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.
•Carbon ion radiotherapy is useful for inoperable head and neck cancers.•Re-irradiation with carbon ion radiotherapy after recurrence was explored.•Long-term efficacy and toxicity profiles were ...examined in recurrent disease.•Re-irradiation using carbon ions is moderately efficacious, with moderate toxicity.•Carbon ion radiotherapy is a viable treatment option for recurrent head and neck tumors.
Locoregional recurrence after carbon-ion radiotherapy (CIRT) for primary head and neck malignancies, such as malignant mucosal melanoma, adenoid cystic carcinoma, and sarcoma, occurs occasionally. However, the treatment options are limited. We report on the toxicity and efficacy of re-irradiation using carbon ions for recurrent head and neck malignancies after CIRT.
Data of 48 patients with recurrent head and neck malignancies treated with re-irradiation with CIRT at our institution (2007–2016) were retrospectively analyzed. Twenty-one patients (43.8%) had malignant mucosal melanoma, 17 (35.4%) had adenoid cystic carcinoma, six (12.5%) had bone and soft tissue sarcomas, and four patients (8.3%) had other disease types. Tumor recurrences at re-irradiation were located in the paranasal cavity (n = 18, 37.5%), nasal cavity (n = 9, 18.8%), nasopharynx (n = 4, 8.3%), orbit (n = 3, 6.3%), cavernous sinus (n = 3, 6.3%), and at other sites (n = 11, 22.9%). The median dose of initial CIRT and that at re-irradiation were 57.6 Gy and 54.0 Gy (relative biological effectiveness RBE), respectively. None of the patients received concurrent chemotherapy.
The median follow-up period after re-irradiation was 27.1 months. Five patients (10.4%) developed Grade 3 acute toxicities and 18 (37.5%) developed Grade ≥3 late toxicities, including Grade 5 central nervous system necrosis in one patient. The 2-year local control, locoregional control, progression-free survival, and overall survival rates were 40.5, 33.5%, 29.4%, and 59.6%, respectively.
Re-irradiation using carbon ions may be a reasonable treatment option with tolerable toxicity for patients with recurrent head and neck malignancies after CIRT.
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.
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.
Background
Most of the primary sphenoid sinus tumors present with locally advanced stages with involvement of adjacent critical structures and are not amenable to radical resection. We sought to ...evaluate the safety and efficacy of carbon‐ion radiotherapy (C‐ion RT) for sphenoid sinus malignancies.
Methods
This is a retrospective analysis of 22 patients of primary sphenoid carcinomas treated with definitive C‐ion RT.
Results
Adenoid cystic carcinoma was the most common histology (15 patients, 68.2%). The median follow‐up of this cohort was 48.5 months. The actuarial local control and overall survival at 5 years were 51.0% and 62.7%, respectively. Grade 4 visual impairment and grade 4 brain necrosis were seen in six and one patient, respectively.
Conclusion
C‐ion RT can provide a reasonably good clinical outcome in locally advanced sphenoid sinus malignancies with a marginally higher late toxicity profile because of extremely close proximity of the target volume to critical structures.
To evaluate the efficacy and safety of carbon-ion radiation therapy (RT) for mucosal melanoma of the head and neck (MMHN) in the Japan Carbon-Ion Radiation Oncology Study Group study.
Patients with ...MMHN with N0-1M0 status who were treated with carbon-ion RT at 4 institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. Two hundred sixty patients (male, 111; female, 149; median age, 68 years) with histologically proven MMHN were enrolled.
Primary sites included the nasal cavity in 178 patients, paranasal sinuses in 43, oral cavity in 27, and pharynx in 12. Eighty-six patients had T3 tumors, 147 had T4a tumors, and 27 had T4b tumors. Two hundred fifty-one patients were diagnosed with N0 disease, and 9 with N1 disease. The median total dose and number of fractions were 57.6 Gy RBE (relative biological effectiveness) and 16, respectively. Chemotherapy including dimethyl traizeno imidazole carboxamide was used concurrently in 129 patients. The median follow-up duration was 22 months (range, 1-132 months). The 2-year overall survival and local control rates were 69.4% and 83.9%, respectively. Multivariate analysis showed that gross tumor volume and concurrent chemotherapy were significant prognostic factors for overall survival. Grade 3 and grade 4 late morbidities were observed in 27 and 7 patients (5 developed ipsilateral blindness, 1 mucosal ulcer, and 1 second malignant disease in the irradiated volume), respectively. No patients developed grade 5 late morbidities.
Carbon-ion RT is a promising treatment option for MMHN.
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.
To evaluate the safety and efficacy of carbon-ion radiation therapy (C-ion RT) for locally advanced sinonasal malignant tumors in a multicenter retrospective study (J-CROS 1402 HN).
Clinical data ...were collected for patients who had sinonasal malignant tumors of stage N0-1M0 and received C-ion RT at 4 institutions in Japan between November 2003 and December 2014. Of the 458 patients, 393 had naïve tumors and 65 had recurrent tumors. The tumors were located in the nasal cavity (n = 263), maxillary sinus (n = 109), ethmoid sinus (n = 71), and other locations (n = 15). The histologic types were mucosal melanoma (n = 221, 48%), adenoid cystic carcinoma (n = 122, 27%), squamous cell carcinoma (n = 31, 7%), olfactory neuroblastoma (n = 30, 7%), adenocarcinoma (n = 21, 5%), and other types (n = 33, 7%). Of the 458 patients, 300 (66%) had T4 tumors. All patients received definitive C-ion RT.
The median follow-up period was 25.2 months for all patients (range, 1.4-132.3 months). The 2-year overall survival and local control rates were 79.6% and 84.1%, respectively. As analyzed according to histology, the 2-year overall survival rate was 68.0% for mucosal melanoma, 96.8% for adenoid cystic carcinoma, 70.0% for squamous cell carcinoma, 96.7% for olfactory neuroblastoma, and 89.7% for adenocarcinoma. Regarding late toxicities, 17% of patients developed grade 3 and 4 toxicities, of which visual impairment was the most common.
The results of our multicenter study have demonstrated that C-ion RT can provide excellent clinical outcomes with acceptable late toxicities in patients who have locally advanced sinonasal malignant tumors.
A retrospective multicenter study was carried out to assess the clinical outcomes of carbon‐ion radiotherapy for head and neck malignancies (Japan Carbon‐Ion Radiation Oncology Study Group J‐CROS ...study: 1402 HN). We evaluated the safety and efficacy of carbon‐ion radiotherapy in patients with major salivary gland carcinoma. Sixty‐nine patients treated with carbon‐ion radiotherapy at four Japanese institutions were analyzed. Thirty‐three patients (48%) had adenoid cystic carcinomas, 10 (14%) had mucoepidermoid carcinomas, and 26 (38%) had other disease types. Three patients (4%) had T1 disease, 8 (12%) had T2, 25 (36%) had T3, and 33 (48%) had T4. The median radiation dose was 64 Gy (relative biological effectiveness) in 16 fractions. The median gross tumor volume was 27 mL. The median follow‐up period was 32.7 months. The 3‐year local control rate and overall survival rate were 81% and 94%, respectively. Regarding acute toxicities, seven patients had grade 3 mucositis and seven had grade 3 dermatitis. Regarding late toxicities, one patient had grade 3 dysphagia and one had a grade 3 brain abscess. No grade 4 or worse late reactions were observed. In conclusion, definitive carbon‐ion radiotherapy was effective with acceptable toxicity for major salivary gland carcinomas.
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