Chemoradiation For Pancreatic Cancer Research Articles

A Pilot Study of Diffusion-Weighted MRI in Patients Undergoing Neoadjuvant Chemoradiation for Pancreatic Cancer

PURPOSE: In the current study we examined the ability of diffusion MRI (dMRI) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation. METHODS: We performed a prospective pilot study of dMRI in patients with resectable pancreatic cancer. Patients underwent dMRI prior to neoadjuvant chemoradiation. Surgical specimens were graded according to the percent tumor cell destruction. Apparent diffusion coefficient (ADC) maps were used to generate whole-tumor derived ADC histogram distributions and mean ADC values. The primary objective of the study was to correlate ADC parameters with pathologic and CT response. RESULTS: Ten of the 12 patients enrolled on the study completed chemoradiation and had surgery. Three were found to be unresectable at the time of surgery and no specimen was obtained. Out of the 7 patients who underwent pancreaticoduodenectomy, 3 had a grade III histopathologic response (>90% tumor cell destruction), 2 had a grade IIB response (51% to 90% tumor cell destruction), 1 had a grade IIA response (11% to 50% tumor cell destruction), and 1 had a grade I response (>90% viable tumor). Median survival for patients with a grade III response, grade I-II response, and unresectable disease were 25.6, 18.7, and 6.1months, respectively. There was a significant correlation between pre-treatment mean tumor ADC values and the amount of tumor cell destruction after chemoradiation with a Pearson correlation coefficient of 0.94 (P = .001). Mean pre-treatment ADC was 161 × 10−5mm2/s (n = 3) in responding patients (>90% tumor cell destruction) compared to 125 × 10−5mm2/s (n = 4) in non-responding patients (>10% viable tumor). CT imaging showed no significant change in tumor size in responders or non-responders. CONCLUSIONS: dMRI may be useful to predict response to chemoradiation in pancreatic cancer. In our study, tumors with a low ADC mean value at baseline responded poorly to standard chemoradiation and would be candidates for intensified therapy.

Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) CONCLUSION: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

The art and science of radiation therapy for gastrointestinal cancers.

The use of radiotherapy to treat gastrointestinal cancers has evolved in a gradual, step-wise fashion over the past six decades. By nature, gastrointestinal cancers are often diagnosed at a locally advanced stage. This fact, combined with the inherent sensitivity of most parts of the luminal gastrointestinal tract to high-dose radiation, has meant that radiation is often best used as part of a multimodality regimen, instead of as a sole curative modality. At times progress may have seemed modest and incremental, but when we look back, it is indeed remarkable how far we have come and how much our treatments have improved. We now have technology that allows us to extend life, cure disease while preserving critical organs, and ablate previously untouchable tumors. The era of modern gastrointestinal radiation therapy arguably began in the 1960’s, when investigators first combined fractionated radiotherapy with concomitant 5-fluoruracil (5-FU). This approach was ultimately carried forth into large cooperative group trials in rectal, pancreatic, gastric and other cancers, and showed benefit both in the adjuvant setting and as a definitive therapy (1-4). In the following two decades, investigators at Wayne State University discovered that chemoradiation with a combination of 5-FU and mitomycin C could be used as a non-surgical, organ-sparing option in the treatment of anal cancer (5), while RTOG 85-01 established that a subset of esophageal cancers could be cured by radiation combined with 5-FU and cisplatinum, again without the need for radical surgery (6). In the 1990’s, an elegant series of prospective studies at the University of Michigan brought important breakthroughs in the understanding of hepatic radiation tolerance (7). In conjunction with improvements in computers and linear accelerator technology, these efforts bore further fruit in the 2000’s, as prospective studies showcased the power and safety of stereotactic body radiotherapy (SBRT) for liver tumors (8,9). Most recently, we now have definitive evidence that preoperative chemoradiation improves survival in esophageal cancers over surgery alone (10). This list, by no means exclusive, highlights some of the major landmarks and turning points on our quest to overcome some of the most difficult-to-treat human cancers. This issue reviews some areas of recent progress, new knowledge, and controversy in the field of gastrointestinal radiation oncology. In the first article, Dr. Lloyd and I explore the nuances that may allow us to enhance the therapeutic ratio of esophageal chemoradiation, now well established as a standard of care (11). Dr. Regine and colleagues then offer a masterful and balanced look at the very controversial area of adjuvant chemoradiation for pancreatic cancer (12). The liver has traditionally been an organ that radiation oncologists have been hesitant to treat. The next two articles explore emerging therapies with great potential for local control of hepatic tumors. Dr. Kennedy, one of the preeminent authorities on hepatic radioembolization, offers a fascinating review of this very promising modality (13). Dr. Scorsetti looks at progress in liver SBRT, where remarkable advances in biological understanding and technology allow us to deliver treatment with previously unthinkable power and precision (14). In the next section, Dr. Jabbour’s team shares their expertise in the very technically demanding subject of radiation for anal cancers, where recent innovations with intensity modulated radiation therapy (IMRT) have led to significant therapeutic gains (15). Similarly, Dr. Sun Myint and Dr. Kovacs demonstrate that techniques with a long history of use in rectal and anal cancer such as contact therapy and interstitial brachytherapy have been recently improved by technological developments. In expert hands, these techniques can be used to deliver to highly effective and personalized treatments with minimal morbidity (16,17). With regard to the application of new radiation therapy techniques, gastrointestinal cancers offer some unique challenges and difficulties. Dr. Chen addresses the problem of organ motion, an issue that constantly threatens to degrade the radiation oncologist’s therapeutic advantage, particularly in the abdomen (18). Dr. Lo leads a team of experts in an outstanding review of the tolerance of the gastrointestinal organs to the high-dose-per-fraction radiation that will be an increasingly important part of our anti-cancer arsenal (19). There is actually a lot going on just below the surface in gastrointestinal radiation oncology. Doors have swung partly or fully closed on some indications, in that radiotherapy is no longer considered a primary part of treatment, or there are other options. Yet there are also new areas with incredible potential that we are just beginning to appreciate. Some of these techniques require new skills and many have steep learning curves. However, this should not dissuade us, nor should the ongoing need to perform the sometimes complex prospective trials needed to prove their value as we continue our search for the best possible treatments for our patients.

Neoadjuvant therapy for resectable and borderline resectable pancreatic cancer

Neoadjuvant chemoradiation for resectable and borderline resectable pancreatic cancer has been widely investigated in the past two decades. Research demonstrates that this therapy may help improve surgical margins, reduce rates of lymph node positivity, allow for earlier initiation of systemic therapy, and select for patients with aggressive disease in whom surgery may not be warranted. This review presents the data for neoadjuvant chemoradiation in pancreatic cancer with a focus on resectable and borderline resectable disease.

Inhibition of Protein Phosphatase 2A Radiosensitizes Pancreatic Cancers by Modulating CDC25C/CDK1 and Homologous Recombination Repair

To identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer and thus improve survival, we conducted an siRNA library screen in pancreatic cancer cells. We investigated PPP2R1A, a scaffolding subunit of protein phosphatase 2A (PP2A) as a lead radiosensitizing target. We determined the effect of PP2A inhibition by genetic (PPP2R1A siRNA) and pharmacologic (LB100, a small molecule entering phase I clinical trials) approaches on radiosensitization of Panc-1 and MiaPaCa-2 pancreatic cancer cells both in vitro and in vivo. PPP2R1A depletion by siRNA radiosensitized Panc-1 and MiaPaCa-2 cells, with radiation enhancement ratios of 1.4 (P < 0.05). Likewise, LB100 produced similar radiosensitization in pancreatic cancer cells, but minimal radiosensitization in normal small intestinal cells. Mechanistically, PPP2R1A siRNA or LB100 caused aberrant CDK1 activation, likely resulting from accumulation of the active forms of PLK1 (pPLK1 T210) and CDC25C (pCDC25C T130). Furthermore, LB100 inhibited radiation-induced Rad51 focus formation and homologous recombination repair (HRR), ultimately leading to persistent radiation-induced DNA damage, as reflected by γ-H2AX expression. Finally, we identified CDC25C as a key PP2A substrate involved in LB100-mediated radiosensitization as depletion of CDC25C partially reversed LB100-mediated radiosensitization. In a mouse xenograft model of human pancreatic cancer, LB100 produced significant radiosensitization with minimal weight loss. Collectively, our data show that PP2A inhibition radiosensitizes pancreatic cancer both in vitro and in vivo via activation of CDC25C/CDK1 and inhibition of HRR, and provide proof-of-concept evidence that PP2A is a promising target for the improvement of local therapy in pancreatic cancer.

Preoperative chemoradiotherapy for pancreatic cancer encountered vertebral compression fractures.

227 Background: Preoperative chemoradiotherapy (CRT) with gemcitabine (GEM) for pancreatic cancer at our institute achieved excellent cure rates, while treated patients encountered vertebral compression fractures (VCFs) frequently. Methods: From January 2006 to December 2011, 220 patients (male/female: 134/86, median age: 66 (range: 33-84)) with resectable pancreatic cancer have been treated with preoperative CRT with GEM. This method consisted of concurrent radiotherapy (50-60 Gy in 25 fractions over 5 weeks) and chemotherapy (GEM 1,000 mg/m2intravenous, weekly for 12-15 weeks, 3 times during 4 weeks). Three-dimensional conformal radiotherapy was used and its fields covered both primary pancreatic tumor and retropancreatic tissues with 50 Gy level. Boost irradiation to the roots of celiac and superior mesenteric arteries with 2.4 Gy/fr using field-within-field technique has been started since 2009. The risk factors for VCF and its causes were retrospectively analyzed for 1,308 Th10-L3 vertebral bodies. Results: Follow-up time from the initiation of CRT ranged from 3.4-73.9 months (median: 17.9). Median overall survival time of these patients was 40.6 months. Radical surgery was completed in 164 patients (75%). Twenty-five patients (11%) diagnosed as VCF (CTCAE v4.0 grade1/2: 12/13) and 22 of them were at 3.6-23 months from CRT. Cumulative incidence rates at 2 years were 18.9% in total, 8.5% in male and 38.4% in female (p = 0.0002). Corresponding rates were 5.1% in age &lt; 60 and 24.9% in age ≥ 60 (p = 0.0107). On their courses 37 de novo VCFs (Th10/11/12/L1/2/3: 2/3/11/13/7/1) were observed at first and 9 patients repeated VCFs near the initial VCFs. Dose-volume factors of each vertebral bodies also significantly correlated with VCF; vertebrae whose mean dose were &lt; 38 Gy/ ≥ 38 Gy developed VCFs in 2.7%/10.0% at 2 years (p &lt; 0.0001), vertebrae whose V30 were &lt; 80%/≥80% developed VCFs in 2.4%/10.6% (p &lt; 0.0001). Conclusions: Besides women and higher age, dose-volume factors of radiotherapy were risk of developing VCF in patients with pancreatic cancer after preoperative CRT with GEM. These findings should be considered to avoid VCFs as late adverse event after CRT for pancreatic cancer, especially in IMRT era.

EL29 - Hepatobiliary Pancreatic Cancer: Cutting-Edge Drug Therapy

ABSTRACT Chemotherapy appears to prolong survival in patients with advanced pancreatic cancer (PC) or biliary tract cancer (BTC) and can take clinical benefits and improve quality of life since the clinical use of gemcitabine (Gem) in 1999 in Japan [1]. Many investigators have struggled to prove the superiority of Gem-contained combination therapy to Gem monotherapy for PC patients. Unfortunately, they all failed to prove the better survival benefit except Gem plus Erlotinib (GE) [2]. GE therapy demonstrate to be superior both in metastatic and locally advanced PC (HR 0.81). Many patients with GE therapy suffer from skin rush, and sometimes are afraid of a risk of Interstitial lung diseases (ILD). French investigators created a new standard chemotherapy which does not contain Gem: FOLFIRINOX. FORFIRINOX regimen can deliver a much better survival benefit rather than Gem monotherapy in metastatic PC, although it increased both hematological and non-hematological adverse effects (AE). Gem plus S1 (GS) showed both good survival benefits and anti-tumor effect in previous phase II studies [3,4]. We carried phase III study called GEST trial in Japan and Taiwan, which aimed to make sure the superiority of GS to Gem and non-inferiority of S1 to Gem. However, we can prove only non-inferiority of S1 to Gem in OS both in metastatic and locally advanced PC [5]. It is not clear whether radiotherapy should be useful or beneficial for locally advanced PC. Moreover, we do not have a good answer which drug we should administer when we plan the chemoradiotherapy for PC. Currently, there are some randomized phase II studies of chemoradiotherapy for PC in Japan, one is a study of chemoradiotherapy using GS combination compared with GS therapy, and the other is a study of Gem monotherapy followed by S1-chemoradiothrapy compared with S1-chemoradiotherapy. We need a well-designed phase II or phase III trial to prove a benefit of radiotherapy in PC near the future. But it is difficult to standardize a procedure of radiotherapy in many institutions even only in Japan. Gem plus cisplatin (CisGem) showed a better OS compared with Gem6) in BTC [6]. Kanai et al. study a phase I study of CisGem plus S1 in BTC (KHBO1002) [7]. We need to develop much more chemotherapy or chemoradiotherapy in PC or BTC, because we do not have enough agents to administer and there are many clinical questions still.

Su1356 Pre-Operative ERCP Placement of Non-Foreshortening Uncoated Self-Expanding Metal Biliary Stents Permits Successful Neoadjuvant Chemoradiation for Pancreatic Cancer

Su1356 Pre-Operative ERCP Placement of Non-Foreshortening Uncoated Self-Expanding Metal Biliary Stents Permits Successful Neoadjuvant Chemoradiation for Pancreatic Cancer

S1450: Biliary Decompression During Neoadjuvant Chemoradiation for Pancreatic Cancer: Plastic vs. Metal Stents

S1450: Biliary Decompression During Neoadjuvant Chemoradiation for Pancreatic Cancer: Plastic vs. Metal Stents

Aprepitant/5HT-3 antagonist (EMEND) for the prevention of chemoradiation-induced nausea and vomiting (CRINV) in patients receiving gemcitabine/ 5-FU–based chemoradiation and concurrent upper abdominal radiation for pancreatic cancer

e20661 Background: Significant chemoradiation-induced nausea and vomiting (CRINV) occurs in patients (pts) receiving chemoradiation for pancreatic cancer. The aim of this trial was to determine if prophylactic Aprepitant/5HT-3/dexamethasone added to standard chemoradiation resulted in less CRINV when compared to historical controls. Methods: Pts with locally advanced or resected pancreatic cancer received wkly Gemcitabine (200 mg/m2) and continuous infusion 5-fluorouracil (5-FU) or oral capecitabine with concurrent radiation (50.4 Gy). Aprepitant (125 mg p.o.) was given each Monday (day 1) of each week 1 hr before the gemcitabine infusion and on days 2 and 3 (80 mg p.o.) - 1 hour prior to the radiation. A 5HT-3 antagonist was given orally 30–60 minutes prior to the chemotherapy and dexamethasone (12 mg) was given on day 1 and repeated at a dose of 8 mg on days 2 and 3 with the aprepitant. Grade III/IV nausea was assessed using NCI CTC v. 3.0. The Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) questionnaire was completed at baseline prior to the start of all therapy, Time 1 (T#1), repeated at the end of the first week (T#2) and then repeated again at the end of the last full week of chemoradiation (T#3). Results: Of the 17 patients available for analysis, CTC grade III nausea and grade IV vomiting was observed in one patient (6%) during the entire treatment course. Utilizing the MAT at T#1, T#2 and T#3 respectively; 3/15, 4/15 and 2/13 pts reported experiencing any level of nausea. At those same time points; 0/15, 1/15 and 0/13 pts reported vomiting. The range of the average degree of nausea reported on a scale from 1–10 (worst) was 2.5 -3.67 over the study period. During treatment, 54–64% of participants reported no nausea/vomiting (N/V). For those patients who experienced N/V, it was rated as mild to moderate with only 3 of 17 requiring additional anti-emetics. Conclusions: Prophylactic Aprepitant/5HT-3/dexamethasone therapy resulted in minimal CRINV for pts receiving upper abdominal chemoradiation in this feasibility study. This regimen may be soon be integrated in to future CALGB pancreatic chemoradiation trials. [Table: see text]

Accrediting radiation technique in a multicentre trial of chemoradiation for pancreatic cancer

Before a multicentre trial of 3-D conformal radiotherapy to treat cancer of the pancreas, participating clinicians were asked to complete an accreditation exercise. This involved planning two test cases according to the study protocol, then returning hard copies of the plans and dosimetric data for review. Any radiation technique that achieved the specified constraints was allowed. Eighteen treatment plans were assessed. Seven plans were prescribed incorrect doses and two of the planning target volumes did not comply with protocol guidelines. All plans met predefined normal tissue dose constraints. The identified errors were attributable to unforeseen ambiguities in protocol documentation. They were addressed by feedback and corresponding amendments to protocol documentation. Summary radiobiological measures including total weighted normal tissue equivalent uniform dose varied significantly between centres. This accreditation exercise successfully identified significant potential sources of protocol violations, which were then easily corrected. We believe that this process should be applied to all clinical trials involving radiotherapy. Due to the limitations of data analysis with hard-copy information only, it is recommended that complete planning datasets from treatment-planning systems be collected through a digital submission process.

Occlusion Rate and Complications of Plastic Biliary Stents in Patients Undergoing Neoadjuvant Chemoradiotherapy for Pancreatic Cancer Associated with Biliary Obstruction

Occlusion Rate and Complications of Plastic Biliary Stents in Patients Undergoing Neoadjuvant Chemoradiotherapy for Pancreatic Cancer Associated with Biliary Obstruction

SU11248 (Sunitinib) Sensitizes Pancreatic Cancer to the Cytotoxic Effects of Ionizing Radiation

SU11248 (sunitinib) is a small-molecule tyrosine kinase inhibitor which targets VEGFR and PDGFR isoforms. In the present study, the effects of SU11248 and ionizing radiation on pancreatic cancer were studied. For in vitro studies human pancreatic adenocarcinoma cells lines were treated with 1 microM SU11248 1 h before irradiation. Western blot analysis was used to determine the effect of SU11248 on radiation-induced signal transduction. To determine if SU11248 sensitized pancreatic cancer to the cytotoxic effects of ionizing radiation, a clonogenic survival assay was performed using 0-6 Gy. For in vivo assays, CAPAN-1 cells were injected into the hind limb of nude mice for tumor volume and proliferation studies. SU11248 attenuated radiation-induced phosphorylation of Akt and ERK at 0, 5, 15, and 30 min. Furthermore, SU11248 significantly reduced clonogenic survival after treatment with radiation (p < 0.05). In vivo studies revealed that SU11248 and radiation delayed tumor growth by 6 and 10 days, respectively, whereas combined treatment delayed tumor growth by 30 days. Combined treatment with SU11248 and radiation further attenuated Brdu incorporation by 75% (p = 0.001) compared to control. SU11248 (sunitinib) sensitized pancreatic cancer to the cytotoxic effects of radiation. This compound is promising for future clinical trials with chemoradiation in pancreatic cancer.

M1104 The First Clinical Experience of Capsule Endoscope “MiroCam” Using a Novel Transmission Technolongy and a Prospective Trial to Diagnose Radiation Enteritis in Patients Receiving Chemoradiotherapy for Pancreatic Cancer

uL) (hazard ratio 2.25; p=0.005). Conclusion: The incidence of PNALD is quite high in a cohort of infants with NEC undergoing surgical treatment. Although the strongest risk factor is pre-operative PN exposure, thrombocytopenia, resection of small intestine and loss of the ileocecal valve are also associated with the development of PNALD. Further analysis is underway to define other risk factors in this multicenter, prospective study.

Adjuvant therapy for pancreatic cancer

Pancreatic cancer is uniformly fatal unless it can be surgically resected. Survival rates for the 15% to 20% of patients who have resectable disease, however, are a disappointing 10% to 30%, depending on the status of margins and surrounding lymph nodes. In the mid-1980s, a landmark study by the Gastrointestinal Tumor Study Group was the first to demonstrate a survival benefit from adjuvant therapy in the form of chemoradiation. Since then, several studies in both North America and Europe have tested the role of adjuvant chemotherapy or chemoradiation in pancreatic cancer, and the results have stirred great controversy. For this review, the evidence for adjuvant therapy in pancreatic cancer was examined, and the significant practice differences that exist between North American and European oncologists were highlighted. The authors investigated the results from the European Study Group for Pancreatic Cancer-1 trial and the reasons why that study has served to reinforce rather than resolve these trans-Atlantic differences. They also reviewed preliminary data from more recent adjuvant trials and explored the possible benefits of a neoadjuvant approach.

Long-term Survival and Metastatic Pattern of Pancreatic and Periampullary Cancer After Adjuvant Chemoradiation or Observation

The role of adjuvant chemoradiation in pancreatic cancer remains unclear. This report presents the long-term follow-up results of EORTC trial 40891, which assessed the role of chemoradiation in resectable pancreatic cancer. Two hundred eighteen patients were randomized after resection of the primary tumor. Eligible patients had T1-2 N0-N1a M0 pancreatic cancer or T1-3 N0-N1a M0 periampullary cancers, all histologic proven. Patients in the treatment group (n = 110) underwent postoperative chemoradiation (40 Gy plus 5-FU). Patients in the control group (n = 108) had no further adjuvant treatment. After a median follow-up of 11.7 years, 173 deaths (79%) have been reported. The overall survival did not differ between the 2 treatment groups (Chemoradiation treatment vs. death rate ratio 0.91, 95% CI: 0.68-1.23, P value 0.54). The 10-year overall survival was 18% in the whole population of patients (8% in the pancreatic head cancer group and 29% in the periampullary cancer group). These results confirm the previous short-term analysis, indicating no benefit of adjuvant chemoradiation over observation in patients with resected pancreatic cancer or periampullary cancer. Patients with pancreatic cancer may survive more than 10 years. Only 1 of 31 cases recurred after year 7.

Future Chemoradiation Strategies in Pancreatic Cancer

Although not universally accepted, 5-fluorouracil (5-FU)-based chemoradiation is considered a standard treatment for patients with localized pancreatic cancer. Randomized trials have indicated that chemoradiation improves median survival of both locally advanced and resected pancreatic cancer. While the use of adjuvant chemoradiation in pancreatic cancer has been called into question since the publication of the European Study Group for Pancreatic Cancer (ESPAC)-1 trial, this study has not changed standard practice in the United States. All randomized trials investigating adjuvant chemoradiation have reported significant local as well as distant disease control limitations, making the study of novel chemoradiation and adjuvant chemotherapy important. Selected centers are investigating neoadjuvant chemoradiation in radiographically resectable patients. Advantages of neoadjuvant chemoradiation compared to postoperative therapy include increased local control, increased access to therapy, addressing the systemic disease recurrence risk without delay, and optimal patient selection for pancreaticoduodenectomy through exclusion of patients with rapidly progressive metastatic disease. In the years since it was approved for use in pancreatic cancer, gemcitabine has stood the test of time as a systemic agent but has not been widely adopted as a radiosensitzer in pancreatic cancer. Single-arm clinical trials that initially explored gemcitabine as a radiosensitzer in locally advanced pancreatic cancer demonstrated the potential for significant toxicity without dramatic improvements in efficacy. Recent strategies for improving the efficacy of chemoradiation include improved chemoradiation sensitization through the concurrent incorporation of molecular targeted agents, and the use of new radiation technology such as intensity-modulated radiotherapy (IMRT) and stereotactic radiotherapy. Herein, we discuss the relative merits of strategies that seek to improve outcome through these novel means and present recent data from novel strategies that will provide the background for future trials.

Progress of Concurrent Chemoradiotherapy for Pancreatic Cancer

Progress of Concurrent Chemoradiotherapy for Pancreatic Cancer

On Statistical Reanalysis, the EORTC Trial Is a Positive Trial for Adjuvant Chemoradiation in Pancreatic Cancer

On Statistical Reanalysis, the EORTC Trial Is a Positive Trial for Adjuvant Chemoradiation in Pancreatic Cancer

The argument for pre-operative chemoradiation for localized, radiographically resectable pancreatic cancer

Although not universally accepted, chemoradiation is considered a standard adjuvant treatment for patients with resected pancreatic cancer. Theoretical advantages of reduced toxicity and increased efficacy with the use of pre-operative chemoradiation compared to post-operative adjuvant chemoradiation have recently been validated with the publication of a phase III trial in the adjuvant treatment of rectal cancer. Additional advantages of pre-operative chemoradiation that apply specifically to pancreatic cancer include increased access to therapy in patients treated before surgery, addressing the systemic disease recurrence risk without delay, and optimal patient selection for pancreaticoduodenectomy through exclusion of patients with rapidly progressive metastatic disease. Critical components of a pre-operative treatment strategy for pancreatic cancer include adherence to a strict definition of resectability, accurate radiographic staging capable of identifying patients with potentially resectable disease, and a safe and efficient means of obtaining a tissue diagnosis and relieving biliary obstruction. Herein, we discuss the rationale for the use of pre-operative chemoradiation in pancreatic cancer, the results of treatment, and future strategies to address the pattern of disease recurrence.