Impact of radiotherapy on the quality of life of elderly ... - Springer Link

Clin Transl Oncol (2008) 10:498-504 DOI 10.1007/s12094-008-0239-0

R E S E A R C H A RT I C L E S

Impact of radiotherapy on the quality of life of elderly patients with localized breast cancer. A prospective study Juan Ignacio Arraras · Ana Manterola · Miguel Ángel Domínguez · Fernando Arias · Elena Villafranca · Pilar Romero · Enrique Martínez · José Juan Illarramendi · Esteban Salgado

Received: 27 December 2007 / Accepted: 5 June 2008

Abstract Introduction There are few studies on the effect on quality of life (QL) of cancer-related illness and treatment in elderly patients. The aim of this work was to evaluate prospectively QL in a sample of elderly patients with stages I–III breast cancer who started radiotherapy treatment and compare their QL with that of a sample of younger patients. Materials and methods Forty-eight patients, ≥ 65 years of age completed the European Organization for Research and Treatment of Cancer (EORTC) QL questionnaires QLQ-C30 and QLQ-BR23, and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) daily activities scale three times throughout treatment and follow-up periods. Clinical and demographic data were also recorded. Fifty patients ages 40–64 years with the same disease stage and treatment modality had previously completed the QL questionnaires. QL scores, changes in them among the three assessments, differences between groups

based on clinical factors, and differences between the two samples were calculated. Results QL scoring was good and stable (> 70/100 points) in most areas, in line with clinical data. Light and moderate limitations occurred in global QL and some emotional, sexual, and treatment-related areas. Moderate decreases (10–20) appeared in some toxicity-related areas, which recovered during the follow-up period. Breast-conservation and sentinel-node patients presented higher scores in emotional areas. There were few QL differences among agebased samples. Conclusions QL and clinical data indicate radiotherapy was well tolerated. Age should not be the only factor evaluated when deciding upon treatment for breast cancer patients. Keywords Quality of life · Breast cancer · Elderly · Radiotherapy · Assessment

Introduction J.I. Arraras · A. Manterola · M.A. Domínguez · F. Arias · E. Villafranca · P. Romero · E. Martínez Radiotherapeutic Oncology Department Hospital of Navarre C/ Irunlarrea, 3 ES-31008 Pamplona, Spain J.I. Arraras · J.J. Illarramendi · E. Salgado Medical Oncology Department Hospital of Navarre C/ Irunlarrea, 3 ES-31008 Pamplona, Spain J.I. Arraras (쾷) C/ Monasterio de Urdax, 1 – 5º D ES-31007 Pamplona, Spain e-mail: [email protected]

Cancer in elderly people occurs more frequently in the Western Countries due to the ageing of the population and the increase in life expectancy. However, the majority of treatments have been designed for young patients. Furthermore, there is little information on the effect of the illness and the treatments on the quality of life (QL) in elderly patients [1, 2]. The incidence of breast cancer increases with age. In Western countries, approximately 50% of women with this illness are older than 65 years of age [3], whereas most patients with breast cancer included in clinical trials are younger than 60 years of age [4]. In a study carried out in 50 Spanish hospitals [5], 24% of patients diagnosed between 1990 and 1993 with breast cancer were 61–70 years

Clin Transl Oncol (2008) 10:498-504

of age, and 15.8% were older than 70 years of age. Of breast cancer patients diagnosed between 1994 and 1997, 24.8% were 61–70 years of age and 19.2% were older than 70 years of age. In Navarre, between 1998 and 2000, 58.7% of the women diagnosed with cancer (any site) were older than 65 years of age; 28.5 % of all cancer diagnosed in women in this period was breast cancer [6]. A study by Truong et al. [7] indicates that more research is necessary pertaining older patients, and that research should also include a QL evaluation. Elderly patients comprise a differentiated and heterogeneous group with regard to characteristics, which means that treatment must be more individualized than for younger patients. Some factors that distinguish them from younger patients, which may explain this heterogeneity and which may even interfere with oncology treatment, are the frequent presence of comorbidity, QL, disablement, loss of independence, physiological changes of aging, and changes in social support systems [8, 9]. Watters et al. [1] believe that a brake exists among professionals with respect to referring elderly patients with breast cancer in its initial stages to oncology and offering treatment such as radiotherapy. Professionals tend to believe that the elderly are fragile by definition, or they foresee that treatment will have adverse effects. Repetto et al. [10] consider that most barriers limiting treatment of cancer in the elderly are potentially surmountable. Comorbidity increases with age and may affect diagnosis, treatment, and prognosis of cancer [4]. The most frequent pathologies are arthrosis, hypertension, and digestive and cardiovascular diseases. There is a need to evaluate comorbidity, but emphasis should not so much consider the number of diseases, but should place more importance on the subject’s functionality. Studies that compare radical and conservative surgery in breast cancer patients with localized disease show evidence in favor of advantages in QL in the second group [11]. De Haes et al. [12] believe that elderly patients have fewer possibilities of being given conservative surgery, so they emphasize the importance of research that compares both types of surgery in older patients. The extent of surgery in elderly breast cancer patients may be limited, among other factors, by comorbidity, which means it is important to study the possible advantages of less aggressive surgery if this does not jeopardize tumor control [3]. One current area of research is that of age differences related to the impact of breast cancer and QL. Research by Kroenke et al. [13] is noteworthy in that they found that QL in patients younger than 40 years of age is more affected in physical and psychosocial aspects when compared with patients between 40 and 64, or older. Therefore younger patients are being considered to comprise a differentiated group. The objectives of our study were to evaluate QL prospectively in a group of older patients with breast cancer and localized disease who were starting radiotherapy treatment with or without endocrine therapy. We also evaluated

499

changes produced in QL among the different evaluations carried out, contrasted those scores with clinical data from the sample. We also compared QL of this sample with those of a group of younger patients in the same stages of illness and treatment.

Materials and methods Patients Calculation of the sample size was carried out with the IMIM Granmo 5.2 [14] program with a power of 0.8, an alpha risk of 0.01, the use of a two-tailed test, and a 40% subject loss. This offered an initial estimation of 39 subjects. Given that the intention was that of working with nonparametric tests, the sample size increased by 10% to 43 subjects. Using this estimation, a consecutive sample of 50 patients who initiated treatment in the Radiotherapeutic Oncology Department of the Hospital of Navarre between December 2004 and January 2006 were invited to participate in the study. Inclusion criteria were breast cancer in stages I–III, 65 years of age or older, and starting radiotherapy for first time. Two main groups of patients were selected: newly diagnosed, and those with exclusively local or regional relapses, with a negative extension search and without having undergone radiotherapy previously in the area. The criteria for exclusion were treatment that included chemotherapy, cognitive state did not permit treatment evaluation, or a life expectancy of less than 3 months. Furthermore QL data was taken from a second sample of 50 patients aged between 40 and 64 years of age with characteristics similar to those of this investigation: breast cancer in stages I–III who had received radiotherapy with or without endocrine therapy and without chemotherapy between January 1996 and June 1997. Data from this subsample, together with that of other patients, had been analyzed in a previous investigation [15].

Treatment Patients initiated radiotherapy with or without endocrine therapy. They may have previously undergone surgery for breast cancer. Radiotherapy was organized into three main groups: (1) local, followed or not by a boost at the end of the sessions; (2) locoregional, including nodes of the axilla–supraclavicular homolateral area; (3) regional – in relapses, only the node areas could be radiated. Depending on the state of the patients, the possibility existed of carrying out rest periods between radiotherapy sessions or reducing the dosage; these patients were kept in the study. Patients treated with endocrine therapy had, as a general rule, already started this treatment before beginning radiotherapy.

500


Table 1 Content of the European Organization for Research and Treatment of Cancer (EORTC) general questionnaire (QLQ-C30) and breast cancer module(QLQ-BR23) Scale or item QLQ-C30 Functional scalesa Symptom scales and/or itemsb QLQ-BR23 Functioning scales and/or itemsa Symptoms scales and/or itemsb

Description Physical, role, cognitive, emotional, social, global quality of life Scales of fatigue, nausea and vomiting, pain. Individual items on dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact Scales of body image, sexual functioning. Individual items on sexual enjoyment, future perspective. Scales of arm symptoms, breast symptoms, systemic therapy side effects. Individual item on upset by hair loss

aScores range from 0 to 100, where a higher score represents a higher functional level, bScores range from 0 to 100, where a higher score represents a greater degree of symptoms

Three subgroups were included with respect to surgery: (1) to the breast (radical or conservative), (2) breast combined with a mode of surgery in the axilla (axillary dissection, sentinel node), and (3) patients without surgery (in some relapses).

Measurements Three points of assessment were proposed for QL and DA: the first and final day of radiotherapy, and the follow-up consultation 6 weeks after finalizing treatment. Patients in the 1996 sample had been subject to the same evaluation points.

Evaluation Statistical analysis This study was approved by the Ethics Committee of the Hospital of Navarre and followed the directions of the Declaration of Helsinki. After giving informed consent, patients answered the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) general questionnaire [16] and the specific module for breast EORTC QLQ-BR23 [17] (Table 1). Both instruments have been validated for use in Spain by our team [18, 19]. Questionnaires with less than 70% of the items answered were excluded [20]. Comprehensive geriatric assessment is an interdisciplinary evaluation plan of different areas that cover the heterogeneity of elderly patients. Various authors recommend its use with cancer patients [2, 8, 21]. Based on this plan and in order to approximate the evaluation of QL to the needs of the geriatric patient, a scale of daily activities (DA), the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) [22] and an assessment of limiting comorbidity were added. The IDDD scale evaluates personal care and complex DA. Values from 33 to 36 are considered normal. The scores in these three instruments were considered to be the main results of the study. Biographical and clinical data were compiled: presence of limiting comorbidity, diagnostic group (new/relapsed), type of surgery to the breast and axilla (first measurement), radiotherapy modality, administration or not of endocrine therapy (second measurement), toxicity levels through selected items from the National Cancer Institute (NCI) Common Toxicity Criteria scale [23], and performance status using the Karnofsky scale [24] (both in the three measurements).

We investigated the frequencies of QL and DA scores and clinical and biographical variables. Within QL scores, we considered an affectation of 30 points or more as moderate and an affectation of 20–29 points as light. We used the Mann–Whitney U test to compare organized groups in the first measurement according to breast surgery (radical/conservative) and in the axilla (sentinel node/axilla emptying), excluding in both analyses patients with relapses and according to the presence or absence of limiting comorbidity, with the entire sample. Changes between the three measurements in QL and DA scores were studied using the Friedman test, and the Wilcoxon test with the criteria of Bonferroni were applied to determine between which pairs of measurements the differences appeared. In addition, differences in mean QL scores were evaluated between pairs of measurements, with significant differences in patients who completed each pair of measurements (a change of less than 5 points was considered as less than a little, of 5–10 as little, of 10–20 moderate, and higher than 20 very much) [25]. We also compared scores in the QL questionnaires in the three measurements of patients from the current sample with those of younger patients by using the Mann–Whitney U test. In all analyses, a value of p < 0.01 was considered significant.

Results Forty-eight of the 50 patients invited to participate in the investigation (96%) completed the first two measurements,


501

Table 2 Characteristics of the sample Characteristics

No.

Age (range 65–87) Marital status Single Married Widowed Separated Education level Lower than primary Primary Secondary or university Diagnostic group New Relapse Limiting comorbidity Yes No Karnofsky 1 measurement Karnofsky 2 measurement Karnofsky 3 measurement DA 1 measurement (min 33 max 48) DA 2 measurement (min 33 max 49) DA 3 measurement (min 33 max 48) Breast surgery Conservative Mastectomy Without surgery Axilla surgery Node emptying Sentinel node Without surgery Radiotherapy Local Locoregional Regional Endocrine therapy Yes No Second-measurement toxicity Skin: level 2 Skin: level 3 Dysphagia level 2 Fatigue level 2 Pain level 2 Third-measurement toxicity Skin level 2

48

Percentage

1 32 12 3

2.1 66.6 25 6.3

29 19 0

60.4 39.6 0

41 7

85.4 14.6

30 18

62.5 37.5

39 8 1

81.2 16.7 2.1

10 20 18

22.8 41.7 35.5

33 14 1

68.8 29.1 2.1

43 5

89.6 10.4

3 ind. 1 ind. 2 ind. 2 ind. 1 ind.

6.3 2.1 4.2 4.2 2.1

1 ind.

2.2

Mean

SD

72.3

5.7

94.9 90.2 94.6 35 35.2 34.5

6.5 6.2 5.6 4.4 4.2 2.9

SD standard deviation, DA 1–3 evaluation of daily activities using the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) scale, toxicity levels 2–4 number of patients and percentage of the sample; toxicity levels were evaluated using items selected from the National Cancer Institute (NCI) Common Toxicity Criteria scale

and forty-six completed a third. All questionnaires were included in the analysis, as more than 70% of the questions were answered. The reasons for not completing the questionnaires of the third measurement were administrative failures (changes in the days programmed for follow-up interviews, etc). In general, patients welcomed the opportunity of having an interview in which to comment upon their biopsychosocial functioning.

The biographical and clinical characteristics of the sample are presented in Table 2. Married patients and those with a level of education below primary level predominate in this sample. Most patients received a first diagnosis of breast cancer. The limiting comorbidities were arterial hypertension (22 patients; 45.8%), arthrosis (19; 39.6%), heart failure (3; 6.3%), hip fracture (2; 4.2%), and chronic obstructive pulmonary disorder (1; 2.2%). Performance status mean val-

502


Table 3 Quality-of-life scores [mean and standard deviation (SD)] in the European Organization for Research and Treatment of Cancer (EORTC) general questionnaire (QLQ-C30) First measurement Areas Functional scale Physical Role Emotional Cognitive Social Global Symptom scale Fatigue Nausea vomiting Pain Dyspnea Sleep disturbance Appetite loss Constipation Diarrhea Financial impact

Second measurement

Third measurement

Mean

SD

Mean

SD

Mean

SD

94.8 94.8 82.1 93.7 93.1 59.5

12.8 12.9 18.5 12.2 14.5 12.0

88.5 87.5 82.0 91.3 92.3 56.4

16.8 16.8 17.7 12.8 18.2 11.2

93.7 96.8 85.9 92.0 95.7 66.5

11.2 11.9 14.1 13.2 10.8 14.8

10.6 1.4 9.8 9 27.8 5.6 12.5 2.8 4.2

15.9 4.7 13.2 16.5 28.6 12.5 24.4 9.3 17.7

25.0 0.4 20.5 4.1 32.6 9.7 14.6 0.7 4.8

18.6 2.5 17.6 11.4 30.9 19.4 22.7 5.0 18.2

10.1 0.5 9.4 3.6 22.5 2.8 16.7 0.7 5.1

14.2 2.8 15.6 10.5 22.3 9.3 27.0 4.9 19.8

In the functional scales, scores ranged from 0 to 100, and the higher values indicate better functioning. In symptom and item scale, scores ranged from 0 to 100, and the higher values indicate a higher level of symptoms

ues in the three measurements corresponded to high levels. Mean scores in the DA scale were located within the normal range, with the high values corresponding to a patient with a hip fracture. Conservative surgery, study of the sentinel node, and local radiotherapy predominated. Neither rest nor reduction of radiotherapy dosages was necessary. Most patients underwent endocrine therapy. Only one patient in the second measurement presented grade 3 toxicity. QL scores in the first measurement were high in the majority of areas evaluated. Moderate limitations occurred in the global QL, future perspective, sexual functioning, and sexual enjoyment (affectation > 30). In the following measurements, moderate affectations occurred in the same factors, as well as in addition to sleep disturbance in the second measurement: Light affectation (between 20 and 29

points) appeared in future perspective, and upset by hair loss in the first measurement; fatigue, pain, and breast symptoms in the second measurement; and sleep disturbance in the third (Tables 3 and 4). Comparisons carried out between groups organized according to type of surgery lent a significant difference in future perspective and values of significance close to those for criteria in body image (p = 0.05) in favor of conservative surgery. A better body image was found in patients with sentinel node as opposed to node emptying. No significant differences were found in groups organized in accordance with the presence of comorbidity. On comparing the three measurements in the QL questionnaires in five areas, a significant worsening was found for the second measurement (worsening less than little in

Table 4 Quality-of-life scores [mean and standard deviation (SD)] in the European Organization for Research and Treatment of Cancer (EORTC) breast cancer module (QLQ-BR23) First measurement

Second measurement

Third measurement

Areas

Mean

SD

Mean

SD

Mean

SD

Body imagea Sexual functioninga Arm symptomsb Breast symptomsb Systemic therapy side effectsb Sexual enjoymenta Future perspectivea Upset by hair lossb

97.4 2.4 8.8 8.7 9.1 20.0 58.3 25

7.3 9.7 16.9 12.4 9.7 18.2 35.4 23.6

97.6 1.1 13.2 25.2 12.0 20 52.1 16.7

6.2 5.6 17.2 20.6 10.9 44.7 32.2 25.2

97.8 2.9 5.5 8.3 9.1 33.3 59.4 11.1

6.9 13.3 9.8 10.8 9.1 27.2 33.7 19.2

aFunctional

scales: scores ranged from 0 to 100, and the higher values indicate better functioning, bsymptom scales and items: scores ranged from 0 to 100, and the higher values indicate a higher level of symptoms


physical functioning; little in role; and moderate in fatigue, pain, and breast symptoms), which were followed by improvement in the third measurement. No significant differences between the first and third measurements occurred in any of these areas. Furthermore, improvement occurred in the third measurement in relation to the second in arm symptoms (little change) and in global QL (moderate change). On the IDDD scale, no significant differences occurred between this analysis and the previous analysis. On comparing QL scores of of this sample with those of patients aged between 40 and 64 years, significant differences were found in favor of younger patients in the three measurements in the area of global QL and in sexual functioning in the first and second measurements and pain in the second; and in favor of the group of elderly patients in breast symptoms in the third measurement.

Discussion QL evaluation of elderly patients is highly useful in aspects such as decision making regarding treatments to be given or designing specific psychosocial interventions for their age group. Watters et al. [1] believe that elderly patients are less inclined to exchange QL for an improvement in survival. The first aspect to be emphasized is the high participation in the three measurements. Results of biographical and clinical variables of the sample are representative of the patients treated in our center. The frequency of comorbidity was somewhat less than those found in other investigations with patients in similar stages and of similar ages to ours [8] owing to the fact that we gathered information on limiting comorbidity alone. Performance status and DA values indicated a good functional level throughout these three measurements. There were no rests or reductions or abandonment of radiotherapy, which indicates that this treatment was well tolerated. The predominance of less aggressive surgical and radiotherapy treatments may have contributed to patients’ good state of health. The scores in questionnaires QLQ-C30 and QLQ-BR23 indicated that patients considered their QOL as satisfactory in the majority of areas evaluated in the three measurements. Affectations were presented in very few areas, and these were light or moderate in character. These scores coincide with those of other studies [9, 26–28]. This data is more noteworthy if one takes into account that maximum QL values (0 or 100) are not expected in the nonclinical population and the conclusions of Kroenke et al. [13]. Those authors consider that an important part of the deterioration that occurs over time in patients with breast cancer older than 65 years of are more related to age than to the illness or treatment. A factor that may have contributed to appropriate QL scores is that patients may consider that certain limitations are normal, taking into consideration their age and illness [29]. The lowest score on the overall QL scale in relation to other scales was observed in the reference values of the

503

EORTC questionnaire [30]. The limitations on future perspective and sleep disturbance may be related to a process of emotional adaptation to the illness and treatment. It would be interesting to evaluate these affectations in emotional areas with a longer follow-up to determine whether they improve, as encountered by Ganz et al. [9] in a sample of breast cancer patients similar in ages and stages to those in this study. The patients indicated having had a low level of sexual activity, and in addition, when sexual activity did occur, they found limitations with respect to satisfaction, independent of radiotherapy treatment. On the other hand, in the second measurement, light alterations occurred in areas that were related to treatment. The differences among types of surgery in our study were in accordance with those found by De Haes et al. [12] in elderly patients in favor of conservative surgery in terms of body image and, in our study, in terms of concern for the future as well. This orientates us toward the convenience of proposing conservative surgery for elderly patients. Comparisons between types of axilla surgery in our study were also in accordance with those found in other studies, with patients of different ages in favor of a better QL in the group with sentinel node [31–34]. Results of comparisons between the different measurements indicated primarily that the QL of patients in this sample, after a brief follow-up period, was as good as at the beginning of treatment. These comparisons are in line with that no significant differences are observed in the DA Scale. Some generally low-intensity reductions occurred in areas directly and indirectly related to radiotherapy toxicity, and were followed by recovery. These reductions and recoveries were in accordance with those observed by Back et al. [35]. The combined data of the questionnaires and the toxicity scale indicate that these treatments were mildly toxic and that appropriate toxicity control was applied. Improvement in the third measurement in arm symptoms indicated a reduction in the direct consequences of surgery and in overall QL of posttreatment recovery. The results of the comparisons among patients between 40 and 64 years of age or older reflected that their QL was generally similar throughout the different measurements, and they are mostly coincidental with those of the other studies, such as that of Watters et al. [1], who compared the QL of patients older and younger than 65 years of age in stages I–III. They found, in accordance with our results, that in functional areas, similar values arose between both groups. They also found better scores in elderly patients with respect to future perspective and emotional functioning. We attributed this difference to the fact that in our investigation, we did not include patients younger than 40 years of age [11].

Conclusions The QL of patients who completed the different measurements was good. Limited changes occurred in some areas

504


related to treatment; however, after a short posttreatment follow-up, the patients recovered their initial QL level. The combined values of QL, toxicity, performance status, DA, and the fact that all patients followed the treatment without changes confirms that the treatment was well tolerated and that all patients were in suitable condition for receiving it. The few differences found in comparing the two groups of References 1. Watters JM, Yau JC, O’ Rourke K et al (2003) Functional status is well maintained in older woman during adjuvant chemotherapy for breast cancer. Ann Oncol 14:1744–1750 2. Repetto L, Comandini D (2000) Cancer in the elderly: assessing patients for fitness. Crit Rev Oncol Haematol 35:155–160 3. International Breast Cancer Study Group (2006) Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group trial 10–93. J Clin Oncol 24: 337–344 4. Fehlauer F, Tribius S, Mehnert A, Rades D (2005) Health related quality of life in long term breast cancer survivors treated with breast conserving therapy: impact of age at therapy. Breast Cancer Res Treat 92:217–222 5. Martín M, Mahillo E, Llombart-Cussac A et al (2006). The "El Álamo" project (1990–1997): two consecutive hospital-based studies of breast cancer outcomes in Spain. Clin Transl Oncol 8(7): 508–518 6. Ardanaz E, Moreno C, Pérez de Rada ME et al (2004) Incidencia de cáncer en Navarra (1998– 2000). An sis sanit navar 27(3):373–380 7. Truong PT, Wong E, Bernstein V et al (2004) Adjuvant radiation therapy after breast-conserving surgery in elderly women with early-stage breast cancer: controversy or consensus?. Clin Breast Cancer 4(6):407–414 8. Extermann M, Meyer J, McGinnis M et al (2004) A comprehensive geriatric intervention detects multiple problems in older breast cancer patients. Crit Rev Oncol Haematol 49:69–75 9. Ganz P, Guadagnolli E, Landrum M et al (2003) Breast cancer in older women: quality of life and psychosocial adjustment in the 15 months after diagnosis. J Clin Oncol 21:4027–4033 10. Repetto L, Venturino A, Fratino L et al (2003) Geriatric oncology: a clinical approach to the older patient with cancer. Eur J Cancer 39(7):870–880 11. Curran D, Van Dongen J, Aaronson NK et al (1998) Quality of life of early-stage breast cancer patients treated with radical mastectomy or breast conserving procedures: results of the EORTC trial 10801. Eur J Cancer 34:307–314 12. De Haes JCJM, Curran D, Aaronson NK, Fentiman IS (2003) Quality of life in breast cancer patients aged over 70 years, participating in the

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

patients by age reaffirm the idea that age should not be taken as the only factor when deciding on the type of oncology treatment to be given. Acknowledgements This study received the support of a grant from the Health Department of the Government of Navarre.

EORTC 10850 randomised clinical trial. Eur J Cancer 39:945–951 Kroenke CH, Rosner B, Chen WY et al (2004) Functional impact of breast cancer by age at diagnosis. J Clin Oncol 22:1849–1856 Marrugat J, Vila J, Pavessi M, Sanz F (1998) Estimación del tamaño de la muestra en la investigación clínica y epidemiológica. Med Clin 111: 267–276 Arraras JI, Illarramendi JJ, Tejedor M et al (2000) Quality of life in Spanish breast cancer patients assessed with the EORTC questionnaires. Rev Oncologia 3(2):100–106 Aaronson NK, Ahmezdai S, Bergman B et al (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality of life instrument for use in intentional clinical trials. J Natl Cancer Inst 85:365–376 Sprangers M, Groenvold M, Arraras JI et al (1996) The EORTC Breast Cancer-Specific Quality-of-Life Questionnaire Module (QLQ-BR23): first results from a three-country field study. J Clin Oncol 14 (10):2756–2768 Arraras JI, Arias F, Tejedor M et al (2001) The EORTC QLQ-C30 (version 3.0) Quality of Life questionnaire. validation study for Spain with head and neck cancer patients. Psycho-oncology 11:249–256 Arraras JI, Tejedor M, Illarramendi JJ et al (2001) El cuestionario de calidad de vida para cáncer de mama de la EORTC, QLQ-BR23. Estudio psicométrico con una muestra española. Psic Conduc 9 (1):81–98 Fayers P, Aaronson N, Bjordal K et al (2001) EORTC QLQ-C30 Scoring Manual, 3rd edn. EORTC, Brussels Chen CC, Kenefick AL, Tang ST, McCorkle R (2004) Utilization of comprehensive geriatric assessment in cancer patients. Crit Rev Oncol Hematol 49(1):53–67 Bohm P, Peña-Casanova J, Aguilar M et al (1998) Clinical validity and utility of the interview for deterioration of daily living in dementia for Spanish-speaking communities. Int Psychogeriatr 10: 261–270 National Cancer Institute (1998) NCI Common toxicity criteria. National Cancer Institute, New York. http://ctep.cancer.gov/reporting/ctc_archive. html Karnofsky DA, Burchenal JH (1949) The evaluation of chemotherapeutic agents in cancer. In: McLeod CM (ed) Evaluation of chemotherapeutic agents. University Press, New York, pp 191–205

25. Osoba D, Rodrigues G, Myles J et al (1998) Interpreting the significance of changes in health-related Quality of Life scores. J Clin Oncol 16:139– 144 26. Amichetti M, Caffo O (2001) Quality of life in patients with early stage breast carcinoma treated with conservation surgery and radiotherapy. An Italian monoinstitutional study. Tumori 87(2):78– 84 27. Given CW, Given B, Azzouz F et al (2000) Comparison of changes in physical functioning of elderly patients with new diagnoses of cancer. Med Care 38(5):482–493 28. Prescott RJ, Kunkler IH, Williams LJ et al (2006) Assessing the impact of adjuvant breast radiotherapy on quality of life in low risk older patients following breast conservation. Personal communication. 29th Annual San Antonio Breast Cancer Symposium, 2006 dic 14–17, San Antonio. Breast Cancer Res Treat 100(Suppl 1):S198 29. Bernhard J, Lowy A, Maibach R, Hurny C (2001) Response shift in the perception of health for utility evaluation. An explorative investigation. Eur J Cancer 37(14):1729–1735 30. Fayers P, Weeden S, Curran D (1998) EORTC QLQ-C30: reference values. EORTC, Brussels 31. Mansel RE, Fallowfield L, Kissin M et al (2006) Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst 3; 98(9):599–609 32. Rietman JS, Geertzen JH, Hoekstra HJ et al (2006) Long-term treatment related upper limb morbidity and quality of life after sentinel lymph node biopsy for stage I or II breast cancer. Eur J Surg Oncol 32(2):148–152 33. Barranger E, Dubernard G, Fleurence J et al (2005) Subjective morbidity and quality of life alter sentinel node biopsy and axillary lymph node dissection for breast cancer. J Surg Oncol 92(1): 17–22 34. Purushotham AD, Upponi S, Klevesath MB et al (2005) Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial. J Clin Oncol 23(19): 4312–4321 35. Back M, Ahern V, Delaney G et al. New South Wales Breast Radiation Oncology Group (2005) Absence of adverse early quality of life outcomes of radiation therapy in breast conservation therapy for early breast cancer. Australas Radiol 49(1): 39–43