Anthropometric Changes in Patients with Pancreatic Cancer Undergoing Preoperative Therapy and Pancreatoduodenectomy
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The changes in body composition that occur in response to therapy for localized pancreatic ductal adenocarcinoma (PDAC) and during the early survivorship period, as well as their clinical significance, are poorly understood.
One hundred twenty-seven consecutive patients with PDAC who received preoperative therapy followed by pancreatoduodenectomy (PD) at a single institution between 2009 and 2012 were longitudinally evaluated. Changes in skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured on serial computed tomography images obtained upon presentation, prior to pancreatectomy, and approximately 3 and 12 months after surgery.
Prior to therapy, patients’ mean baseline BMI was 26.5 ± 4.7 kg/m2 and 63.0% met radiographic criteria for sarcopenia. During a mean 5.4 ± 2.3 months of preoperative therapy, minimal changes in SKM (− 0.5 ± 7.8%, p > 0.05), VAT (− 1.8 ± 62.6%, p < 0.001), and SAT (− 4.8 ± 27.7%, p < 0.001) were observed. In contrast, clinically significant changes were observed on postoperative CT compared to baseline anthropometry: SKM − 4.1 ± 10.7%, VAT − 38.7 ± 30.2%, and SAT − 24.1 ± 22.6% (all p < 0.001) and these changes persisted at one year following PD. While anthropometric changes during preoperative therapy were not independently associated with survival, SKM gain between the postoperative period and one-year follow-up was associated with improved overall survival (OR 0.50, 95% CI 0.29–0.87).
In contrast to the minor changes that occur during preoperative therapy for PDAC, significant losses in key anthropometric parameters tend to occur over the first year following PD. Ongoing SKM loss in the postoperative period may represent an early marker for worse outcomes.
KeywordsPancreatic ductal adenocarcinoma Body composition Neoadjuvant therapy Whipple Pancreatoduodenectomy Pancreatectomy
This work was supported in part by the National Institutes of Health/National Cancer Institute under award number P30CA016672 (used the Clinical Trials Support Resource and the Biostatistics Resource Group). Additional support provided by the Knox Family fund.
All authors made substantial contributions to the
- conception or design of the work; or the acquisition, analysis, or interpretation of data for the work
- drafting the work or revising it critically for important intellectual content
- final approval of the version to be published
- agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Compliance with Ethical Standards
The University of Texas MD Anderson Cancer Center’s (MDACC) institutional review board approved this retrospective study.
- 2.L. Martin, L. Birdsell, N. Macdonald, T. Reiman, M.T. Clandinin, L.J. McCargar, R. Murphy, S. Ghosh, M.B. Sawyer, V.E. Baracos, Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index, J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 31 (2013) 1539–1547. https://doi.org/10.1200/JCO.2012.45.2722.CrossRefGoogle Scholar
- 4.Y. Choi, D.-Y. Oh, T.-Y. Kim, K.-H. Lee, S.-W. Han, S.-A. Im, T.-Y. Kim, Y.-J. Bang, Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index, PloS One. 10 (2015) e0139749. https://doi.org/10.1371/journal.pone.0139749.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.K. Fearon, F. Strasser, S.D. Anker, I. Bosaeus, E. Bruera, R.L. Fainsinger, A. Jatoi, C. Loprinzi, N. MacDonald, G. Mantovani, M. Davis, M. Muscaritoli, F. Ottery, L. Radbruch, P. Ravasco, D. Walsh, A. Wilcock, S. Kaasa, V.E. Baracos, Definition and classification of cancer cachexia: an international consensus, Lancet Oncol. 12 (2011) 489–495. https://doi.org/10.1016/S1470-2045(10)70218-7.CrossRefPubMedGoogle Scholar
- 8.A.B. Cooper, R. Slack, D. Fogelman, H.M. Holmes, M. Petzel, N. Parker, A. Balachandran, N. Garg, A. Ngo-Huang, G. Varadhachary, D.B. Evans, J.E. Lee, T. Aloia, C. Conrad, J.-N. Vauthey, J.B. Fleming, M.H.G. Katz, Characterization of Anthropometric Changes that Occur During Neoadjuvant Therapy for Potentially Resectable Pancreatic Cancer, Ann. Surg. Oncol. 22 (2015) 2416–2423. https://doi.org/10.1245/s10434-014-4285-2.CrossRefPubMedGoogle Scholar
- 9.C. Yip, V. Goh, A. Davies, J. Gossage, R. Mitchell-Hay, O. Hynes, N. Maisey, P. Ross, A. Gaya, D.B. Landau, G.J. Cook, N. Griffin, R. Mason, Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer, Eur. Radiol. 24 (2014) 998–1005. https://doi.org/10.1007/s00330-014-3110-4.CrossRefPubMedGoogle Scholar
- 10.I.J.G. Rutten, D.P.J. van Dijk, R.F.P.M. Kruitwagen, R.G.H. Beets-Tan, S.W.M. Olde Damink, T. van Gorp, Loss of skeletal muscle during neoadjuvant chemotherapy is related to decreased survival in ovarian cancer patients, J. Cachexia Sarcopenia Muscle. 7 (2016) 458–466. https://doi.org/10.1002/jcsm.12107.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.T. Akahori, M. Sho, S. Kinoshita, M. Nagai, S. Nishiwada, T. Tanaka, T. Tamamoto, C. Ohbayashi, M. Hasegawa, K. Kichikawa, Y. Nakajima, Prognostic Significance of Muscle Attenuation in Pancreatic Cancer Patients Treated with Neoadjuvant Chemoradiotherapy, World J. Surg. 39 (2015) 2975–2982. https://doi.org/10.1007/s00268-015-3205-3.CrossRefPubMedGoogle Scholar
- 12.R.F. Hwang, H. Wang, A. Lara, H. Gomez, T. Chang, N. Sieffert, Y. Moon, S. Ram, S. Zimmerman, J.H. Lee, P.W.T. Pisters, E.P. Tamm, J.B. Fleming, J.L. Abbruzzese, D.B. Evans, Development of an integrated biospecimen bank and multidisciplinary clinical database for pancreatic cancer, Ann. Surg. Oncol. 15 (2008) 1356–1366. https://doi.org/10.1245/s10434-008-9833-1.CrossRefPubMedGoogle Scholar
- 13.G.R. Varadhachary, E.P. Tamm, J.L. Abbruzzese, H.Q. Xiong, C.H. Crane, H. Wang, J.E. Lee, P.W.T. Pisters, D.B. Evans, R.A. Wolff, Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy, Ann. Surg. Oncol. 13 (2006) 1035–1046. https://doi.org/10.1245/ASO.2006.08.011.CrossRefPubMedGoogle Scholar
- 14.J.M. Cloyd, M.H.G. Katz, L. Prakash, G.R. Varadhachary, R.A. Wolff, R.T. Shroff, M. Javle, D. Fogelman, M. Overman, C.H. Crane, E.J. Koay, P. Das, S. Krishnan, B.D. Minsky, J.H. Lee, M.S. Bhutani, B. Weston, W. Ross, P. Bhosale, E.P. Tamm, H. Wang, A. Maitra, M.P. Kim, T.A. Aloia, J.-N. Vauthey, J.B. Fleming, J.L. Abbruzzese, P.W.T. Pisters, D.B. Evans, J.E. Lee, Preoperative Therapy and Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: a 25-Year Single-Institution Experience, J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract. 21 (2017) 164–174. https://doi.org/10.1007/s11605-016-3265-1.CrossRefGoogle Scholar
- 15.J.M. Cloyd, C.H. Crane, E.J. Koay, P. Das, S. Krishnan, L. Prakash, R.A. Snyder, G.R. Varadhachary, R.A. Wolff, M. Javle, R.T. Shroff, D. Fogelman, M. Overman, H. Wang, A. Maitra, J.E. Lee, J.B. Fleming, M.H.G. Katz, Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma, Cancer. 122 (2016) 2671–2679. https://doi.org/10.1002/cncr.30117.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.C.-W.D. Tzeng, J.B. Fleming, J.E. Lee, L. Xiao, P.W.T. Pisters, J.-N. Vauthey, E.K. Abdalla, R.A. Wolff, G.R. Varadhachary, D.R. Fogelman, C.H. Crane, A. Balachandran, M.H.G. Katz, Defined clinical classifications are associated with outcome of patients with anatomically resectable pancreatic adenocarcinoma treated with neoadjuvant therapy, Ann. Surg. Oncol. 19 (2012) 2045–2053. https://doi.org/10.1245/s10434-011-2211-4.CrossRefPubMedGoogle Scholar
- 17.M.H.G. Katz, J.E. Lee, P.W.T. Pisters, R. Skoracki, E. Tamm, J.B. Fleming, Retroperitoneal Dissection in Patients with Borderline Resectable Pancreatic Cancer: Operative Principles and Techniques, J. Am. Coll. Surg. 215 (2012) e11–e18. https://doi.org/10.1016/j.jamcollsurg.2012.05.015.CrossRefPubMedPubMedCentralGoogle Scholar
- 18.C.-W.D. Tzeng, J.B. Fleming, J.E. Lee, X. Wang, P.W.T. Pisters, J.-N. Vauthey, G. Varadhachary, R.A. Wolff, M.H.G. Katz, Yield of clinical and radiographic surveillance in patients with resected pancreatic adenocarcinoma following multimodal therapy, HPB. 14 (2012) 365–372. https://doi.org/10.1111/j.1477-2574.2012.00445.x.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.M. Mourtzakis, C.M.M. Prado, J.R. Lieffers, T. Reiman, L.J. McCargar, V.E. Baracos, A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care, Appl. Physiol. Nutr. Metab. Physiol. Appl. Nutr. Metab. 33 (2008) 997–1006. https://doi.org/10.1139/H08-075.CrossRefGoogle Scholar
- 20.J.M. Cloyd, H. Wang, M.E. Egger, C.-W.D. Tzeng, L.R. Prakash, A. Maitra, G.R. Varadhachary, R. Shroff, M. Javle, D. Fogelman, R.A. Wolff, M.J. Overman, E.J. Koay, P. Das, J.M. Herman, M.P. Kim, J.-N. Vauthey, T.A. Aloia, J.B. Fleming, J.E. Lee, M.H.G. Katz, Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma. JAMA Surg. (2017) Nov 1;152(11):1048–1056.Google Scholar
- 22.N. Pecorelli, G. Carrara, F. De Cobelli, G. Cristel, A. Damascelli, G. Balzano, L. Beretta, M. Braga, Effect of sarcopenia and visceral obesity on mortality and pancreatic fistula following pancreatic cancer surgery, Br. J. Surg. 103 (2016) 434–442. https://doi.org/10.1002/bjs.10063.CrossRefPubMedGoogle Scholar
- 23.N. Amini, G. Spolverato, R. Gupta, G.A. Margonis, Y. Kim, D. Wagner, N. Rezaee, M.J. Weiss, C.L. Wolfgang, M.M. Makary, I.R. Kamel, T.M. Pawlik, Impact Total Psoas Volume on Short- and Long-Term Outcomes in Patients Undergoing Curative Resection for Pancreatic Adenocarcinoma: a New Tool to Assess Sarcopenia, J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract. 19 (2015) 1593–1602. https://doi.org/10.1007/s11605-015-2835-y.CrossRefGoogle Scholar
- 24.A.J. Benjamin, M.M. Buschmann, A. Schneider, B.A. Derstine, J.F. Friedman, S.C. Wang, W. Dale, K.K. Roggin, Can Comprehensive Imaging Analysis with Analytic Morphomics and Geriatric Assessment Predict Serious Complications in Patients Undergoing Pancreatic Surgery?, J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract. 21 (2017) 1009–1016. https://doi.org/10.1007/s11605-017-3392-3.CrossRefGoogle Scholar
- 25.M.D. Sur, J.P. Namm, J.A. Hemmerich, M.M. Buschmann, K.K. Roggin, W. Dale, Radiographic Sarcopenia and Self-reported Exhaustion Independently Predict NSQIP Serious Complications After Pancreaticoduodenectomy in Older Adults, Ann. Surg. Oncol. 22 (2015) 3897–3904. https://doi.org/10.1245/s10434-015-4763-1.CrossRefPubMedGoogle Scholar
- 26.S. Buettner, D. Wagner, Y. Kim, G.A. Margonis, M.A. Makary, A. Wilson, K. Sasaki, N. Amini, F. Gani, T.M. Pawlik, Inclusion of Sarcopenia Outperforms the Modified Frailty Index in Predicting 1-Year Mortality among 1,326 Patients Undergoing Gastrointestinal Surgery for a Malignant Indication, J. Am. Coll. Surg. 222 (2016) 397–407.e2. https://doi.org/10.1016/j.jamcollsurg.2015.12.020.CrossRefPubMedGoogle Scholar
- 27.P. Peng, O. Hyder, A. Firoozmand, P. Kneuertz, R.D. Schulick, D. Huang, M. Makary, K. Hirose, B. Edil, M.A. Choti, J. Herman, J.L. Cameron, C.L. Wolfgang, T.M. Pawlik, Impact of sarcopenia on outcomes following resection of pancreatic adenocarcinoma, J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract. 16 (2012) 1478–1486. https://doi.org/10.1007/s11605-012-1923-5.CrossRefGoogle Scholar
- 33.D. Hashimoto, A. Chikamoto, M. Ohmuraya, S. Abe, S. Nakagawa, T. Beppu, H. Takamori, M. Hirota, H. Baba, Impact of Postoperative Weight Loss on Survival After Resection for Pancreatic Cancer, JPEN J. Parenter. Enteral Nutr. 39 (2015) 598–603. https://doi.org/10.1177/0148607114520992.CrossRefPubMedGoogle Scholar
- 35.S.E. Lee, J.H. Lee, K.W. Ryu, B. Nam, C.G. Kim, S.R. Park, M.-C. Kook, Y.-W. Kim, Changing pattern of postoperative body weight and its association with recurrence and survival after curative resection for gastric cancer, Hepatogastroenterology. 59 (2012) 430–435. https://doi.org/10.5754/hge09218.CrossRefPubMedGoogle Scholar
- 36.J.L. Davis, L.V. Selby, J.F. Chou, M. Schattner, D.H. Ilson, M. Capanu, M.F. Brennan, D.G. Coit, V.E. Strong, Patterns and Predictors of Weight Loss After Gastrectomy for Cancer, Ann. Surg. Oncol. 23 (2016) 1639–1645. https://doi.org/10.1245/s10434-015-5065-3.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.X.B. D’Journo, M. Ouattara, A. Loundou, D. Trousse, L. Dahan, T. Nathalie, C. Doddoli, J.F. Seitz, P.-A. Thomas, Prognostic impact of weight loss in 1-year survivors after transthoracic esophagectomy for cancer, Dis. Esophagus Off. J. Int. Soc. Dis. Esophagus. 25 (2012) 527–534. https://doi.org/10.1111/j.1442-2050.2011.01282.x.CrossRefGoogle Scholar
- 38.J. Moran, E. Guinan, P. McCormick, J. Larkin, D. Mockler, J. Hussey, J. Moriarty, F. Wilson, The ability of prehabilitation to influence postoperative outcome after intra-abdominal operation: A systematic review and meta-analysis. Surgery. (2016). https://doi.org/10.1016/j.surg.2016.05.014.
- 39.D.R. Fogelman, H. Holmes, K. Mohammed, M.H.G. Katz, C.M. Prado, J. Lieffers, N. Garg, G.R. Varadhachary, R. Shroff, M.J. Overman, C. Garrett, R.A. Wolff, M. Javle, Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer?, J. Cachexia Sarcopenia Muscle. 5 (2014) 307–313. https://doi.org/10.1007/s13539-014-0145-y.CrossRefPubMedPubMedCentralGoogle Scholar
- 41.A. Ngo-Huang, N. Parker, V.A. Martinez, M.Q. Petzel, D. Fogelman, H.M. Holmes, S.S. Dhah, M. Katz, Poster 68 Feasibility of a Prehabilitation Program for Patients with Potentially Resectable Pancreatic Cancer: Pilot Study, PM R. 8 (2016) S183. https://doi.org/10.1016/j.pmrj.2016.07.111.CrossRefPubMedGoogle Scholar
- 42.C. Afaneh, D. Gerszberg, E. Slattery, D.S. Seres, J.A. Chabot, M.D. Kluger, Pancreatic cancer surgery and nutrition management: a review of the current literature, Hepatobiliary Surg. Nutr. 4 (2015) 59–71. https://doi.org/10.3978/j.issn.2304-3881.2014.08.07.PubMedPubMedCentralGoogle Scholar
- 44.T.P. Yeo, S.A. Burrell, P.K. Sauter, E.P. Kennedy, H. Lavu, B.E. Leiby, C.J. Yeo, A progressive postresection walking program significantly improves fatigue and health-related quality of life in pancreas and periampullary cancer patients, J. Am. Coll. Surg. 214 (2012) 463–475; discussion 475-477. https://doi.org/10.1016/j.jamcollsurg.2011.12.017.CrossRefPubMedGoogle Scholar
- 45.S. Okumura, T. Kaido, Y. Hamaguchi, Y. Fujimoto, T. Masui, M. Mizumoto, A. Hammad, A. Mori, K. Takaori, S. Uemoto, Impact of preoperative quality as well as quantity of skeletal muscle on survival after resection of pancreatic cancer, Surgery. 157 (2015) 1088–1098. https://doi.org/10.1016/j.surg.2015.02.002.CrossRefPubMedGoogle Scholar
- 46.S. Taguchi, N. Akamatsu, T. Nakagawa, W. Gonoi, A. Kanatani, H. Miyazaki, T. Fujimura, H. Fukuhara, H. Kume, Y. Homma, Sarcopenia Evaluated Using the Skeletal Muscle Index Is a Significant Prognostic Factor for Metastatic Urothelial Carcinoma, Clin. Genitourin. Cancer. 14 (2016) 237–243. https://doi.org/10.1016/j.clgc.2015.07.015.CrossRefPubMedGoogle Scholar
- 47.L. Ebbeling, D.J. Grabo, M. Shashaty, R. Dua, S.S. Sonnad, C.A. Sims, J.L. Pascual, C.W. Schwab, D.N. Holena, Psoas:lumbar vertebra index: central sarcopenia independently predicts morbidity in elderly trauma patients, Eur. J. Trauma Emerg. Surg. Off. Publ. Eur. Trauma Soc. 40 (2014) 57–65. https://doi.org/10.1007/s00068-013-0313-3.CrossRefGoogle Scholar
- 48.M.J. Englesbe, J.S. Lee, K. He, L. Fan, D.E. Schaubel, K.H. Sheetz, C.M. Harbaugh, S.A. Holcombe, D.A. Campbell, C.J. Sonnenday, S.C. Wang, Analytic morphomics, core muscle size, and surgical outcomes, Ann. Surg. 256 (2012) 255–261. https://doi.org/10.1097/SLA.0b013e31826028b1.CrossRefPubMedGoogle Scholar
- 49.A.J. Cruz-Jentoft, J.P. Baeyens, J.M. Bauer, Y. Boirie, T. Cederholm, F. Landi, F.C. Martin, J.-P. Michel, Y. Rolland, S.M. Schneider, E. Topinková, M. Vandewoude, M. Zamboni, European Working Group on Sarcopenia in Older People, Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People, Age Ageing. 39 (2010) 412–423. https://doi.org/10.1093/ageing/afq034.CrossRefPubMedPubMedCentralGoogle Scholar
- 50.M. Muscaritoli, S.D. Anker, J. Argilés, Z. Aversa, J.M. Bauer, G. Biolo, Y. Boirie, I. Bosaeus, T. Cederholm, P. Costelli, K.C. Fearon, A. Laviano, M. Maggio, F. Rossi Fanelli, S.M. Schneider, A. Schols, C.C. Sieber, Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics,” Clin. Nutr. Edinb. Scotl. 29 (2010) 154–159. https://doi.org/10.1016/j.clnu.2009.12.004.CrossRefGoogle Scholar
- 51.R.A. Fielding, B. Vellas, W.J. Evans, S. Bhasin, J.E. Morley, A.B. Newman, G. Abellan van Kan, S. Andrieu, J. Bauer, D. Breuille, T. Cederholm, J. Chandler, C. De Meynard, L. Donini, T. Harris, A. Kannt, F. Keime Guibert, G. Onder, D. Papanicolaou, Y. Rolland, D. Rooks, C. Sieber, E. Souhami, S. Verlaan, M. Zamboni, Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia, J. Am. Med. Dir. Assoc. 12 (2011) 249–256. https://doi.org/10.1016/j.jamda.2011.01.003.CrossRefPubMedGoogle Scholar