Abstract:HighlightsHigh LET and high RBE of carbon ion made it a promising tool for treating pancreatic cancers.Dose averaged LET minimum within the GTV is significantly associated with local control.Outcome of CIRT in pancreatic cancers can be improved by modulating dose averaged LET within the GTV.
“…A recent retrospective analysis on the C-ion treatment plans at NIRS suggest that the LET is positively associated to local control of pancreas tumors. In particular, patients with higher minimum dose-averaged LET values in the gross tumor volume had lower probability of local failure compared to those with minimum LET values below 40 keV/μm [ 127 ]. Approaches to extend the high-LET regions (LET painting [ 128 , 129 ]), also using multiple ions [ 130 ], in the tumor are very promising for next-generation particle therapy, especially when specific radioresistant regions have to be targeted such as hypoxic volumes [ 131 ] or cancer stem cell niches [ 132 ].…”
Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons, which have physical advantages compared to X-rays but a similar biological response. In addition to the ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal heavy ion should have lower toxicity in the entrance channel (normal tissue) and be exquisitely effective in the target region (tumor). Carbon ions have been chosen because they represent the best combination in this direction. Normal tissue toxicities and second cancer risk are similar to those observed in conventional radiotherapy. In the target region, they have increased relative biological effectiveness and a reduced oxygen enhancement ratio compared to X-rays. Some radiobiological properties of densely ionizing carbon ions are so distinct from X-rays and protons that they can be considered as a different “drug” in oncology, and may elicit favorable responses such as an increased immune response and reduced angiogenesis and metastatic potential. The radiobiological properties of carbon ions should guide patient selection and treatment protocols to achieve optimal clinical results.
“…A recent retrospective analysis on the C-ion treatment plans at NIRS suggest that the LET is positively associated to local control of pancreas tumors. In particular, patients with higher minimum dose-averaged LET values in the gross tumor volume had lower probability of local failure compared to those with minimum LET values below 40 keV/μm [ 127 ]. Approaches to extend the high-LET regions (LET painting [ 128 , 129 ]), also using multiple ions [ 130 ], in the tumor are very promising for next-generation particle therapy, especially when specific radioresistant regions have to be targeted such as hypoxic volumes [ 131 ] or cancer stem cell niches [ 132 ].…”
Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons, which have physical advantages compared to X-rays but a similar biological response. In addition to the ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal heavy ion should have lower toxicity in the entrance channel (normal tissue) and be exquisitely effective in the target region (tumor). Carbon ions have been chosen because they represent the best combination in this direction. Normal tissue toxicities and second cancer risk are similar to those observed in conventional radiotherapy. In the target region, they have increased relative biological effectiveness and a reduced oxygen enhancement ratio compared to X-rays. Some radiobiological properties of densely ionizing carbon ions are so distinct from X-rays and protons that they can be considered as a different “drug” in oncology, and may elicit favorable responses such as an increased immune response and reduced angiogenesis and metastatic potential. The radiobiological properties of carbon ions should guide patient selection and treatment protocols to achieve optimal clinical results.
“…It is worth mentioning here the work of Hagiwara et al [57], indicating the potential value of microdosimetric data for the clinical outcome of ion beam therapy. In this clinical-based investigation, the outcomes of local control and overall survival in pancreatic tumors are assessed with retrospective studies and examined in relation to the dose mean LET.…”
Section: Prospective Of Microdosimetry In the Clinicsmentioning
“…The clinical relationship between LET distribution within a tumor and tumor control has been explored in CIRT. Hagiwara and colleagues studied the influence of dose-averaged LET on CIRT-irradiated pancreatic tumor control in 2020 ( 48 ), retrospectively evaluating 18 patients treated with 55.2 Gy (RBE) CIRT at a median of 22 months. Four infield central local recurrences were noted.…”
Section: Let and Rbementioning
confidence: 99%
“…While dose was uniform throughout the tumor, LET was lower within the central compartment of the target volume, owing to how particle paths were overlapped to generate a spread out Bragg peak. Notably, local control was improved in those patients with higher minimum dose-averaged LET within the gross tumor volume (GTV), independent of the minimal dose and D98 delivered ( 48 ). Improved dose-averaged LET within the GTV may thereby improve local control, though the ability to fully control the LET within the tumor target may be limited by the LET distribution inherent to the carbon-ion beam, and the tumor’s relationship to nearby radiosensitive organs.…”
Research into high linear energy transfer (LET) radiotherapy now spans over half a century, beginning with helium and deuteron treatment in 1952 and today ranging from fast neutrons to carbon-ions. Owing to pioneering work initially in the United States and thereafter in Germany and Japan, increasing focus is on the carbon-ion beam: 12 centers are in operation, with five under construction and three in planning. While the carbon-ion beam has demonstrated unique and promising suitability in laboratory and clinical trials toward the hypofractionated treatment of hypoxic and/or radioresistant cancer, substantial developmental potential remains. Perhaps most notable is the ability to paint LET in a tumor, theoretically better focusing damage delivery within the most resistant areas. However, the technique may be limited in practice by the physical properties of the beams themselves. A heavy-ion synchrotron may provide irradiation with multiple heavy-ions: carbon, helium, and oxygen are prime candidates. Each ion varies in LET distribution, and so a methodology combining the use of multiple ions into a uniform LET distribution within a tumor may allow for even greater treatment potential in radioresistant cancer.
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