For hypo-fractionated multi-ion therapy (HFMIT), the stochastic microdosimetric kinetic (SMK) model had been developed to estimate the biological effectiveness of radiation beams with wide linear ...energy transfer (LET) and dose ranges. The HFMIT will be applied to radioresistant tumors with oxygen-deficient regions. The response of cells to radiation is strongly dependent on the oxygen condition in addition to radiation type, LET and absorbed dose. This study presents an adaptation of the SMK model to account for oxygen-pressure dependent cell responses, and develops the oxygen-effect-incorporated stochastic microdosimetric kinetic (OSMK) model. In the model, following assumptions were made: the numbers of radiation-induced sublethal lesions (double-strand breaks) are reduced due to lack of oxygen, and the numbers of oxygen-mediated lesions are reduced for radiation with high LET. The model parameters were determined by fitting survival data under aerobic and anoxic conditions for human salivary gland tumor cells and V79 cells exposed to helium-, carbon-, and neon-ion beams over the LET range of 18.5-654.0 keV
m
. The OSMK model provided good agreement with the experimental survival data of the cells with determination coefficients >0.9. In terms of oxygen enhancement ratio, the OSMK model reproduced the experimental data behavior, including slight dependence on particle type at the same LET. The OSMK model was then implemented into the in-house treatment planning software for the HFMIT to validate its applicability in clinical practice. A treatment plan with helium- and neon-ion beams was made for a pancreatic cancer case assuming an oxygen-deficient region within the tumor. The biological optimization based on the OSMK model preferentially placed the neon-ion beam to the hypoxic region, while it placed both helium- and neon-ion beams to the surrounding normoxic region. The OSMK model offered the accuracy and usability required for hypoxia-based biological optimization in HFMIT treatment planning.
•Clinical trials in pancreatic cancer.•Efficacy of carbon ion radiotherapy in pancreatic cancer.•Summary of carbon ion radiotherapy in pancreatic cancer.
Despite all efforts, pancreatic cancer ...remains a highly lethal disease. Only surgical resection offers a realistic chance of survival. But at diagnosis the majority of patients suffer from unresectable disease. Whereas guidelines clearly recommend systemic treatments in metastatic disease, data is limited to support a specific treatment option for locally advanced or borderline resectable pancreatic cancer. Therefore, there is an urgent need to improve treatment schemes addressing patients that suffer from unresectable pancreatic cancer. Chemotherapy, photon radiotherapy and combinations of both have shown improved local control rates but there is still a lack of evidence demonstrating an overall survival benefit of photon radiotherapy if no surgical resection is achieved. Impressive results of Japanese Phase I/II-trials investigating carbon ion radiotherapy in pancreatic cancer attracted global attention. Several studies have been initiated to validate and intensify this promising issue. This review gives an overview of the evidence and current use of carbon ion radiotherapy in pancreatic cancer.
Background
This study aimed to assess the safety and efficacy of carbon-ion radiotherapy (CIRT) for salvage of previously X-ray-irradiated (XRT) locally recurrent rectal cancer (LRRC).
Methods
...Between September 2005 and December 2017, 77 patients with LRRC were treated with CIRT re-irradiation. All the patients had received prior XRT with a median dose of 50.0 Gy (range 20–74 Gy), principally for neoadjuvant or adjuvant recurrence prophylaxis in 34 patients and for recurrence in 43 patients. The total CIRT dose of 70.4 Gy (RBE) (gray relative biologic effectiveness) was administered in 16 fixed fractions during 4 weeks (4.4 Gy RBE per fraction).
Results
All the patients completed the scheduled treatment course. None of the patients received resection after CIRT. Acute grade 3 toxicities occurred for eight patients (10 %), including five grade 3 pelvic infections (2 involving pain and 1 involving neuropathy). Late grade 3 toxicities occurred for 16 patients (21 %): 13 with late grade 3 pelvic infections, 9 with gastrointestinal toxicity, 1 with skin toxicity, 2 with pain, and 4 with neuropathy. No grade 4+ toxicity was noted. The overall local control rates (infield + out-of-field recurrence) were 69 % at 3 years and 62 % at 5 years. In the planning target volume (PTV), the infield recurrence rates were 90 % and 87 % respectively. The control rates for regional recurrence were 85 % at 3 years and 81 % at 5 years. The median overall survival time was 47 months. The survival rates were 61 % at 3 years and 38 % at 5 years.
Conclusion
Carbon-ion re-irradiation of previously X-ray-irradiated locally recurrent rectal cancer appears to be safe and effective, providing good local control and survival advantage without unacceptable morbidity.
The aim of this multi-institutional study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally advanced pancreatic cancer (LAPC).
Patients with LAPC treated with ...C-ion RT from April 2012 to December 2014 at 3 institutions were retrospectively analyzed. Patients with pathologically-confirmed invasive ductal adenocarcinoma of the pancreas were eligible. The prescribed dose was 52.8 Gy (relative biological effectiveness weighted absorbed dose; RBE) or 55.2 Gy (RBE) in 12 fractions. Overall survival (OS), distant metastasis-free survival (DMFS), local recurrence (LR), and toxicity were evaluated.
In total, 72 patients were included in this study. Tumors in the head of the pancreas were seen in 30 patients (42%), while those in the body or tail of the pancreas were seen in 42 patients (58%). Fifty-six patients (78%) received concurrent chemotherapy. The OS rates were 73% (95% confidence interval CI, 62%-84%) at 1 year, and 46% (95% CI, 31%-61%) at 2 years with a median OS of 21.5 months (95% CI, 11.8-31.2 months). The 1- and 2-year DMFS rates were 41% (95% CI, 29%-52%) and 28% (95% CI, 16%-40%), respectively. The 1- and 2-year cumulative incidences of LR were 16% (95% CI, 9%-26%) and 24% (95% CI, 14%-36%), respectively. Nineteen patients (26%) experienced acute grade 3 or 4 hematological toxicities. Two patients (3%) had grade 3 anorexia. Late gastrointestinal (GI) grade 3 toxicity was observed in 1 patient (1%). No patients developed late grade 4 or 5 toxicity.
The first multi-institutional analysis of C-ion RT for LAPC indicated relatively favorable outcomes with limited toxicities, especially for tumors not in close proximity to GI tract.
•We analyzed 64 LAPC patients treated with C-ion RT at single institution.•The median survival time and 2-year OS were 25.1 months and 53%.•Only four patients experienced acute grade 3 ...toxicities.•C-ion RT for LAPC showed relatively favorable outcome and limited toxicity.
The aim of this study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for unresectable locally advanced pancreatic cancer (LAPC).
Patients with LAPC treated with definitive C-ion RT between April 2014 and July 2017 were analyzed retrospectively. The prescribed dose was 55.2 Gy (relative biological effectiveness RBE weighted absorbed dose) in 12 fractions. Overall survival (OS), local control (LC), progression free survival (PFS), and toxicity were evaluated.
Sixty-four patients were enrolled. All patients completed planned course of C-ion RT. The median follow-up time for survivors from the initiation of C-ion RT was 24.4 months (range, 5.1–46.1 months). Median survival time was 25.1 months. Two-year OS, LC, and PFS were 53% (95% confidence interval CI, 39%–66%), 82% (95% CI, 66%–91%), and 23% (95% CI, 14%–36%), respectively. Four patients experienced acute grade 3 toxicities including 3 gastrointestinal (GI) toxicities. There was no grade 3 or more late toxicity.
The clinical results of C-ion RT for LAPC at our institution were comparable to those of a recent multi-institutional analysis.
Background
Chordoma is a rare, locally invasive neoplasm of the axial skeleton. Complete resection is often difficult, especially for the upper‐cervical (C1‐2) spine. We evaluated the efficacy and ...safety of carbon‐ion radiotherapy (CIRT) for unresectable C1‐2 chordoma.
Methods
Patients with C1‐2 chordoma treated with definitive CIRT (60.8 Gy RBE in 16 fractions) were retrospectively analyzed. We evaluated OS, LC, PFS, and toxicity.
Results
Nineteen eligible patients all completed the planned course of CIRT. With the median follow‐up 68 months (range: 29–144), median OS was 126 months (range: 36‐NA). Five‐year OS, LC, and PFS were 68.4% (95% CI, 42.8%–84.4%), 75.2% (46.1%–90.0%), and 64.1% (36.3%–82.3%), respectively. Regarding acute toxicity of grade ≥3, there was only one grade 3 mucositis. Late toxicity included radiation‐induced myelitis (grade 3 in 1 patient; 5.3%), and compression fractures (n = 5; 26.3%).
Conclusions
High‐dose CIRT is a promising treatment option for unresectable upper cervical chordoma.
In this study, the stopping-power ratios (SPRs) of mouthpiece materials were measured and the errors in the predicted SPRs based on conversion table values were further investigated. The SPRs of the ...five mouthpiece materials were predicted from their computed tomography (CT) numbers using a calibrated conversion table. Independently, the SPRs of the materials were measured from the Bragg peak shift of a carbon-ion beam passing through the materials. The errors in the SPRs of the materials were determined as the difference between the predicted and measured values. The measured SPRs (errors) of the Nipoflex 710™ and Bioplast™ ethylene–vinyl acetate copolymers (EVAs) were 0.997 (0.023) and 0.982 (0.007), respectively. The SPRs of the vinyl silicon impression material, light-curable resin, and bis-acrylic resin were 1.517 (0.134), 1.161 (0.068), and 1.26 (0.101), respectively. Among the five tested materials, the EVAs had the lowest SPR errors, indicating the highest human-tissue equivalency.
Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer.
A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 ...lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction.
During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval CI, 80%-93%) and 59% (95% CI, 50%-68%), respectively.
Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.
Carbon-ion Radiotherapy for Colorectal Cancer Yamada, Shigeru; Takiyama, Hirotoshi; Isozaki, Yuka ...
Journal of the Anus, Rectum and Colon,
04/2021, Volume:
5, Issue:
2
Journal Article
Peer reviewed
Open access
Heavy-ion radiotherapy (RT) is a kind of particle RT, and carbon-ion beam constitutes the primary delivery method of heavy-ion RT. Unlike the conventional photon modalities, particle RT, in ...particular carbon-ion radiotherapy (CIRT), offers unique physical and biological advantages. Particle therapy allows for substantial dose delivery to tumors with minimal surrounding tissue damage. In addition, CIRT in particular possesses biological advantages such as inducing increased double-strand breaks in DNA structures, causing irreversible cell damage independently of cell cycle or oxygenation, more so than proton or photon. It can be expected that CIRT is effective on radioresistant cancers such as colorectal cancers (CRCs). We introduced the results of CIRT for local recurrent rectal cancer, lung metastasis, liver metastasis, and lymph node metastasis.
We aimed to investigate the dosimetric effects of a spacer placed between the pancreas and surrounding gastrointestinal structures in intensity-modulated radiation therapy (IMRT) planning to provide ...more effective radiation therapy for locally advanced pancreatic cancer (LAPC).
Treatment planning was performed for six patients with LAPC based on computed tomography images without spacers and with 5-mm or 10-mm spacers virtually inserted under the supervision of a hepatobiliary pancreatic surgeon. The prescription dose was 63 Gy in 28 fractions.
With the exception of one case of pancreatic head cancer, planning target volume receiving ≥95% of the prescribed dose (PTV V95) was achieved by 90% or more by inserting a spacer, and by 95% or more in all 3 cases of pancreatic body and tail cancer by inserting a 10-mm spacer.
IMRT with appropriate spacer placement may help provide high-dose treatment for LAPC and improve associated patient outcomes.
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