Calculating dose-averaged linear energy transfer in an analytical treatment planning system for carbon-ion radiotherapy.

BACKGROUND: Compelling evidence shows the association between the relative biological effectiveness (RBE) of carbon-ion radiotherapy (CIRT) and the dose averaged linear energy transfer (LETd). However, the ability to calculate the LETd in commercially available treatment planning systems (TPS) is lacking. PURPOSE: This study aims to develop a method of calculating the LETd of CIRT plans that could be robustly carried out in RayStation (V10B, Raysearch, Sweden). METHODS: The calculation used the fragment spectra in RayStation for the CIRT treatment planning. The dose-weighted averaging procedure was supported by the microdosimetric kinetic model (MKM). The MKM-based pencil beam dose engine (PBA, v4.2) for calculating RBE-weighted doses was reformulated to become a LET-weighted calculating engine. A separate module was then configured to inversely calculate the LETd from the absorbed dose of a plan and the associated fragment spectra. In this study, the ion and energy-specific LET table in the LETd module was further matched with the values decoded from the baseline data of the Syngo TPS (V13C, Siemens, Germany). The LETd distributions of several monoenergetic and modulated beams were calculated and validated against the values derived from the Syngo TPS and the published data. RESULTS: The differences in LETds of the monoenergetic beams between the new method and the traditional method were within 3% in the entrance and Bragg-peak regions. However, a larger difference was observed in the distal region. The results of the modulated beams were in good agreement with the works from the published literature. CONCLUSIONS: The method presented herein reformulates the MKM dose engine in the RayStation TPS to inversely calculate LETds. The robustness and accuracy were demonstrated.

Proton and carbon ion radiation therapy for locally advanced pancreatic cancer: A phase I dose escalation study.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of proton and carbon ion radiation therapy (PCRT) for locally advanced pancreatic cancer (LAPC). METHODS: A single-institution, phase I dose escalation study was performed. The proton dose of 50.4 GyE in 28 fractions was delivered to clinical target volume, and carbon ion as a boost dose to gross tumor volume escalated from 12 GyE to 18 GyE with 3 GyE per fraction in 3 dose levels. The dose limiting toxicity (DLT) was defined as any treatment-related grade (G)3 or higher of non-hematological toxicity. The MTD was exceeded if ≥2 patients in a dose level developed DLT. RESULTS: From May 2015 to July 2016, ten patients were enrolled, 3 in dose level 1, 4 in dose level 2, and 3 in dose level 3. With a median follow-up of 17.4 months, no patient developed a DLT, and the acute G1-2 of gastrointestinal (GI) and hepatic toxicity occurred in 40% of patients, and G1 of GI late toxicity, in 30%. The median overall survival was 17.3 months. CONCLUSION: Higher than 50.4 GyE could be given by PCRT with slight toxicity and good tolerance for LAPC, and the tumor control and survival had been improved, but not significantly. Better outcome may be achieved using carbon ion radiation therapy with higher biological equivalent dose.

Dosimetric comparison between carbon, proton and photon radiation for renal retroperitoneal soft tissue sarcoma recurrence or metastasis after radical nephrectomy.

OBJECTIVE: To compare the dosimetric difference between various modalities in the radiation treatment for renal retroperitoneal soft tissue sarcoma recurrence or metastasis (RRSTSRM) after radical nephrectomy, and assess the dosimetric advantage on protecting the organs at risk (OARs) in the carbon and proton radiotherapy for the patients with a single kidney. METHODS: A total of 12 patients with RRSTSRM who underwent radical nephrectomy were enrolled in this study. Carbon, proton, and photon radiotherapy were implemented for treatment planning. The prescription dose was fulfilled by simultaneously integrated boosting technique, with giving the planning target volume-1 (PTV-1) 51Gy (RBE) and planning target volume-2 (PTV-2) 60 Gy (RBE). Doses in the patient's spinal cord, stomach, duodenum, bowel, colon, and contralateral kidney were evaluated. The normal tissue complication probability (NTCP) of the duodenum, bowel, colon, and contralateral kidney was derived under Lyman-Kutcher-Burman (LKB) estimation. RESULTS: In the carbon plans, the percentage volume of 95% prescription dose (V95%) covering PTV-1 (PTV-2) was 95.93% ± 3.42% (95.61% ± 4.26%). No significant dosimetric difference on the target was obtained between the four radiation modalities (P > .05). The percentage volume of receiving 40 Gy (RBE) [V40Gy (RBE)] in the duodenum could be reduced from 12.94% ± 15.99% in the IMRT plans to 6.36% ± 8.79% (8.44% ± 12.35%) in the carbon (proton) plans (P < .05). The V40Gy (RBE) in the bowel could be reduced from 13.48% ± 13.12% in the IMRT plans to 7.04% ± 9.32% (7.34% ± 9.89%) in the carbon (proton) plans (P < .05). The mean value of NTCP for the duodenum was 0.43 ± 0.47 (0.45 ± 0.48) by using carbon (proton) radiation. The value was 0.05 (0.03) lower than the IMRT plans on average, with a reduction of 0.20 (0.13) for the patients with lesions <5 mm away from the duodenum. The mean doses of the contralateral kidney were 0.28 ± 0.37 Gy (RBE) [0.28 ± 0.40 Gy (RBE)] in the IMCT (IMPT) plans, which was 92.43% (92.43%) lower than the value in the IMRT plans respectively (P < .05). CONCLUSION: Compared to the conventional radiation techniques, particle radiotherapy of carbon and proton could significantly spare more OARs in the treatment for RRSTSRM after radical nephrectomy. Patients, especially those whose residuals are close to the duodenum would potentially benefit from the particle radiation therapy for RRSTSRM on the decrease in radiation-related side-effect.

Conversion and validation of rectal constraints for prostate carcinoma receiving hypofractionated carbon-ion radiotherapy with a local effect model.

BACKGROUND: The study objective was to establish the local effect model (LEM) rectum constraints for 12-, 8-, and 4-fraction carbon-ion radiotherapy (CIRT) in patients with localized prostate carcinoma (PCA) using microdosimetric kinetic model (MKM)-defined and LEM-defined constraints for 16-fraction CIRT. METHODS: We analyzed 40 patients with PCA who received 16- or 12-fraction CIRT at our center. Linear-quadratic (LQ) and RBE-conversion models were employed to convert the constraints into various fractionations and biophysical models. Based on them, the MKM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to 12-, 8-, and 4-fraction CIRT using the LQ model. Then, MKM constraints were converted to LEM using the RBE-conversion model. Meanwhile the LEM LQ strategy converted MKM rectum constraints for 16-fraction CIRT to LEM using the RBE-conversion model. Then, LEM constraints were converted from 16-fraction constraints to the rectum constraints for 12-, 8-, and 4-fraction CIRT using the LQ model. The LEM constraints for 16- and 12-fraction CIRT were evaluated using rectum doses and clinical follow-up. To adapt them for the MKM LQ strategy, CNAO LEM constraints were first converted to MKM constraints using the RBE-conversion model. RESULTS: The NIRS (i.e. DMKM|v, V-20%, 10%, 5%, and 0%) and CNAO rectum constraints (i.e. DLEM|v, V-10 cc, 5 cc, and 1 cc) were converted for 12-fraction CIRT using the MKM LQ strategy to LEM 37.60, 49.74, 55.27, and 58.01 Gy (RBE), and 45.97, 51.70, and 55.97 Gy (RBE), and using the LEM LQ strategy to 39.55, 53.08, 58.91, and 61.73 Gy (RBE), and 49.14, 55.30, and 59.69 Gy (RBE). We also established LEM constraints for 8- and 4-fraction CIRT. The 10-patient RBE-conversion model was comparable to 30-patient model. Eight patients who received 16-fraction CIRT exceeded the corresponding rectum constraints; the others were within the constraints. After a median follow-up of 10.8 months (7.1-20.8), No ≥ G1 late rectum toxicities were observed. CONCLUSIONS: The LEM rectum constraints from the MKM LQ strategy were more conservative and might serve as the reference for hypofractionated CIRT. However, Long-term follow-up plus additional patients is necessary.

RBE-weighted dose conversions for carbon ionradiotherapy between microdosimetric kinetic model and local effect model for the targets and organs at risk in prostate carcinoma.

BACKGROUND AND PURPOSE: The aim of this study was to establish curves for the conversion of RBE-weighted doses for targets and organs at risk (OARs) from the microdosimetric kinetic model (MKM) calculation to that of the local effect model I (LEM) for carbon ion radiotherapy (CIRT) for prostate carcinoma (PCA). MATERIALS AND METHODS: This study was performed in the experimental treatment planning system (eTPS, V8A, Raystation, Sweden), which incorporates both MKM and LEM. CIRT plans from 10 PCA patients were collected. There were 5 steps to establish the curves: (1) design MKM plans in eTPS; (2) recalculate the physical doses from MKM to LEM and create a LEM plan in eTPS; (3) plot the RBE-weighted MKM to LEM conversion curves; (4) convert the MKM rectum constraint dose volume histogram (DVH) from NIRS to a LEM DVH; and (5) compare patients' rectum DVHs and follow-up with the converted constraint DVH. RESULTS: The conversion factors for MKM doses of 0.18 Gy (RBE) to 4.55 Gy (RBE) per fraction to LEM doses were 2.72-1.06. For fraction sizes of >1 Gy (RBE), the conversion factors matched Fossati's curve and for fraction sizes of <1.00 Gy (RBE) the values were on the extrapolated Fossati's curve. A LEM rectum constraint DVH was established. Ten patients' rectum DVHs were all lower than LEM constraint DVHs. No complications were reported clinically. CONCLUSION: For PCA receiving CIRT, the RBE-weighted doses using MKM for targets and OARs could be converted to LEM doses using conversion curves.

An in-silico comparison of proton beam and IMRT for postoperative radiotherapy in completely resected stage IIIA non-small cell lung cancer.

INTRODUCTION: Post-operative radiotherapy (PORT) for stage IIIA completely-resected non-small cell lung cancer (CR-NSCLC) has been shown to improve local control; however, it is unclear that this translates into a survival benefit. One explanation is that the detrimental effect of PORT on critical organs at risk (OARs) negates its benefit. This study reports an in-silico comparative analysis of passive scattering proton therapy (PSPT)- and intensity modulated proton therapy (IMPT) with intensity modulated photon beam radiotherapy (IMRT) PORT. METHODS: The computed tomography treatment planning scans of ten patients with pathologic stage IIIA CR-NSCLC treated with IMRT were used. IMRT, PSPT, and IMPT plans were generated and analyzed for dosimetric endpoints. The proton plans were constructed with two or three beams. All plans were optimized to deliver 50.4 Gy(RBE) in 1.8 Gy(RBE) fractions to the target volume. RESULTS: IMPT leads to statistically significant reductions in maximum spinal cord, mean lung dose, lung volumes treated to 5, 10, 20, and 30 Gy (V5, V10, V20, V30), mean heart dose, and heart volume treated to 40 Gy (V40), when compared with IMRT or PSPT. PSPT reduced lung V5 but increased lung V20, V30, and heart and esophagus V40. CONCLUSIONS: IMPT demonstrates a large decrease in dose to all OARs. PSPT, while reducing the low-dose lung bath, increases the volume of lung receiving high dose. Reductions are seen in dosimetric parameters predictive of radiation pneumonitis and cardiac morbidity and mortality. This reduction may correlate with a decrease in dose-limiting toxicity and improve the therapeutic ratio.

Reducing toxicity from craniospinal irradiation: using proton beams to treat medulloblastoma in young children.

PURPOSE: We report on a radiation treatment technique that has reduced the dose to critical normal structures in children with medulloblastoma. PATIENTS AND METHODS: Three children between the ages of 3 and 4 with stage M2 or M3 medulloblastoma were treated between 2001 and 2003 with craniospinal irradiation using protons. Patients received 36 cobalt gray equivalent to the craniospinal axis, then 18 cobalt gray equivalent to the posterior fossa. The cranium was treated with opposed lateral fields. The spine was treated with three matched posteroanterior fields, with the beam stopping just beyond the thecal sac. The posterior fossa was then treated with alternating posteroanterior, right posterior oblique, and left posterior oblique fields, with the beam stopping just proximal to the cochlea. The use of general anesthesia and pre-porting with diagnostic-quality x-rays allowed precise patient positioning. RESULTS: Craniospinal irradiation delivered via conformal proton irradiation substantially reduced the dose to the cochlea and vertebral bodies and virtually eliminated the exit dose through thorax, abdomen, and pelvis. Despite concurrent chemotherapy, a clinically significant lymphocyte count reduction was not seen. Patients tolerated treatment well; acute side effects (e.g., nausea, decreased appetite, and odynophagia) were mild. All patients completed therapy without interruption. CONCLUSION: Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae. This technique may be especially advantageous in children with a history of myelosuppression, who might not other wise tolerate irradiation.