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Modeling Combined Chemotherapy and Particle Therapy for Locally Advanced Pancreatic Cancer.

Durante M, Tommasino F, Yamada S - Front Oncol (2015)

Bottom Line: Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond.We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose.We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung , Darmstadt , Germany ; Department of Physics, Trento Institute for Fundamental Physics and Applications (TIFPA), National Institute for Nuclear Physics (INFN), University of Trento , Trento , Italy.

ABSTRACT
Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols using gemcitabine and hypofractionated X-rays are ongoing in several clinical trials. Recent results indicate that charged particle therapy substantially increases local control of resectable and unresectable pancreas cancer, as predicted from previous radiobiology studies considering the high tumor hypoxia. Combination with chemotherapy improves the overall survival (OS). We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose. We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules. Further hypofractionation using charged particles may result in improved local control and survival. A comparative clinical trial using the standard X-ray scheme vs. the best current standard with carbon ions is crucial and may open new opportunities for this deadly disease.

No MeSH data available.


Related in: MedlinePlus

One-year survival as a function of the BED for patients undergoing X-ray radiotherapy plus gemcitabine (red symbols), or other chemotherapy drugs (blue symbols). Data are reported in Tables 2 and 4. The lines show the result of the fit (Eq. 3), which was performed assuming that γ50 and D50 are obtained by fitting the data in treatments using radiotherapy only (Figure 1). The only free fitting parameter is the chemotherapy survival CS (see Table 3). The results suggest that the final outcome does not strongly depend on the specific chemotherapy treatment, although some advantage seems to be associated to the use of gemcitabine.
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Figure 3: One-year survival as a function of the BED for patients undergoing X-ray radiotherapy plus gemcitabine (red symbols), or other chemotherapy drugs (blue symbols). Data are reported in Tables 2 and 4. The lines show the result of the fit (Eq. 3), which was performed assuming that γ50 and D50 are obtained by fitting the data in treatments using radiotherapy only (Figure 1). The only free fitting parameter is the chemotherapy survival CS (see Table 3). The results suggest that the final outcome does not strongly depend on the specific chemotherapy treatment, although some advantage seems to be associated to the use of gemcitabine.

Mentions: Meta-analysis of the clinical data has already shown an advantage in chemoradiation compared to radiotherapy or chemotherapy alone (10). Most clinical trials for LAUPC resort to chemoradiation protocols. Gemcitabine (Table 3) is often regarded as the standard treatment. Several other drugs, such as capecitabine, fluorouracil (5-FU), cisplatin, docetaxel, cetuximab, and fluoropyrimidine prodrug S-1, have been used in the past or in new trials (Table 4), and often combination of gemcitabine and any of the other drugs (Table 5) are applied. The standard X-ray course is 50.4 Gy in 1.8 Gy/fraction, giving a BED of 63 Gy. We did not find significant differences in the groups treated with different drugs, considering the very high scatter of the data also due to the completely different protocols adopted. Figure 3 shows, for example, a comparison of the data in Tables 3 and 4, pointing only to a slight trend for better results in protocols using gemcitabine compared to other drugs. Figure 4 shows the fit of all the data compared to X-rays alone. Having fixed the γ50 and D50 parameters, we estimated the only parameter CS = 0.36 ± 0.01 (Table 2). The radiation dose corresponding to this survival probability RS = CS can be estimated by Eq. 2 as(6)BED (chemo – equivalent)=D501−ln1−RSRS4γ50 leading to a chemo-equivalent dose of 94 Gy. This high value underlines the large improvement that chemotherapy gives on the survival of LAUPC patients. Dale and co-workers (16) estimated 43.6 Gy for the BED chemo-equivalent in bladder cancer. They also demonstrated that the chemo-equivalent dose is not a constant and will be of course much lower if we calculate it for a higher survival level.


Modeling Combined Chemotherapy and Particle Therapy for Locally Advanced Pancreatic Cancer.

Durante M, Tommasino F, Yamada S - Front Oncol (2015)

One-year survival as a function of the BED for patients undergoing X-ray radiotherapy plus gemcitabine (red symbols), or other chemotherapy drugs (blue symbols). Data are reported in Tables 2 and 4. The lines show the result of the fit (Eq. 3), which was performed assuming that γ50 and D50 are obtained by fitting the data in treatments using radiotherapy only (Figure 1). The only free fitting parameter is the chemotherapy survival CS (see Table 3). The results suggest that the final outcome does not strongly depend on the specific chemotherapy treatment, although some advantage seems to be associated to the use of gemcitabine.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492201&req=5

Figure 3: One-year survival as a function of the BED for patients undergoing X-ray radiotherapy plus gemcitabine (red symbols), or other chemotherapy drugs (blue symbols). Data are reported in Tables 2 and 4. The lines show the result of the fit (Eq. 3), which was performed assuming that γ50 and D50 are obtained by fitting the data in treatments using radiotherapy only (Figure 1). The only free fitting parameter is the chemotherapy survival CS (see Table 3). The results suggest that the final outcome does not strongly depend on the specific chemotherapy treatment, although some advantage seems to be associated to the use of gemcitabine.
Mentions: Meta-analysis of the clinical data has already shown an advantage in chemoradiation compared to radiotherapy or chemotherapy alone (10). Most clinical trials for LAUPC resort to chemoradiation protocols. Gemcitabine (Table 3) is often regarded as the standard treatment. Several other drugs, such as capecitabine, fluorouracil (5-FU), cisplatin, docetaxel, cetuximab, and fluoropyrimidine prodrug S-1, have been used in the past or in new trials (Table 4), and often combination of gemcitabine and any of the other drugs (Table 5) are applied. The standard X-ray course is 50.4 Gy in 1.8 Gy/fraction, giving a BED of 63 Gy. We did not find significant differences in the groups treated with different drugs, considering the very high scatter of the data also due to the completely different protocols adopted. Figure 3 shows, for example, a comparison of the data in Tables 3 and 4, pointing only to a slight trend for better results in protocols using gemcitabine compared to other drugs. Figure 4 shows the fit of all the data compared to X-rays alone. Having fixed the γ50 and D50 parameters, we estimated the only parameter CS = 0.36 ± 0.01 (Table 2). The radiation dose corresponding to this survival probability RS = CS can be estimated by Eq. 2 as(6)BED (chemo – equivalent)=D501−ln1−RSRS4γ50 leading to a chemo-equivalent dose of 94 Gy. This high value underlines the large improvement that chemotherapy gives on the survival of LAUPC patients. Dale and co-workers (16) estimated 43.6 Gy for the BED chemo-equivalent in bladder cancer. They also demonstrated that the chemo-equivalent dose is not a constant and will be of course much lower if we calculate it for a higher survival level.

Bottom Line: Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond.We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose.We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung , Darmstadt , Germany ; Department of Physics, Trento Institute for Fundamental Physics and Applications (TIFPA), National Institute for Nuclear Physics (INFN), University of Trento , Trento , Italy.

ABSTRACT
Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols using gemcitabine and hypofractionated X-rays are ongoing in several clinical trials. Recent results indicate that charged particle therapy substantially increases local control of resectable and unresectable pancreas cancer, as predicted from previous radiobiology studies considering the high tumor hypoxia. Combination with chemotherapy improves the overall survival (OS). We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose. We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules. Further hypofractionation using charged particles may result in improved local control and survival. A comparative clinical trial using the standard X-ray scheme vs. the best current standard with carbon ions is crucial and may open new opportunities for this deadly disease.

No MeSH data available.


Related in: MedlinePlus