Locally advanced unresectable pancreatic adenocarcinoma is characterized by poor survival despite chemotherapy and conventional radiation therapy (RT). Recent advances in real-time image-guided stereotactic radiosurgery (SRS) have made it possible to treat these cancers in two to four fractions followed by systemic chemotherapy.
The aims of this study includes the following: (1) obtain local control of the disease; (2) improve the survival of these unresectable patients; (3) evaluate the toxicity of SRS; and (4) report results of the largest series from a single center.
Pancreatic SRS involves delivery of high doses of accurately targeted radiation given non-invasively in two to four fractions. We treated 85 consecutive patients with locally advanced and recurrent pancreatic adenocarcinoma from February 2004 to November 2009. Age range: 36-88 years, median 66 years; sex: 50 males, 35 females; race: 79 Caucasian, five African American, one Asian; histology: 80 adenocarcinoma, three islet cell, two other. Pre-SRS staging: T(3-4) 85; N(+) 16, N(x) 57, N(0) 12; M(0) 64, M(1) 21. All patients were unresectable at the time of SRS. Seventy-one had no prior surgical resection, and 14 had local recurrence after prior surgical resection. Twenty-nine patients had progression of disease after prior conventional RT. Location of the tumor: head, 57; body and tail, 28. Pre-SRS chemotherapy was given in 48 patients. All patients received gemcitabine-based chemotherapy regimen after SRS. Median tumor volume was 60 cm(3). PET/CT scans done in 55 patients were positive in 52 and negative in three patients. Average maximum standard uptake value was 6.9. Pain score on a scale of 1-10 was: 0-3 in 54, 4-7 in 18, and 8-10 in 13 patients. SRS doses ranged from 15 to 30 Gy with a mean dose of 25.5 Gy delivered in 3 days divided in equal fractions. Mean conformality index was 1.6, and mean isodose line was 80%.
Tumor control: complete, partial, and stable disease were observed in 78 patients for the duration of 3-36 months with median of 8 months. Pain relief was noted in majority of patients lasting for 18-24 weeks. Most of the patients died of distant disease progression while their primary tumor was controlled. Overall median survival from diagnosis was 18.6 months and from SRS it was 8.65 months. For the group of 35 patients with adenocarcinoma without prior surgical resection or RT and no distant metastases, the average and 1-year survival from diagnosis was 15 months and 50%, respectively, and from SRS it was 11.15 months and 30.5%, respectively.
A total of 19 (22.37%) patients developed grades III/IV GI toxicity including duodenitis, 12 (14.1%); gastritis, 11 (12.9%); diarrhea, three (3.5%); and renal failure was noted in one (1.2%). Three patient had both gastritis and duodenitis. Toxicity was significantly more prevalent in the first 40 patients compared with the last 45 patients (32.5 vs 13.9%).
SRS for unresectable pancreatic carcinoma can be delivered in three fractions with minimal morbidity and a local tumor control rate of 91.7%. The survival is comparable or better than the reported results for advanced pancreatic cancer, specifically for the group of previously untreated patients with unresectable tumors. Development of distant metastases remains a significant factor.
"If we consider PFS and OS, data were comparable to those obtained with the conventional fractionation. In the study of Mahadevan et al. and Didolkar et al, median OS was 20 and 18.6 months respectively, even though these data were calculated from the diagnosis and not from the SBRT treatment, as widely shown in other experiences [14,15]. "
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy and safety of stereotactic body radiotherapy (SBRT) in patients with either unresectable locally advanced pancreatic adenocarcinoma or by locally recurrent disease after surgery.
Between January 2010 and October 2011, 30 patients with unresectable or recurrent pancreatic adenocarcinoma underwent exclusive SBRT. Twenty-one patients (70%) presented with unresectable locally advanced disease and 9 patients (30%) showed local recurrence after surgery. No patients had metastatic disease. Gemcitabine-based chemotherapy was administered to all patients before SBRT. Prescription dose was 45Gy in 6 daily fractions of 7.5Gy. SBRT was delivered using the volumetric modulated arc therapy (VMAT) by RapidArc. Primary end-point of this study was freedom from local progression (FFLP), secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity.
Median Clinical Target Volume (CTV) was 25.6 cm3 (3.2-78.8 cm3) and median Planning Target Volume (PTV) was 70.9 cm3 (20.4- 205.2 cm3). The prescription dose was delivered in 25 patients (83%), in 5 patients (17%) it was reduced to 36Gy in 6 fractions not to exceed the dose constraints of organs at risk (OARs). Median follow-up was 11 months (2--28 months). FFLP was 91% at 6 months, 85% at median follow-up and 77% at 1 and 2 years. For the group with prescription dose of 45Gy, FFLP was 96% at 1 and 2 years. The median PFS was 8 months. The OS was 47% at 1 year and median OS was 11 months. At the end of the follow-up, 9 patients (32%) were alive and 4 (14%) were free from progression. No patients experienced G >= 3 acute toxicity.
Our preliminary results show that SBRT can obtain a satisfactory local control rate for unresectable locally advanced and recurrent pancreatic adenocarcinoma. This fractionation schedule is feasible, and no G >= 3 toxicity was observed. SBRT is an effective emerging technique in the multi-modality treatment of locally advanced pancreatic tumors.
"SBRT techniques rely on image-guided radiotherapy (IGRT) to allow radiation dose escalation to tumors while simultaneously minimizing the dose to surrounding normal tissue through the use of radiographic imaging to verify target delineation and treatment delivery. Prospective phase I and phase II studies3839 and two retrospective studies4041 show that SBRT is a safe and effective approach for treating patients with PC. In addition, hypofractionated SBRT can be effectively delivered with acceptable side effects and minimal interference to gemcitabine chemotherapy.42 "
[Show abstract][Hide abstract] ABSTRACT: Endoscopic ultrasound (EUS) can help diagnose diseases with high accuracy because it overcomes the limitations of gastrointestinal gas and abdominal fat. The emergence of curved linear-array echoendoscopy has significantly promoted the applications of the technique to new levels. The advancement has appeared from EUS imaging to EUS-guided fine needle aspiration, drainage and injection. Computed tomography and magnetic resonance imaging present certain limitations for diagnosing pancreatic tumors due to the specificity of the location of such growths. In addition, traditional chemotherapy does not show ideal results because pancreatic cancer (PC) exhibits hypovascular characteristics. Interventional EUS can overcome these limitations and has potential to become the mainstream method of PC local treatment in the future. This paper reviews the use of interventional EUS in the treatment of PC based on previous studies.
[Show abstract][Hide abstract] ABSTRACT: The dismal prognosis of pancreatic cancer reflects into the increased recurrence rate, even after R0 pancreaticoduodenectomy. Although, conventional radiation-, chemo- or surgical therapy in much selected cases, seem to work out favorably long term, less invasive and non-toxic methods with more immediate results are always preferred, concerning the already aggravated status of this group of patients. We present hereby a comprehensive review of the literature concerning the treatment of recurrent pancreatic cancer based on the case of a patient who 20 months after a pancreaticoduodenectomy developed portal hypertension and symptomatic first degree esophageal, gastric and mesenteric varices, caused by the nearly complete splenic vein obstruction at the portal vein confluence. The varices were revascularized by a percutaneous transhepatic placement of an endovascular stent into the splenic vein, along with a sequent stereotactic body radiation therapy for the local tumor control. Thanks to the accuracy and safety of the present combined treatment, the patient one year later presents control of the disease and its complications. Our paper is the first in the international literature that tries to review all the treatment modalities available (surgical, adjuvant, neoadjuvant and palliative therapy) and their efficacy, concerning the locally recurrent pancreatic cancer; furthermore, we tried to analyze the application of the above mentioned combined therapeutic approach in similar cases, elucidating simultaneously all the questions that arise. The limited existing data in the international literature and the lack of randomized controlled trials make this effort difficult, but the physician should be aware after all of all the available and innovative treatment modalities, before he chooses one. Finally, we would like to emphasize the fact that not only the local control but also the management of the complications are important for a prolonged median survival and a better quality of life after all.
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