The size of film piece and analysis ROI used for calibration slightly affected the film response. Both transmission and reflection scanning modes can be used to analyze the Gafchromic XRQA2, with the reflection mode having a somewhat lower calibration uncertainty. Scanning films on alternate sides using transmission mode significantly affects the optical density. The film response was shown to be energy dependent. The films reached stability in about 6 h after exposure. The film response was proven to be independent of irradiation angle except when the beam is parallel to the film surface.
Purpose
Pancreatic cancer (PC) is the fourth cause of death from cancer in the western world. Majority of patients present with advanced unresectable disease responding poorly to most chemotherapeutic agents. Chemotherapy for PC might be improved by adjusting it to individual genetic profiles. We attempt to identify genetic predictors of chemosensitivity to broad classes of anticancer drugs.
Experimental Design
Using a panel of genetically defined human PC cell lines, we tested gemcitabine (anti-metabolite), docetaxel (anti-microtubule), mitomycin C (alkylating), irinotecan (topoisomerase I inhibitor), cisplatin (crosslinking), KU0058948 (Parp1 inhibitor), triptolide (terpenoid drug) and artemisinin (control).
Results
All PC cell lines were sensitive to triptolide and docetaxel. Most PC cells were also sensitive to gemcitabine and MMC. The vast majority of PC cell lines were insensitive to cisplatin, irinotecan, and a Parp1 inhibitor. However, individual cell lines were often sensitive to these compounds in unique ways. We found that DPC4/SMAD4 inactivation sensitized PC cells to cisplatin and irinotecan by 2–4 fold, but they were modestly less sensitive to gemcitabine. PC cells were all sensitive to triptolide and 18% were sensitive to the Parp1 inhibitor. P16/CDKN2A inactivated PC cells were 3–4 fold less sensitive to gemcitabine and MMC.
Conclusions
Chemosensitivity of PC cells correlated with some specific genetic profiles. These results support the hypothesis that genetic subsets of pancreatic cancer exist, and these genetic backgrounds may permit one to personalize the chemotherapy of PC in the future. Further work will need to confirm these responses and determine their magnitude in vivo.
Dose response curves of Gafchromic XRQA2 film and nanoDot OSLDs indicated that the dose responses of these two dosimeters were different even at the same photon energy when different filters were used. Uncertainty levels of both dosimetry systems were below 6% at doses above 1 cGy. Both dosimetry systems gave almost similar estimation of doses (within uncertainties) in many cases, with exceptions of some cases when the discrepancy was around 20%-30%. New versions of the CBCT systems (investigated in this study) resulted in lower imaging doses compared with doses reported on earlier versions in previous studies.
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