A Dosimetric Model of Duodenal Toxicity After Stereotactic Body Radiotherapy for Pancreatic Cancer

BACKGROUND: This study was undertaken to determine outcomes of stereotactic body radiotherapy for colorectal liver metastases in a pooled patient cohort. METHODS: Patients with colorectal liver metastases from 3 institutions were included if they had 1 to 4 lesions, received 1 to 6 fractions of stereotactic body radiotherapy, and had radiologic imaging 3 months post-treatment. Sixty-five patients with 102 lesions treated from August 2003 to May 2009 were retrospectively analyzed. A tumor control probability (TCP) model was used to estimate the 3-fraction dose required for >90% local control after converting the schedule into biologically equivalent dose (BED), single-fraction equivalent dose, or linear quadratic model-based single-fraction dose. RESULTS: Forty-seven (72%) patients had 1 chemotherapy regimen before stereotactic body radiotherapy, and 27 (42%) patients had 2 regimens. The median followup was 1.2 years (range, 0.3-5.2 years). The median dose was 42 gray (Gy; range, 22-60 Gy). When evaluated separately by multivariate analysis, total dose (P ¼ .0015), dose/fraction (P ¼ .003), and BED (P ¼ .004) all correlated with local control by lesion. On multivariate analysis, nonactive extrahepatic disease was associated with overall survival (OS; P ¼ .046), and sustained local control was closely correlated (P ¼ .06). By using single-fraction equivalent dose, BED, or linear quadratic model-based single-fraction dose in the TCP model, the estimated dose range needed for 1-year local control >90% is 46 to 52 Gy in 3 fractions. CONCLUSIONS: Liver stereotactic body radiotherapy is well tolerated and effective for colorectal liver metastases. The strong correlation between local control and OS supports controlling hepatic disease even for heavily pretreated patients. For a 3-fraction regimen of stereotactic body radiotherapy, a prescription dose of 48 Gy should be considered, if normal tissue constraints allow. Cancer 2011;117:4060-

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“…The radiation tolerance of these organs remains unknown, and studies are beginning to address these issues. [46][47][48] …”

Section: Discussionmentioning

confidence: 99%

Stereotactic body radiotherapy for colorectal liver metastases

Chang

Swaminath

Kozak

et al. 2011

Cancer

Self Cite

264

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“…Wei et al demonstrated that LB100 treatment at concentrations of 1 or 3 mM did not radiosensitize normal, small intestinal epithelial cells (CCL ¡ 241), which has clinical significance given that the proximity of normal duodenal tissue is the dose-limiting factor in the radiotherapy of pancreatic tumors. 138 However, treatment of both pancreatic cancer cell lines exhibited radiation dose enhancement factors ranging from 1.2 to 1.4. The authors also found that LB100 treatment with and without radiation led to increased levels of pPlk1, phosphorylated cdc25c, and subsequent cell cycle-promoting activity of dephosphorylated Cdk1.…”

Section: Pancreatic Cancermentioning

confidence: 99%

LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential

Zhang

et al. 2015

Cancer Biology & Therapy

103

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“…Therefore, the use of this technique may allow the administration of a high radiation dose to the target, while delivering a reduced dose to the Planning Target Volume (PTV) subvolume overlapping the duodenal wall. 22,23 Furthermore, several authors proposed the use of radiotherapy as preoperative treatment. [24][25][26] The reason is that most patients have a locally advanced and, therefore, unresectable tumor at diagnosis.…”

Section: Introductionmentioning

confidence: 99%