Particle beam radiation therapy (PBRT), using proton and heavy ion (mainly carbon ion in clinical practice) beams, provides precise cancer treatment by targeting tumor sites while sparing healthy tissues, by leveraging the Bragg peak for superior dose distribution. Proton beams have a relative-biological-effectiveness (RBE) of 1.1, which is slightly higher than that of photon beams. And carbon ions have an RBE of 2-3 due to their high linear energy transfer, thus being more advantageous for radioresistant and hypoxic tumors. Treatment strategies include single-beam and mixed-beam approaches, the latter of which combines the advantages of different particles and is an important direction of cancer treatment research. PBRT faces challenges such as managing moving targets and dose uncertainties, requiring advanced techniques like respiratory gating and adaptive planning. Additionally, the scarcity of randomized clinical trials (RCTs) limits PBRT's clinical validation. Existing RCTs, such as those from MD Anderson, indicate the benefits, as well as the need for further studies to confirm PBRT's long-term efficacy and safety. Future research should compare PBRT to photon therapy and explore the therapeutic benefit of combining PBRT with systemic therapies like immunotherapy. Reviewing the clinical practice and research of PBRT, and further discussing its cost-effectiveness in tumor treatment, can provide readers with a comprehensive understanding and promote the development and application of PBRT in cancer treatment.

Objective:To compare dose distributions between photon versus proton and carbon ion radiotherapy (particle therapy, PT) among patients with gross tumors, and to evaluate the safety and efficacy of PT for thymic malignancies (TM).Methods:From Sept 2015 to Aug 2018, 19 patients with TM who underwent non-palliative PT using pencil beam scanning technique in our hospital and had at least one follow-up were retrospectively analyzed. Diseases staged from Ⅰ-Ⅳ B including 15 Ⅲ-Ⅳ B. All the patients had pathological diagnosis with 10 thymomas, 6 carcinomas and 3 neuroendocrine tumors of the thymus. A set of dosimetric comparisons were conducted in patients with gross tumors at a total dose of 66 GyE, in 33 fractions for photon or proton beams and in 22 fractions for carbon ion beams. Five patients without any local treatment and 7 patients after R2 resection received radical radiotherapy of proton 44.0-48.4 GyE in 20-22 fractions plus carbon ion 21.0-23.1 GyE in 7 fractions, 1 case after complete resection (R0 resection) had proton 45 GyE in 25 fractions, 5 cases after R1 resection had proton 60.0-61.6 GyE in 28-30 fractions and 1 case of recurrence after postoperative radiotherapy had only carbon ion 60 GyE in 20 fractions. Results:The median follow up time was 19.0 (2.4-42.9) months. There were 13 patients with gross tumors, with a median largest diameter of 5.7 (2.7-12.8) cm. The dosimetric study showed that proton and carbon-ion plans significantly reduced the maximum dose to the spinal cord, the mean doses to the organs at risk (OARs) including the lung/heart/esophagus, and the integral dose of the exposed area about 25%-65% compared to photon plans. No other toxicities ≥ grade 3 were observed except one myocardial infarction (grade 4 late toxicity). There was no local failure observed. Metastasis to regional lymph node, lung, pleura, skull base, bone or liver occurred in 4 patients with Ⅲ-Ⅳ B stage disease in 6.1-22.8 months after treatment. The 2-year local control and overall survival rates were 100%, disease free survival and distant metastasis free survival rates were 64.6%. Conclusions:For TMs, PT has significant advantages over photon in terms of sparing OARs, and is safe and effective in patients with TMs after short-time follow-up.

Objective:To investigate the safety and efficacy of proton beam radiation therapy (PBRT) in patients with World Health Organization (WHO) GradeⅠ/Ⅱ meningioma.Methods:Twenty-six patients with intracranial ( n=8, 30.8%) or skull-base ( n=18, 69.2%) meningioma treated with PBRT from May 2015 to October 2018 were analyzed retrospectively. The median age of the cohort was 42 years (range 15-79 years). Eight patients had WHO Grade Ⅰ meningioma, and 9 had WHO Grade Ⅱ meningioma, respectively. Nine patients had clinical (radiological) diagnosis without histology. Seven patients received post-surgical PBRT (2 patients underwent Simpson Ⅰ-Ⅲ resection, 5 patients underwent Simpson Ⅳ-Ⅴ resection); 10 patients were irradiated for local recurrence after initial surgical resection. Results:All patients completed planned PBRT without break, and the median dose was 54 Gray-Equivalent (GyE) (range 50.4-60 GyE, 1.8-2 GyE/daily fraction). With a median follow-up of 22.2 (range 1.6-36.4) months, the 2-year overall survival and progression-free survival rates were both 100%. Grade Ⅰ skin erythema and alopecia were observed in 22 patients and Grade Ⅰ mucositis was observed in 2 patients. No acute of late toxicities of Grade 2 or above was observed.Conclusions:PBRT appeared to be a favorable treatment option for intracranial and skull base meningioma. Treatment-induced adverse effects and early response to PBRT were both highly acceptable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.

Objective:To evaluate the short-term tumor control and toxicity of recurrent skull base and cervical spine chordoma and chondrosarcoma in patients treated with pencil beam scanning proton and heavy ion therapy.Methods:Between June 30 th, 2014 and July 30 th, 2018, a total of 45 skull base and cervical spine chordoma ( n=39) and chondrosarcoma ( n=6) patients (28 males and 17 females; mean age at initial presentation of 44 years, range, 14-76 years) were treated in our center for the course of radiotherapy. The median maximum tumor volume was 57 cm 3 (range, 6.6-231.7 cm 3). There were 31 post-operative recurrent patients and 14 post-operative and post-radiated recurrent patients. One patient received proton therapy, 21 patients received combined proton and carbon ion therapy, 23 patients received carbon ion therapy. Results:All patients completed the whole course of the treatment. The median follow-up time was 29 months (range: 8-57 months), the 2-year overall survival (OS), local control (LC), and progression-free survival (PFS) were 82.7%, 85.3%, and 73.8%, respectively. There were no other grade 3-4 acute or late radiation-induced toxicity except one grade 3 acute mucositis. The 2-year OS rates for patients after first-time radiation vs. re-irradiation were 96.2% and 50.3% ( χ2=16.969, P<0.05). Conclusions:The short-term outcomes of pencil beam scanning proton and heavy ion therapy for recurrent skull base and cervical spine chordoma and chondrosarcoma is favorable. Further study is needed for long-term efficacy and safety.

Objective To evaluate the short-term efficacy and toxicities of intensity-modulated carbon ion radiotherapy (IMCT) for patients with locoregionally recurrent nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT).Methods A total of 112 patients with locoregionally recurrent nasopharyngeal carcinoma undergoing salvaging IMCT between May 2015 and February 2018were enrolled in the study.All patients previously received one course of definitive X-ray IMRT.Among them,10 patients (9％) were diagnosed with stage Ⅰ,26 patients (23％) with stage Ⅱ,41 patients (37％) with stage Ⅲ and 35 patients (31％) with stage Ⅳnasopharyngeal carcinoma,respectively.The median age of the cohort was 48 years (range,17-70 years) old.The median dose to the gross tumor volume (GTV) was 60 GyE (range,50-69 GyE).Results With a median follow-up time of 20 months (range,5-45 months),20 patients died and 42 patients developed local recurrence.The 2-year overall survival (OS) and local progression-free survival (LPFS) rates were 85％ and 52％.Both univariate and multivariate analyses demonstrated that stage Ⅳ disease was associated with significantly worse OS.No predictors were found for LPFS.No acute toxicity of grade 3 or higher was observed during reirradiation.Severe (grade 3 or above) late toxicities included xerostomia (n =1),hearing impairment (n =2),temporal lobe injury (n =1) and mucosal necrosis (n =19).Conclusions IMCT is an efficacious and safe treatment for patients with locoregionally recurrent nasopharyngeal carcinoma with acceptable toxicity profile.Long-term follow-up is necessary to further evaluate the long-term efficacy and late toxicities.

Objective:To investigate the dosimetric difference between glioma patients treated by particle (proton+ carbon ion) and photon radiotherapy.Methods:Twelve previously-treated glioma patients were selected, and given with the same total dose of 60.00 Gy [RBE]. Two types of planning target volumes (PTVs) including PTV-ion and PTV-photon were expended from clinical target volumes according to range uncertainty and patient setup errors. Based on PTV-ion, proton plans with sequential carbon ion boost (particle plan) were created. Following the same prescription, two types of photon intensity-modulated radiotherapy (IMRT) plans were established to achieve similar target coverage and compare the dose of organs at risk.Results:Target coverages of three types of plans had no statistical difference (all P>0.05). The median integral dose of normal brain of all patients receiving particle plan was merely 44.90% of the minimum number from photon plans ( P<0.001). Compared with the minimum number from photon plans, particle radiotherapy decreased the mean dose of brain stem[(6.83±6.22) Gy[RBE] vs. (15.10±10.11) Gy[RBE], P=0.001)], the maximum dose of chiasm[(47.76±20.80) Gy[RBE] vs. (49.59±20.52) Gy[RBE], P=0.009)] and the mean dose of contralateral hippocampus (0.26±9.08) Gy[RBE] vs. (16.28±11.14) Gy[RBE], P=0.002), respectively. Conclusions:Particle radiotherapy can achieve similar target coverage while maintaining lower normal tissue doses to the photon radiotherapy. Photon planion can increase the doses to adjuvant normal tissues.

Objective:To test the usefulness of PET-range verification (RV) method for proton radiation accuracy verification in poly (methyl methacrylate) (PMMA) phantom using off-line PET/CT scanning.Methods:Proton irradiation dose of 2 Gy and 4 Gy were delivered in PMMA phantom. Given the difference of clinical target volume (CTV), 7 subgroups with different depth (5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0 cm) were set for each dose (14 radiation plans or radiation fields). PET/CT scan was performed 10 min after irradiation of 48-221 MeV proton beam. A co-registration between CT from treatment planning system and PET/CT was performed, as well as the smoothing and normalization of PET/CT data. The region of interest (ROI) and profile lines were drawn with the Raystation PET-RV software. The predictive induced radioactivity and the measured induced radioactivity profile lines were analyzed to evaluate the Δ R50, namely, the error at the position corresponding to 50% of the maximum predictive induced radioactivity at the end of both curves. Results:The size of each ROI was 5.0 cm×5.0 cm×2.5 cm. Profile lines were evenly distributed with the interval of 3 mm, and totally 289 pairs of profile lines were drew. The 2 Gy- and 4 Gy-dose groups yielded similar mean depth errors (Δ R50 between 1 mm and -1 mm with a standard deviation <1 mm). Conclusions:The off-line PET/CT scanning of PMMA phantom reveals a good agreement between predicted and measured PET data, with error of ±1 mm. The PET-RV method can be extended to clinical cases′ verification in human body treatment with further investigation.

Objective    To describe the effect of sequential pulmonary balloon angioplasty for patients with chronic thromboembolic pulmonary hypertension, who was accompanied with progressed pulmonary hypertension after pulmonary endarterectomy surgeries. Methods    From 2014 to December 2017, 7 patients were treated with a combination therapy of pulmonary endarterectomy and sequential pulmonary balloon angioplasty. There were 1 male and 6 females at age of 58 (43–59) years. A follow-up period of more than 1 year was accomplished. The result of right sided heart catheterization and ultrasonic cardiogram between and after the pulmonary endarterectomy or balloon angioplasty was collected. Results    Seven patients were treated with a combination of pulmonary endarterectomy and sequential pulmonary balloon angioplasty, which included 1 patient of single pulmonary balloon angioplasty and 6 patients of multiple pulmonary balloon angioplasties. The balloon dilation times was 2 (2–6), and the number of segments during each single balloon dilatation was 3–5, compared with the first clinical results before  the first balloon dilation, systolic pulmonary artery pressure [53 (47–75) mm Hg vs. 45 (40–54) mm Hg, P=0.042), mean pulmonaryartery pressure [38 (29–47) mm Hg vs. 29 (25–39) mm Hg, P=0.043], N terminal-B type natriuretic peptide [1 872 (1 598–2 898) pg/ml vs. 164 (72–334) pg/ml, P=0.018] improved significantly after the last balloon angioplasty. Heart function classification (NYHA) of all the 7 patients were recovered to Ⅰ-Ⅱclasses (P<0.05). Conclusion    Sequential pulmonary balloon angioplasty after pulmonary endarterectomy can further reduce the patient's right heart after load, improve the heart function for patients with progressed pulmonary hypertension after pulmonary endarterectomy surgeries.

Objective: To evaluate the dosimetric difference between carbon ion radiotherapy and photon radiotherapy for treating tumors at lacrimal system. Methods: Using the CT images of 10 patients with tumors at lacrimal system, the carbon ion plan, the photon volume intensity modulation plan (VMAT) and the fixed wild photon intensity modulation radiotherapy (IMRT) plan were generated. The prescription was 54 Gy(RBE) in 18 fractions for clinical target volume (CTV) and 63 Gy(RBE) in 18 fractions for CTV-boost. Dosimetric differences of organ at risks were compared based on the same planning target volumes (PTVs) with similar dose coverages. Results: There was no statistically significant difference in the PTV coverage among three plans (P>0.05). Compared to VMAT and IMRT plans, carbon ion plans reduced the mean doses of eyeballs, mean doses and near-maximum doses of optical nerves of both ipsilateral ( t=7.35, 3.79, 4.66, 8.48, 2.52, 2.76, P<0.05) and contralateral eyes (t=3.87, 10.49, 9.16, 4.43, 6.53, 5.12, P<0.05), while the mean dose of brain was decreased from(5.65±3.58) and (5.76±2.09)Gy(RBE) to (0.81±0.90)Gy(RBE) (t=6.76, 17.33, P<0.05). Conclusions Compared to photon VMAT or IMRT, carbon ion could reduce the doses to optical critical organs around tumors. Thus, carbon ion radiotherapy has potential to reduce patients′ radiation related side-effects.

Objective: To investigate the effect of lipiodol as embolization agents in liver, after transcatheter arterial chemoembolization, on dose calculation under the carbon ion treatment plan. Methods: The actual relative linear stopping powers(RLSP)in pure lipiodol, pure gel and lipiodol-gel mixture, together with the correctd RLSPs from their CT images, were compared.In seven typical cases with lipiodol deposition area, carbon ion treatment plan was performed for the original lipiodol images.Successively on the basis of analysis that has made, the RLSP in lipiodol deposition area was corrected to be as in normal liver tissue, for which the carbon ion treatment plan was again performed.A comparison was made of differences in water equivalent depth (WED) and dose distribution on different CT images. Results: The RLSP value corrected according to CT image HU value, lipiodol, and lipiodol-gel mixture may increase by 4.6%-139.0% compared with the measured value. In seven typical cases, deposited lipiodol can cause WED to increase by (0.89±0.41) cm along the field track and RBE by(3.83±1.71)Gy within the 1 cm of distal area of target. Conclusions In order to improve the accuracy of dose distribution calculation, the HU value and/or RLSP in deposited lipiodol area in liver after transcatheter arterial chemoembolization should being corrected to be as in the normal liver tissue.