Chemoradiotherapy Versus Chemotherapy Alone for Unresected Nonmetastatic Gallbladder Cancer: National Practice Patterns and Outcomes

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Purpose: Current guidelines recommend chemotherapy (CT) with or without radiotherapy for unresected nonmetastatic gallbladder cancer (GC), with little consensus. However, several small-volume, single-institution studies have documented the efficacy of local therapy for this population. This is the largest study to date evaluating outcomes of chemoradiotherapy (CRT) versus CT alone in unresected nonmetastatic GC. Methods: The National Cancer Database was queried for primary GC cases (2004–2013) receiving CT alone or CRT. Patients receiving resection or lack of CT were excluded, as were those with metastatic disease or unknown M classification. Logistic regression analysis ascertained factors associated with CRT delivery. Kaplan-Meier analysis evaluated overall survival (OS) between both cohorts. Cox proportional hazards modeling determined variables associated with OS. Results: In total, 1,199 patients were analyzed (CRT: n=327, 27%; CT: n=872, 73%). Groups were evenly balanced, with no factor on multivariate logistic regression analysis statistically predicting for receipt of a particular paradigm. Median OS in the CRT and CT groups was 12.9 versus 7.8 months, respectively (P=.001). On multivariate analysis, OS was associated with age and years of treatment (P=.001 each). Notably, receipt of CRT independently predicted for improved OS (P=.001). Conclusions: CRT, compared with CT alone, was independently associated with improved survival in unresected nonmetastatic GC. Although causation is not implied, these results support the necessity for prospective CRT evaluation.

Correspondence: Chi Lin, MD, PhD, Department of Radiation Oncology, University of Nebraska Medical Center, Fred & Pamela Buffett Cancer Center, 505 South 45th Street, Omaha, NE 68106. E-mail: clin@unmc.edu
  • 1.

    Benson AB III, D'Angelica MI, Abbot D. NCCN Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers. Version 3.2017. Accessed September 19, 2017. To view the most recent version of these guidelines, visit NCCN.org.

    • Search Google Scholar
    • Export Citation
  • 2.

    Macdonald OK, Crane CH. Palliative and postoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11:941954.

  • 3.

    Hoehn RS, Wima K, Ertel AE. Adjuvant therapy for gallbladder cancer: an analysis of the National Cancer Data Base. J Gastrointest Surg 2015;19:17941801.

    • Search Google Scholar
    • Export Citation
  • 4.

    Mantripragada KC, Hamid F, Shafqat H, Olszewski AJ. Adjuvant therapy for resected gallbladder cancer: analysis of the National Cancer Data Base. J Natl Cancer Inst 2016;109:djw202.

    • Search Google Scholar
    • Export Citation
  • 5.

    Grove MK, Hermann RE, Vogt DP, Broughan TA. Role of radiation after operative palliation in cancer of the proximal bile ducts. Am J Surg 1991;161:454458.

    • Search Google Scholar
    • Export Citation
  • 6.

    Tollenaar RA, van de Velde CJ, Taat CW. External radiotherapy and extrahepatic bile duct cancer. Eur J Surg 1991;157:587589.

  • 7.

    Buskirk SJ, Gunderson LL, Schild SE. Analysis of failure after curative irradiation of extrahepatic bile duct carcinoma. Ann Surg 1992;215:125131.

    • Search Google Scholar
    • Export Citation
  • 8.

    Lu JJ, Bains YS, Abdel-Wahab M. High-dose-rate remote afterloading intracavitary brachytherapy for the treatment of extrahepatic biliary duct carcinoma. Cancer J 2002;8:7478.

    • Search Google Scholar
    • Export Citation
  • 9.

    Crane CH, Macdonald KO, Vauthey JN. Limitations of conventional doses of chemoradiation for unresectable biliary cancer. Int J Radiat Oncol Biol Phys 2002;53:969974.

    • Search Google Scholar
    • Export Citation
  • 10.

    Deodato F, Clemente G, Mattiucci GC. Chemoradiation and brachytherapy in biliary tract carcinoma: long-term results. Int J Radiat Oncol Biol Phys 2006;64:483488.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ghafoori AP, Nelson JW, Willett CG. Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 2011;81:654659.

    • Search Google Scholar
    • Export Citation
  • 12.

    Habermehl D, Lindel K, Rieken S. Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection: analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation. Strahlenther Onkol 2012;188:795801.

    • Search Google Scholar
    • Export Citation
  • 13.

    Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol 2008;15:683690.

    • Search Google Scholar
    • Export Citation
  • 14.

    Stahl JM, Corso CD, Verma V. Trends in stereotactic body radiation therapy for stage I small cell lung cancer. Lung Cancer 2017;103:1116.

  • 15.

    Haque W, Verma V, Butler EB, Teh BS. Patterns of care and outcomes of multi-agent versus single-agent chemotherapy as part of multimodal management of low grade glioma. J Neurooncol 2017;133:369375.

    • Search Google Scholar
    • Export Citation
  • 16.

    Haque W, Verma V, Butler EB, Teh BS. National practice patterns and outcomes for T4b urothelial cancer of the bladder [published online ahead of print September 6, 2017]. Clin Genitourin Cancer, doi:10.1016/j. clgc.2017.08.013.

    • Search Google Scholar
    • Export Citation
  • 17.

    Moreno AC, Verma V, Hofstetter WL, Lin SH. Patterns of care and treatment outcomes of elderly patients with stage I esophageal cancer: analysis of the National Cancer Data Base. J Thorac Oncol 2017;12:11521160.

    • Search Google Scholar
    • Export Citation
  • 18.

    McMillan MT, Ojerholm E, Verma V. Radiation treatment time and overall survival in locally advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2017;98:11421152.

    • Search Google Scholar
    • Export Citation
  • 19.

    Verma V, Ryckman JM, Simone CB II, Lin C. Patterns of care and outcomes with the addition of chemotherapy to radiation therapy for stage I nasopharyngeal cancer [published online ahead of print July 19, 2017]. Acta Oncol, doi:10.1080/0284186X.2017.1351039.

    • Search Google Scholar
    • Export Citation
  • 20.

    Verma V, Ahern CA, Berlind CG. National Cancer Data Base report on pneumonectomy versus lung-sparing surgery for malignant pleural mesothelioma. J Thorac Oncol 2017;12:17041714.

    • Search Google Scholar
    • Export Citation
  • 21.

    Haque W, Verma V, Butler EB, Teh BS. Definitive chemoradiation at high volume facilities is associated with improved survival in glioblastoma. J Neurooncol 2017;135:173181.

    • Search Google Scholar
    • Export Citation
  • 22.

    Haque W, Verma V, Butler EB, Teh BS. Radical cystectomy versus chemoradiation for muscle-invasive bladder cancer: impact of treatment facility and sociodemographics. Anticancer Res 2017;37:56035608.

    • Search Google Scholar
    • Export Citation
  • 23.

    Bott MJ, Patel AP, Verma V. Patterns of care in hilar node-positive (N1) non-small cell lung cancer: a missed treatment opportunity? J Thorac Cardiovasc Surg 2016;151:15491558.

    • Search Google Scholar
    • Export Citation
  • 24.

    Haque W, Verma V, Butler EB, Teh BS. Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base [published online ahead of print September 22, 2017]. J Gastrointest Oncol 2017, doi: 10.21037/jgo.2017.09.12.

    • Search Google Scholar
    • Export Citation
  • 25.

    Verma V, Simone CB, Lin C. Human papillomavirus and nasopharyngeal cancer. Head Neck 2017, doi: 10.1002/hed.24978.

  • 26.

    Haque W, Verma V, Butler EB, Teh BS. Addition of chemotherapy to hypofractionated radiotherapy for glioblastoma: practice patterns, outcomes, and predictors of survival [published online ahead of print October 31, 2017]. J Neurooncol 2017, doi: 10.1007/s11060-017-2654-y.

    • Search Google Scholar
    • Export Citation
  • 27.

    Verma V, Allen PK, Simone CB II. Association of treatment at high-volume facilities with survival in patients receiving chemoradiotherapy for nasopharyngeal cancer [published online ahead of print November 2, 2017]. JAMA Otolaryngol Head Neck Surg 2017, doi:10.1001/jamaoto.2017.1874.

    • Search Google Scholar
    • Export Citation
  • 28.

    Verma V, Allen PK, Simone CB II. Addition of definitive radiotherapy to chemotherapy in patients with newly diagnosed metastatic nasopharyngeal cancer. J Natl Compr Canc Netw 2017;15:13831391.

    • Search Google Scholar
    • Export Citation
  • 29.

    Haque W, Verma V, Butler EB, Teh BS. Chemotherapy versus chemoradiation for node-positive bladder cancer: practice patterns and outcomes from the National Cancer Data Base. Bladder Cancer 2017;3:283291.

    • Search Google Scholar
    • Export Citation
  • 30.

    Haque W, Verma V, Bernicker E. Management of pathologic node-positive disease following initial surgery for clinical T1-2 N0 esophageal cancer: patterns of care and outcomes from the National Cancer Data Base [published online ahead of print November 30, 2017]. Acta Oncol 2017, doi: 10.1080/0284186X.2017.1409435.

    • Search Google Scholar
    • Export Citation
  • 31.

    Haque W, Lewis GD, Verma V. The role of adjuvant chemotherapy in locally advanced bladder cancer [published online ahead of print December 11, 2017]. Acta Oncol 2017, doi: 10.1080/0284186X.2017.1415461.

    • Search Google Scholar
    • Export Citation
  • 32.

    Glimelius B, Hoffman K, Sjoden PO. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 1996;7:593600.

    • Search Google Scholar
    • Export Citation
  • 33.

    Haque W, Verma V, Fakhreddine M. Addition of chemotherapy to definitive radiotherapy for IB1 and IIA1 cervical cancer: analysis of the National Cancer Data Base. Gynecol Oncol 2017;144:2833.

    • Search Google Scholar
    • Export Citation
  • 34.

    Verma V, McMillan MT, Grover S. Stereotactic body radiation therapy and the influence of chemotherapy on overall survival for large (≥5 centimeter) non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2017;97:146154.

    • Search Google Scholar
    • Export Citation
  • 35.

    Brunner TB, Schwab D, Meyer T, Sauer R. Chemoradiation may prolong survival of patients with non-bulky unresectable extrahepatic biliary carcinoma. A retrospective analysis. Strahlenther Onkol 2004;180:751757.

    • Search Google Scholar
    • Export Citation
  • 36.

    Shinohara ET, Mitra N, Guo M, Metz JM. Radiotherapy is associated with improved survival in adjuvant and palliative treatment of extrahepatic cholangiocarcinomas. Int J Radiat Oncol Biol Phys 2009;74:11911198.

    • Search Google Scholar
    • Export Citation
  • 37.

    Fuller CD, Wang SJ, Choi M. Multimodality therapy for locoregional extrahepatic cholangiocarcinoma: a population-based analysis. Cancer 2009;115:51755183.

    • Search Google Scholar
    • Export Citation
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