Clinical Cancer Research CR Helping Patients Frontiers in Basic Cancer Research
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bukowski, R. M.
Right arrow Articles by Elson, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bukowski, R. M.
Right arrow Articles by Elson, P.
Clinical Cancer Research Vol. 10, 6310S-6314S, September 15, 2004
© 2004 American Association for Cancer Research

Proceedings of the First International Conference

Prognostic Factors in Patients with Advanced Renal Cell Carcinoma

Development of an International Kidney Cancer Working Group

Ronald M. Bukowski1, Sylvie Negrier2 and Paul Elson1

1 Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, Ohio; and 2 Centre Leon Berard, Lyon, France


   ABSTRACT
Top
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 OPEN DISCUSSION
 REFERENCES
 
The identification of prognostic factors in patients with metastatic renal cell carcinoma represents an area of increasing interest. Multiple publications identifying pertinent clinical and laboratory variables have appeared since 1986. The current study of 353 patients with advanced disease treated at The Cleveland Clinic from 1987 to 2002 was conducted to additionally assess and validate a model proposed recently by investigators from Memorial Sloan-Kettering Cancer Center. The data presented are similar to those reported previously, which demonstrated that patients with metastatic renal cell carcinoma can be categorized into good-, intermediate-, and poor-risk groups, using readily available clinical factors. Additionally, comparability of patients in this database to a group treated recently in France was assessed. These two groups appear similar in their distribution of various clinical factors and survival. Finally, a group of international investigators has been developed to provide a comprehensive database of >4,000 patients with metastatic renal cell carcinoma to provide and validate a single model that can be used to predict survival. This project is now under way.


   INTRODUCTION
Top
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 OPEN DISCUSSION
 REFERENCES
 
In the United States, renal cell carcinoma accounts for 2.5% of cancer incidence and 2% of cancer mortality (1) . Recent epidemiologic studies suggest that the incidence of all stages of renal cell carcinoma is increasing (2) . More than 30,000 new cases of renal cell carcinoma will be diagnosed in the United States in 2004 (3) . Renal cell carcinoma is a surgical disease if detected early, and 4-year survival rates for patients with disease confined to the kidney (stages T1 and T2) is ~90% to 95% (4 , 5) . Once metastatic disease develops, the prognosis for long-term survival is poor, with 5-year survival ranging from 0% to 20% (3 , 4 , 6) . Unfortunately, approximately one third of patients have metastatic disease at the time of diagnosis, and 50% of patients undergoing curative surgery can be expected to experience relapse at distant sites (4 , 5) . Coupled with the lack of effective systemic therapy and the highly variable natural history, the poor outlook for patients with metastatic renal cell carcinoma highlights the need to define patient and disease factors that are associated with outcome. Identification of a reliable set of prognostic factors in patients with metastatic disease would provide an important tool to help optimize patient selection for specific treatment strategies. This will also assist the interpretation of clinical trials by providing information on how therapy is affecting the natural history of the disease.

Reports in the literature vary with respect to the identification of patient and disease characteristics that are prognostic for survival in patients with metastatic renal cell carcinoma (7, 8, 9, 10, 11, 12, 13) . Although some factors have consistently been found to be of value (e.g., performance status), the previous reports have evaluated different factors and used variable definitions of some factors, such as metastatic-free interval.

A historical perspective of this area indicates that the first report addressing this issue appeared in 1986 (14) . The authors at that time noted that factors predicting outcome for patients with metastatic disease included performance status, the presence of pulmonary metastases, and the metastatic-free interval. Subsequently, several reports appeared in 1988 (7 , 8) that reviewed the same issue. In 1988, Elson et al. (7) published an analysis of 670 patients who had been treated with chemotherapy. The features that were associated with survival in a multivariate analysis included Eastern Cooperative Oncology Group performance status (0 to 1 versus 2 to 3), time from initial diagnosis (>1 year versus ≤1 year), number of metastatic sites, prior cytotoxic chemotherapy, and recent weight loss. Additional analyses have appeared recently, and multiple reports analyzing prognostic factors in patients with metastatic renal cell carcinoma have been published (15, 16, 17, 18, 19, 20, 21, 22) . In these reports, no factor independently predicted survival. When reviewed as a whole, the same factors were not evaluated by all of the investigators, several issues with regard to coding of factors among studies are present, definitions have sometimes varied, and the population of patients treated has sometimes been different. This latter factor may be relevant, because patients who have received extensive prior therapy may have a different prognosis from those who are untreated. Additionally, patients who were treated before 1990 in the era before cytokines were used routinely and those receiving cytokine-based therapy after 1990 may have different outcomes (13) .

Table 1Citation outlines some of the prognostic factors that have been examined in patients with renal cell carcinoma. These factors include demographic variables, the type of prior therapy, characteristics of the primary tumor, various immunologic factors, disease factors such as site and disease-free intervals, various biochemical parameters, and, more recently, molecular markers.


View this table:
[in this window]
[in a new window]

  		Table 1 Prognostic factors in renal cell carcinoma: variables examined

 
When the database of prognostic factors in patients with renal cell carcinoma is examined, it is clear that additional studies in this area would be helpful. The primary goals of our group at The Cleveland Clinic Taussig Cancer Center and the International Kidney Cancer Working Group project were to evaluate our database with regard to prognostic factors and then to confirm whether it could be used to validate a model proposed by Motzer et al. (12 , 13) In addition, the International Kidney Cancer Working Group is establishing a comprehensive database from centers that treat patients with metastatic renal cell carcinoma. This will be used to develop a set of prognostic factors in patients with metastatic renal cell carcinoma and ultimately to derive a single validated model. Additionally, the database as constructed could serve as a resource to study the natural history of this illness and aid in design and analysis of clinical trials for patients with renal cell carcinoma.


   MATERIALS AND METHODS
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 OPEN DISCUSSION
 REFERENCES
 
The records of patients with metastatic renal cell carcinoma who were enrolled in clinical trials at The Cleveland Clinic Foundation between 1987 and April 2002 were reviewed. These trials consisted primarily of biological response modifiers (Phase I and II trials) as single agents or as combination therapies. Criteria were relatively uniform and included histologic documentation of renal cancer; clinical or biopsy evidence of metastatic disease; bidimensionally measurable disease; Eastern Cooperative Oncology Group performance status ≤1; normal renal, hepatic, and bone marrow function; absence or stable central nervous system metastases; no prior history of cancer; absence of significant cardiac disease; and no recent surgery. Data collected included standard pretreatment patient and disease characteristics, baseline biochemical parameters, best response to treatment, date of first treatment, date of progression, date of death, and last follow-up. Response and progression were defined by standard criteria, and survival was defined from the time from initiation of first treatment to the date of death or last follow-up. The statistical methods used included the log rank test for univariable survival and the Cox proportional hazards for multivariable survival comparisons. Previous reports in the literature and recursive partitioning were used to define cut points for continuous variables, such as age, time from diagnosis, and various biochemical and hematologic parameters.

For the International Kidney Cancer Working Group project, a group of investigators was convened in Lyon, France, in October 2002. The purpose of this meeting, which was supported by the Kidney Cancer Association, was to develop an international consortium of investigators and institutions that have an interest in and treat patients with metastatic renal cell carcinoma. The development of a database containing information on prognostic factors reported previously was initiated. Collection of data on >4,000 previously untreated patients is planned. The data will be analyzed to identify independent, validated predictors of survival. Initially as part of this project, two databases were examined to determine the comparability of patient populations with metastatic renal cell carcinoma in France and the United States. This involved examination of 782 patients treated by the Groupe Francais d’Immunotherapie (23) and 353 patients treated at The Cleveland Clinic (24) . These data were examined for baseline characteristics and comparability of survival.


   RESULTS
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 OPEN DISCUSSION
 REFERENCES
 
Three hundred fifty-three patients at The Cleveland Clinic with no prior history of treatment with systemic therapy and who were treated in approved clinical trials between April 1987 and April 2002 were identified. The variables examined are listed in Table 2Citation . The factors that had an effect on survival in this univariable analysis are also listed. In Table 3Citation , the overall survival of the 353 patients with advanced renal cell carcinoma is summarized. Additionally, the influence of time of study entry and sex is examined. The complete details of this analysis are the subject of another publication.3 A total of 309 patients had information available on the five prognostic factors included in the model of Motzer et al. (13) The median survival of these 309 patients was 14.7 months. Eighty-one percent of patients had died by the time of analysis, and 19% were still alive or lost to follow-up. To validate the model described by Motzer et al. (13) , a stepwise, stratified Cox proportional hazards model, which considered the categorical forms of the factors identified, was used. Histologic or nuclear grade was not considered due to the large proportion of patients missing this type of information. Prior nephrectomy was also not considered because of its correlation with time from diagnosis to entry on study. The results of this analysis are outlined in Table 3Citation and Fig. 1Citation . Using these definitions for the three groups, 19% had no poor prognostic factors and were categorized as favorable risk, 70% had 1 to 2 poor prognostic factors and were, therefore, considered intermediate risk, and 11% were categorized as poor risk. Median survivals for these groups were 28.6, 14.6, and 4.5 months, respectively (P < 0.0001). These data are similar to those reported previously (13) in which 18% of 437 patients analyzed were favorable risk, 62% were intermediate risk, and 20% were poor risk. The survival of these three groups was 29.6, 13.8, and 4.9 months, respectively.


View this table:
[in this window]
[in a new window]

  		Table 2 Prognostic factors for survival in renal cell carcinoma

 

View this table:
[in this window]
[in a new window]

  		Table 3 Cleveland Clinic Foundation validation of the Memorial Sloan-Kettering Cancer Center prognostic factors

 


View larger version (19K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 1. Survival curves for 309 patients with metastatic untreated renal cell carcinoma divided into three groups (low risk, intermediate risk, and high risk) using the prognostic factor criteria published previously by Motzer et al. (13) .

 
Therefore, the database from The Cleveland Clinic can be used to validate an existing prognostic model. Additional analyses have been performed on these data, and identification of other relevant prognostic factors is planned.3

As part of the International Kidney Cancer Working Group project, preliminary studies were then performed to determine the availability of a database that could be used for the planned analysis of prognostic factors. Initially, the databases from Negrier et al. (23) and The Cleveland Clinic were analyzed to determine their comparability. Tables 4Citation and 5Citation present these data. The distribution of patient factors appears similar between the two groups. The comparability of the survival curves is illustrated in Fig. 2Citation . The curves appear identical and demonstrate the similarities of these two patient populations. This suggests that use of an international database would be a reasonable approach to identify prognostic factors and validate a model for patients with this disease.


View this table:
[in this window]
[in a new window]

  		Table 4 International Kidney Cancer Working Group

 

View this table:
[in this window]
[in a new window]

  		Table 5 International Kidney Cancer Working Group

 


View larger version (19K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 2. Survival curves of two groups of patients with untreated renal cell carcinoma: 353 patients treated at The Cleveland Clinic from 1987 to 2002 and 782 patients treated by the Groupe Francais d’Immunotherapie (23) .

 
At a meeting in Lyon, France, a group of investigators was convened to determine the availability of databases for this purpose. Table 6Citation outlines the International Kidney Cancer Working Group and the participants. It is estimated that >4,000 patients with no prior therapy will be available for inclusion in this database. A group of statisticians (P. Elson, The Cleveland Clinic Center, Cleveland, OH; J. Manola, Dana-Farber Cancer Institute, Boston, MA; and M. Mazumdar, Memorial Sloan-Kettering Cancer Center, New York, NY) has been appointed to oversee the development, population, and administration of this database. Data collection is in progress.


View this table:
[in this window]
[in a new window]

  		Table 6 International Kidney Cancer Working Group: Participants

 

   DISCUSSION
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
OPEN DISCUSSION
 REFERENCES
 
The identification of prognostic factors that predict survival for patients with metastatic renal cell carcinoma has been undertaken by a variety of groups. Using data from The Cleveland Clinic (24) , we have demonstrated the validity of the model proposed by Motzer et al. (13) Patients with this disease can be separated into good-, intermediate-, and poor-risk groups based on factors identified previously. Different median survivals for these groups are found. Use of this model to identify patients for various trials is now under way. One study with CCI-779 has targeted the poor-risk group identified by Motzer et al. (13) as the population to treat with interferon {alpha}, CCI-779, or the combination. In a Cleveland Clinic trial that used interleukin 2 and thalidomide (25) , this same model has been used to select renal cell carcinoma patients characterized by good and intermediate survival patterns. These studies are for patients with no prior systemic therapy, a population similar to that analyzed in the various publications (12 , 13) . In clinical trials that target previously treated patients, development of a separate and valid model is required.

Refining this model and determining additional risk groups using other independent prognostic factors have been undertaken. The International Kidney Cancer Working Group is now collecting data from >4,000 patients with metastatic renal cell carcinoma for these purposes. This will provide a database to validate and construct a model to determine prognosis in patients with metastatic renal cell carcinoma. Introduction of other variables such as carbonic anhydrase IX expression, levels of T-lymphocyte apoptosis, and T-lymphocyte T-cell receptor {zeta} levels can also be used to additionally refine these approaches. The International Kidney Cancer Working Group project should provide the necessary sample of untreated patients from a variety of international locations to develop an acceptable model for renal cell carcinoma outcome in patients with metastatic disease.


   OPEN DISCUSSION
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 OPEN DISCUSSION
REFERENCES
 
Dr. James C. Yang: We all call things slightly differently. A clear cell tumor is not a clear cell tumor to all pathologists, and there has got to be a better way to identify a VHL mutated or inactivated tumor versus a non-VHL mutated or inactivated tumor.

Dr. Ronald M. Bukowski: What we’re trying to do is develop a model that’s generally applicable across broad categories of institutions and that requires factors that are easily done and readily available. So often pathology and the molecular studies we are talking about are not available and will not be for a while, so this is our initial effort to develop at least a uniform model that can be applied across institutions and across countries.


   FOOTNOTES
 
Presented at the First International Conference on Innovations and Challenges in Renal Cancer, March 19–20, 2004, Cambridge, Massachusetts.

Grant support: Kidney Cancer Association and the Zito Chair for Cancer Research.

Requests for reprints: Ronald M. Bukowski, Experimental Therapeutics Program, Cleveland Clinic Taussig Cancer Center, R35, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. Phone: 216-444-6825; Fax: 216-444-0114; E-mail: bukowsr{at}cc.ccf.org

3 Mekhail TM, Gawda RA, Abou Mari G, et al. Validation and extension of the Memorial Sloan Kettering Prognostic Factor Model for survival in patients with previously untreated metastatic renal cell carcinoma, manuscript in preparation. Back


   REFERENCES
Top
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 OPEN DISCUSSION
 REFERENCES
 

  1. Greenlee RT, Murray T, Bolden S, Wingo PA Cancer statistics 2000. CA Cancer J. Clin 2000;50:7-33.[Abstract]
  2. Chow WH, Deves SS, Warren JL, Fraumeni JF, Jr Rising incidence of renal cell cancer in the United States. J Am Med Assoc 1999;281:1628-31.[Abstract/Free Full Text]
  3. Motzer RJ, Bander NH, Nanus DM Renal cell carcinoma. N Engl J Med 1996;335:865-75.[Free Full Text]
  4. Figlin RA Renal cell carcinoma: management of advanced disease. J. Urol 1999;161:381-6.discussion 386–7[CrossRef][Medline]
  5. Linehan WM, Zbar B, Bates SE, Zelesky MJ, Yang JC Cancer of the kidney and ureter Devita HS, Jr Hellman S Rosenberg VT eds. . Cancer: principles and practice of oncology 6th edition. 20011362-83. Lippincott-Raven Publishers Philadelphia
  6. Lanigan D Prognostic factors in renal cell carcinoma. Br J Urol 1995;75:565-71.[Medline]
  7. Elson PJ, Witte RS, Trump DL Prognostic factors for survival in patients with recurrent or metastatic renal cell carcinoma. Cancer Res 1988;48:7310-3.[Abstract/Free Full Text]
  8. DeForges A, DeRay A, Klink M, Ghosn M, Kramar A, Droz P Prognostic factors of adult metastatic renal carcinoma: a multivariate analysis. Semin Surg Oncol 1988;4:149-54.
  9. Palmer PA, Vinke J, Phillip T, et al Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2. Ann Oncol 1992;3:475-80.[Abstract/Free Full Text]
  10. Fossa SD, Kramar A, Droz JP Prognostic factors and survival in patients with metastatic renal cell carcinoma treated with chemotherapy or interferon-alpha. Eur J Cancer 1994;30A:1310-4.
  11. Lopez Hanninen E, Kirchner H, Atzpodien J Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients. J Urol 1996;155:19-25.[CrossRef][Medline]
  12. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999;17:2530-40.[Abstract/Free Full Text]
  13. Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002;20:289-96.[Abstract/Free Full Text]
  14. Maldazys JD, deKernion JB Prognostic factors in metastatic renal carcinoma. J Urol 1986;136:376-9.[Medline]
  15. Gelb AB Renal cell carcinoma: current prognostic factors. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer 1997;80:981-6.[CrossRef][Medline]
  16. Srigley JR, Hutter RV, Gelb AB, et al Current prognostic factors - renal cell carcinoma: Workgroup No. 4 Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer 1997;80:994-6.[CrossRef][Medline]
  17. Henson DE, Fielding LP, Grignon DJ, et al College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors: summary. Members of the Cancer committee. Arch Pathol Lab Med 1995;119:1109-12.[Medline]
  18. Canobbio L, Rubagotti A, Miglietta L, et al Prognostic factors for survival in patients with advanced renal cell carcinoma treated with interleukin-2 and interferon-alpha. J Cancer Res Clin Oncol 1995;121:753-6.[CrossRef][Medline]
  19. Citterio G, Bertuzzi A, Tresoldi M, et al Prognostic factors for survival in metastatic renal cell carcinoma: retrospective analysis from 109 consecutive patients. Eur Urol 1997;31:286-91.[Medline]
  20. Landonio G, Biaocchio C, Cattaneo D, et al Retrospective analysis of 156 cases of metastatic renal cell carcinoma: evaluation of prognostic factors and response to different treatments. Tumori 1994;80:468-72.[Medline]
  21. Mani S, Todd MB, Katz K, Poo WJ Prognostic factors for survival in patients with metastatic renal cancer treated with biological response modifiers. J Urol 1995;154:35-40.[CrossRef][Medline]
  22. Minasian LM, Motzer RJ, Gluck L, Mazumdar M, Vlanis V, Krown S Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow up. J Clin Oncol 1993;11:1368-75.[Abstract/Free Full Text]
  23. Negrier S, Escudier B, Gomez F, et al Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol 2002;13:1460-8.[Abstract/Free Full Text]
  24. Abou-Jawde RM, Mekhail T, Bou Meri GF, et al Prognostic factors for survival in previously untreated metastatic renal cell cancer (RCC): a comprehensive evaluation and validation of established risk groups. Proc Am Soc Clin Oncol 2003;22:385a
  25. Olencki T, Malki S, Mekhail T, Dreicer R, Elson P, Wood L, Bukowski R Phase I trial of thalidomide and interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma (RCC). Proc ASCO 2003;22:387a



This article has been cited by other articles:


Home page
 Therapeutic Advances in Medical OncologyHome page
J. M.G. Larkin, E. L.S. Kipps, C. J. Powell, and C. Swanton
Review: Systemic therapy for advanced renal cell carcinoma
Therapeutic Advances in Medical Oncology, July 1, 2009; 1(1): 15 - 27.
[Abstract] [PDF]

Home page
 NEJMHome page
G. Hudes, M. Carducci, P. Tomczak, J. Dutcher, R. Figlin, A. Kapoor, E. Staroslawska, J. Sosman, D. McDermott, I. Bodrogi, et al.
Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma
N. Engl. J. Med., May 31, 2007; 356(22): 2271 - 2281.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
D. Strumberg, J. W. Clark, A. Awada, M. J. Moore, H. Richly, A. Hendlisz, H. W. Hirte, J. P. Eder, H.-J. Lenz, and B. Schwartz
Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Sorafenib: A Review of Four Phase I Trials in Patients with Advanced Refractory Solid Tumors
Oncologist, April 1, 2007; 12(4): 426 - 437.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. S. Lam, A. Breda, A. S. Belldegrun, and R. A. Figlin
Evolving Principles of Surgical Management and Prognostic Factors for Outcome in Renal Cell Carcinoma
J. Clin. Oncol., December 10, 2006; 24(35): 5565 - 5575.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Parton, M. Gore, and T. Eisen
Role of Cytokine Therapy in 2006 and Beyond for Metastatic Renal Cell Cancer
J. Clin. Oncol., December 10, 2006; 24(35): 5584 - 5592.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. Donskov and H. von der Maase
Impact of Immune Parameters on Long-Term Survival in Metastatic Renal Cell Carcinoma
J. Clin. Oncol., May 1, 2006; 24(13): 1997 - 2005.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bukowski, R. M.
Right arrow Articles by Elson, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bukowski, R. M.
Right arrow Articles by Elson, P.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online