Validation of the Comprehensive Geriatric Assessment as a Predictor of Mortality in Elderly Glioblastoma Patients
Abstract
:1. Introduction
2. Material and Methods
3. Statistical Analysis
4. Results
5. Discussion
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Farina, P.; Lombardi, G.; Bergo, E.; Roma, A.; Zagonel, V. Treatment of Malignant Gliomas in Elderly Patients: A Concise Overview of the Literature. BioMed Res. Int. 2014, 2014, 734281. [Google Scholar] [CrossRef] [PubMed]
- Fisher, J.L.; Schwartzbaum, J.A.; Wrensch, M.; Wiemels, J.L. Epidemiology of Brain Tumors. Neurol. Clin. 2007, 25, 867–890. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stupp, R.; Mason, W.P.; van den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; et al. Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N. Engl. J. Med. 2005, 352, 987–996. [Google Scholar] [CrossRef] [PubMed]
- Rusthoven, C.G.; Koshy, M.; Sher, D.J.; Perry, J.R.; Laperriere, N.; Mason, W.P. Radiation plus Temozolomide in Patients with Glioblastoma. N. Engl. J. Med. 2017, 376, 2195–2197. [Google Scholar] [PubMed]
- Minniti, G.; Lombardi, G.; Paolini, S. Glioblastoma in Elderly Patients: Current Management and Future Perspectives. Cancers 2019, 11, 336. [Google Scholar] [CrossRef] [PubMed]
- Hartmann, C.; Meyer, J.; Balss, J.; Capper, D.; Mueller, W.; Christians, A.; Felsberg, J.; Wolter, M.; Mawrin, C.; Wick, W.; et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: A study of 1,010 diffuse gliomas. Acta Neuropathol. 2009, 118, 469–474. [Google Scholar] [CrossRef] [PubMed]
- Roa, W.; Brasher, P.M.; Bauman, G.; Anthes, M.; Bruera, E.; Chan, A.; Fisher, B.; Fulton, D.; Gulavita, S.; Hao, C.; et al. Abbreviated Course of Radiation Therapy in Older Patients with Glioblastoma Multiforme: A Prospective Randomized Clinical Trial. J. Clin. Oncol. 2004, 22, 1583–1588. [Google Scholar] [CrossRef]
- Wick, W.; Platten, M.; Meisner, C.; Felsberg, J.; Tabatabai, G.; Simon, M.; Nikkhah, G.; Papsdorf, K.; Steinbach, J.P.; Sabel, M.; et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: The NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012, 13, 707–715. [Google Scholar] [CrossRef]
- Repetto, L.; Fratino, L.; Audisio, R.A.; Venturino, A.; Gianni, W.; Vercelli, M.; Parodi, S.; Lago, D.D.; Gioia, F.; Monfardini, S.; et al. Comprehensive Geriatric Assessment Adds Information to Eastern Cooperative Oncology Group Performance Status in Elderly Cancer Patients: An Italian Group for Geriatric Oncology Study. J. Clin. Oncol. 2002, 20, 494–502. [Google Scholar] [CrossRef]
- Monfardini, S.; Ferrucci, L.; Fratino, L.; Del Lungo, I.; Serraino, D.; Zagonel, V. Validation of a multidimensional evaluation scale for use in elderly cancer patients. Cancer 1996, 77, 395–401. [Google Scholar] [CrossRef]
- Balducci, L.; Yates, J. General guidelines for the management of older patients with cancer. Oncol. (Williston Park. N.Y.) 2000, 14, 221–227. [Google Scholar]
- Balducci, L. Management of chemotherapy-induced neutropenia in the older cancer patient. Oncol. (Williston Park. N.Y.) 2006, 20, 26–31. [Google Scholar]
- Brunello, A.; Fontana, A.; Zafferri, V.; Panza, F.; Fiduccia, P.; Basso, U.; Copetti, M.; Lonardi, S.; Roma, A.; Falci, C.; et al. Development of an oncological-multidimensional prognostic index (Onco-MPI) for mortality prediction in older cancer patients. J. Cancer Res. Clin. Oncol. 2016, 142, 1069–1077. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Extermann, M.; Hurria, A. Comprehensive Geriatric Assessment for Older Patients with Cancer. J. Clin. Oncol. 2007, 25, 1824–1831. [Google Scholar] [CrossRef]
- Basso, U.; Tonti, S.; Bassi, C.; Brunello, A.; Pasetto, L.M.; Scaglione, D.; Falci, C.; Beda, M.; Aversa, S.M.L.; Stefani, M.; et al. Management of Frail and Not-Frail elderly cancer patients in a hospital-based geriatric oncology program. Crit. Rev. Oncol. 2008, 66, 163–170. [Google Scholar] [CrossRef]
- Basso, U.; Monfardini, S. Multidimensional geriatric evaluation in elderly cancer patients: A practical approach. Eur. J. Cancer Care 2004, 13, 424–433. [Google Scholar] [CrossRef]
- Malmstrom, A.; Gronberg, B.H.; Marosi, C.; Stupp, R.; Frappaz, D.; Schultz, H.; Abacioglu, U.; Tavelin, B.; Lhermitte, B.; Hegi, M.E.; et al. 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. 2012, 13, 916–926. [Google Scholar] [CrossRef]
- Conwell, Y.; Forbes, N.T.; Cox, C.; Caine, E.D. Validation of a Measure of Physical Illness Burden at Autopsy: The Cumulative Illness Rating Scale. J. Am. Geriatr. Soc. 1993, 41, 38–41. [Google Scholar] [CrossRef]
- Katz, S.; Grotz, R.C.; Downs, T.D.; Cash, H.R. Progress in Development of the Index of ADL. Gerontology 1970, 10, 20–30. [Google Scholar] [CrossRef]
- Lawton, M.P.; Brody, E.M. Assessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living. Gerontology 1969, 9, 179–186. [Google Scholar] [CrossRef]
- Folstein, M.F.; Folstein, S.E.; McHugh, P.R. “Mini-Mental State”. A Practical Method for Grading the Cognitive State of Patients for the Clinician. J. Psychiatr. Res. 1975, 12, 189–198. [Google Scholar] [CrossRef]
- Yesavage, J.A.; Brink, T.; Rose, T.L.; Lum, O.; Huang, V.; Adey, M.; Leirer, V.O. Development and validation of a geriatric depression screening scale: A preliminary report. J. Psychiatr. Res. 1982, 17, 37–49. [Google Scholar] [CrossRef]
- Balducci, L.; Stanta, G. Cancer in the frail patient. A coming epidemic. Hematol. Clin. N. Am. 2000, 14, 235–250. [Google Scholar] [CrossRef]
- Freyer, G.; Geay, J.-F.; Touzet, S.; Provencal, J.; Weber, B.; Jacquin, J.-P.; Ganem, G.; Mathieu, N.T.; Gisserot, O.; Pujade-Lauraine, E. Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: A GINECO study. Ann. Oncol. 2005, 16, 1795–1800. [Google Scholar] [CrossRef] [PubMed]
- Maione, P.; Perrone, F.; Gallo, C.; Manzione, L.; Piantedosi, F.; Barbera, S.; Cigolari, S.; Rosetti, F.; Piazza, E.; Robbiati, S.F.; et al. Pretreatment Quality of Life and Functional Status Assessment Significantly Predict Survival of Elderly Patients with Advanced Non—Small-Cell Lung Cancer Receiving Chemotherapy: A Prognostic Analysis of the Multicenter Italian Lung Cancer in the Elderly Study. J. Clin. Oncol. 2005, 23, 6865–6872. [Google Scholar] [PubMed]
- Extermann, M.; Aapro, M.; Bernabei, R.; Cohen, H.J.; Droz, J.P.; Lichtman, S.; Mor, V.; Monfardini, S.; Repetto, L.; Sorbye, L.; et al. Use of Comprehensive Geriatric Assessment in Older Cancer Patients: Recommendations from the Task Force on CGA of the International Society of Geriatric Oncology (SIOG). Crit. Rev. Oncol. Hematol. 2005, 55, 241–252. [Google Scholar] [CrossRef] [PubMed]
- Mohile, S.G.; Dale, W.; Somerfield, M.R.; Hurria, A. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology Summary. J. Oncol. Pract. 2018, 14, 442–446. [Google Scholar] [CrossRef]
- Collard, R.M.; Boter, H.; Schoevers, R.A.; Oude Voshaar, R.C. Prevalence of Frailty in Community-Dwelling Older Persons: A Systematic Review. J. Am. Geriatr. Soc. 2012, 60, 1487–1492. [Google Scholar] [CrossRef]
- Brunello, A.; Ahcene-Djaballah, S.; Lettiero, A.; Tierno, G.; Fiduccia, P.; Guglieri, I.; Dadduzio, V.; Maruzzo, M.; Schiavon, S.; Lonardi, S.; et al. Prevalence of pain in patients with cancer aged 70 years or older: A prospective observational study. J. Geriatr. Oncol. 2019, 10, 637–642. [Google Scholar] [CrossRef]
- Deluche, E.; Leobon, S.; Lamarche, F.; Tubiana-Mathieu, N. First validation of the G-8 geriatric screening tool in older patients with glioblastoma. J. Geriatr. Oncol. 2019, 10, 159–163. [Google Scholar] [CrossRef]
- Cloney, M.; D’Amico, R.; Lebovic, J.; Nazarian, M.; Zacharia, B.E.; Sisti, M.B.; Bruce, J.N.; McKhann, G.M.; Iwamoto, F.M.; Sonabend, A.M. Frailty in Geriatric Glioblastoma Patients: A Predictor of Operative Morbidity and Outcome. World Neurosurg. 2016, 89, 362–367. [Google Scholar] [CrossRef] [PubMed]
- Fiorentino, A.; Caivano, R.; Chiumento, C.; Cozzolino, M.; Clemente, S.; Pedicini, P.; Fusco, V. Comorbidity assessment and adjuvant radiochemotherapy in elderly affected by glioblastoma. Med. Oncol. 2012, 29, 3467–3471. [Google Scholar] [CrossRef] [PubMed]
- Basch, E.; Deal, A.M.; Dueck, A.C.; Scher, H.I.; Kris, M.G.; Hudis, C.; Schrag, D. Overall Survival Results of a Trial Assessing Patient-Reported Outcomes for Symptom Monitoring During Routine Cancer Treatment. JAMA 2017, 318, 197–198. [Google Scholar] [CrossRef] [Green Version]
- Renovanz, M.; Hechtner, M.; Kohlmann, K.; Janko, M.; Nadji-Ohl, M.; Singer, S.; Ringel, F.; Coburger, J.; Hickmann, A.K. Compliance with Patient-Reported Outcome Assessment in Glioma Patients: Predictors for Drop Out. Neurooncol. Pract. 2018, 5, 129–138. [Google Scholar] [CrossRef] [PubMed]
Variable | Category | N (%) |
---|---|---|
Number of patients | 113 | |
Age at diagnosis | Mean ± SD | 71.7 ± 4.6 |
Median | 71.3 (range 65–84) | |
Gender | Male | 72 (64) |
Female | 41 (36) | |
MGMT | Methylated | 42 (44) |
Not methylated | 54 (56) | |
KPS | 100–70 | 90 (80) |
60–30 | 23 (20) | |
Type of surgery | Radical | 37 (33) |
Partial | 72 (63) | |
Biopsy | 4 (4) | |
Treatment | Yes | 106 (94) |
No | 7 (6) | |
Type of treatment | RT + TMZ | 90 (80) |
RT 60 Gy (standard) | 54 (60) | |
RT 40 Gy (hypofractionated) | 36 (40) | |
TMZ or RT alone | 16 (14) | |
Best supportive care | 7 (6) | |
Maintenance TMZ cycles (median) | 3.9 | |
CGA | Fit | 40 (35) |
Vulnerable | 33 (30) | |
Frail | 40 (35) |
Variables | Fit | Vulnerable | Frail | p |
---|---|---|---|---|
RT+TMZ | 39/40 (98%) | 30/33 (90%) | 21/40 (52%) | <0.001 |
RT 60 Gy (standard) | 25/29 (64%) | 21/30 (70%) | 8/21 (38%) | 0.06 |
RT 40 Gy (hypofractionated) | 14/39 (36%) | 9/30 (30%) | 13/21 (62%) | 0.06 |
KPS 100–70 | 40/40 (100%) | 31/33 (94%) | 19/40 (47%) | <0.001 |
Maintenance TMZ Cycles (median) | 5.2 | 5 | 2.8 | 0.03 |
Administration of TMZ | 40/40 (100%) | 31/33 (94%) | 34/40 (85%) | 0.03 |
Radical Surgery | 18/40 (45%) | 10/33 (33%) | 9/40 (22%) | 0.09 |
Biopsy | 0/40 (0%) | 1/33 (3%) | 3/40 (7%) | 0.2 |
Methylated MGMT | 15/34 (44%) | 16/32 (50%) | 15/30 (50%) | 0.8 |
Univariate Analysis | |||||||
---|---|---|---|---|---|---|---|
Variables | PFS | OS | |||||
Median (ms) | 95% CI | p | Median (ms) | 95% CI | p | ||
CGA | 0.2 | 0.1 | |||||
Fit | 11.2 | 6.07–16.4 | 16.5 | 14.6–18.2 | |||
Vulnerable | 7.7 | 4.6–10.7 | 12.1 | 8.1–16.1 | |||
Frail | 7.1 | 5.7–8.4 | 10.3 | 8.8–11.8 | |||
CGA (fit vs. unfit) | 0.25 | 0.04 | |||||
Fit | 11.2 | 6.07–16.4 | 16.5 | 14.6–18.2 | |||
Unfit | 7.2 | 5.8–8.6 | 10.6 | 8.3–12.9 | |||
MGMT | 0.002 | 0.01 | |||||
met | 11.7 | 8.8–14.5 | 16.4 | 11.9–20.9 | |||
unmet | 7.2 | 6.3–8.1 | 12.1 | 9.7–14.5 | |||
Radical surgery | 0.3 | 0.1 | |||||
yes | 10.3 | 7.3–13.3 | 14.73 | 11.9–17.5 | |||
no | 7.1 | 6.2–7.9 | 10.7 | 7.9–13.5 | |||
KPS | <0.001 | 0.008 | |||||
100–70 | 9.4 | 6.8–11.9 | 14.3 | 12.05–16.5 | |||
≤60 | 6.0 | 4.9–7.04 | 10.3 | 3.9–16.6 | |||
RT+TMZ | 0.006 | 0.001 | |||||
yes | 8.1 | 6.1–10.1 | 14.3 | 12.4–16.1 | |||
no | 6 | 2.5–9.4 | 8.2 | 5.7–10.8 |
Multivariate Analysis | ||||||
---|---|---|---|---|---|---|
Variables | PFS | OS | ||||
HR | 95% CI | p | HR | 95% CI | p | |
CGA | ||||||
Fit | Rif. | Rif. | ||||
Vulnerable | 1.1 | 0.4–1.7 | 0.7 | 1.5 | 1.1–2.09 | 0.05 |
Frail | 1.6 | 0.7–3.3 | 0.2 | 2.2 | 1.2–5.4 | 0.04 |
CGA (unfit vs. fit) | - | - | - | 1.8 | 1.2–2.8 | 0.02 |
MGMT (met vs. unmet) | 0.4 | 0.2–0.8 | 0.009 | 0.4 | 0.2–0.7 | 0.001 |
Radical Surgery (yes vs. no) | - | - | - | 0.9 | 0.7–1.2 | 0.7 |
KPS (100–70 vs. ≤60) | 0.4 | 0.1–0.8 | 0.01 | 0.4 | 0.2–0.9 | 0.05 |
RT+TMZ (yes vs. not) | 0.7 | 0.3–1.5 | 0.4 | 0.8 | 0.4–1.5 | 0.5 |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lombardi, G.; Bergo, E.; Caccese, M.; Padovan, M.; Bellu, L.; Brunello, A.; Zagonel, V. Validation of the Comprehensive Geriatric Assessment as a Predictor of Mortality in Elderly Glioblastoma Patients. Cancers 2019, 11, 1509. https://doi.org/10.3390/cancers11101509
Lombardi G, Bergo E, Caccese M, Padovan M, Bellu L, Brunello A, Zagonel V. Validation of the Comprehensive Geriatric Assessment as a Predictor of Mortality in Elderly Glioblastoma Patients. Cancers. 2019; 11(10):1509. https://doi.org/10.3390/cancers11101509
Chicago/Turabian StyleLombardi, Giuseppe, Eleonora Bergo, Mario Caccese, Marta Padovan, Luisa Bellu, Antonella Brunello, and Vittorina Zagonel. 2019. "Validation of the Comprehensive Geriatric Assessment as a Predictor of Mortality in Elderly Glioblastoma Patients" Cancers 11, no. 10: 1509. https://doi.org/10.3390/cancers11101509
APA StyleLombardi, G., Bergo, E., Caccese, M., Padovan, M., Bellu, L., Brunello, A., & Zagonel, V. (2019). Validation of the Comprehensive Geriatric Assessment as a Predictor of Mortality in Elderly Glioblastoma Patients. Cancers, 11(10), 1509. https://doi.org/10.3390/cancers11101509