SAN FRANCISCO (EGMN) – A new diagnosis of diabetes may help identify older adults who will develop pancreatic cancer while there is still time for screening and early detection, researchers reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
In an observational study of more than 20,000 older adults with pancreatic cancer, 10 antecedent diagnoses were found to be significantly associated with the cancer diagnosis.
Of these, a diagnosis of new-onset diabetes preceded the cancer diagnosis by the greatest amount of time – more than 2 years, on average – or potentially enough time to catch the cancer early with targeted screening. A diagnosis of abdominal pain was second, at 1.5 years.
Late diagnosis is a major contributor to the generally “dismal” survival of pancreatic cancer, lead investigator Dr. Elizaveta Ragulin-Coyne said in an interview.
“Colonoscopy screening works great, mammography works great. But those cancers are really a lot more common, so it makes sense to screen the whole population,” she commented.
By contrast, pancreatic cancer is relatively uncommon, so population-based screening with current tests would generate many false positives. At present, only individuals from families having hereditary pancreatic cancers associated with certain mutations are screened.
The goal of the study was therefore to identify “the factors that can precede the diagnosis of pancreatic cancer, that sort of can act as red flags to identify that population at risk,” she explained. “So we are trying to identify the risk-rich population of individuals who can benefit from potential future screening.”
The investigators analyzed data from the U.S. Surveillance, Epidemiology, and End Results (SEER) database for the years 1991-2005 and the linked Medicare database for the years 1991-2007 to identify older adults with a diagnosis of pancreatic cancer and diagnoses preceding the cancer.
They evaluated 30 possible antecedent diagnoses for their association with the pancreatic cancer diagnosis, and narrowed it down to 10 that were significantly associated (P less than .05) in a stepwise logistic regression analysis: acute pancreatitis, chronic pancreatitis, cyst-pseudocyst, other pancreatic disease, bile duct obstruction, diabetes, weight loss, jaundice, abdominal pain, and hepatomegaly.
The 22,493 study patients were 77 years old on average; 55% were women and 86% were white, according to results reported in a poster session at the meeting.
The 10 antecedent diagnoses ranged in prevalence in this population from a low of 4% for hepatomegaly to a high of 76% for abdominal pain. A diagnosis of diabetes was seen in 45%.
In most cases, the median time between the antecedent diagnosis and the pancreatic cancer diagnosis was less than 3 months. The exceptions were abdominal pain, diagnosed a median of 18 months before the cancer, and diabetes, diagnosed a median of 28 months before the cancer.
The latter intervals are long enough to provide a window of opportunity for intervention, according to Dr. Ragulin-Coyne, a surgical resident and research fellow at the University of Massachusetts Medical Center in Worcester.
“It doesn’t make sense if you have preceding diagnoses within a month before, it doesn’t really make a difference,” she explained. “But if it’s over 6 months or over a year, it is actually clinically significant because you can hypothesize that those people are potentially at an early stage and could have more interventions that give you a possibility of cure.”
The average number of antecedent diagnoses decreased with increasing stage of pancreatic cancer at diagnosis, from 3.91 among patients with stage 0 disease to 2.04 among patients with stage IV disease.
This finding initially seemed counterintuitive, Dr. Ragulin-Coyne said. But perhaps patients having more advanced cancer at diagnosis have had less contact with the health care system in general, and therefore have fewer diagnoses on record.
In a logistic regression model among just the patients with an antecedent diabetes diagnosis, the odds of the gap between that diagnosis and the pancreatic cancer diagnosis being greater than 24 months were higher for nonwhite versus white patients; for patients aged 75-84 years or aged 85 years or older, compared with those aged 65-74 years; and for patients in the Midwest versus the Northeast.
The reason pancreatic cancer is diagnosed earlier in some patients and later in others is not yet clear, but it is likely multifactorial, according to Dr. Ragulin-Coyne.
“We can make guesses, whether it is socioeconomic or cultural or there is something else in play.” For example, some patients may “tell the doctor about all their symptoms and get worked up early and get their doctors concerned more,” she said. “But if they never come to the physician or they never mention what’s going on, they get diagnosed late.”
In any case, identifying the reasons will be critical to moving all patients into the early diagnosis group. “I think that will ultimately be the best thing if, when they come, we can offer them treatments and cure and options, versus just saying, unfortunately, it’s too late,” she commented.
The investigators have obtained the SEER data for all similar older adults without a pancreatic cancer diagnosis, and using a matched analysis, plan to develop and test a prediction nomogram using the information from their study. “Stay tuned for that,” she advised.
“Screening for pancreatic cancer will be a great future tool,” Dr. Ragulin-Coyne concluded, while also cautioning that there is still much work to be done before some type of population-based screening becomes a reality.
Dr. Ragulin-Coyne reported having no conflicts of interest related to the study.

爱思唯尔全球医学资讯

马萨诸塞州大学医学中心ElizavetaRagulin-Coyne博士在美国临床肿瘤学会主办的胃肠系统肿瘤研讨会上报告称，新诊断糖尿病可能有助于早期确定将来易患胰腺癌的老年患者，从而有时间对其进行筛查和早期检查。

由于胰腺癌并不十分常见，而以现行方法进行人群筛查将会产生许多假阳性结果，因而目前只对具有与某些突变有关的遗传性胰腺癌家族史的个体进行筛查，但延误诊断是胰腺癌患者普遍生存不佳的主要原因。为此，研究者对美国监测、流行病学和最终结果(SEER)数据库1991~2005年资料以及相关的联邦医保数据库1991~2007年资料进行了分析，旨在确认老年胰腺癌确诊患者和既往病史的相关性，以便对高危人群进行针对性筛查，使之得到早期诊治。

研究者分析了22,493例老年胰腺癌患者的资料，平均年龄77岁，55%为女性，86%为白种人。他们对既往确诊的30种疾病与胰腺癌的可能相关性进行评估，并应用逐步Logistic回归分析法，确定10种既往确诊疾病具有显著相关性，即急性胰腺炎、慢性胰腺炎、囊肿-假性囊肿、其他胰腺疾病、胆管梗阻、糖尿病、体重减轻、黄疸、腹痛以及肝肿大。其中发病率最低的疾病是肝肿大(4%)，最高为腹痛(76%)，糖尿病发病率为45%。

大部分既往诊断与胰腺癌诊断的中位间隔时间为3个月，但腹痛和糖尿病例外，前者中位间隔时间为18个月，后者为28个月，后者可以为对目标人群进行胰腺癌筛查和早期干预提供足够的时间。

对既往诊断为糖尿病的患者进行Logistic回归分析，结果显示，在既往糖尿病确诊与胰腺癌确诊间隔超过24个月的可能性方面，非白种人>白种人，75~84岁或≥85岁患者>65~74岁患者，中西部地区患者>东北部地区患者。其原因尚不清楚，可能与社会经济、文化或其他多种因素有关。

此外，分析还显示，胰腺癌确诊时癌症分期越高的患者，既往确诊的疾病种数越少。胰腺癌0期和IV期患者的既往确诊疾病种数分别为3.91种和2.04种。研究者认为可能与晚期癌症确诊患者平时就医次数较少、诊断记录较少有关。

基于上述结果，研究者还计划对SEER数据库中所有相似年龄段的非胰腺癌老年患者的资料进行分析，以期开发和测试一种老年胰腺癌预测列线图，实现胰腺癌筛查和早期干预。

研究者无利益冲突披露。