCCA) treated with adjuvant chemoradiation therapy (CRT). METHODS: In this single-institution retrospective analysis of 80 patients who had GBC (n = 29), eCCA (n = 43), or iCCA (n = 8) treated with curative-intent resection and adjuvant CRT from 2007 to 2017, the median radiation dose was 50.4 Gy (range 36-65 Gy) with concurrent 5-fluorouracil (5-FU) chemotherapy. All but two of the patients received adjuvant chemotherapy. The 2-year locoregional failure (LRF), 2-year recurrence-free survival (RFS), and 2-year overall survival (OS), and univariate predictors of LRF, RFS, and OS were calculated for the entire cohort and for a subgroup excluding patients with iCCA (n = 72). The predictors of biliary interventions also were assessed. RESULTS: Of the 80 patients (median follow-up period, 30.5 months; median OS, 33.9 months), 54.4% had American Joint Committee on Cancer (AJCC) stage 1 or 2 disease, 57.1% were lymph node-positive, and 66.3% underwent margin-negative resection. For the entire cohort, 2-year LRF was 23.8%, 2-year RFS was 43.7%, and 2-year OS was 62.1%. When patients with iCCA were excluded, the 2-year LRF was 22.6%, the 2-year RFS was 43.9%, and the 2-year OS was 59.2%. In the overall and subgroup univariate analyses, lymph node positivity was associated with greater LRF, whereas resection margin was not. Biliary intervention was required for 12 (63.2%) of the 19 patients with LRF versus 11 (18%) of the 61 patients without LRF (P < 0.001). Of the 12 patients with LRF who required biliary intervention, 4 died of biliary complications. CONCLUSIONS: The LRF rates remained significant despite adjuvant CRT. Lymph node positivity may be associated with increased risk of LRF. Positive margins were not associated with greater LRF, suggesting that CRT may mitigate LRF risk for this group. An association between LRF and higher rates of subsequent biliary interventions was observed, which may yield significant morbidity. Novel strategies to decrease the rates of LRF should be considered.
Authors: T Todoroki; K Ohara; T Kawamoto; N Koike; S Yoshida; H Kashiwagi; M Otsuka; K Fukao Journal: Int J Radiat Oncol Biol Phys Date: 2000-02-01 Impact factor: 7.038
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Authors: Attila Nakeeb; Khoi Q Tran; Michael J Black; Beth A Erickson; Paul S Ritch; Edward J Quebbeman; Stuart D Wilson; Michael J Demeure; William S Rilling; Kulwinder S Dua; Henry A Pitt Journal: Surgery Date: 2002-10 Impact factor: 3.982
Authors: John N Primrose; Richard P Fox; Daniel H Palmer; Hassan Z Malik; Raj Prasad; Darius Mirza; Alan Anthony; Pippa Corrie; Stephen Falk; Meg Finch-Jones; Harpreet Wasan; Paul Ross; Lucy Wall; Jonathan Wadsley; Jeff T R Evans; Deborah Stocken; Raaj Praseedom; Yuk Ting Ma; Brian Davidson; John P Neoptolemos; Tim Iveson; James Raftery; Shihua Zhu; David Cunningham; O James Garden; Clive Stubbs; Juan W Valle; John Bridgewater Journal: Lancet Oncol Date: 2019-03-25 Impact factor: 41.316