Type of Proposal
24-3-2015 10:00 AM
24-3-2015 10:50 AM
Schulich School of Medicine Windsor
Faculty Sponsor (Optional)
Importance of the Project
The purpose of this study is to determine the current OS of pancreatic patients treated at Windsor Regional Hospital’s Cancer Centre based on stage of disease. Secondary questions included determining the OS of late metastatic pancreatic cancer patients treated with chemotherapy versus supportive therapy alone. Furthermore, OS was compared based on the response of these patients to chemotherapy in order to determine if patient response to therapy can help clinicians better predict patient prognosis. This study also examined whether adjuvant therapy (chemotherapy, radiation, or both) after surgical resection of localized disease, as well as margin & nodal status, had any effect on disease free survival (DFS) and OS. This article adds to the growing body of evidence that will aid clinicians in estimating a prognosis and directing treatment for this devastating disease.
Existing State of Knowledge
Multiple clinical trials have supported the use of adjuvant chemotherapy in resected pancreatic cancer patients, however the use of CRT in adjuvant treatment remains a debated topic, and currently there are no randomized controlled trials demonstrating the superiority of the addition of radiotherapy with modern delivery techniques to adjuvant chemotherapy alone ( (9); (2); (10)). Furthermore, efforts are now focused on increasing the resectability of locoregional disease by incorporating neoadjuvant treatment prior to surgery. However, adjuvant CRT is generally agreed to benefit surgically resected patients with adverse risk factors for locoregional disease recurrence that include: older age, large tumour size, advanced tumour stage, high histological grade, elevated CA19-9 level, positive lymph nodes, and positive surgical margins.
In this study, 80 of 278 patients (29%[M1] ) were diagnosed with localized disease and subsequently treated with surgical resection, compared to the 8.7-20% listed in the literature ( (11); DiMarco et al 2007[M2] ). Of these patients, 22% had no documented disease recurrence [M3] either locally or systemically by the conclusion of This is a retrospective analysis so there be potential bias in patient selection)the study, which is comparable to the 80% recurrence rate after macroscopic excision [M4] alone in the literature (2). Patients treated with surgical resection alone had a median OS of 10.53 months, which falls just below the range of 11-20.2 months found in multiple published studies which may reflect the lack of exclusion of patients based on negative prognostic risk factors such as post-op Ca19-9 level, tumor size, and others mentioned above (2). Patients treated with adjuvant therapy (chemotherapy or CRT[M5] ) had a median OS of 18.80 months which is comparable to past studies ranging from 17.1-23.2 [M6] months. Adjuvant therapy was found to significantly increase median OS once adjusting for margin and nodal status between groups (P= 0.013). Of note was that patients with intermediate margins (at or within 1mm)—determined by pathological microscopic examination of surgically resected tumour tissue—did not have a significantly different median OS when compared to patients with negative margins (P=0.450), while positive margins significantly reduced OS (P=0.001). This is in agreement with multiple published studies demonstrating that margin status is independently associated with OS ( (12); (13); (14); (15); (10)), however this is the first study to our knowledge [M7] (probably yes )(check with DR HIRMIZ as well difference b/w positive vs intermediate margins )that has involved analysis of intermediate margin status. This single institution analysis demonstrates an OS benefit with adjuvant treatment in surgical patients (?NODAL STAUS) consistent with previous studies.
In this study, metastatic pancreatic cancer patients who received chemotherapy had a significantly longer median OS of 6.07 months compared to 2.50 months with supportive therapy alone, and this remained true after multivariate adjusted Cox regression analysis. These results are in line with past studies that involved advanced stage pancreatic cancer treated with single-agent Gem, as well as Gem plus other cytotoxic and targeted agents, which had a median OS range of 4.1-9.5 months (1). The OS survival benefit of chemotherapy was not of the same magnitude seen in other studies, and this may be due to the significant proportion of patients treated with GEM (75%). In the metastatic patient group, age was not found to be significantly associated with OS while female gender was a protective prognostic factor (P=0.02), thus this study adds to the list of independent adverse prognostic factors for OS including synchronous metastasis and low baseline albumin (8). Moore et al (2007) also found that female gender was significantly associated with increased OS, however contrary to our study both Moore et al (2007) and Conroy et al (2011) found that age significantly effected OS[M8] .
OS survival in the metastatic disease group of patients underperforms the OS survival of 11.1 months seen with FOLFIRINOX therapy (8), however Conroy et al involved patients with ECOG scores exclusively between 0-1. Furthermore, FOLFIRINOX is currently the most effective chemotherapy regime only in a certain subset of pancreatic cancer patients (good performance status, low bilirubin levels, and age ≤75 years) at the cost of higher toxicity ( (6); (7); (8)). While this study did include patients treated with FOLFIRINOX, the majority were treated with Gem (75%[M9] ) and hence this likely explains the lower median OS when compared to studies using solely FOLFIRINOX therapy.
In patients with metastatic disease treated with chemotherapy, response to therapy was found to significantly affect OS (P
Primary question: Determine the current overall survival (OS) of pancreatic patients treated at Windsor Regional Hospital’s Cancer Centre based on stage of disease.
This retrospective chart review examined the OS of 278 pancreatic ductal adenocarcinoma patients treated Jan 1st 2002 – May 9th 2013.
Exclusion criteria: unconfirmed diagnosis via biopsy or radiology, cause of death being unlikely due to diagnosis of pancreatic cancer, & certain tumors.
The date of diagnosis was defined as the date at which pathological evaluation of a tissue biopsy taken from the primary tumour or metastasis confirmed malignancy. If no tissue biopsy was performed, the date of diagnosis was instead defined as the date of the first CT scan confirming the presence of a mass. Disease status was determined based on the patient’s clinical presentation & radiological findings. Response to treatment was determined using CT scan, and listed as “not documented” if they deteriorated rapidly and no CT evaluation was performed prior to date of last contact. Patients receiving any form of chemotherapy intended to treat the pancreatic cancer, regardless of regime completion, were placed into the “chemotherapy” group, while the rest were placed in the “supportive therapy only” group. Patients undergoing any surgical procedure with curative intent were placed in the “surgery” group.
Data were analyzed using Kaplan-Meier and multivariate Cox-regression analyses as appropriate based on an alpha of 0.05.
OS was significant (P
This single institution analysis demonstrates OS significantly differed based on disease status at diagnosis. Advanced-stage patients with stable or partial response to chemotherapy had increased OS, as did adjuvant treatment surgical patients with localized disease once adjusting for margins. Unique to this study, patients with intermediate margins did not have significantly different OS when compared to those with negative margins.
Future directions would include building up the patient list so that an analysis can be made to determine which chemotherapy modalities lead to significantly longer OS.
Comparison of survival in pancreatic ductal adenocarcinoma patients treated with various modalities based on stage of disease: a single-centre study.