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• W2606069155 abstract "We thank Serin et al. for their probing questions about our study1Li D. Prigerson H.G. Kang J. Maciejewski P.K. Impact of radiation therapy on aggressive care and quality of life near death.J Pain Symptom Manage. 2017; 53: 25-32Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar and appreciate this opportunity to respond and to clarify our results. We agree that age is an important consideration, as associated comorbidities and physiology may impact functional reserve and, potentially, tolerance to radiation therapy (RT). Indeed, epidemiologic data demonstrating 60% of cancer diagnoses, and 70% of all cancer deaths, occur in individuals aged 65 years or older.2Berger N.A. Savvides P. Koroukian S.M. et al.Cancer in the elderly.Trans Am Clin Climatol Assoc. 2006; 117 (discussion 155–156): 147-155PubMed Google Scholar, 3Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview.Cancer. 1997; 80: 1273-1283Crossref PubMed Scopus (533) Google Scholar In our study, we did not exclude patients based on age. Although our mean age is 58.6 years, we reported a standard deviation of 12.6 in Table 1, reflecting at least 30% of patients to be aged 65 years or older. Importantly, as shown in Table 1, there was no statistically significant association between age and use of radiotherapy, thus, not meeting our criteria as a statistical confounder that would need to be accounted for in our modeling of quality of life outcomes. Most retrospective studies on radiation as a single modality do not reveal significant differences in tolerance to radiation between elderly and younger patients;4Gomez-Millan J. Radiation therapy in the elderly: more side effects and complications?.Crit Rev Oncol Hematol. 2009; 71: 70-78Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar however, the combination of radiation and chemotherapy has been shown to increase acute toxicity in the elderly.5Schild S.E. Mandrekar S.J. Jatoi A. et al.The value of combined-modality therapy in elderly patients with stage III nonsmall cell lung cancer.Cancer. 2007; 110: 363-368Crossref PubMed Scopus (48) Google Scholar Current American Society of Radiation Oncology guidelines recommend against combining palliative RT with chemotherapy, as there is no evidence to demonstrate improved outcomes.6Lutz S. Berk L. Chang E. et al.Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline.Int J Radiat Oncol Biol Phys. 2011; 79: 965-976Abstract Full Text Full Text PDF PubMed Scopus (655) Google Scholar With appropriate patient selection and utilization of palliative RT, patients experience benefit regardless of age. We would like to point out that the pivotal trials assessing benefit of palliative RT enrolled patients with median age of 65 years or older,7Hartsell W.F. Scott C.B. Bruner D.W. et al.Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases.J Natl Cancer Inst. 2005; 97: 798-804Crossref PubMed Scopus (643) Google Scholar, 8Dennis K. Wong K. Zhang L. et al.Palliative radiotherapy for bone metastases in the last 3 months of life: worthwhile or futile?.Clin Oncol (R Coll Radiol). 2011; 23: 709-715Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar, 9Steenland E. Leer J.W. van Houwelingen H. et al.The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.Radiother Oncol. 1999; 52: 101-109Abstract Full Text Full Text PDF PubMed Scopus (557) Google Scholar, 10van der Linden Y.M. Lok J.J. Steenland E. et al.Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment.Int J Radiat Oncol Biol Phys. 2004; 59: 528-537Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar or mean age of 64 years,9Steenland E. Leer J.W. van Houwelingen H. et al.The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.Radiother Oncol. 1999; 52: 101-109Abstract Full Text Full Text PDF PubMed Scopus (557) Google Scholar, 10van der Linden Y.M. Lok J.J. Steenland E. et al.Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment.Int J Radiat Oncol Biol Phys. 2004; 59: 528-537Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar and showed tolerability and pain control in the entire patient cohort. At present, advanced age in and of itself should not be used an exclusion criteria for palliative RT; better selection criteria are needed. Accurate evaluation of preexisting comorbidities is also important when selecting patients for palliative therapy. The Charlson comorbidity index (CCI), originally published in 1987, was selected for several reasons. Although not perfect, it is the most commonly used index, validated in numerous studies, including cancer and elderly patients.11Jorgensen T.L. Hallas J. Friis S. Herrstedt J. Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality.Br J Cancer. 2012; 106: 1353-1360Crossref PubMed Scopus (183) Google Scholar, 12Satariano W.A. Silliman R.A. Comorbidity: implications for research and practice in geriatric oncology.Crit Rev Oncol Hematol. 2003; 48: 239-248Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Thus, the reported CCI in our patient cohort can be readily compared with measurements from other studies. We strived to define comorbidity as the burden of illness unrelated to the cancer diagnosis, to avoid confounding. As such, it is preferable that hematological parameters are not taken into account. In addition, the CCI was significantly associated with other measures of physical dysfunction and disability such as the Eastern Cooperative Oncology Group (ECOG) performance status score and the McGill measures of symptom burden and quality of life (data not shown), and neither CCI or ECOG status were significantly associated with RT use. Thus, our results are unlikely to have changed if we had used other measures of physical dysfunction. Although Serin et al. argue that CCI has limitations in discriminating mild versus moderate comorbidity, the papers cited are not relevant to our particular study for two reasons; first, the Nakaya et al. publication focuses exclusively on a Japanese subset of patients, validating the CCI in a non-Western patient cohort; Yurkovich et al.13Yurkovich M. Avina-Zubieta J.A. Thomas J. Gorenchtein M. Lacaille D. A systematic review identifies valid comorbidity indices derived from administrative health data.J Clin Epidemiol. 2015; 68: 3-14Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar point out flaws in the use of CCI in administrative health data set and acknowledge that a limitation in their study is their specific focus on administrative data alone, without evaluation on chart reviews or patient-reported data. Our study did not use an administrative health data set, but extracted records from medical charts. To establish guidelines, the American Society of Radiation Oncology provided measures of quality palliative RT, supporting use of short RT regimens ranging from 1 to 10 treatments total.6Lutz S. Berk L. Chang E. et al.Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline.Int J Radiat Oncol Biol Phys. 2011; 79: 965-976Abstract Full Text Full Text PDF PubMed Scopus (655) Google Scholar Advanced techniques such as intensity-modulated RT, stereotactic body RT, and use of concurrent chemotherapy are not recommended except within the confines of a clinical trial.6Lutz S. Berk L. Chang E. et al.Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline.Int J Radiat Oncol Biol Phys. 2011; 79: 965-976Abstract Full Text Full Text PDF PubMed Scopus (655) Google Scholar, 14Rodrigues G. Videtic G.M. Sur R. et al.Palliative thoracic radiotherapy in lung cancer: an American Society for Radiation Oncology evidence-based clinical practice guideline.Pract Radiat Oncol. 2011; 1: 60-71Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar Palliative RT takes weeks to months to take effect,15Jones J.A. Lutz S.T. Chow E. Johnstone P.A. Palliative radiotherapy at the end of life: a critical review.CA Cancer J Clin. 2014; 64: 296-310Crossref PubMed Scopus (77) Google Scholar and yields the most benefit when delivered early during the disease trajectory, when patients live long enough to benefit. Administered appropriately, RT can reduce pain, shrink tumors and even, as we found in our study,1Li D. Prigerson H.G. Kang J. Maciejewski P.K. Impact of radiation therapy on aggressive care and quality of life near death.J Pain Symptom Manage. 2017; 53: 25-32Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar improve overall quality of life in patients with advanced cancer. However, when RT is administered close to death in patients with poor performance status, we find it lacks efficacy,1Li D. Prigerson H.G. Kang J. Maciejewski P.K. Impact of radiation therapy on aggressive care and quality of life near death.J Pain Symptom Manage. 2017; 53: 25-32Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar consistent with studies demonstrating that approximately 50% of patients experiencing worsening symptoms despite treatment.16Gripp S. Mjartan S. Boelke E. Willers R. Palliative radiotherapy tailored to life expectancy in end-stage cancer patients: reality or myth?.Cancer. 2010; 116: 3251-3256Crossref PubMed Scopus (100) Google Scholar Although shorter course regimens may have need for retreatment, this is likely not a relevant consideration in patients with short life expectancy, who will not live long enough to experience recurrence of pain. Studies finding retreatment rates to be higher with single fraction radiation note at least three-month follow-up was required to assess need for additional RT. The median life expectancy of our patient cohort was 3.8 months. Clearly, the decision to deliver palliative RT requires careful evaluation of a combination of factors, including prognosis, comorbidities, performance status, concurrent systemic therapy, as well as overall impact on patient's quality of life. We agree that lack of RT details in our study is a limitation, but we hope to address this in the future by collecting this in our currently ongoing studies. Re: Impact of Radiation Therapy on Aggressive Care and Quality of Life Near DeathJournal of Pain and Symptom ManagementVol. 53Issue 6PreviewWe have read the manuscript titled “Impact of Radiation Therapy on Aggressive Care and Quality of Life Near Death” by Li et al. with great interest;1 however, there are some key aspects for proper practical implications. Full-Text PDF Open Archive" @default.
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