Jeff Kim

Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas

The authors report on the local control and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma.

SINGLE-FRACTION STEREOTACTIC BODY RADIATION THERAPY AND SEQUENTIAL GEMCITABINE FOR THE TREATMENT OF LOCALLY ADVANCED PANCREATIC CANCER

PURPOSE This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. RESULTS All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year. CONCLUSION Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

A dosimetric model of duodenal toxicity after stereotactic body radiotherapy for pancreatic cancer

INTRODUCTION Dose escalation for pancreas cancer is limited by the tolerance of adjacent normal tissues, especially with stereotactic body radiotherapy (SBRT). The duodenum is generally considered to be the organ at greatest risk. This study reports on the dosimetric determinants of duodenal toxicity with single-fraction SBRT. METHODS AND MATERIALS Seventy-three patients with locally advanced unresectable pancreatic adenocarcinoma received 25 Gy in a single fraction. Dose-volume histogram (DVH) endpoints evaluated include V(5) (volume of duodenum that received 5 Gy), V(10), V(15), V(20), V(25), and D(max) (maximum dose to 1 cm(3)). Normal tissue complication probability (NTCP) was evaluated with a Lyman model. Univariate and multivariate analyses were conducted with Kaplan-Meier and Cox regression models. RESULTS The median time to Grade 2-4 duodenal toxicity was 6.3 months (range, 1.6-11.8 months). The 6- and 12-month actuarial rates of toxicity were 11% and 29%, respectively. V(10)-V(25) and D(max) all correlated significantly with duodenal toxicity (p<0.05). In particular, V(15)≥9.1 cm(3) and V(15)<9.1 cm(3) yielded duodenal toxicity rates of 52% and 11%, respectively (p=0.002); V(20)≥3.3 cm(3) and V(20)<3.3 cm(3) gave toxicity rates of 52% and 11%, respectively (p=0.002); and D(max)≥23 Gy and D(max)<23 Gy gave toxicity rates of 49% and 12%, respectively (p=0.004). Lyman NTCP model optimization generated the coefficients m=0.23, n=0.12, and TD(50)=24.6 Gy. Only the Lyman NTCP model remained significant in multivariate analysis (p=0.001). CONCLUSIONS Multiple DVH endpoints and a Lyman NTCP model are strongly predictive of duodenal toxicity after SBRT for pancreatic cancer. These dose constraints will be valuable in future abdominal SBRT studies.

EUS-guided gold fiducial insertion for image-guided radiation therapy of pancreatic cancer: 50 successful cases without fluoroscopy.

BACKGROUND Image-guided radiation therapy (IGRT) accurately delivers a high dose of potentially tumoricidal radiation to its target while sparing adjacent healthy tissue. Application of IGRT to unresectable pancreatic cancer requires the use of fiducials to track the precise location of the tumor. Fiducial markers have been successfully placed endoscopically. OBJECTIVE To determine the feasibility of EUS-guided gold fiducial placement for IGRT. DESIGN Prospective case series. SETTING Tertiary medical center. PATIENTS Consecutively referred patients with locally advanced unresectable pancreatic adenocarcinoma for EUS-guided insertion of gold fiducials from December 2006 to February 2009. INTERVENTIONS Under only EUS guidance, fiducial markers were deployed into or near the tumor by using a 19-gauge needle. In most cases, a sterile water injection technique was used to insert the fiducials. Fluoroscopy was not used in any case. MAIN OUTCOME MEASUREMENTS Successful placement of an adequate number of fiducials to proceed with IGRT as determined by CT. RESULTS Fifty-seven consecutive patients were included. Fifty cases (88%) were successful. Of the cases in which fiducial placement was attempted and follow-up was adequate, 94% (50 of 53) of cases were successful. LIMITATIONS Single-center, nonrandomized study. CONCLUSIONS EUS-guided fine-needle insertion was safe and effective in delivering gold fiducial markers for image-guided radiation therapy. Fluoroscopy was not required for successful fiducial placement.

Detection of solitary humeral metastasis from pancreatic adenocarcinoma with F-18 FDG PET/CT.

In this case report, we present the F-18 FDG PET-CT images of an isolated humeral metastasis in a 52-year-old man with locally advanced pancreatic adenocarcinoma. The intense focal uptake in the right proximal humerus was incidentally detected during a routine 6-month follow-up scan after treatment to the primary with gemcitabine chemotherapy and stereotactic radiotherapy. A subsequent MRI scan confirmed a lytic lesion that correlated with the PET-CT abnormality and a CT-guided biopsy demonstrated metastatic adenocarcinoma consistent with a pancreatic primary tumor. FDG PET has been reported to be effective in detecting previous occult sites of disease. Though the incidence of isolated bone metastases from primary gastointestinal malignancies is rare and detection of any type of metastases for pancreatic cancer usually is associated with an extremely poor prognosis, aggressive treatment of symptomatic bone metastases is an important part of the overall management to maximize the quality of life.