Future Chemoradiation Strategies in Pancreatic Cancer

Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Seminars in Oncology (Impact Factor: 3.9). 09/2007; 34(4):335-46. DOI: 10.1053/j.seminoncol.2007.05.001
Source: PubMed


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.

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    • "All possible AEs will be assessed by the RTOG Scale. These AEs rarely occur in conventional radiotherapy using considerably higher doses (neoadjuvant 5 × 5 Gy for rectal or gastric cancer, 54 Gy in pancreatic cancer) [17,18]. "
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    ABSTRACT: Insufficient migration and activation of tumor specific effector T cells in the tumor is one of the main reasons for inadequate host anti-tumor immune response. External radiation seems to induce inflammation and activate the immune response. This phase I/II clinical trial aims to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with colorectal liver metastases. This is an investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II trial. Patients undergoing elective hepatic resection due to colorectal cancer liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be applied by external beam radiotherapy using a 6 MV linear accelerator (Linac) with intensity modulated radiotherapy (IMRT) technique two days prior to surgical resection. All patients admitted to the Department of General-, Visceral-, and Transplantion Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility into this trial, and written informed consent is obtained before inclusion. The primary objective is to assess the effect of active local external beam radiation dose on, tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include radiogenic treatment toxicity, postoperative morbidity and mortality, local tumor control and recurrence patterns, survival and quality of life. Furthermore, frequencies of systemic tumor reactive T cells in blood and bone marrow will be correlated with clinical outcome. This is a randomized controlled patient blinded trial to assess the safety and efficiency of low dose radiotherapy on metastasis infiltrating T cells and thus potentially enhance the antitumor immune response. NCT01191632.
    Full-text · Article · Sep 2011 · BMC Cancer
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    • "The response to systemic chemotherapy is poor, with an approximately 20% response rate. The conventional radiation dose to the tumor volume is not large enough to cure patients because pancreatic tumors move markedly as patients breathe, and are surrounded by the duodenum, which is the dose-limiting organ [16]. Compared with chemotherapy alone or radiotherapy alone, chemoradiotherapy prolongs median survival somewhat, to approximately 9-12 months, in those with locally advanced unresectable disease [5]. "
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    ABSTRACT: Helical tomotherapy, an advanced intensity-modulated radiation therapy with integrated CT imaging, permits highly conformal irradiation with sparing of normal tissue. Capecitabine, a pro-drug of 5-FU that induces thymidine phosphorylase can achieve higher levels of intracellular 5-FU when administered concurrently with radiation. We evaluated the feasibility as well as the clinical outcome of concurrent administration of capecitabine with tomotherapy in patients with advanced pancreatic cancer. Nineteen patients with advanced pancreatic cancer including primarily unresectable disease and recurrence after curative surgery were included in the study. Two planning target volumes (PTV) were entered: PTV1 is gross tumor volume; and PTV2, the volume of the draining lymph nodes. The total doses to target 1 and target 2 were 55 and 50 Gy, respectively. Capecitabine at 1600 mg/m2/day was administered on each day of irradiation. Twenty six measurable lesions were evaluated. Overall in-field response rate was 42.3%; partial responses were achieved in 53.3% of the pancreatic masses, 28.6% of distant metastatic lesions and 25.0% of regional lymph nodes. The median duration of follow-up after tomotherapy was 6.5 months. None of the lesions showed in-field progression. Treatment was well tolerated with only minor toxicities such as grade 1 nausea (one patient), grade 1 hand-foot syndrome (one patient) and grade 1/2 fatigue (three patients). Helical tomotherapy with concurrent capecitabine is a feasible option without significant toxicities in patients with advanced pancreatic cancer. We achieved excellent conformal distribution of radiation doses and minimal treatment-related toxicities with promising target volume responses.
    Full-text · Article · Jun 2010 · Radiation Oncology

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