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Utilization of palliative radiotherapy for bone metastases near end of life in a population-based cohort Tiwana, Manpreet S; Barnes, Mark; Kiraly, Andrew; Olson, Robert A Jan 10, 2016

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RESEARCH ARTICLE Open AccessUtilization of palliative radiotherapy forbone metastases near end of life in apopulation-based cohortManpreet S. Tiwana1,2, Mark Barnes1, Andrew Kiraly2 and Robert A. Olson1,2,3*AbstractBackground: Palliative radiotherapy (PRT) can significantly improve quality of life for patients dying of cancer withbone metastases. However, an aggressive cancer treatment near end of life is an indicator of poor-quality care. Butthe optimal rate of overall palliative RT use near the end of life is still unknown. We sought to determine thepatterns of palliative radiation therapy (RT) utilization in patients with bone metastases towards their end of life in apopulation-based, publicly funded health care system.Methods: All consecutive patients with bone metastases treated with RT between 2007 and 2011 were identifiedin a provincial Canadian cancer registry database. Patients were categorized as receiving RT in the last 2 weeks, 2–4weeks, or >4 weeks before their death. Associations between RT fractionation utilization by these categories, andpatient and provider characteristics were assessed through logistic regression.Results: Of the 16,898 courses 1734 (10.3) and 709 (4.2 %) were prescribed to patients in the last 2–4 weeks and<2 weeks of their life, respectively. Primary lung (8 %) and gastrointestinal (6.9 %) cancers received palliative RTmore commonly in the last 2 weeks of life (OR 3.72 [2.86–4.84] & 3.33 [2.42–4.58] respectively, p <0.001). Among the709 patients who received RT in the last 2 weeks of life, 350 (49), 167 (24), and 127 (18 %) were for spine, pelvis,and extremity metastases, respectively. RT was prescribed most frequently to spine (5 %) and extremity (4 %)metastases p <0.001 in the last two weeks of life, though only varied between 1 % (sternum) and 5 % (spine) bysite of metastases. Single fraction RT was prescribed more commonly in the last 2 weeks of life (64.2 %), comparedto individuals who received RT 2–4 weeks (54.5), and >4 weeks (47.9 %) before death (p <0.001).Conclusions: This population-based analysis found that only 4 % of patients with bone metastases receivedradiation therapy during the last 2 weeks of their life in our population-based, publicly funded program, though itwas significantly higher in patients with lung cancer and those with metastases to the spine or extremity.Appropriately, use of multiple fractions palliative RT was less common in patients closer to death.Keywords: Bone metastases, Palliative, Radiation therapy, End of lifeBackgroundApproximately half of prescribed radiotherapy (RT) isdelivered with palliative intent across North America[1, 2]. Palliative RT has numerous indications, andprimarily includes the treatment of painful bonemetastases [2]. Palliative RT for bone metastases pro-vides successful pain relief, preservation of function,and maintenance of skeletal integrity with minimal riskof serious side effects [3, 4].Palliative RT for bone metastases reduces pain in themajority of patients, though often takes several weeks [5].The use of palliative RT use in the final weeks of life oftherefore may have limited clinical use and may actuallyimpair quality of life for patients and their families nearthe end of life [5].The optimal rate of palliative RT use near the end oflife is still unknown [5]. The use of systemic therapies atthe end of life has been extensively studied, and same is* Correspondence: rolson2@bccancer.bc.ca1BC Cancer Agency-Centre for the North, Prince George, Canada2University of Northern British Columbia, Prince George, CanadaFull list of author information is available at the end of the article© 2016 Tiwana et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Tiwana et al. BMC Palliative Care  (2016) 15:2 DOI 10.1186/s12904-015-0072-5warranted for optimal rate of palliative RT usage in suchpatients [6, 7]. An overly aggressive cancer treatment atthe end of life may be an indicator of poor-quality care[6–8]. The total palliative RT dose, the dose per fractionand the technique of irradiation use may vary with thetreatment aim in patients with bone metastases [9].British Columbia (BC) provides 100 % of the radiationtherapy in the province as a, publicly-funded servicewith no direct costs to patients. We previously publishedinitial results demonstrating variation in RT prescribingpractices for bone metastases in BC, where we demon-strated an association between fractionation and prognosis[10]. The primary objective of this current study is toexplore the patterns of RT usage in patients with bonemetastases towards their end of life. Understanding thepatterns of palliative RT in patients with bone metastaseswill help us measure our quality and consistency of end oflife care across the province.MethodsStudy design and cohort selectionThis population-based retrospective study usedadministrative data to define a cohort of patientswho received palliative RT for bone metastases during2007 through 2011. This study was approved by the jointUniversity of British Columbia and BC Cancer Agency(BCCA) Research Ethics Board.Data source and extractionPatient data was extracted through the BCCA CancerAgency Information System. The RT parameters wereretrieved from BCCA’s RT database [11] and includedsite of RT, date of RT, dose, and fractionation. Thesedatabases were used to abstract patient, provider andtreatment characteristics. Patient chart reviews, and re-view of RT plans where necessary, were performed to iden-tify the various patient and physician related parametersassociated with palliative RT in bone metastases. Theprovincial radiation therapy facilities up to 2011 werelocated in Abbotsford, Kelowna, Surrey, Vancouver &Victoria.Patient and treatment variablesThe patients who received RT for bone metastases at theBC Cancer Agency from 2007 to 2011 were included inthe analysis. The commonly occurring primary tumoursites were categorized as prostate, breast, lung, lymphoma,and gastro-intestinal (GI). The key sites of skeletal metas-tases were classified as spine, pelvis, extremity, rib,sternum, and ‘skull’, the latter of which included orbit andjaw. For descriptive analyses, RT fractionation was classi-fied into single fraction (SF) or multiple fractions (MF).Statistical analysisTime to death was calculated from last course of palliativeRT. This time interval (in weeks) was categorized intothree groups :< 2, and 2–4, and > 4 weeks. Association be-tween these categories and the variables was analyzedthrough descriptive statistics, and chi-square test.Subsequently, univariable and multivariable linearregression analyses were performed to assess theseassociations. P values were two-sided, and values lessthan .05 were considered statistically significant. Analyseswere conducted using the SPSS statistical software pack-age, version 19.0 (Chicago, IL).ResultsA total of 16,898 courses of palliative RT were deliveredto 8301 patients from 2007 to 2011. Baseline patient andtreatment related factors are summarized Table 1, andhave also been presented in an earlier publication10. Themedian survival for the entire cohort was 18 weeks(95 % CI 17.49–18.51).Of the 16,898 courses 1734 (10.3) and 709 (4.2 %)were prescribed to patients in the last 2–4 weeks and<2 weeks of their life, respectively (Table 1). Table 2highlights the univariate analysis on the utilization ofpalliative RT in the last 2 weeks of life. Single fractionRT was prescribed more frequently in patients with ashorter time from RT to end of life (Fig. 1).Multivariable logistic regression is presented in Table 3,demonstrating a significant association between use ofRT in the last 2 weeks of life and site of primary, site ofmetastases, and BCCA Centre (Table 3). Lung cancerpatients (p < 0.001), and those receiving RT to spinalmetastases (p < 0.001), were more likely to receive RT inthe last 2 weeks of life (Table 3).DiscussionWe demonstrated that 4 and 10 % of palliative RTcourses were delivered to patients with bone metastasesduring the last 2 weeks, or last 2–4 weeks of their life,respectively in a large population based, publiclyfunded provincial RT program. Patients with lung andgastrointestinal cancers, or those receiving RT to theirspine or extremity, were most likely to receive RT nearthe end of their life. Appropriately, longer multiplefraction (MF) RT courses were utilized less frequentlyfor patients near their end of life.Our finding of a 4 and 10 % utilization of palliative RTfor bone metastases in last 2 or 2–4 weeks of life, thoughon the low end, are consistent with previous literature.The reported overall palliative RT utilization rates dur-ing the last 2 weeks of life are in the range of 2.2–14 %[2, 12–16]. Our relatively lower utilization rates ofpalliative RT for bone metastases in this study could bemultifactorial, including accurate prognostication byTiwana et al. BMC Palliative Care  (2016) 15:2 Page 2 of 5treating physicians, a lack of financial incentive to offerRT in this publicly funded system, or patient’s choice todecline treatment [10, 17] Unfortunately, this cannot beassess in a retrospective study design.Other authors state that the choice to offer palliativeRT should be guided by life expectancy, though may alsobe influenced by a patient’s site of primary disease orTable 2 Clinical and provider characteristics associated with theuse of palliative RT utilization in the last 2 weeks of lifeCharacteristic Proportion whoreceived RT in thelast 2 weeks of lifeP valueAge (years) <51 (n =1364) 5.0 % 0.2751–70 (n =7477) 4.2 %>70 (n =8057) 4.0 %Male (n =8491) 4.0 % 0.14Primary tumour Prostate (n =3218) 2.2 % <0.001Breast (n =3959) 1.3 %Lung (n =3777) 7.9 %Hematological (n =1887) 3.0 %Gastrointestinal (n =1319) 6.9 %Other (n =2738) 5.1 %SkeletalmetastasisSpine (n =7134) 4.9 % <0.001Pelvis (n =4826) 3.5 %Extremity (n =2897) 4.4 %Ribs (n =1362) 3.5 %Skull (n =393) 3.8 %Sternum (n =286) 1.0 %BCCA centre Abbotsford (n =946) 4.4 % 0.01Kelowna (n =3221) 3.3 %Surrey (n =2750) 4.8 %Vancouver (n =6056) 3.9 %Victoria (n =3925) 4.8 %RT radiation therapy, BCCA british columbia cancer agency64.2%54.5%47.9%0%20%40%60%80%100%<2 weeks 2-4 weeks > 4 weeksPercentage utilization of SFRTTime (from last palliative RT to death)Fig. 1 Percentage utilization of single fraction radiation therapy (SFRT), by time from last course of RT to deathTable 1 Baseline patient, treatment, and provider characteristicsProportion Proportion(Overall) (Last 2 weeks of life)RT course,n = 16,898RT course,n = 709Age (years) <51 8.1 % 8.3 %51–70 44.2 % 45.8 %>70 47.7 % 45.8 %Male 50.2 % 47.5 %Primary tumour Prostate 19.0 % 10.2 %Breast 23.4 % 7.3 %Lung 22.4 % 42.0 %Hematological 11.2 % 8.0 %GI 7.8 % 12.8 %others 16.2 % 19.6 %Skeletal metastasis Spine 42.2 % 49.4 %Pelvis 28.6 % 23.6 %Extremity 17.1 % 17.9 %Ribs 8.1 % 6.6 %Sternum 1.7 % 0.4 %Skull 2.3 % 2.1 %SFRT 49.2 % 64.2 %BCCA centre Abbotsford 5.6 % 5.9 %Kelowna 19.1 % 15.1 %Surrey 16.3 % 18.6 %Vancouver 35.8 % 33.7 %Victoria 23.2 % 26.7 %SFRT single fraction radiation therapy, BCCA british columbia cancer agencyTiwana et al. BMC Palliative Care  (2016) 15:2 Page 3 of 5area requiring palliation [18–20]. Indeed, we found asignificant variation in the use of RT near the end of life,based on primary tumor site (most common for lungand GI cancer) and site requiring palliative RT (mostcommon for spine and extremity) (Tables 2 and 3). Wehypothesize the higher use of end of life RT in lung and GIcancers may be a factor of their worse prognosis, wheretreating physicians may be less accurately predicting theirpoor prognosis. Perhaps the use of prognostic indices coulddecrease the use of potential futile RT near the end of life,which unfortunately we cannot assess within thisretrospective study [5, 21–23].Furthermore, we hypothesize that the more frequentuse of RT near the end of life for spine and extremitymetastases is related to the severity of the symptomsthey produce. As an example, physicians are likely morereluctant to withhold RT for a spinal cord compressionor a fractured extremity, than they are for a fractured ribor painful sternum, irrespective of prognosis. Wepropose that physicians adopt more uniform use ofprognostic tools before offering palliative RT, as it is un-likely that patients receiving RT in the last 2 weeks, evenif they are suffering from a spinal cord compression orfractured extremity, given the required 2–4 weeks to seea clinical benefit. Finally, a more convenient and appro-priate single fraction RT (SFRT) was prescribed in 64 %of the palliative RT courses to patients who died within2 weeks of receiving RT. Multiple studies have shownand confirmed the benefit and efficacy of SFRT near endof life [18, 24, 25].This study should be interpreted in the context of itsstrengths and limitations. Unfortunately, due to theretrospective nature of the study, information on pa-tients’ cultural beliefs, their decision about treatment,hospital admission, or whether the bone metastaseswere complicated by fracture or neurological comprom-ise was not available. Further, the efficacy of palliativeRT in terms of pain control was also not analyzeddue to the nature of study design. However, thispopulation-based provincial study is relatively freefrom referral and selection bias, and choice of RT pre-scription is not influenced by physician remuneration orpatient’s ability to pay in this public healthcare model withphysicians on salary.ConclusionsThis population-based analysis found that only 4 and 10 %of patients with bone metastases received radiotherapyduring the last 2 weeks, or 2–4 weeks of their life, respect-ively. Radiotherapy near the end of life was used mostfrequently for lung and gastrointestinal cancers, poten-tially as a result of their inherently worse prognosis whichphysicians are not accurately predicting. End of life RTwas also used frequently for patients receiving RT to thespine or extremity, which we hypothesize, is because ofthe potential severity of symptoms in these sites, such asspinal cord compression or fractured extremity. However,given the likely futility in offering RT during the lasttwo weeks of life, our research supports the morewidespread adoption of prognostic tool use prior toprescribing palliative RT. Appropriately, the use ofmultiple fractions palliative RT course was less fre-quently used in patients with a shorter lifespan.AbbreviationsRT: radiotherapy; BCCA: BC Cancer Agency; HSDA: health service deliveryarea; CAIS: cancer agency information system; OR: odds ratio; CI: confidenceinterval; SFRT: single fraction radiation therapy; GI: gastrointestinal.Competing interestsWe have read and understood BMC Palliative Care’s policy on disclosingconflicts of interest and declare that we have none.Authors’ contributionsRAO: study conception; data acquisition; conducted the statistical analysis;drafting and revision of the manuscript; MST, MB, AK: contributed to dataanalysis, drafting and revising the draft manuscript critically for importantintellectual content All of the authors approved the final version submittedfor publication. All authors read and approved the final manuscript.Table 3 Multivariable logistic regression analysis on palliative RTutilization in the last 2 weeks of lifeCharacteristic Odds ratio toreceive RT in last2 weeks of life(>1 favors RT)95 %confidenceintervalPvalueAge of patient (continuous) 0.99 0.99–1.00 0.41PatientgenderFemale ReferenceMale 0.87 0.74–1.01 0.07PrimarytumourProstate ReferenceBreast 0.57 0.40–0.82 0.002Lung 3.72 2.86–4.84 <0.001Haematological 1.29 0.91–1.85 0.15Gastrointestinal 3.33 2.42–4.58 <0.001Others 2.35 1.76–3.14 <0.001SkeletalmetastasisSpine ReferencePelvis 0.67 0.55–0.81 <0.001Extremity 0.87 0.71–1.08 0.21Ribs 0.66 0.48–0.90 0.01Sternum 0.22 0.07–0.69 0.01Skull 0.85 0.49–1.45 0.55BCCAcentreVancouver ReferenceAbbotsford 1.14 0.81–1.59 0.46Kelowna 0.86 0.68–1.09 0.20Surrey 1.29 1.09–1.62 0.03Victoria 1.34 1.09–1.62 0.005RT radiation therapy, BCCA british columbia cancer agencyTiwana et al. BMC Palliative Care  (2016) 15:2 Page 4 of 5AcknowledgementsThis work was supported in part from funding from the University of BritishColumbia and the University of Northern British Columbia.Author details1BC Cancer Agency-Centre for the North, Prince George, Canada. 2Universityof Northern British Columbia, Prince George, Canada. 3University of BritishColumbia, Vancouver, Canada.Received: 19 June 2015 Accepted: 7 December 2015References1. Janjan NA. An emerging respect for palliative care in radiation oncology.J Palliat Med. 1998;1:83–8.2. Guadagnolo BA, Liao KP, Elting L, Giordano S, Bucholz TA, Ya-Chen TS. Useof radiation therapy in the last 30 days of life among a large population-based cohort of elderly patients in the United States. J Clin Oncol. 2013;31:80–7.3. Chow E, Harris K, Fan G, Tsao M, Wai MS. Palliative radiotherapy trials forbone metastases: A systematic review. J Clin Oncol. 2007;25:1423–36.4. 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Comparativemultidisciplinary prediction of survival in patients with advanced cancer.Support Care Cancer. 2014;22:611–7.24. Lutz S, Korytko T, Nguyen J, Khan L, Chow E, Corn B. Palliative radiotherapy:when is it worth it and when is it not? Cancer J. 2010;16:473–82.25. Hayman JA, Abrahamse PH, Lakhani I, Earle CC, Katz SJ. Use of palliativeradiotherapy among patients with metastatic non-small-cell lung cancer. IntJ Radiat Oncol Biol Phys. 2007;69:1001–7.•  We accept pre-submission inquiries •  Our selector tool helps you to find the most relevant journal•  We provide round the clock customer support •  Convenient online submission•  Thorough peer review•  Inclusion in PubMed and all major indexing services •  Maximum visibility for your researchSubmit your manuscript atwww.biomedcentral.com/submitSubmit your next manuscript to BioMed Central and we will help you at every step:Tiwana et al. BMC Palliative Care  (2016) 15:2 Page 5 of 5

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