Radiotherapy For Pancreatic Cancer Research Articles

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.

725P - Pathological Proof and Survival for Patients with Biliary-Tract or Pancreatic Tumor

ABSTRACT As recommended by ESMO, a final pathological diagnosis (PD) has to be obtained before any chemotherapy, radiotherapy or other non-surgical oncological therapy for pancreatic or biliary tract cancer. PD is also required for inclusion in a clinical trial. In practice, it is sometimes difficult to obtain this pathological proof because of difficult access or poor performance status. Treatment decision is then collegial, based on a clinical, radiological and biological suspicion. We studied patient survival based on availability of PD from the cancer registry of Lille and its region (800 000 inh. - North France). We reviewed patients records over 15 years old diagnosed in 2005 or 2008 for a pancreatic or biliary tract cancer (neuroendocrine excluded). The point was made on 01/12/2011. Patients were divided into 5 groups: PD and surgery (PD-Surg), PD and radiotherapy or chemotherapy (PD-RC), PD and untreat (PD-Un), no PD and radiotherapy or chemotherapy (noPD-RC), no PD and untreat (noPD-Un). Observed survival analysis was obtained from Kaplan-Meier method and statistical significance from log-rank test. Males accounted for 45.8% of 260 patients. The average age was 71.8 years (+/- 12.1). 59.6% were diagnosed as pancreas cancer. PD was not obtained in 54.2% (60% in pancreas and 45.7% in biliary tract respectively). Seven patients were lost of follow-up. PD-Surg PD-RC noPD-RC PD-Un noPD-Un n (%) 45 (17.3) 44 (16.9%) 37 (14.2%) 30 (11.5%) 104 (40%) Median survival (days) 709 198 203 76 60 p > 0.2 p > 0.9 2 years survival 46.7% 6.8% 2.9% 0% 2.1% 27 patients were alive beyond 24 month: 21 in PD-Surg group, 3 in PD-RC, 1 in noPD-RC and 2 in noPD-Un. In conclusion, the absence of PD is common in clinical practice, without apparent impact on survival. 14.2% of patient were treated without PD. These patients are not take account in current recommendations. Centralized monitoring of this condition would be required. In the absence of treatment plan, PD is not essential. Disclosure All authors have declared no conflicts of interest.

A case of hemorrhagic gastroduodenitis after proton beam radiation for pancreatic cancer with multiple hemorrhagic risk factors: successful treatment with argon plasma coagulation.

Radiation-induced gastroduodenitis is a well-known but rare disorder causing uncontrollable hemorrhage and has not been reported as a complication of proton beam therapy in radiation treatment. Argon plasma coagulation (APC) has been shown to be effective and safe in the management of radiation-induced hemorrhagic gastroduodenitis. We describe a case of hemorrhagic gastroduodenitis after proton beam radiation therapy for pancreatic cancer with multiple hemorrhagic risk factors, which was treated successfully with APC. A 62-year-old man was diagnosed as having early pancreatic cancer that was incidentally detected on computed tomography when screening for hepatocellular carcinoma. He opted to receive radical proton beam radiation for pancreatic cancer but not surgery because he had multiple risk factors such as liver cirrhosis due to hepatitis C virus and chronic renal failure that required hemodialysis. Three months later, however, he developed hemorrhagic gastroduodenitis induced by proton beam radiation although the cancer had been eradicated. Initially, he required frequent blood transfusions, but his disease condition improved dramatically after several endoscopic treatments using APC. The patient has been free of relapse after pancreatic cancer for >2years.

Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer.

BackgroundRadiotherapy (RT) is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV) in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI) in the preoperative and definitive treatment of pancreatic cancer.MethodsThe anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries.ResultsWe proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided.ConclusionsThe proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.

Study of inter-fractional variations and adaptive radiotherapy in pancreatic cancer

Objective To quantitatively characterize the inter-fractional anatomy variations and advantages of dosimetry for the adaptive radiotherapy in pancreatic cancer.Methods A total of 226 daily CT images acquired from 10 patients with pancreatic cancer treated with image-guided radiotherapy were analyzed retrospectively.Targets and organs at risk (OARs) were delineated by the atlas-based automatic segmentation and modified by the skilled physician.Various parameters,including the center of mass (COM) distance,the maximal overlap ratio (MOR) and the Dice coefficient (DC),were used to quantify the inter-fractional organ displacement and deformation.The adaptive radiation therapy (ART) was applied to handle the daily GT images.The dose distributions parameters from the ART plan were compared with those from the repositioning plan.Results The inter-fractional anatomy variations of pancreas head were obvious in the pancreatic cancer irradiation.The mean COM distance,MOR and DC of pancreas head after the bony or soft tissue alignment and registration was ( 7.8 ± 1.3 ) mm,( 87.2 ± 8.4 )％ and ( 77.2 ±7.9)％ respectively.Compared with the repositioning plan,the ART plan had better target coverage and OARs sparing.For example,the mean V100 of PTV was improved from (93.32 ± 2.89) ％ for repositioning plan to ( 96.03 ± 1.42) ％ for ART plan with t =2.79,P =0.008 and the mean V50.4 for duodenum was reduced from (43.4 ± 12.71 )％ for the repositioning plan to (15.6 ± 6.25)％ for the ART plan with t =3.52,P=0.000.Conclusions The ART can effectively account for the obvious inter-fractional anatomy variations in pancreatic cancer irradiation and be used to escalate the radiotherapy dose for the pancreatic cancer,which will lead to a promising higher local control rate. Key words: Pancreatic neoplasms/radiotherapy; Radiotherapy,image-guided; Radiotherapy,adaptive; Inter-fractional position variations

Role of radiation therapy in the management of pancreatic cancer

Local failure remains a major issue for patients with both resectable and locally advanced pancreatic cancer. The role of radiation therapy in the management of this disease is less clear and represents an area of some controversy. The objective of this review is to present the rationale for radiation therapy in pancreatic cancer, as well as to discuss the potential limitations and caveats of the currently available studies.

Intraoperative Radiotherapy for Pancreatic Cancer: 30-Year Experience in a Single Institution in Japan

To analyze retrospectively the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (± EBRT) for localized pancreatic cancer in the past three decades and to analyze prognostic factors by multivariate analysis. Records for 322 patients with pancreatic cancer treated by IORT ± EBRT in Tohoku University Hospital between 1980 and 2009 were reviewed. One hundred ninety-two patients who had no distant organ metastases or dissemination at the time of laparotomy were enrolled in the present study. Eighty-three patients underwent gross total resection (R0: 48 patients, R1: 35 patients), and 109 patients underwent only biopsy or palliative resection. Fifty-five patients underwent adjuvant EBRT, and 124 underwent adjuvant chemotherapy. The median doses of IORT and EBRT were 25 and 40 Gy, respectively. The median follow-up period was 37.5 months. At the time of the analysis, 166 patients had disease recurrence, and 35 patients had local failure. The 2-year local control (LC) and overall survival (OS) rates were 71.0% and 16.9%, respectively. Comparison of the results for each decade showed that OS was significantly improved decade by decade (2-year: 25.0% vs. 18.8% vs. 4.2%, p < 0.001). Multivariate analysis showed that degree of resection (R0-1 vs. R2, hazard ratio = 1.97, p = 0.001) and adjuvant chemotherapy (yes vs. no, hazard ratio = 1.54, p = 0.028) had significant impacts on OS. Late gastrointestinal morbidity of Common Terminology Criteria for Adverse Events version 3.0 grade 4 or 5 was observed in four patients. Excellent local control for pancreatic cancer with few cases of severe late toxicity was achieved by using IORT. OS of patients with pancreatic cancer treated by IORT ± EBRT improved significantly decade by decade. Multivariate analysis showed that degree of resection and adjuvant chemotherapy had significant impacts on OS.

Characterization and Management of Interfractional Anatomic Changes for Pancreatic Cancer Radiotherapy

To quantitatively characterize interfractional anatomic variations in pancreatic cancer radiotherapy (RT) and to study dosimetric advantages for using an online adaptive replanning scheme to account for these variations. Targets and organs at risk (OAR) were delineated by autosegmentation based on daily computed tomography (CT) images acquired using a respiration-gated in-room CT during daily image-guided RT (IGRT) for 10 pancreatic cancer patients. Various parameters, including the maximum overlap ratio (MOR) between the volumes based on planning and daily CTs for a structure, while the overlapping volumes were maximized, were used to quantify the interfractional organ deformation with the intrafractional variations largely excluded. An online adaptive RT (ART) was applied to these daily CTs. To evaluate the dosimetric benefits of ART, the dose distributions from the online ART were compared to those from the repositioning in the current standard IGRT practice. The interfractional anatomic variations, particularly the organ deformation, are significant during pancreas irradiation. For the patients studied, the average MORs of all daily CTs were 80.2%, 61.7%, and 72.2% for pancreatic head, duodenum, and stomach, respectively. The online ART leads to improved dosimetric plan with better target coverage and/or OAR sparing than IGRT repositioning. For the patients studied, the mean V(50.4 Gy) (volume covered by 50.4 Gy) for the duodenum was reduced from 43.4% for IGRT to 15.6% for the online ART scheme. The online adaptive RT scheme can effectively account for the significant interfractional anatomic variations observed in pancreas irradiation. The dosimetric advantages with the online ART may enable safe dose escalation in radiation therapy for pancreatic cancer.

An autopsy study to clarify characteristics of local recurrence after extended pancreatectomy with intraoperative radiation therapy in patients with pancreatic cancer

Local relapses frequently occur even after curative resection of pancreatic cancer. To control local recurrence, we adopted extended radical resection combined with intraoperative radiation therapy. A retrospective review was conducted on 41 patients who underwent extended radical pancreatectomy combined with intraoperative radiation therapy for pancreatic cancer. Fourteen patients underwent autopsies. We took en bloc specimens of the abdominal aorta with surrounding connective tissue to evaluate histological characteristics of local status at autopsies. Autopsies disclosed microscopic local recurrence in five (36%) of the 14 patients, although no evidence of local relapse was observed in either follow-up images or macroscopic findings at autopsy. Of the three patients with R1 resection, two had no local recurrence microscopically at autopsy. Histological features of local recurrence in autopsy samples showed small numbers of cancer cells surrounded by thick connective tissue without mass formation. The autopsy study revealed that a characteristic of local recurrence after this treatment was tiny cancer cells scattered in dense connective tissue; these cells were undetected by follow-up imaging.

Dosimetric investigation of breath-hold intensity-modulated radiotherapy for pancreatic cancer

To experimentally investigate the effects of variations in respiratory motion during breath-holding (BH) at end-exhalation (EE) on intensity-modulated radiotherapy (BH-IMRT) dose distribution using a motor-driven base, films, and an ionization chamber. Measurements were performed on a linear accelerator, which has a 120-leaf independently moving multileaf collimator with 5-mm leaf width at the isocenter for the 20-cm central field. Polystyrene phantoms with dimensions of 40 × 40 × 10 cm were set on a motor-driven base. All gantry angles of seven IMRT plans (a total of 35 fields) were changed to zero, and doses were then delivered to a film placed at a depth of 4 cm and an ionization chamber at a depth of 5 cm in the phantom with a dose rate of 600 MU/min under the following conditions: pulsation from the abdominal aorta and baseline drift with speeds of 0.2 mm/s (BD(0.2mm/s)) and 0.4 mm/s (BD(0.4mm/s)). As a reference for comparison, doses were also delivered to the chamber and film under stationary conditions. In chamber measurements, means ± standard deviations of the dose deviations between stationary and moving conditions were -0.52% ± 1.03% (range: -3.41-1.05%), -0.07% ± 1.21% (range: -1.88-4.31%), and 0.03% ± 1.70% (range: -2.70-6.41%) for pulsation, BD(0.2mm/s), and BD(0.4mm/s), respectively. The γ passing rate ranged from 99.5% to 100.0%, even with the criterion of 2%/1 mm for pulsation pattern. In the case of BD(0.4mm/s), the γ passing rate for four of 35 fields (11.4%) did not reach 90% with a criterion of 3%/3 mm. The differences in γ passing rate between BD(0.2mm/s) and BD(0.4mm/s) were statistically significant for each criterion. Taking γ passing rates of > 90% as acceptable with a criterion of 3%/3 mm, large differences were observed in the γ passing rate between the baseline drift of ≤5 mm and that of >5 mm (minimum γ passing rate: 92.0% vs 82.7%; p < 0.01). This study suggested that the baseline drift of >5 mm should be avoided in the BH-IMRT.

The importance of local control in pancreatic cancer

The ECOG E4201 study adds another piece of information to a growing body of evidence pointing strongly to the importance of local control and the role of radiotherapy in unresectable pancreatic cancer. Based on this evidence, we believe radiotherapy should be used routinely in this setting.

Dosimetric and motion analysis of margin-intensive therapy by stereotactic ablative radiotherapy for resectable pancreatic cancer

BackgroundThe retroperitoneal margin is a common site of positive surgical margins in patients with resectable pancreatic cancer. Preoperative margin-intensive therapy (MIT) involves delivery of a single high dose of ablative radiotherapy (30 Gy) focused on this surgically inaccessible margin, utilizing stereotactic techniques in an effort to reduce local failure following surgery. In this study, we investigated the motion of regional organs at risk (OAR) utilizing 4DCT, evaluated the dosimetric effects of abdominal compression (AC) to reduce regional motion, and compared various planning techniques to optimize MIT.Methods10 patients were evaluated with 4DCT scans. All 10 patients had scans using AC and seven of the 10 patients had scans both with and without AC. The peak respiratory abdominal organ and major vessel centroid excursion was measured. A "sub-GTV" region was defined by a radiation oncologist and surgical oncologist encompassing the retroperitoneal margin typically lateral and posterior to the superior mesenteric artery (SMA), and a 3-5 mm margin was added to constitute the PTV. Identical 3D non-coplanar SABR (3DSABR) plans were designed for the average compression and non-compression scans. Compression scans were planned with 3DSABR, coplanar IMRT (IMRT), and Cyberknife (CK) planning techniques. Dose volume analysis was undertaken for various endpoints, comparing OAR doses with and without AC and for different planning methods.ResultsThe mean PTV size was 20.2 cm3. Regional vessel motion of the SMA, celiac trunk, and renal vessels was small (< 5 mm) and not significantly impacted by AC. Mean pancreatic motion was > 5 mm, so AC has been used in all patients enrolled thus far. AC did not significantly increase OAR dose including the stomach and traverse colon. There were several statistically significant differences in the doses to OARs as a function of the type of planning modality used.ConclusionsAC does not significantly reduce the limited motion of structures in close proximity to the MIT target and does not significantly increase the dose to OARs that can be displaced by the compression plate. The treatment planning techniques evaluated in this study have different advantages with no clearly superior method in our analysis. Dose to adjacent vessels may be reduced with 3DSABR or IMRT techniques, while conformality is increased with IMRT or CK.

Dosimetric Comparison of RapidArc versus CyberKnife for Stereotactic Body Radiation Therapy for Pancreatic Cancer

Dosimetric Comparison of RapidArc versus CyberKnife for Stereotactic Body Radiation Therapy for Pancreatic Cancer

Daily Dose Variations in Normal Organs during Radiation Therapy for Pancreatic Cancer

Daily Dose Variations in Normal Organs during Radiation Therapy for Pancreatic Cancer

Role of α5β1 Integrin Up-regulation in Radiation-Induced Invasion by Human Pancreatic Cancer Cells

Radiotherapy is used in the management of pancreatic cancer because of its high propensity for locoregional relapse: one third of patients succumb to localized disease. Thus, strategies to improve the efficacy of radiotherapy in pancreatic cancer are important to pursue. We used naturally serum-free, selectively permeable basement membranes and confocal microscopy of fluorescent antibody-stained human Panc-1, MiaPaCa-2, and BxPC-3 pancreatic cancer cell lines to investigate the effects of ionizing radiation on α5β1 integrin fibronectin receptor expression and on α5β1-mediated invasion. We report that radiation rapidly induces pancreatic cancer cell invasion, and that radiation-induced invasion is caused by up-regulation of α5β1 integrin fibronectin receptors by transcriptional and/or postendocytic recycling mechanisms. We also report that radiation causes α5β1 up-regulation in Panc-1, MiaPaCa-2, and BxPC-3 tumor xenografts and that upregulated α5β1 colocalizes with upregulated early or late endosomes in Panc-1 or BxPC-3 tumors, respectively, although it may colocalize significantly with both endosome types in MiaPaCa-2 tumors. Our results suggest that systemic inhibition of α5β1-mediated invasion might be an effective way to reduce radiation-induced pancreatic cancer cell invasion, thereby improving the efficacy of radiotherapy.

Potential Relative Biological Effectiveness of High-LET versus Photon Radiotherapy in Pancreatic Cancer

Potential Relative Biological Effectiveness of High-LET versus Photon Radiotherapy in Pancreatic Cancer

Impact of Curcumin, Raspberry Extract, and Neem Leaf Extract on Rel Protein-Regulated Cell Death/Radiosensitization in Pancreatic Cancer Cells

Nuclear factor κB (NF-κB) plays an intrinsic role in promoting growth, angiogenesis, and metastasis in pancreatic cancer (PC) and serves as a mechanism underlying therapeutic resistance. Accordingly, we investigated the efficacy of bioactive phytochemicals in inhibiting radiotherapy (RT)-induced NF-κB activity, signaling, and NF-κB-dependent regulation of cell death. Panc-1, BxPC-3, and MIA PaCa-2 cells exposed to 10 Gy (single high dose [SDR]) or 2 Gy/d for 5 days (fractionated radiation [FIR]) with or without curcumin (CUR), neem leaf extract (NLE), or black raspberry extract (RSE) were analyzed. Radiotherapy profoundly induced NF-κB-DNA-binding activity with relatively robust activation after FIR. Curcumin, NLE, and RSE significantly inhibited both constitutive and RT-induced NF-κB. Furthermore, quantitative polymerase chain reaction profiling of 88 NF-κB pathway molecules demonstrated that CUR, NLE, and RSE comprehensively, yet differentially inhibited FIR/SDR-induced genes. Functionally, CUR, NLE, and RSE markedly conferred RT-inhibited cell viability/survival, robustly activated caspase-3/7 activity, and subsequent cell death. More importantly, NF-κB overexpression and silencing studies demonstrate that these compounds potentiate RT-induced cell death by targeting RT-induced NF-κB. These data strongly imply that CUR, NLE, and RSE may serve as effective "deliverables" to potentiate RT in PC cure and further throw light that these phytochemicals-induced cell killing may involve selective regulation of RT-induced NF-κB.

Safety and Efficacy of Intraoperative Radiotherapy with Image-guided Enzyme Targeting Radiosensitization (KORTUC-IORT) for Advanced Pancreatic Cancer

Based on our experimental results that demonstrated hydrogen peroxide to be a strong radiosensitizer in a highly radioresistant osteosarcoma cell line, we developed a new radiosensitizer injection technique in which hydrogen peroxide and sodium hyaluronate are injected immediately prior to intraoperative radiotherapy (IORT) for advanced pancreatic cancer, named KORTUC-IORT (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas + IORT). The purpose of this study was to evaluate the safety and efficacy of KORTUC-IORT in pancreatic cancer patients.

Abstract PR7: An oncolytic vaccinia virus encoding the human sodium iodide symporter facilitates long-term deep-tissue image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer

Abstract To assess therapeutic response and potential toxicity of oncolytic virotherapy, a noninvasive, deep-tissue imaging modality is needed. This study aimed to assess the feasibility, parameters, determining factors of serial imaging and long-term monitoring of systemic virotherapy together with radiotherapeutic response of pancreatic cancer xenografts treated with a vaccinia virus encoding the human sodium iodide symporter (hNIS), GLV-1 hi 53. hNIS, an intrinsic plasma membrane protein, mediates the active transport, and trapping of iodine mainly in the thyroid and some extrathyroidal tissues such as the stomach. Pancreatic cancer xenografts (PANC-1) in nude mice were treated systemically or intratumorally with GLV-1h153 and serially imaged using 124I-PET at 1, 2, 3, and 5 weeks post virus injection and 4 hours post radiotracer injection. At week 1 and 2 post virus injection, mice were also imaged at 1, 8, 24, 48, and 72 hours post radiotracer injection in order to obtain time-activity curves for dosimetry calculations of radioiodine uptake. The PET signal intensity was compared with tumor therapeutic response and optical imaging. Tumors were histologically analyzed for morphology and presence of virus particles. Autoradiography was performed utilizing technecium-pertechtenate and gamma-scintigraphy to assess determining factors for radiouptake in tumors. Combination therapy with GLV-1h153 and systemic radioiodine was also explored. GLV-1h153 successfully facilitated serial long-term imaging of virotherapy with PET signal intensity correlating to antitumor response. Colonization of tumors with GLV-1h153 mediated radioiodine uptake at potentially therapeutic doses. Successful radiouptake required presence of virus, adequate blood flow, and viable tissue, while loss of signal intensity was linked to tumor death and necrosis. Finally, combining systemically administered GLV-1h153 and 131I led to enhanced tumor kill when compared to virus or 131I treatment alone (P&amp;lt;0.001). GLV-1h153 is thus a promising oncolytic agent for the treatment, long-term imaging, and monitoring of the therapeutic response of cancer. GLV-1h153 provided insights into tumor biological activity and facilitated enhanced tumor kill when combined with systemic targeted radiotherapy. Further investigation into parameters and potential synergistic effects of combination therapy is warranted. This abstract is also presented as Poster C7. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR7.

SU‐E‐T‐44: Model Prediction of Radiation Induced Duodenal Toxicity for a Dose Escalation in Radiation Therapy of Pancreatic Cancer Using Published Reports

Purpose: Safe dose escalation for RT of pancreatic cancer is limited by the surrounding organs at risk, particularly the duodenum, which is adjacent to the pancreas. The purpose of this work is to estimate the radiation induced duodenal toxicity using dose‐volume response data extracted from the literature for a proposed dose escalation of 72 Gy in 28 fractions via IMRT simultaneously integrated boost.Methods: Two patients treated for pancreatic cancer at our institution were randomly selected to retrospectively alter their treatment plan to simulate the testing dose escalation of 50.4 and 72 Gy in 28 fractions to the pancreatic head and the GTV, respectively. The report by Murphy et al. on SBRT of Grade 2 or higher duodenal toxicity was used to estimate NTCP using testing protocol DVHs. The Modified LQ model by Guerrero and Li was used to calculate the iso‐effective dose in the testing protocol producing the same effect as doses in the SBRT regime. Additional analysis of NTCP variation considered alpha‐beta ratios of 3 to 5 Gy for small bowel/duodenum late effects. Results: The testing protocol iso‐effective dose, D, associated with 25 Gy in a single fraction had a median value of 61.2 Gy and ranged from 56.3 to 68.0 Gy. The first patient had a high estimated risk of toxicity (0.45) due to the duodenal volume being greater than 0.21 cubic centimeters. A lower risk of toxicity was estimated for the second patient due to the duodenal volume being less than 0.21 cubic centimeters. Conclusion: Estimates of duodenal toxicity can be made despite the limited number of toxicity data available. A conservative dose‐volume constraint would limit 0.21 cubic centimeters of the duodenal volume to no more than 56 Gy. The estimates of duodenal toxicity exhibit a dependence on the value of alpha‐beta ratio of the duodenum.