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Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation

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Abstract

Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion. Logistic regression and proportional hazards modeling identified predictors of hospitalization and overall survival (OS). Median age was 59 years (range, 23-90) and 83 % had Karnofsky performance status (KPS) score ≥ 70. Twenty-six percent of patients underwent gross total resection, 77 % received ≥ 59.4 Gy of radiotherapy, and 89 % received concurrent temozolomide. Median OS was 15.6 months (IQR, 8.5-26.8 months). Forty-three percent of patients were hospitalized during the CRT phase; OS was 10.7 vs. 17.8 months for patients who were vs. were not hospitalized, respectively (P < .001). Nearly half of the hospitalizations were due to generalized weakness (17 % of hospitalizations), seizures (16 %), or venous thromboembolism (13 %). On multivariate analysis, age (odds ratio [OR], 1.03; 95 % CI, 1.002-1.060; P = .034) and KPS (OR, 0.95; 95 % CI, 0.93-0.97; P < .001) were associated with risk of hospitalization. Hospitalization during the CRT phase was associated with decreased OS (adjusted hazard ratio, 1.47; 95 % CI, 1.01-2.13; P = .043), after adjustment for known prognostic factors. Hospitalization during the CRT phase is common among glioblastoma patients in the temozolomide era and is associated with shorter overall survival.

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References

  1. Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-Oncol 14(Suppl 5):v1–49

    Article  PubMed Central  PubMed  Google Scholar 

  2. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  CAS  PubMed  Google Scholar 

  3. Alexander BM, Ligon KL, Wen PY (2013) Enhancing radiation therapy for patients with glioblastoma. Expert Rev Anticancer Ther 13:569–581

    Article  CAS  PubMed  Google Scholar 

  4. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507

    Article  CAS  PubMed  Google Scholar 

  5. Arvold ND, Wang Y, Zigler C, Schrag D, Dominici F (2014) Hospitalization burden and survival among older glioblastoma patients. Neuro-Oncol 16:1530–1540

    Article  PubMed  Google Scholar 

  6. Manzano J-GM, Luo R, Elting LS, George M, Suarez-Almazor ME (2014) Patterns and predictors of unplanned hospitalization in a population-based cohort of elderly patients with GI cancer. J Clin Oncol. doi:10.1200/JCO.2014.55.3131

    PubMed  Google Scholar 

  7. Zhang B, Nilsson ME, Prigerson HG (2012) Factors important to patients’ quality of life at the end of life. Arch Intern Med 172:1133–1142

    PubMed Central  PubMed  Google Scholar 

  8. Sizoo EM, Pasman HRW, Buttolo J, Heimans JJ, Klein M, Deliens L, Reijneveld JC, Taphoorn MJB (2012) Decision-making in the end-of-life phase of high-grade glioma patients. Eur J Cancer Oxf Engl 48:226–232

    Article  Google Scholar 

  9. Williams MV (2013) A requirement to reduce readmissions: take care of the patient, not just the disease. J Am Med Assoc (JAMA) 309:394–396

    Article  CAS  Google Scholar 

  10. Brooks GA, Li L, Uno H, Hassett MJ, Landon BE, Schrag D (2014) Acute hospital care is the chief driver of regional spending variation in medicare patients with advanced cancer. Health Aff Proj Hope 33:1793–1800

    Article  Google Scholar 

  11. Sijben AE, McIntyre JB, Roldán GB, Easaw JC, Yan E, Forsyth PA, Parney IF, Magliocco AM, Bernsen H, Cairncross JG (2008) Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89:97–103

    Article  PubMed  Google Scholar 

  12. Brandes AA, Franceschi E, Tosoni A, Benevento F, Scopece L, Mazzocchi V, Bacci A, Agati R, Calbucci F, Ermani M (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115:3512–3518

    Article  CAS  PubMed  Google Scholar 

  13. Minniti G, De Sanctis V, Muni R et al (2008) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88:97–103

    Article  CAS  PubMed  Google Scholar 

  14. Niewald M, Berdel C, Fleckenstein J, Licht N, Ketter R, Rübe C (2011) Toxicity after radiochemotherapy for glioblastoma using temozolomide–a retrospective evaluation. Radiat Oncol Lond Engl 6:141

    Article  CAS  Google Scholar 

  15. Curran WJ, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE (1993) Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 85:704–710

    Article  PubMed  Google Scholar 

  16. Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL Jr (2004) Prognostic importance of comorbidity in a hospital-based cancer registry. J Am Med Assoc (JAMA) 291:2441–2447

    Article  CAS  Google Scholar 

  17. Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346

    Article  CAS  PubMed  Google Scholar 

  18. National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (2014). Available at: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed 15 Sept 2014

  19. Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol Off J Am Soc Clin Oncol 28:1963–1972

    Article  Google Scholar 

  20. Taillibert S, Laigle-Donadey F, Sanson M (2004) Palliative care in patients with primary brain tumors. Curr Opin Oncol 16:587–592

    Article  PubMed  Google Scholar 

  21. Pace A, Di Lorenzo C, Capon A et al (2012) Quality of care and rehospitalization rate in the last stage of disease in brain tumor patients assisted at home: a cost effectiveness study. J Palliat Med 15:225–227

    Article  PubMed  Google Scholar 

  22. Nuño M, Ly D, Ortega A, Sarmiento JM, Mukherjee D, Black KL, Patil CG (2014) Does 30-Day readmission affect long-term outcome among glioblastoma patients? Neurosurgery 74:196–205

    Article  PubMed  Google Scholar 

  23. Grossman SA, Ye X, Lesser G, Sloan A, Carraway H, Desideri S, Piantadosi S, NABTT CNS Consortium (2011) Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res Off J Am Assoc Cancer Res 17:5473–5480

    Article  CAS  Google Scholar 

  24. Gerber DE, Grossman SA, Zeltzman M, Parisi MA, Kleinberg L (2007) The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas. Neuro-Oncol 9:47–52

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Romano PS, Mark DH (1994) Bias in the coding of hospital discharge data and its implications for quality assessment. Med Care 32:81–90

    Article  CAS  PubMed  Google Scholar 

  26. Yao P, Wiggs BR, Gregor C, Sigurnjak R, Dodek P (1999) Discordance between physicians and coders in assignment of diagnoses. Int J Qual Health Care 11:147–153

    Article  CAS  PubMed  Google Scholar 

  27. Kuderer NM, Wolff AC (2014) Enhancing therapeutic decision making when options abound: toxicities matter. J Clin Oncol Off J Am Soc Clin Oncol 32:1990–1993

    Article  Google Scholar 

  28. Bartolo M, Zucchella C, Pace A et al (2012) Early rehabilitation after surgery improves functional outcome in inpatients with brain tumours. J Neurooncol 107:537–544

    Article  PubMed  Google Scholar 

  29. Pace A, Parisi C, Di Lelio M, Zizzari A, Petreri G, Giovannelli M, Pompili A (2007) Home rehabilitation for brain tumor patients. J Exp Clin Cancer Res CR 26:297–300

    CAS  PubMed  Google Scholar 

  30. Roth P, Wick W, Weller M (2010) Steroids in neurooncology: actions, indications, side-effects. Curr Opin Neurol 23:597–602

    Article  CAS  PubMed  Google Scholar 

  31. Lipsitz LA (2013) The 3-night hospital stay and medicare coverage for skilled nursing care. JAMA 310:1441–1442

    Article  CAS  PubMed  Google Scholar 

  32. Zachenhofer I, Donat M, Oberndorfer S, Roessler K (2011) Perioperative levetiracetam for prevention of seizures in supratentorial brain tumor surgery. J Neurooncol 101:101–106

    Article  CAS  PubMed  Google Scholar 

  33. Marras LC, Geerts WH, Perry JR (2000) The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 89:640–646

    Article  CAS  PubMed  Google Scholar 

  34. Perry SL, Bohlin C, Reardon DA, Desjardins A, Friedman AH, Friedman HS, Vredenburgh JJ (2009) Tinzaparin prophylaxis against venous thromboembolic complications in brain tumor patients. J Neurooncol 95:129–134

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Robins HI, O’Neill A, Gilbert M, Olsen M, Sapiente R, Berkey B, Mehta M (2008) Effect of dalteparin and radiation on survival and thromboembolic events in glioblastoma multiforme: a phase II ECOG trial. Cancer Chemother Pharmacol 62:227–233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Perry JR, Julian JA, Laperriere NJ et al (2010) PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost JTH 8:1959–1965

    Article  CAS  PubMed  Google Scholar 

  37. Salmaggi A, Simonetti G, Trevisan E, Beecher D, Carapella CM, DiMeco F, Conti L, Pace A, Filippini G (2013) Perioperative thromboprophylaxis in patients with craniotomy for brain tumours: a systematic review. J Neurooncol 113:293–303

    Article  CAS  PubMed  Google Scholar 

  38. Norden AD, Bartolomeo J, Tanaka S et al (2012) Safety of concurrent bevacizumab therapy and anticoagulation in glioma patients. J Neurooncol 106:121–125

    Article  CAS  PubMed  Google Scholar 

  39. Krumholz HM (2013) Post-hospital syndrome: an acquired, transient condition of generalized risk. N Engl J Med 368:100–102

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9:453–461

    Article  PubMed  Google Scholar 

  41. Roa W, Brasher PMA, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol Off J Am Soc Clin Oncol 22:1583–1588

    Article  CAS  Google Scholar 

  42. Wick W, Platten M, Meisner C et al (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13:707–715

    Article  CAS  PubMed  Google Scholar 

  43. Malmström A, Grønberg BH, Marosi C et al (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 13:916–926

    Article  PubMed  Google Scholar 

  44. Gállego Pérez-Larraya J, Ducray F, Chinot O et al (2011) Temozolomide in elderly patients with newly diagnosed glioblastoma and poor performance status: an ANOCEF phase II trial. J Clin Oncol Off J Am Soc Clin Oncol 29:3050–3055

    Article  Google Scholar 

  45. Minniti G, Scaringi C, Lanzetta G, Terrenato I, Esposito V, Arcella A, Pace A, Giangaspero F, Bozzao A, Enrici RM (2014) Standard (60 Gy) or Short-Course (40 Gy) irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma: a propensity-matched analysis. Int J Radiat Oncol Biol Phys. doi:10.1016/j.ijrobp.2014.09.013

    PubMed  Google Scholar 

  46. Arvold ND, Tanguturi SK, Aizer AA et al (2015) Hypofractionated vs. standard radiotherapy with or without temozolomide for older glioblastoma patients. Int J Radiat Oncol Biol Phys 92(3):384–389

    Article  CAS  PubMed  Google Scholar 

  47. Arvold ND, Reardon DA (2014) Treatment options and outcomes for glioblastoma in the elderly patient. Clin Interv Aging 9:357–367

    PubMed Central  PubMed  Google Scholar 

  48. Sorror ML, Storb RF, Sandmaier BM et al (2014) Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. J Clin Oncol Off J Am Soc Clin Oncol 32:3249–3256

    Article  Google Scholar 

  49. Crawford ED, Grubb R, Black A, Andriole GL, Chen M-H, Izmirlian G, Berg CD, D’Amico AV (2011) Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol Off J Am Soc Clin Oncol 29:355–361

    Article  Google Scholar 

  50. Patnaik JL, Byers T, Diguiseppi C, Denberg TD, Dabelea D (2011) The influence of comorbidities on overall survival among older women diagnosed with breast cancer. J Natl Cancer Inst 103:1101–1111

    Article  PubMed Central  PubMed  Google Scholar 

  51. Fiorentino A, Caivano R, Chiumento C, Cozzolino M, Clemente S, Pedicini P, Fusco V (2012) Comorbidity assessment and adjuvant radiochemotherapy in elderly affected by glioblastoma. Med Oncol Northwood Lond Engl 29:3467–3471

    Article  CAS  Google Scholar 

  52. Balducci M, Fiorentino A, De Bonis P et al (2012) Impact of age and co-morbidities in patients with newly diagnosed glioblastoma: a pooled data analysis of three prospective mono-institutional phase II studies. Med Oncol Northwood Lond Engl 29:3478–3483

    Article  Google Scholar 

  53. Nuño M, Ly D, Mukherjee D, Ortega A, Black KL, Patil CG (2014) Quality of surgical care and readmission in elderly glioblastoma patients. Neuro-Oncol Pract 1:33–39

    Article  Google Scholar 

  54. Hegi ME, Diserens A-C, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003

    Article  CAS  PubMed  Google Scholar 

  55. Wright AA, Keating NL, Balboni TA, Matulonis UA, Block SD, Prigerson HG (2010) Place of death: correlations with quality of life of patients with cancer and predictors of bereaved caregivers’ mental health. J Clin Oncol Off J Am Soc Clin Oncol 28:4457–4464

    Article  Google Scholar 

  56. Zhang B, Wright AA, Huskamp HA, Nilsson ME, Maciejewski ML, Earle CC, Block SD, Maciejewski PK, Prigerson HG (2009) Health care costs in the last week of life: associations with end-of-life conversations. Arch Intern Med 169:480–488

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA, USA

    Rifaquat Rahman

  2. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

    Paul J. Catalano

  3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    Paul J. Catalano

  4. Center for Neuro-Oncology, Dana-Farber/Brigham & Women’s Cancer Center, Boston, MA, USA

    David A. Reardon, Andrew D. Norden, Patrick Y. Wen, Eudocia Q. Lee, Lakshmi Nayak & Rameen Beroukhim

  5. Department of Neurosurgery, Dana-Farber/Brigham & Women’s Cancer Center, Boston, MA, USA

    Ian F. Dunn, Alexandra J. Golby, Mark D. Johnson, E. Antonio Chiocca & Elizabeth B. Claus

  6. School of Public Health, Yale University, New Haven, CT, USA

    Elizabeth B. Claus

  7. Department of Radiation Oncology, Harvard Medical School, Dana-Farber/Brigham & Women’s Cancer Center, 75 Francis Street, ASB1-L2, Boston, MA, 02115, USA

    Brian M. Alexander & Nils D. Arvold

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  1. Rifaquat Rahman
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Rahman, R., Catalano, P.J., Reardon, D.A. et al. Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation. J Neurooncol 124, 137–146 (2015). https://doi.org/10.1007/s11060-015-1820-3

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  • DOI: https://doi.org/10.1007/s11060-015-1820-3

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