JOP. J Pancreas (Online) 2010 Jul 5; 11(4):334-335.

 

 

Clinical Outcome of Pancreatic Cancer Patients with Diabetes Mellitus: Is Diabetes a Poor Prognostic Factor?

 

 

Soonmo Peter Kang¹, Muhammad Wasif Saif²

 

 

¹Department of Medicine, University of Chicago. Chicago, IL, USA. ²Yale Cancer Center, Yale University School of Medicine. New Haven, CT, USA

 

 

Summary

Diabetes mellitus and its related factors such as hyperinsulinemia have been linked to various cancer risks and outcomes. Previous research has offered inconsistent results in terms of relationship between diabetes and pancreatic cancers. Establishing clear association between these two entities may guide us in improving clinical outcomes of pancreatic cancer patients. Two abstracts that examined the association between diabetes mellitus and pancreatic cancer are updated in this paper. Herein, the authors report updated information from the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting in association between pancreatic cancer and diabetes mellitus. The present paper illustrates insufficient knowledge base to draw a conclusion in this topic. However, validation and understanding of the association could have significant clinical implications with respect to cancer prevention, early detection, and treatment. As such, further investigations are warranted to explore the link diabetes and pancreatic cancers.

 

What We Knew Before ASCO 2010

Pancreatic cancer is one of the most lethal diseases in the United States. In year 2009, over 42,000 new cases were diagnosed and 35,240 patients did succumb to deaths due to pancreatic cancer [1]. Factors related to diabetes and insulin resistance, namely hyperglycemia and hyperinsulinemia, have often been associated with pancreatic cancer. However, the association remains unproven and poorly understood [2, 3, 4, 5].

Diabetes is considered a possible risk factor and/or a manifestation of early pancreatic cancer. A stronger relationship between pancreatic cancer and new onset diabetes (compare to long standing diabetes) suggests that type 2 diabetes might be an early clinical indicator of undiagnosed pancreatic cancer [6]. The majority of pancreatic cancer patients have unresectable disease at the time of diagnosis, and treatment outcomes of advanced pancreatic cancer with available chemotherapy agents remain poor. While the entity as common as diabetes will not be considered a screening tool by itself, it may contribute to early diagnosis of pancreatic cancer when combined with other established risk factors.

A retrospective study by Busaidy et al., showed that diabetes may be an independent prognostic factor in patients with resectable pancreatic cancers [7]. Busaidy et al. then sought translational implications by elucidating pathophysiology behind the association. Their in vitro study showed that hyperglycemia and hyperinsulinemia, both conditions commonly seen in diabetics, may promote pancreatic cancer growth and even confer resistance to gemcitabine. The study also suggested that metformin and rosiglitazone can be synergistic with gemcitabine by promoting apoptosis [8]. The study shows that epidemiological findings can be translated into effective interventions.

What We Leant at ASCO 2010

Evidence Against the Association between Diabetes Mellitus and Clinical Outcomes in Patients with Pancreatic Cancer

Olowokure et al. (Abstract #4114) conducted a retrospective study utilizing the Veterans Affairs Central Cancer Registry data accumulated between 1995 and 2008 in order to compare survival data between patients with and without diabetes mellitus [9]. In patients with stage I-IV pancreatic cancers, having diabetes mellitus did not confer worse prognosis, in fact diabetic had statistically significant superior median survival (Table 1) [9].

 

 

Table 1. Results of two retrospective studies presented at the 2010 ASCO Annual Meeting, examining association between diabetes mellitus and pancreatic cancer.
Abstract Author	Sample size		Endpoints in comparison	Comparison of patients with pancreatic cancer
	Diabetics	Non diabetics		Diabetics	Non diabetics
#4114 Olowokure et al. [9]	1,326	3,402	Median survival	4.2 months	3.5 months
				P=0.048
#4117 Shama et al. [10]	92	252	Frequency of perineural invasion	94.6%	86.5%
				P=0.037
			Overall survival	30.2%	20.1%
				P=0.024

 

 

Evidence Supporting the Association of Diabetes with Perineural Invasion and Overall Survival in Surgically Resected Patients with Pancreatic Cancer

A retrospective study (Abstract #4117) tested a hypothesis that there may be association between perineural invasion, diabetes, and survival of pancreatic cancer patients by reviewing medical records of 344 patients who underwent resection of pancreatic cancer between 2004 and 2008. Data captured included diagnosis, presence of perineural invasion, American Joint Committee on Cancer (AJCC) TNM stage, and overall survival. Perineural invasion was significantly more common in patients with diabetes. Perineural invasion and diabetes were independent predictors for survival after adjusting for AJCC TNM stage. This study further corroborates the suggestion that understanding the biology rendering the association between diabetes and perineural invasion may guide us in discovering novel therapeutic targets for pancreatic cancer (Table 1) [10].

Commentary

The association between diabetes and pancreatic cancers are intriguing as identification of modifiable prognostic factors can lead to better understanding of the biology of cancer. In turn, knowledge of tumor biology can result in discoveries of new therapeutic targets which will be instrumental in improving the clinical outcomes of pancreatic cancer patients.

The link between diabetes mellitus and pancreatic cancer has been largely unclear due to the paucity of available data. This year’s abstracts, while adding to our knowledge base and being hypothesis generating, clearly do not provide compelling arguments in either direction. Further studies to validate this association would be a logical first step. At the same time, translational and clinical studies to identify appropriate interventions (i.e. aggressive diabetes mellitus management and novel targeted therapy) will be necessary in exploiting this potentially important association between diabetes and pancreatic cancer for the benefit of our patients.

 

Key words Diabetes Mellitus; Pancreatic Neoplasms; Prognosis

Abbreviations AJCC: American Joint Committee on Cancer; ASCO: American Society of Clinical Oncology

Conflict of interest The authors have no potential conflicts of interest

Correspondence
Muhammad Wasif Saif
Yale Cancer Center
Yale University School of Medicine
333 Cedar Street, FMP 116
New Haven, CT
USA
Phone: +1-203.737.1569
Fax: +1-203.785.3788
E-mail: wasif.saif@yale.edu

 

References

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer Statistics, 2009. CA Cancer J Clin 2009; 59:225-49. [PMID 19474385]

2. Grote VA, Becker S, Kaaks R. Diabetes mellitus type 2: an independent risk factor for cancer? Exp Clin Endocrinol Diabetes 2010; 118:4-8. [PMID 20127570]

3. Tsugane S, Inoue M. Insulin resistance and cancer: epidemiological evidence. Cancer Sci 2010; 101:1073-9. [PMID 20345478]

4. Saruç M, Karaarslan M, Rasa K, Saygili O, Ince U, Baysal C, et al. Pancreatic cancer and glucose metabolism. Turk J Gastroenterol 2009; 20:257-60. [PMID 20084568]

5. Saruc M, Pour PM. Diabetes and its relationship to pancreatic carcinoma. Pancreas 2003; 26:381-7. [PMID 12717272]

6. Garg P, Gupta, R. Pancreatic cancer and diabetes: is diabetes a risk factor or the outcome? J Clin Oncol 2007; 25(18 Suppl):15123.

7. Busaidy N, Yazbeck C, Shah P, Evans D, Li D, Geraci JM, Weiser M. Survival of resectable pancreatic cancer patients with diabetes. J Clin Oncol 2006; 24(18 Suppl):4098.

8. Feng Y, Busaidy N, Yeung S. Differential impact of anti-diabetic treatment on pancreatic cancer cell growth in cell culture conditions mimicking different stages in the natural history of diabetes mellitus type 2. J Clin Oncol 2008; 26:(15 Suppl):4640.

9. Olowokure O, Beg MS, Ali S, Tandra A, Safa M, Havlin K, Ahmad SA. Is diabetes mellitus (DM) associated with worse outcomes in pancreatic cancer (PC)? J Clin Oncol 2010; 28(15 Suppl):4114.

10. Shama MA,Tanaka M, Curley SA, Abbruzzese JL, Li D. Association of diabetes with perineural invasion and overall survival in surgically resected patients with pancreatic cancer. J Clin Oncol 2010; 28(15 Suppl):4117.