Despite the large number of patients undergoing. Quality of Life and Mood in Older Patients After Major Lung Resection

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1 ORIGINAL ARTICLES: Quality of Life and Mood in Older Patients After Major Lung Resection Mark K. Ferguson, MD, Carolyn M. Parma, BA, Amy D. Celauro, MS, PA-C, and Wickii T. Vigneswaran, MD Department of Surgery, The University of Chicago, Chicago, Illinois Background. The increasing percentage of older patients undergoing lung resection for cancer necessitates a better understanding of long-term outcomes in this population. We studied the associations among quality of life, mood, clinical factors, and age after major lung resection. Methods. Outcomes for quality of life and mood questionnaires were compared with clinical factors for older (>70 years) and younger (<70 years) patients who recovered from major lung resection for stage I or II lung cancer from 1996 to 2006 and were without evidence of recurrence. Results. Of 221 eligible patients, 124 completed questionnaires; 55 (44%) were older (age 76 4 years). The time from resection was years. Despite similar comorbidities, older patients were more likely to experience pulmonary (11% versus 3%; p 0.14), cardiovascular (9% versus 1%; p 0.087), or any complications (25% versus 12%; p 0.045). Quality of life function, mood, and symptom scores were similar between the two groups except older patients experienced worse physical function (p 0.067), fatigue (p 0.068), and dyspnea (p 0.094). Postoperative pulmonary complications were related to physical function and dyspnea scores. Covariates for worst quartile scores were percent predicted forced expiratory volume in the first second (physical function, role function, fatigue, pain, and dyspnea) and pulmonary complications (physical function). Conclusions. Quality of life after recovery from lung resection is similar for older and younger patients despite an increased frequency of postoperative complications among older patients. Important quality of life and symptom score differences are related to percent predicted forced expiratory volume in the first second. This information may help with patient selection and preoperative counseling. (Ann Thorac Surg 2009;87: ) 2009 by The Society of Thoracic Surgeons Despite the large number of patients undergoing surgery for lung cancer, few attempts have been made to rigorously study quality of life (QOL) and mood in surgical patients. When compared with preoperative values, QOL is substantially worse at the time of hospital discharge after surgery, but returns toward preoperative values within 3 to 9 months of surgery [1 4]. Long-term negative influences on QOL and mood include recurrent cancer and extent of resection, the latter factor being particularly evident in patients who have undergone pneumonectomy. Lung cancer commonly affects older individuals. The number of patients who are 70 years or older undergoing resection for lung cancer at our institution increased by 50% during two decades, from 20% in the 1980s to 30% in the interval beginning in In general, older patients are less likely to undergo major lung resection for early stage cancer than are younger patients, despite the fact that long-term outcomes are similar for operative survivors [5, 6]. Failure to recommend surgery for older Accepted for publication Dec 26, Presented at the Fifty-fifth Annual Meeting of the Southern Thoracic Surgical Association, Austin, TX, Nov 5 8, Address correspondence to Dr Ferguson, Department of Surgery, 5841 S Maryland Ave, MC 5035, Chicago, IL 60637; mferguso@surgery. bsd.uchicago.edu. patients with early stage lung cancer may be based in part on the relatively high rate of disabilities among these patients compared with the general population and because of the perceived poorer QOL and mood in elderly patients. Mood and QOL issues in the elderly population are quantitatively different than in the general population. The incidence of depression is as high as 40% to 50% in elderly patients who are diagnosed with cancer [7]. Comorbid medical conditions, chronic pain, and functional disability are all associated with an increased risk of depression in the elderly, and these factors are relevant because they are also common outcomes after lung resection for bronchogenic carcinoma [8]. There remain a number of issues regarding QOL and mood in older surgical patients that have not been adequately investigated. The objectives of the current study were to assess the influence of age, preoperative comorbid factors, and postoperative complications on postoperative QOL and mood, and to identify predictors of poor postoperative QOL and mood. Patients and Methods Patients who underwent major lung resection for early stage lung cancer from 1996 to 2006 were identified from a prospective database maintained by the Thoracic Sur by The Society of Thoracic Surgeons /09/$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 1008 FERGUSON ET AL Ann Thorac Surg QUALITY OF LIFE AFTER LUNG RESECTION 2009;87: Fig 1. Flow diagram indicating the methods for selecting eligible patients for this study. gery Service at The University of Chicago Medical Center. Patients were contacted by mail, by telephone, or in person during a clinic visit. Institutional review board approval and specific individual patient consent were obtained for this study. Inclusion criteria were (1) at least 3 months after major resection (lobectomy, bilobectomy, pneumonectomy) for pathologic stage I or II non small cell lung cancer; (2) no preoperative chemotherapy or radiation therapy; (3) no postoperative chemotherapy within 3 months of participation; (4) no postoperative radiation therapy; and (5) age of at least 21 years. Data regarding the patients general medical condition, surgical therapy, and operative outcomes were abstracted from the administrative database, the hospital medical record, and office shadow files. Complications were categorized as pulmonary (pneumonia, prolonged intubation, reintubation, air leak more than 7 days, lobar collapse requiring intervention), cardiovascular (pulmonary embolism, myocardial infarction, new postoperative arrhythmia, need for intravenous inotropic agents), other, and any complication. All participating patients completed two standard questionnaires for measuring mood and QOL: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Lung Cancer Questionnaire (EORTC QLQ- LC13) [9]. In addition, patients who underwent surgery during the years 2003 to 2006 also completed the shortform version of the Depression Anxiety Stress Scales (DASS-21) questionnaire, which evaluates mood including anxiety, depression, and stress [10]. Participants filled out the questionnaires on only one occasion. Responses to the QLQ-C30 and QLQ-LC13 questionnaires were scored according to procedures devised by the EORTC and available in a scoring manual [11]. Separate raw scores for QLQ-C30 and QLQ-LC13 were totaled for segments of the questionnaire, and each segment sum was linearly transformed to a standardized scale of 0 to 100. For scales depicting mood, QOL, and function scores, higher scores represent a healthier mood, higher global quality of life, and higher level of function. In the scales for symptoms, lower scores represent a lower severity of symptoms. Responses to the DASS-21 questionnaire were scored according to standard procedures [12]. In the DASS-21 mood questionnaire lower scores represent a lower level of moodrelated symptoms. Missing scores were imputed by determining the average raw score for that segment of the questionnaire. None of the segments was missing answers for half or more of the questions, thus no patient segments were excluded from analysis. Depression was formally assessed in patients operated on during 2003 to 2006 using the DASS-21 questionnaire and was compared with a depression assessment derived from the EORTC questionnaire. The DASS-21 score for depression was converted to a Z score by subtracting the Table 1. Demographic and Clinical Data for Eligible Patients Who Were and Were Not Included in the Study Variable Not Included Included p Value Men 51 (52.6%) 65 (52.4%) 0.74 Age at time of operation (y) Diabetes mellitus 12 (12.8%) 18 (14.8%) 0.80 Hypertension 61 (63.5%) 57 (46.3%) Prior MI 11 (11.8%) 8 (6.6%) 0.19 COPD 22 (22.7%) 41 (33.6%) 0.09 PS 0 or 1 87 (91.6%) 113 (94.2%) 0.61 FEV 1 % ppofev 1 % Dlco% ppodlco% Percent of lung resected COPD chronic obstructive pulmonary disease (FEV 1 /forced vital capacity 0.7 and FEV 1 % 80); Dlco% preoperative diffusing capacity for carbon monoxide expressed as a percent of predicted; FEV 1 % preoperative forced expiratory volume in the first second expressed as a percent of predicted; MI myocardial infarction; ppo predicted postoperative value; PS Eastern Cooperative Oncology Group performance status.

3 Ann Thorac Surg FERGUSON ET AL 2009;87: QUALITY OF LIFE AFTER LUNG RESECTION Table 2. Demographic and Clinical Data for Patients Who Completed Questionnaires Variable Age 70 y Age 70 y p Value Men 38 (55.1%) 27 (49.1%) 0.51 Current age (y) Interval between operation and questionnaire completion (y) Diabetes mellitus 8 (11.8%) 10 (18.5%) 0.30 Hypertension 31 (44.9%) 26 (48.2%) 0.72 Prior MI 2 (2.9%) 6 (11.3%) 0.07 COPD 19 (27.5%) 22 (40.0%) 0.14 PS 0 or 1 63 (91.3%) 50 (90.9%) 0.99 FEV 1 % ppofev 1 % Dlco% ppodlco% Percent of lung resected Release 14, 2003) and Systat (Version 12, Systat Software, Inc, Chicago, IL). Scores were dichotomized using the quartile representing poor QOL, symptoms, or mood as one group and the remaining three quartiles as the other group. Using dichotomized results, scores for mood, symptoms, and QOL were compared with preoperative factors (coexisting medical conditions, pulmonary function, performance status) and postoperative factors (pulmonary complications, cardiovascular complications, other complications, extent of resection) to identify predictors of poor QOL and mood. Analyses included 2 test or Fisher s exact test as appropriate for categorical data, unpaired Student s t tests for continuous variables, and linear regression. Multivariable logistic regression was used to identify covariates for QOL, symptom, and mood scores by including variables with a probability of 0.2 or less on univariate testing and using a backward stepwise technique. For all analyses a probability value of less than 0.05 was determined to be statistically significant. COPD chronic obstructive pulmonary disease (FEV 1 /forced vital capacity 0.7 and FEV 1 % 80); Dlco% preoperative diffusing capacity for carbon monoxide expressed as a percent of predicted; FEV 1 % preoperative forced expiratory volume in the first second expressed as a percent of predicted; MI myocardial infarction; ppo predicted postoperative value; PS Eastern Cooperative Oncology Group performance status. mean, dividing by the standard deviation from the normative data, and then averaging the Z scores. The average Z scores for the DASS-21 depression category were compared with the Z scores for the EORTC questionnaire using values for questions 21 through 24 (Do you feel tense? Do you worry? Do you feel irritable? Do you feel depressed?) using regression techniques. A close relationship between the two instruments for the more recently operated on patient group was identified (r %; p 0.001). Therefore, we used data from the EORTC-derived depression score for all patients in the analysis of mood. Patients were divided into younger ( 70 years old) and older ( 70 years old) groups using their ages at the time of questionnaire completion. Data analyses were performed using Minitab (Minitab Inc, College Station, PA, Results A total of 462 patients underwent major lung resection for cancer during the study period. Of those, 221 were considered qualified for study entry based on the inclusion and exclusion criteria (Fig 1). A total of 124 (57%) patients completed questionnaires. The patients who completed questionnaires were similar to those who did not complete questionnaires, although there was a higher incidence of hypertension among patients who did not complete questionnaires and lung function was somewhat worse among patients who did complete questionnaires (Table 1). Among demographic and clinical variables there were no statistical differences between the younger and older groups other than age, although older patients had somewhat higher frequencies of prior myocardial infarction and chronic obstructive pulmonary disease (Table 2). Age at the time of surgery was younger than 70 years for all patients in the younger group and was 70 years or older for all but 11 patients in the older group; only 5 patients in the older group were younger than 68 at the time of surgery. A greater number of older patients underwent pneumonectomy, and the older patient group Table 3. Surgical Treatment and Clinical Outcomes Variable All Patients Age 70 y Age 70 y p Value Operation Lobectomy or bilobectomy 121 (97.6%) 69 (100%) 52 (94.5%) Pneumonectomy 3 (2.4%) 0 3 (5.5%) Stage Ia or Ib 118 (95.2%) 66 (95.7%) 52 (94.5%) 0.99 IIa or IIb 6 (4.8%) 3 (4.3%) 3 (5.5%) Postoperative hospital stay Pulmonary complication 8 (6.5%) 2 (2.9%) 6 (10.9%) 0.14 Cardiovascular complication 6 (4.8%) 1 (1.4%) 5 (9.1%) Other complication 17 (13.7%) 7 (10.1%) 10 (18.2%) 0.20 Any complication 22 (17.7%) 8 (11.6%) 14 (25.5%) 0.045

4 1010 FERGUSON ET AL Ann Thorac Surg QUALITY OF LIFE AFTER LUNG RESECTION 2009;87: Table 4. Quality of Life Outcomes More Than 6 Months After Major Lung Resection a Variable All Patients Age 70 y Age 70 y p Value QLQ-C30 Global health status Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning Fatigue Pain Dyspnea QLQ-LC13 Dyspnea Pain in chest DASS-21 Stress Anxiety Depression Overall score a Better global status and function are indicated by higher scores. Worse mood and symptoms are indicated by higher scores. experienced a longer duration of postoperative stay, a higher incidence of cardiovascular complications, and a significantly higher incidence of any complications compared with the younger group (Table 3). Questionnaires were completed an average of 2.6 years after lung resection surgery (range, 3 months to 6.4 years; 95% were completed 6 months after surgery; 83% were completed 12 months after surgery). Quality of life, symptom, and mood scores were not related to the time interval between surgery and questionnaire completion as assessed by regression analysis. Quality of life and mood were generally similar between the younger and older groups of patients (Table 4). Although there were no statistically significant differences in scores between the older and younger groups, older patients had poorer physical function, more fatigue, greater dyspnea, and less depression. Age at the time of questionnaire completion was inversely related to physical function score (p 0.002) and was directly related to fatigue score (p 0.006) and dyspnea scores (p for QLQ-C30; p for QLQ-LC13). The DASS-21 depression score tended to improve with age (p 0.064). The QLQ-C30-derived depression score was unrelated to patient age at the time of questionnaire completion (p 0.25). Postoperative complications and hospital length of stay were, overall, not related to subsequent QOL, symptom, or mood scores on univariate analysis. An exception was the category of pulmonary complications, which was related to physical function score (p 0.025) and dyspnea scores (p for QLQ-C30; p for QLQ-LC13). Postoperative hospital length of stay was inversely related to physical function score (p 0.005) and was directly related to dyspnea scores (p for QLQ- C30; p for QLQ-LC13). Dyspnea (QLQ-LC13) was strongly related to physical function score (p 0.001; r %) but was not related to any other QOL, mood, or symptom score (other than QLQ-C30 dyspnea score). Multivariable analyses were used to identify covariates for the worst quartile of the QOL, mood, and symptom Table 5. Outcomes of Multivariable Analyses for Covariates Determining Worst Quartile for Quality of Life, Symptom, and Mood Scores Variable Covariate Odds Ratio a 95% CI p Value Physical function FEV 1 % Pulmonary complication Role function FEV 1 % Fatigue FEV 1 % Pain (QLQ-C30) FEV 1 % Dyspnea (QLQ-LC13) FEV 1 % a The odds ratio for FEV 1 % is calculated per 10 percentage points increase in that covariate. CI confidence interval; FEV 1 % preoperative forced expiratory volume in the first second expressed as a percent of predicted.

5 Ann Thorac Surg FERGUSON ET AL 2009;87: QUALITY OF LIFE AFTER LUNG RESECTION scores listed in Table 3. No important covariates were identified for global, emotional function, cognitive function, social function, and depression or other mood scores. One covariate, percent predicted forced expiratory volume in the first second, was a strong determinant of the worst quartile of physical function, role function, fatigue, pain, and dyspnea scores. The occurrence of pulmonary complications was also associated with physical function outcome (Table 5). Comment Advances in surgical and anesthetic techniques have allowed lung resection to be performed with greater safety in older patients. Operative mortality in older patients has now declined to the point where this risk is no longer a major impediment to formal lung resection [5, 6, 13]. As a result, the short-term risk of surgery has become somewhat less of a concern than the need to provide overall optimal disease management. With the growing number of older lung cancer patients being referred for surgery, it is increasingly important to characterize long-term outcomes after resection, particularly with regard to QOL and mood, in this patient group. In this study we investigated QOL outcomes in younger and older lung cancer patients who underwent major lung resection, and investigated the relationship of these outcomes to comorbid factors, physiologic status, and short-term surgical outcomes. We chose to use the EORTC instruments QLQ-C30 and QLQ-LC13 for evaluation of QOL in our population because they were specifically created for cancer patients and are well validated for individual lung cancer stages. The DASS-21 instrument was selected to enhance our ability to assess mood, which is not a focus of the EORTC instruments. The patient population that responded to the questionnaires is representative of our patients undergoing resection for lung cancer with three exceptions. First, patients who suffered operative mortality were not available to study. Although there are techniques for considering such patients in QOL outcomes, we chose not to use those tools for this study. Second, a substantial proportion of patients did not participate in the study. However, the participation rate that we observed is typical for such studies, and the group of nonparticipants appeared similar to the participating patients [14, 15]. However, it is possible that the nonparticipating patients had considerably different QOL outcomes than did the group of participants. Finally, all of the patients in the study underwent open resection, which could skew outcomes compared with results for patients who undergo minimally invasive resection [16]. Quality of life and symptom scores from this study are similar to those from the general population reported for the QLQ-C30 tool with the exception that the patients in our study had higher global scores, lower physical function scores, lower pain scores, and higher dyspnea scores [11]. These differences may be attributable in part to the fact that the reference population was younger than the population in the current study. Despite the fact that older patients in our study had more comorbidities and 1011 experienced a higher incidence of postoperative complications than did younger patients, older and younger patients shared similar functional QOL, symptoms, and mood after recovery from surgery. The exceptions to this included higher fatigue and dyspnea symptom scores and lower physical functioning scores in the older population, whereas younger patients had higher depression scores. These trends are similar to those reported for equivalent age ranges among patients with all stages of lung cancer [11]. Our surgical patients were presumably chosen for or were more likely to agree to surgery in part because of their positive outlook. Our study supports two important general views: the perception that older individuals have higher rates of depression and lower overall QOL is incorrect (at least in such patients undergoing surgery for early stage lung cancer), and it is inappropriate to recommend against surgery for these patients on that basis alone. Pain is an important determinant of QOL. In our study, the median pain score was 0, 7 patients (5.6%) reported scores of 35% or greater, 15 patients (12%) reported scores of 20% or greater, and 38 patients (30.6%) reported pain of any type. The latter finding is strikingly similar to the incidence of pain in a recent study of lung resection patients queried 2 years postoperatively, in which approximately 30% of patients without recurrence of cancer had the same or worse pain compared with preoperatively [15]. Our impression is that only 5% or so of our patients would characterize their symptoms as chronic pain. We identified a relationship between pulmonary complications and postoperative hospital length of stay as perioperative factors and physical function and dyspnea as QOL factors. The fact that dyspnea and physical function were closely related QOL variables in our data set may help explain some of the similarities in these statistical relationships. The methods used in our study do not permit assessment of whether physical function and dyspnea were determinants of increased risk of pulmonary complications and prolonged postoperative length of stay or whether those complications resulted in poorer physical function and dyspnea scores. A primary objective of this study was to identify methods for predicting which patients might experience poorer QOL than the typical patient after major lung resection. Many of the QOL, symptoms, and mood scores were unrelated to any preoperative factors or operative outcomes. However, we identified percent predicted forced expiratory volume in the first second as a consistent predictor of physical function, role function, fatigue, pain, and dyspnea. Others have explored preoperative factors related to intermediate-term QOL, and identified preoperative dyspnea, diffusing capacity, or no physiologic measures as predictors of poor outcomes [17 20]. The differences in these findings may be attributed in part to the use of different tools and differing time frames for QOL measurement. For example, there are important differences in the design of our study and that of the report of Handy and colleagues [17] that make comparisons difficult. Their QOL assessment took place at 6 months postoperatively, a much shorter interval than our

6 1012 FERGUSON ET AL Ann Thorac Surg QUALITY OF LIFE AFTER LUNG RESECTION 2009;87: average postoperative interval; their study interval may have occurred before complete recovery from surgery. Ten percent of their patients had resections less than lobectomy, possibly permitting surgery on some patients with impaired lung diffusing capacity for carbon monoxide, enabling an evaluation of the relationship between very low diffusing capacity and QOL. Only 2 of our 124 patients had a lung diffusing capacity for carbon monoxide less than 45, preventing any meaningful evaluation of the effects of substantially low diffusing capacity on QOL. There are several potential shortcomings of this study. It was not performed longitudinally, and thus we did not track changes with time or changes related to preoperative status. The number of patients studied is small relative to the number of patients in our database, making conclusions about the absence of significant differences less certain than is ideal. We studied patients who underwent surgery during a span of more than a decade, during which time changes in practice patterns and surgical techniques might have influenced the long-term QOL outcomes. Despite these potential shortcomings, we believe that our findings are clinically useful. As we and others have shown, age alone is not a predictor of poorer QOL after major lung resection. Therefore, anticipated QOL based on age alone should not be used to select patients for lung surgery. We identified percent predicted forced expiratory volume in the first second as an important predictor of risk for poorer scores for physical function, role function, fatigue, pain, and dyspnea, all of which contribute to poor overall healthrelated QOL. Physicians have used percent predicted forced expiratory volume in the first second to assess operative risk for patients for decades, and it has been known to predict overall survival independent of lung cancer stage [21 23]. Our study indicates that this factor also should be taken into consideration when assessing a patient s eligibility for major lung resection from the perspective of long-term QOL. References 1. Dales RE, Belanger R, Shamji FM, Leech J, Crepeau A, Sachs HJ. Quality-of-life following thoracotomy for lung cancer. J Clin Epidemiol 1994;47: Zieren HU, Muller JM, Hamberger U, Pichlmaier H. Quality of life after surgical therapy of bronchogenic carcinoma. Eur J Cardiothorac Surg 1996;10: Mangione CM, Goldman L, Orav EJ, et al. Health-related quality of life after elective surgery: measurement of longitudinal outcomes. J Gen Intern Med 1997;12: Burfeind WR Jr, Tong BC, O Branski E, et al. Quality of life outcomes are equivalent after lobectomy in the elderly. J Thorac Cardiovasc Surg 2008;136: Rostad H, Naalsund A, Strand T-E, Jacobsen R, Talleraas O, Norstein J. Results of pulmonary resection for lung cancer in Norway, patients older than 70 years. Eur J Cardiothorac Surg 2005;27: Birim O, Zuydendorp HM, Maat APWM, Kappetein AP, Eijkemans MJC, Bogers AJJC. Lung resection for non smallcell lung cancer in patients older than 70: mortality, morbidity, and late survival compared with the general population. Ann Thorac Surg 2003;76: Gebretsadik M, Jayaprabhu S, Grossberg GT. Mood disorders in the elderly. Med Clin N Am 2006;90: Djernes JK. Prevalence and predictors of depression in populations of elderly: a review. Acta Psychiatr Scand 2006; 113: Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ- C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85: Henry JD, Crawford JR. The short-form version of the Depression Anxiety Stress Scales (DASS-21): construct validity and normative data in a large non-clinical sample. Br J Clin Psychol 2005;44: Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. The EORTC QLQ-C30 scoring manual, 3rd ed. European Organisation for Research and Treatment of Cancer, Brussels, Antony MM, Bieling PJ, Cox BJ, Enns MW, Swinson RP. Psychometric properties of the 42-item and 21-item versions of the Depression Anxiety Stress Scales in clinical groups and a community sample. Psychol Assess 1998;10: Schneider T, Pfannschmidt J, Muley T, et al. A retrospective analysis of short and long-term survival after curative pulmonary resection for lung cancer in elderly patients. Lung Cancer 2008;62: Balduyck B, Hendriks J, Lauwers P, Van Schil P. Quality of life evolution after lung cancer surgery: a prospective study in 100 patients. Lung Cancer 2007;56: Kenny PM, King MT, Viney RC, et al. Quality of life and survival in the 2 years after surgery for non small-cell lung cancer. J Clin Oncol 2008;26: Li WW, Lee TW, Lam SS, et al. Quality of life following lung cancer resection: video-assisted thoracic surgery versus thoracotomy. Chest 2002;122: Handy JR Jr, Asaph JW, Skokan L, et al. What happens to patients undergoing lung cancer surgery? Outcomes and quality of life before and after surgery Chest 2002;122: Win T, Sharples L, Wells FC, Ritchie AJ, Munday H, Laroche CM. Effect of lung cancer surgery on quality of life. Thorax 2005;60: Paull DE, Thomas ML, Meade GE, et al. Determinants of quality of life in patients following pulmonary resection for lung cancer. Am J Surg 2006;192: Brunelli A, Socci L, Refai M, Salati M, Xiumé F, Sabbatini A. Quality of life before and after major lung resection for lung cancer: a prospective follow-up analysis. Ann Thorac Surg 2007;84: Ferguson MK, Karrison T. Does pneumonectomy for lung cancer adversely influence long-term survival? J Thorac Cardiovasc Surg 2000;119: Varela G, Novoa N, Jiménez MF. Influence of age and predicted forced expiratory volume in 1 s on prognosis following complete resection for non-small cell lung carcinoma. Eur J Cardiothorac Surg 2000;18: Sekine Y, Yamada Y, Chiyo M, et al. Association of chronic obstructive pulmonary disease and tumor recurrence in patients with stage IA lung cancer after complete resection. Ann Thorac Surg 2007;84: DISCUSSION DR TODD L. DEMMY (Buffalo, NY): Mark, given our aging population, congratulations on this timely study. Data like these substantiate the long-term value of our operations, particularly with impending health-care reforms and competing ablative nonsurgical technologies. You had a good survey response rate using this widely preferred quality-of-life instrument. Doing so,

7 Ann Thorac Surg FERGUSON ET AL 2009;87: QUALITY OF LIFE AFTER LUNG RESECTION you showed that older patients who recover are not too different from their younger counterparts. Like others, you related an objective data point, FEV 1 (forced expiratory volume in the first second as percent of predicted), to a subjective quality-of-life score. It is interesting that diffusing capacity, which your group has shown to be a better indicator of surgical complications, was not the surrogate indicator for quality-of-life problems, and you may wish to comment on this. Consistent with other reports, pulmonary dysfunction predicted chronic pain and quality-oflife problems, but in contrast to similar works, your data were not collected longitudinally beginning before surgery, which is, as you noted, a major limitation. I have two questions. Beside the concern that the nonrespondent 43% may have had worse quality of life, thus reducing their interest in participation, your average survey time was 2.5 years, and most lung cancer recurrence events occur before then. Given this plus your broad exclusions for chemotherapy and radiation, your survey best describes the special population of surviving patients cured largely by surgery alone. Can you estimate the number of patients who were excluded and comment on the relative importance of that group to determine how your study relates to our overall population? Finally, when I read your manuscript I noticed the symptom scores had standard deviations that were equal to the mean, but the pain scores, while lower, had standard deviations that were two to three times the mean. This suggests that some of your patients had problems with postthoracotomy pain, and qualityof-life studies recently published in the last several years have shown that this is a problem. One actually documented a favorable pain and physical dimension quality of life for VATS (video-assisted thoracoscopic surgery) over thoracotomy, persisting up to 3 years after surgery. Can you provide data on the incidence of postthoracotomy pain syndrome in your series? Thank you. DR FERGUSON: Thanks very much, Todd. You are right, the Dlco (lung diffusing capacity for carbon monoxide) did not come out as a predictor, nor did we expect it to. We have not found any correlation of diffusing capacity with any of the long-term outcomes in any of our studies thus far. The exclusion of almost half of the patients from the study cohort is for a number of reasons. I would estimate that 20% were excluded because of recurrent cancer, and at least half of the remaining patients could not be identified for follow-up contact, and that is either because they had moved out of the region or perhaps had died of intercurrent causes. As far as we could tell, none had died from cancer causes. You are right, the number of patients is relatively small, leading to some statistical quirkiness of the data, including the standard deviations that you mentioned, particularly for pain. I think this is largely because pain was almost a dichotomous variable in this data set. Most of the patients reported zero pain and those that do have pain have fairly severe pain. My estimate is that it is somewhere in the range of a few percent of the patients, but a few patients can really skew the data set as a result. DR RODNEY LANDRENEAU (Pittsburgh, PA): Mark, when you try to objectify a subjective entity such as quality of life and things, I am wondering about the denominator on the elderly group, because they had to have buy-in to be there, their family or themselves, and so these are the troopers among the older people that came in, and, for the most part, maybe they are just lucky to be alive DR FERGUSON: Well, that may have an influence on the mood scores in these patients. That is one reason why those scores are so much better than in the average patient population. DR LANDRENEAU: That is what I am saying. So it is hard when you are looking at something very subjective and trying to objectify quality of life. Those people had buy-in. These were the guys that said, hey, I want to keep it going, and in fact, you look at the younger folks who are more depressed with their outcome or concerns about their prognosis. It seems to me this would be a great project for the STS database, to look along all tiers, 50 years of age through the octogenarian, to see how they are affected by their therapy and their disease process. DR FERGUSON: Well, the mood findings are not just peculiar to lung cancer patients or lung cancer patients undergoing surgery. The elderly population in general has a better mood score than the general population. DR BRYAN FITCH MEYERS (St. Louis, MO): Mark, when you study quality of life longitudinally, and particularly when you compare across groups, it is always a challenge when there is differential survival in the groups. In the NETT (National Emphysema Treatment Trial), they handled that by giving quality of life of zero to people who died, and then that allowed you to compare the overall quality of life for each strategy. I always thought that that was double taxation where you report the number of deaths and then, because of the deaths, you must lower the reported quality of life of those who survived. I just wondered what your thoughts are about assigning a quality of life of zero to people who die in order to do longitudinal comparison between two groups? DR FERGUSON: Well, it is an important point, and I think it was one of many tools that the NETT trial used to determine quality of life outcomes. We found that tool, as part of the data study monitoring group for the NETT, to be quite useful because it assigned a zero value to those patients who died. But I think for something like lung cancer surgery, where the end point is unknown and you are hoping to cure the patients, it may have less of a role. Obviously with the structure of our study, we did not find it possible to include zero scores for patients who did not make it, but we are looking for a good tool to use for future such studies that can account for mortality in assessing QOL. DR WILLIAM A. COOK (North Andover, MA): I am sure we are all aware of the fact that patients who continue to smoke with bad pulmonary functions have a rather poor prognosis over a 2-year period, and I am wondering what part that increasing pulmonary function problem has had and therefore what relationship did continued smoking or discontinuation of smoking have on these patients, or do you know? DR FERGUSON: I am sorry, I do not have any information about that. In general, I do not operate on patients who are still smoking, so the minimum cutoff is 3 weeks prior to surgery, and I would say our recidivism rate is around 10% to 20%, which provides a relatively small population of patients to study in that regard. So aside from that, I cannot comment on what effect ongoing smoking might have had for a patient s pulmonary function or quality of life.