Comparative Age-Based Prospective Multi-Institutional Observations of 12,367 Patients Enrolled to the American College of Surgeons Oncology Group (ACOSOG) Z901101 Trials (Alliance)

  • Waddah B. Al-Refaie
  • Paul A. Decker
  • Karla V. Ballman
  • Peter W. T. Pisters
  • Mitchell C. Posner
  • Kelly K. Hunt
  • Bryan Meyers
  • Armin D. Weinberg
  • Heidi Nelson
  • Lisa Newman
  • Angelina Tan
  • Jennifer G. Le-Rademacher
  • Arti Hurria
  • Aminah JatoiEmail author
Health Services Research and Global Oncology



The risk of surgery, particularly for older cancer patients with serious, extensive comorbidities, can make this otherwise curative modality precarious. Leveraging data from the American College of Surgeons Oncology Group, this study sought to characterize age-based comparative demographics, adverse event rates, and study completion rates to define how best to conduct research in older cancer patients.


This study relied on clinical data from 21 completed studies to assess whether older patients experienced more grade 3 or worse adverse events and were more likely to discontinue study participation prematurely than their younger counterparts.


The study enrolled 12,367 patients. The median age was 60 years, and 36% of the patients were 65 years of age or older. Among 4008 patients with adverse event data, 1067 (27%) had experienced a grade 3 or worse event. The patients 65 years or older had higher rates of grade 3 or worse adverse events compared to younger patients [32% vs. 24%; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.3–1.7; p < 0.0001]. This association was not observed in multivariate analyses. The study protocol was completed by 97% of the patients. No association was observed between age and trial completion (OR 0.8; 95% CI 0.7–1.1; p = 0.14). Only the older gastrointestinal cancer trial patients were less likely to complete their studies compared to younger patients (OR 0.50; 95% CI 0.30–0.70; p < 0.0001).


Despite higher rates of adverse events, the older patients typically completed the study protocol, thereby contributing relevant data on how best to render care to older cancer patients and affirming the important role of enrolling these patients to surgical trials.



The research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), U10CA180833, U10CA180836, U10CA180858, UG1CA189823, and P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Supplementary material

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Supplementary material 1 (DOCX 54 kb)


  1. 1.
    Smith BD, Smith GL, Hurria A, et al. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009; 27:2758–65.CrossRefGoogle Scholar
  2. 2.
    Freedman RA, Foster JC, Seisler DK, et al. Accrual of older patients with breast cancer to Alliance systemic therapy trials over time: protocol A151527. J Clin Oncol. 2017;35:421–31.CrossRefGoogle Scholar
  3. 3.
    Witherby SM, Muss HB. Special issues related to breast cancer adjuvant therapy in older women. Breast. 2005;14:600–11.CrossRefGoogle Scholar
  4. 4.
  5. 5.
    Shah-Khan M, Boughey JC. Evolution of axillary node staging in breast cancer: clinical implications of the ACOSOG Z0011 trial. Cancer Control. 2012;19:267–76.CrossRefGoogle Scholar
  6. 6.
    Khan S, Sclabas G, Lombardo KR, et al. Pancreatoduodenectomy for ductal adenocarcinoma in the very elderly: is it safe and justified? J Gastrointest Suer. 2010;14:1826–31.CrossRefGoogle Scholar
  7. 7.
    Detillon DDEMA, Veen EJ. Postoperative outcome after pulmonary surgery for non-small cell lung cancer in elderly patients. Ann Thorac Surg. 2018;105:287–93.Google Scholar
  8. 8.
    Waldron RP, Donovan IA, Drumm J, et al. Emergency presentation and mortality from colorectal cancer in the elderly. Br J Surg. 1986;73:214–6.CrossRefGoogle Scholar
  9. 9.
    Hunt KK, Ballman KV, McCall LM, et al. Factors associated with local-regional recurrence after a negative sentinel node dissection: results of the ACOSOG Z0010 trial. Ann Surg. 2012; 256:428–36.CrossRefGoogle Scholar
  10. 10.
    Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection versus no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569–75.CrossRefGoogle Scholar
  11. 11.
    Cornett WR, McCall LM, Petersen RP, et al. Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020. J Clin Oncol. 2006;24:4196–201.CrossRefGoogle Scholar
  12. 12.
    Darling GE, Allen MS, Decker PA, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial.Google Scholar
  13. 13.
    Rusch VW, Hawes D, Decker PA, et al. Occult metastases in lymph nodes predict survival in resectable non-small cell lung cancer: report of the ACOSOG Z0040 trial. J Clin Oncol. 2011;29:4313–9.CrossRefGoogle Scholar
  14. 14.
    Reed CE, Harpole DH, Posther KE, et al. Results of the American College of Surgeons Oncology Group Z0050 trial: the utility of positron emission tomography in staging potentially operable non-small cell lung cancer. J Thorac Cardiovasc Surg. 2003;126:1943–51.CrossRefGoogle Scholar
  15. 15.
    Crook JM, Gomez-Iturriaga A, Wallace K, et al. Comparison of health-related quality of life 5 years after treatment for men who either chose or were randomized to radical prostatectomy or brachytherapy after a SPIRIT Trial education session. Brachytherapy. 2010;9:S23.CrossRefGoogle Scholar
  16. 16.
    Civantos FJ, Zitsch RP, Schuller DE, et al. Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1-T2 oral squamous cell carcinomas: results or a prospective multi-institutional trial. J Clin Oncol. 2010; 28:1395–400.CrossRefGoogle Scholar
  17. 17.
    Picozzi VJ, Abrams RA, Decker PA, et al. Multicenter phase 2 trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alpha-2b-based chemoradiation: ACOSOG trial Z05031. Ann Oncol. 2011;22:348–54.CrossRefGoogle Scholar
  18. 18.
    Ellis MJ, Suman VJ, Hoog J, et al. Randomized phase 2 neoadjuvant comparison between letrozole, anastrazole, and exemestane for postmenopausal women with estrogen receptive-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype: ACOSOG Z1031. J Clin Oncol. 2011;29:2342–9.CrossRefGoogle Scholar
  19. 19.
    Buzdar AU, Suman VJ, Meric-Berstam F, et al. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomized, controlled, phase 3 trial. Lancet Oncol. 2013;14:1317–25.CrossRefGoogle Scholar
  20. 20.
    Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinal lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer. The ACOSOG (Alliance) Clinical Trial. JAMA. 2013;310:1455–61.Google Scholar
  21. 21.
    Grogan EL, Deppen SA, Ballman KV, et al. Accuracy of fluorodeoxyglucose-positron emission tomography within the clinical practice of the American College of Surgeons Oncology Group Z4031 trial to diagnose clinical stage 1 non-small cell lung cancer. Ann Thorac Surg. 2014;97:1142–8.CrossRefGoogle Scholar
  22. 22.
    Fernando HC, Landreneau RJ, Mandrekar SJ, et al. Impact of brachytherapy on local recurrence after sublobar resection: results from ACOSOG Z4032 (Alliance), a phase 3 randomized trial for high-risk operable non-small cell lung cancer. J Clin Oncol. 2014;32:2456–62.CrossRefGoogle Scholar
  23. 23.
    Dupuy DE, Fernando HC, Hillman S, et al. Radiofrequency ablation of stage 1A non-small cell lung cancer in medically inoperable patients: results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial. Cancer. 2015;121:3491–8.CrossRefGoogle Scholar
  24. 24.
    Garcia-Aguilar J, Renfro LA, Chow OS, et al. Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol. 2015;16:1537–46.CrossRefGoogle Scholar
  25. 25.
    DeMatteo RP, Ballman KV, Antonescu CR, et al. Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial. Ann Surg. 2013;258:422–9.CrossRefGoogle Scholar
  26. 26.
    Corless CL, Ballman KV, Antonescu CR, et al. Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial. J Clin Oncol. 2014;32:1563–70.CrossRefGoogle Scholar
  27. 27.
    Schild SE, Mandrekar SJ, Jatoi A, et al. The value of combined-modality therapy in elderly patients with stage III nonsmall cell lung cancer. Cancer. 2007;110:363–8.CrossRefGoogle Scholar
  28. 28.
    Tallarico M, Foster JC, Seisler D, et al. Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (A151611). J Geriatr Oncol. 2018;9:321–8.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Waddah B. Al-Refaie
    • 1
  • Paul A. Decker
    • 2
  • Karla V. Ballman
    • 3
  • Peter W. T. Pisters
    • 4
  • Mitchell C. Posner
    • 5
  • Kelly K. Hunt
    • 4
  • Bryan Meyers
    • 6
  • Armin D. Weinberg
    • 7
  • Heidi Nelson
    • 2
  • Lisa Newman
    • 4
  • Angelina Tan
    • 2
  • Jennifer G. Le-Rademacher
    • 2
  • Arti Hurria
    • 8
  • Aminah Jatoi
    • 2
    Email author
  1. 1.MedStar Georgetown University HospitalWashington, D.C.USA
  2. 2.Alliance Statistics and Data CenterMayo ClinicRochesterUSA
  3. 3.Weill Medical College of Cornell UniversityNew YorkUSA
  4. 4.M.D. Anderson Cancer CenterUniversity of TexasHoustonUSA
  5. 5.University of Chicago Comprehensive Cancer CenterChicagoUSA
  6. 6.Washington University School of MedicineSt. LouisUSA
  7. 7.Baylor College of MedicineHoustonUSA
  8. 8.City of Hope Comprehensive Cancer CenterDuarteUSA

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