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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 CPT with or without additional chemotherapy. Blue symbols refer to patients receiving radiotherapy with C-ions without additional chemotherapy. Green symbols refer to data obtained with proton (triangles) and carbon ions (full squares) in combination with chemotherapy. Data are given in Table 6. The green line shows the result of the fit of data for chemotherapy combined with proton or carbon ions. The fit was performed using γ50 and CS from X-ray + chemotherapy data. The only free parameter is therefore D50. The black and red lines show the results of the fit for X-rays alone and X-rays plus chemotherapy, and are reported for comparison. Fitting parameters are in Table 3.
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Figure 5: One-year survival as a function of the BED for patients undergoing CPT with or without additional chemotherapy. Blue symbols refer to patients receiving radiotherapy with C-ions without additional chemotherapy. Green symbols refer to data obtained with proton (triangles) and carbon ions (full squares) in combination with chemotherapy. Data are given in Table 6. The green line shows the result of the fit of data for chemotherapy combined with proton or carbon ions. The fit was performed using γ50 and CS from X-ray + chemotherapy data. The only free parameter is therefore D50. The black and red lines show the results of the fit for X-rays alone and X-rays plus chemotherapy, and are reported for comparison. Fitting parameters are in Table 3.

Mentions: Although only a few studies are available with CPT, the data in Table 6 show that they are the best current options for LAUPC. A 2-year survival rate around 50% was reached with protons (28) or C-ions (9) in combination with gemcitabine, a value far exceeding any other chemoradiation trial using X-rays and any cocktail of drugs. The data with CIRT alone (no chemotherapy) are clearly superior to those with X-rays alone and comparable to the results with chemoradiation at the same X-rays BED. The best 1-year OSs for combined chemotherapy (gemcitabine) and CPT are those from Hyogo (28) using protons up to 70.2 Gy(RBE) in 26 fractions, but they came at a cost of grade 3–5 toxicity in 10% of the patients, especially gastric ulcer and hemorrhage. CIRT toxicity was much more mild, with 17% of the patients experiencing grade 3 GI toxicity, in the form of appetite loss. Low toxicity was observed for the duodenum, both for protons and 12C-ions. The fit of the chemoradiation with CPT, using the same CS and γ50 parameters calculated for X-rays + chemotherapy, is shown in Figure 5. This fit assumes that CPT does not change the effect of the chemotherapy compared to X-rays, but results in a lower D50 due to biological and/or physical improvements compared to X-rays. Should these improvements be already included in the RBE model used to calculate the equivalent dose in Gy(RBE), we should see the same effect at the same BED [see Ref. (23) for CIRT in Japan; RBE = 1.1 for protons]. Instead, the best fit is reduced to D50 = 75 ± 9 Gy(RBE) for CPT (Table 2). This 50% improvement is caused either by a better physics, enabling treatment of infiltrations in the neuroplexus, or to a better biology, especially to a reduced OER (6) or to a stronger immune response (7) using CPT compared to X-rays.


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 CPT with or without additional chemotherapy. Blue symbols refer to patients receiving radiotherapy with C-ions without additional chemotherapy. Green symbols refer to data obtained with proton (triangles) and carbon ions (full squares) in combination with chemotherapy. Data are given in Table 6. The green line shows the result of the fit of data for chemotherapy combined with proton or carbon ions. The fit was performed using γ50 and CS from X-ray + chemotherapy data. The only free parameter is therefore D50. The black and red lines show the results of the fit for X-rays alone and X-rays plus chemotherapy, and are reported for comparison. Fitting parameters are in Table 3.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: One-year survival as a function of the BED for patients undergoing CPT with or without additional chemotherapy. Blue symbols refer to patients receiving radiotherapy with C-ions without additional chemotherapy. Green symbols refer to data obtained with proton (triangles) and carbon ions (full squares) in combination with chemotherapy. Data are given in Table 6. The green line shows the result of the fit of data for chemotherapy combined with proton or carbon ions. The fit was performed using γ50 and CS from X-ray + chemotherapy data. The only free parameter is therefore D50. The black and red lines show the results of the fit for X-rays alone and X-rays plus chemotherapy, and are reported for comparison. Fitting parameters are in Table 3.
Mentions: Although only a few studies are available with CPT, the data in Table 6 show that they are the best current options for LAUPC. A 2-year survival rate around 50% was reached with protons (28) or C-ions (9) in combination with gemcitabine, a value far exceeding any other chemoradiation trial using X-rays and any cocktail of drugs. The data with CIRT alone (no chemotherapy) are clearly superior to those with X-rays alone and comparable to the results with chemoradiation at the same X-rays BED. The best 1-year OSs for combined chemotherapy (gemcitabine) and CPT are those from Hyogo (28) using protons up to 70.2 Gy(RBE) in 26 fractions, but they came at a cost of grade 3–5 toxicity in 10% of the patients, especially gastric ulcer and hemorrhage. CIRT toxicity was much more mild, with 17% of the patients experiencing grade 3 GI toxicity, in the form of appetite loss. Low toxicity was observed for the duodenum, both for protons and 12C-ions. The fit of the chemoradiation with CPT, using the same CS and γ50 parameters calculated for X-rays + chemotherapy, is shown in Figure 5. This fit assumes that CPT does not change the effect of the chemotherapy compared to X-rays, but results in a lower D50 due to biological and/or physical improvements compared to X-rays. Should these improvements be already included in the RBE model used to calculate the equivalent dose in Gy(RBE), we should see the same effect at the same BED [see Ref. (23) for CIRT in Japan; RBE = 1.1 for protons]. Instead, the best fit is reduced to D50 = 75 ± 9 Gy(RBE) for CPT (Table 2). This 50% improvement is caused either by a better physics, enabling treatment of infiltrations in the neuroplexus, or to a better biology, especially to a reduced OER (6) or to a stronger immune response (7) using CPT compared to X-rays.

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