|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 25, No 19 (July 1), 2007: pp. 2702-2708 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.08.2883 Impact of Psychotherapeutic Support for Patients With Gastrointestinal Cancer Undergoing Surgery: 10-Year Survival Results of a Randomized Trial
From the Department of General and Thoracic Surgery, University Hospitals of Schleswig-Holstein, Kiel; Department of Medical Psychology, University Hospital Hamburg-Eppendorf, Hamburg; Department of Visceral and Transplantation Surgery, University Hospital of Ulm, Ulm, Germany; and the School of Physical and Occupational Therapy, Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada Address reprint requests to Thomas Küchler, PhD, Referenzzentrum Lebensqualität in der Onkologie, Klinik für Allgemeine und Thoraxchirurgie, Universitätskliniken Schleswig-Holstein, Arnold-Heller-Str. 7, 24105 Kiel, Germany; e-mail: tkuechler{at}chirurgie-sh.de
Purpose The impact of psychotherapeutic support on survival for patients with gastrointestinal cancer undergoing surgery was studied. Patients and Methods A randomized controlled trial was conducted in cooperation with the Departments of General Surgery and Medical Psychology, University Hospital of Hamburg, Germany, from January 1991 to January 1993. Consenting patients (N = 271) with a preliminary diagnosis of cancer of the esophagus, stomach, liver/gallbladder, pancreas, or colon/rectum were stratified by sex and randomly assigned to a control group that received standard care as provided on the surgical wards, or to an experimental group that received formal psychotherapeutic support in addition to routine care during the hospital stay. From June 2003 to December 2003, the 10-year follow-up was conducted. Survival status for all patients was determined from our own records and from three external sources: the Hamburg cancer registry, family doctors, and the general citizen registration offices. Results Kaplan-Meier survival curves demonstrated better survival for the experimental group than the control group. The unadjusted significance level for group differences was P = .0006 for survival to 10 years. Cox regression models that took TNM staging or the residual tumor classification and tumor site into account also found significant differences at 10 years. Secondary analyses found that differences in favor of the experimental group occurred in patients with stomach, pancreatic, primary liver, or colorectal cancer. Conclusion The results of this study indicate that patients with gastrointestinal cancer, who undergo surgery for stomach, pancreatic, primary liver, or colorectal cancer, benefit from a formal program of psychotherapeutic support during the inpatient hospital stay in terms of long-term survival.
Psycho-oncology is currently a target of behavioral research in medicine. The effects of psychosocial interventions, although perceived by the lay community to be of benefit, remain controversial.1,2 Moreover, there is still professional debate on the most appropriate timing of the intervention (before, during, or after medical treatment), which approaches are efficacious (standardized or individualized programs: individual, family, or group treatment), and whether or not psychosocial interventions influence survival.3,4 A recent review, covering the period from 1954 to 1999, included 329 psychosocial intervention trials, but only four of those focusing on survival showed at least fair methodology.5 From these studies, with follow-up ranging from 1 to 6 years and sample sizes ranging from 66 to 121 patients, no conclusions or recommendations for psychosocial interventions could be made. In the same year, Spiegel in Nature Reviews Cancer,4 identified five studies with potential benefit for cancer patients’ survival, as well as five studies with neutral results and provided a salient review of these trials. Although the methods differed, both reviews concluded that, despite the growing body of knowledge in this area, further research was necessary. Since 2002, there has been one additional trial.6 While no differences in survival were found, psychological outcomes were positive. In addition, Fawzy et al15 presented the results of their 10-year follow-up and concluded that the intervention effect was still significant for survival, but the relative risk (RR) for those who participated in the intervention (compared with those who did not) decreased compared to the original study (from RR = 6.89 to RR = 2.87).
In 1991, we undertook a randomized trial in the surgical department of the University Hospital of Hamburg-Eppendorf (Germany) to determine if an individualized program of psychotherapeutic support, provided during the inpatient hospital period to patients with gastrointestinal cancer and scheduled for surgery, would promote better quality of life than that perceived by patients not receiving this intervention. Because survivorship status is inherent in quality of life analyses, we first examined if and to what extent the psychotherapeutic support influenced survival. The results were published in 19997 and can be summarized as follows: during the first 2-year follow-up period, 69 of 136 patients in the experimental group and 45 of those 135 in the control group survived. The Kaplan-Meier survival curves found an unadjusted significance level for group differences of P = .002 (log-rank
Objectives
Original Trial: Design and Treatment Regimens The original design, a two-arm randomized trial of standard care as provided in the surgical wards of the University Hospital of Hamburg-Eppendorf (Germany) in the early 1990s, or this standard care plus formal psychotherapeutic support, has been extensively described in a previous article.7 In brief, from January 1991 to January 1993, 271 consenting patients who met defined inclusion criteria, including a preliminary diagnosis of cancer of the esophagus (n = 31), stomach (n = 40), pancreas (n = 40), liver/gallbladder (n = 108), or colon/rectum (n = 52), and who were scheduled for surgery, were stratified by sex, and allocated via a stratified, blocked, randomized design with randomly ordered block sizes to either routine care and services as delivered on the four surgical wards by ward personnel, or to similar care and services but with the addition of an assigned psychotherapist who provided treatment to the patient during both the pre- and postoperative inpatient hospital stay. This individual (one of two such therapists who had received specialized training for the study) provided educational information, a supportive relationship, and ongoing psychotherapeutic counseling to the patients at the bedside. Specifically, the therapist gave individualized care based on findings from the psychotherapeutic intake interview. In general, the therapists provided ongoing emotional and cognitive support to foster "fighting spirit" and to diminish "hope and helplessness."8 Emphasis was placed on assisting the patient in forming questions for the other caregivers. While maintaining appropriate confidentiality, the patient's overall well-being was routinely discussed with the surgical team. More than 95% of inpatient interventions took place on the ward, and the remainder at other places within the hospital. The therapist also encouraged family and social support. Before discharge, the therapist explored the patient's emotional and cognitive interpretation of the surgery, and assisted the patient in planning for the future. Figure 1 provides a flow chart showing the overall study design including patient accrual; Table 1 shows reasons for nonparticipation of screened patients.
Instrumentation and Data Collection Data on patients’ sociodemographic and clinical characteristics, the process of care, and patient outcomes related to survival and quality of life were collected. Before random assignment and surgery, and at 10 to 14 days, and 3, 6, 12, and 24 months after surgery, patients completed European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire C30,9 as well as the disease-specific module for each patient's cancer site. Baseline measurements of characteristics related to the surgical care process were made using defined criteria or established protocols, and were verified by the treating surgeons and/or the pathologists. Details can be found in the previous article.7
10-Year Follow-Up Study
Statistical Analysis
Original Study Group Comparisons Sociodemographic characteristics showed no significant differences by treatment group.7 Similarly, clinical characteristics such as site of tumor, TNM staging, RTC, as well as postoperative treatment regimes at the time of the original study demonstrated no significant differences between experimental and control groups.7 Postoperatively, our surgical investigator reviewed the preoperative information on sites of tumor and reclassified the liver/gallbladder patients using histopathologic information which had become available (Table 2). Again, there were no statistically significant differences between groups, although the experimental group had five patients with extrahepatic metastases from a primary gastrointestinal cancer, compared with one in the control group.
Descriptive Results of the Psychosocial Intervention In addition to the semistructured intake interview, the experimental patients had a median of six contacts (mean 6.91; range, two to 25 contacts) with their psychotherapist. This translates into a mean duration of 222 contact minutes (range, 40 to 1,090 minutes; reassuring contacts of 10 minutes or fewer were not counted) with a median of 22 days in hospital (range, 3 to 144 days). A similar amount of time was spent by the therapist with the doctors and nurses discussing and exchanging patient-related information. For ethical reasons, 34 patients crossed from the control to the experimental group and 10 changed from the experimental to the control group. The patients who crossed to the experimental group received the same amount of treatment, but had no formal intake interview and received more contacts during the postoperative phase. Patients in the experimental group received different types of intervention: supportive therapy (81%), crisis intervention (12.3%), relaxation training (5.8%), and short psychotherapy (0.9%). Almost one third (31.5%) of all psychological interventions focused on information about diagnostic procedures, treatment, and rehabilitation, while the more psychosocial aspects such as life balance/existential matters, future expectations, relationships, and emotional coping were equally distributed with 10% to 15% each. The topics death and dying, silence/nonverbal communication, and small talk each accounted for approximately 5% of the overall treatment time.
Survival at 10 Years During the 10-year follow-up period, 29 of 136 experimental patients and 13 of 135 control patients survived. Table 3 presents information on the survival status by TNM staging, RTC, and sex. A review of our 10-year data shows, that among those with metastases at the time of the original operation, only three of 62 patients in the experimental group and three of 66 patients in the control group were still alive. The results were different for those with local or regional involvement. Of the original patients with local disease, 13 (57%) of 23 patients in the experimental group and three (21%) of 15 in the control group were alive. Similarly, in those with regional involvement five (13%) of 39 patients in the experimental group compared with one (2%) of 41 in the control group were alive. In the group with benign tumors (11 of 11), eight subjects in the experimental group and six control group subjects were alive after 10 years; in those with missing TNM staging data (one of two), no patients were alive.
The cumulative proportions of all patients surviving in these groups are plotted in Figure 2. A visual comparison suggests a clinically important difference, and the test for the equality of survival curves supports a statistically significant difference in survival between patients receiving the experimental intervention and those in the control group (log-rank  2 = 11.73; P = .006). Respecting the intent-to-treat approach, all patients, even those with no or a benign tumor (11 patients in each group), were included in the survival analysis. However, it should be noted that the exclusion of these patients did not affect the results at 10 years. (log-rank 2 = 10.43; P = .001).
Despite the fact that there were no differences in the composition of the experimental and control groups with respect to site of tumor, TNM staging, or RTC,7 adjusted analyses using Cox proportional hazards models were undertaken. The results are presented in Table 4. As presented, neither the hazard ratios nor the P values changed very much with the adjustment for each indicator of disease. In a stepwise regression, other factors like age, sex, and surgical experience were excluded from the model. Because data on additional therapies are based mainly on patient's report, thus being less valid than data from the charts, we decided not to include them in the statistical analysis. It should be noted, however, that the inclusion of the variable additional therapies (Table 2) did not affect the results of uni- or multivariate survival analyses (experimental group > control group) substantially. There are no significant survival differences between patients with or without additional therapy (log-rank 2 = 0.807; P = .369). This result holds true for patients with and without chemotherapy alone (log-rank 2 = 0.212; P = .645).
The focus in the psycho-oncology literature, as initiated by Spiegel et al,10 has been on studies of women with metastatic breast disease. Of the five available randomized trials,6,10,11-13 only that by Spiegel et al10 reported a significant difference in survival for women receiving a psychosocial intervention. In the literature it appears that psychotherapeutic treatment has a more positive impact on patients with leukemia,14 melanoma,15 Hodgkin's disease, non-Hodgkin's lymphoma,16 and (endstage) cancer of different tumor sites.17,18 The original results of this study in terms of survival benefits for the experimental patients were somewhat surprising and had not been hypothesized. Thus, it seems useful to compare our protocol with those of the trials mentioned above to determine which aspects of our approach might be of special importance. Different from several trials,6,10-13 we started our interventions preoperatively, during the diagnostic phase. Clinical experience suggests that this is the time of the greatest anxiety/uncertainty. The therapists were involved preoperatively, to deal with specific anxieties related to surgery. They helped during the first postoperative week when patients have to face two different stressors: physical impairment due to extensive surgery and psychological distress due to uncertainty about the prognosis. The therapists also assisted the patients in coping with predictable stressful events, such as communication of the histopathologic findings or the necessity of adjuvant treatment. Given the low physical and mental state, this often cumulates not just in a significant decrease of hope and confidence, but in a real personal crisis (eg, What will happen with me and my life, to my family?). Based on clinical experience, being present when things happen might be more effective than talking about such events weeks later. Similar to the trial by Fawzy et al,15 we focused not just on active coping but on information about all aspects of surgery and oncological treatment. The discharge interview—when the patients reviewed their time in the hospital—targeted emotional integration of the whole event. It included elements of cognitive-existential therapy as in the trials by Spiegel et al or Kissane et al.6,10 The reason why only some studies of patients receiving psychotherapeutic support do better than some that do not may be related to the timing of the intervention. Perhaps expecting positive effects from psychotherapeutic treatment in patients with metastatic disease is often too late in the course of the disease to have an impact. Stress reduction, if that is the causal mechanism, may have to occur earlier, both in terms of tumor stage and intervention, to achieve positive results. The recent study by Kissane et al6—that examined early-stage cancer with intervention that started after the medical treatment found, like most other studies of breast cancer, psychological benefits but no influence on survival—may support our suggestion. The mechanism of early stress reduction seems to be important, since over the 2-year follow-up we found no indication that pre- and postoperative adjuvant therapies had a substantial impact on survival. The mechanisms of how this supportive approach influences better coping, more awareness toward health behaviors, and enhanced social support remain theoretical because these rather complex concepts were not measured distinctly. Recent results of brain research have begun to identify the molecular basis of emotion, especially fear.19 However, one can only speculate to which extent those results may contribute to explaining the survival results of this study.20 If reduced, fear may influence the immune system to continue to function more efficiently,21 and it may have facilitated better survival in the experimental group. This conjecture, of course, remains purely hypothetical.
Limitations and Weaknesses
Conclusion and Implications
The author(s) indicated no potential conflicts of interest.
Conception and design: Thomas Küchler, Doris Henne-Bruns, Sharon Wood-Dauphinee Provision of study materials or patients: Stefanie Rappat Collection and assembly of data: Stefanie Rappat Data analysis and interpretation: Thomas Küchler, Beate Bestmann, Stefanie Rappat, Doris Henne-Bruns, Sharon Wood-Dauphinee Manuscript writing: Thomas Küchler, Beate Bestmann, Stefanie Rappat, Doris Henne-Bruns, Sharon Wood-Dauphinee Final approval of manuscript: Thomas Küchler, Doris Henne-Bruns, Sharon Wood-Dauphinee Other: Doris Henne-Bruns [principal surgical investigator]
We thank the therapists of the original trial, J. Graul, MD, and K. Holst, MD, the Hamburg Cancer Society, which supported the follow-up-study, the team of the "Referenzzentrum Lebensqualität," and B. Kremer, MD, who facilitated this research within the University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Supported by the Hamburg Cancer Society (Hamburger Krebsgesellschaft). Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Ross L, Boesen EH, Dalton SO, et al: Mind and cancer: Does psychosocial intervention improve survival and psychological well-being? Eur J Cancer 38:1447-1457, 2002[CrossRef][Medline] 2. Chow E, Tsao MN, Harth T: Does psychosocial intervention improve survival in cancer? A meta-analysis. Palliat Med 18:25-31, 2004 3. Spiegel D: Mind matters –group therapy and survival in breast cancer. N Engl J Med 345:1767-1768, 2001 4. Spiegel D: Effects of psychotherapy on cancer survival. Nat Rev Cancer 2:383-389, 2002[CrossRef][Medline] 5. Newell SA, Sanson-Fisher RW, Savolainen NJ: Systematic review of psychological therapies for cancer patients: Overview and recommendations for future research. J Natl Cancer Inst 94:558-584, 2002 6. Kissane DW, Love A, Hatton A, et al: Effect of cognitive-existential group therapy on survival in early-stage breast cancer. J Clin Oncol 22:4255-4260, 2004 7. Kuechler T, Henne-Bruns D, Rappat S, et al: Impact of psychotherapeutic support on gastrointestinal patients undergoing surgery. Hepatogastroenterology 46:322-335, 1999[Medline] 8. Greer S, Moorey S, Watson M: Patients adjustment to cancer: The Mental Adjustment to Cancer (MAC) scale vs. clinical ratings. J Psychosomat Res 33:373-377, 1989[CrossRef][Medline] 9. Aaronson NK, Ahmedzai S, Bergman B, et al: The European Organisation 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 85:365-376, 1993 10. Spiegel D, Bloom JR, Kraemer HC, et al: Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 2:888-891, 1989[CrossRef][Medline] 11. Cunningham AJ, Edmonds CV, Jenkins GP, et al: A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer. Psychooncology 7:508-517, 1998[CrossRef][Medline] 12. Edelmann S, Lemon J, Bell DR, et al: Effects of group cognitive behaviour therapy on the survival time of patients with metastatic breast cancer. Psychooncology 8:474-481, 1999[CrossRef][Medline] 13. Goodwin PJ, Leszcz M, Ennis M, et al: The effect of group psychosocial support on survival in metastatic breast cancer. N Engl J Med 345:1719-1726, 2001 14. Richardson JL, Shelton DR, Krailo M, et al: The effect of compliance with treatment on survival among patients with hematological malignancies. J Clin Oncol 8:356-364, 1990[Abstract] 15. Fawzy FI, Canada AL, Fawzy NW: Malignant melanoma: Effects of a brief, structured. Arch Gen Psychiatry 60:100-103, 2003 16. Ratcliffe MA, Dawson AA, Walker EG: Eysenck personality inventory L-scores in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Psychooncology 4:39-45, 1995[Medline] 17. Linn MW, Linn BS, Harris R: Effects of counseling for late stage cancer patients. Cancer 49:1048-1055, 1982[CrossRef][Medline] 18. Ilnyckyi A, Farber J, Cheang MC, et al: A randomized controlled trial of psychotherapeutic intervention in cancer patients. Ann R Coll Physicians Surg Can 27:93-96, 1994 19. Shumyatsky GP, Tsvetkov E, Malleret G, et al: Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear. Cell 111:905-918, 2002[CrossRef][Medline] 20. Dudai Y: Fear thou not. Nature. 421:325-327, 2003[CrossRef][Medline] 21. Ader R, Felten D, Cohen N: Interaction between the brain and the immune system. Annu Rev Pharmacol Toxicol 30:561-602, 1990[CrossRef][Medline] 22. Berend M, Teren K, Sagermann R, et al: The "Kiel model": A psychooncological support program following international standards. Psychooncology 15:172, 2006 (suppl) Submitted July 19, 2006; accepted February 20, 2007.
Related Editorial
Related Correspondence
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
< .05 for inclusion and 
