Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan

To evaluate preliminary results of proton radiotherapy (PRT) for pediatric patients with rhabdomyosarcoma (RMS). From 1987 to 2014, PRT was conducted as initial radiotherapy in 55 patients (35 males, 20 females, median age 5 years, range 0–19) with RMS at four institutes in Japan. Thirty‐one, 18, and six patients had embryonal, alveolar, and other RMS, respectively. One, 11, 37, and six patients were in IRSG groups I, II, III, and IV, respectively, and the COG risk group was low, intermediate, and high for nine, 39, and seven patients, respectively. The irradiation dose was 36–60 GyE (median: 50.4 GyE). The median follow‐up period was 24.5 months (range: 1.5–320.3). The 1‐ and 2‐year overall survival rates were 91.9% (95% CI: 84.3–99.5%) and 84.8% (95% CI 75.2–94.3%), respectively, and these rates were 100% and 100%, 97.1% and 90.1%, and 57.1% and 42.9% for COG low‐, intermediate‐, and high‐risk groups, respectively. There were 153 adverse events of Grade ≥3, including 141 hematologic toxicities in 48 patients (87%) and 12 radiation‐induced toxicities in nine patients (16%). Proton‐specific toxicity was not observed. PRT has the same treatment effect as photon radiotherapy with tolerable acute radiation‐induced toxicity

Concurrent chemoradiotherapy using proton beams for unresectable locally advanced pancreatic cancer

Background and purposeWe investigated clinical outcomes of proton beam concurrent chemoradiotherapy (CCRT) for unresectable, locally advanced pancreatic cancer (LAPC) patients.Materials and methodsRecords from 42 unresectable LAPC patients (21 male and 21 female, 39–83 years old) with IIB/III clinical staging of 1/41 treated by proton beam CCRT were retrospectively reviewed. Twelve patients received a conventional 50 Gray equivalents (GyE) in 25 fractions protocol and 30 others received a higher dose protocol of 54.0–67.5 GyE in 25–33 fractions. Gemcitabine or S-1 (Tegafur, Gimeracil and Oteracil) was used concurrently. Toxicity, overall survival (OS) and local control (LC) were examined.ResultsAcute adverse events of grades 1, 2, 3 and 4 were found in 4, 15, 17 and 2 patients, respectively. All grade 3 and 4 events were hematologic. Late adverse events of grades 1 and 2 were found in 3 and 2 patients, respectively. No late adverse effects of grade 3 or higher were observed. The 1-year/2-year OS rates from the start of CCRT were 77.8/50.8% with median survival time (MST) of 25.6 months. The 1-year/2-year LC rate from CCRT start was 83.3/78.9% with a median time to local recurrence of more than 36 months. Total irradiation dose was the only significant factor in univariate analyses of OS and LC (p = 0.015 and 0.023, respectively).ConclusionProton beam CCRT lengthened survival periods compared to previous photon CCRT data and higher dose irradiation prolonged LC and OS for unresectable LAPC patients. Proton beam therapy is therefore safe and effective in these cases

A validated proton beam therapy patch-field protocol for effective treatment of large hepatocellular carcinoma

Development of a curative local treatment for large hepatocellular carcinoma (HCC) is an important issue. Here, we investigated the dose homogeneity, safety and antitumor effectiveness of proton beam therapy (PBT) using a patch-field technique for large HCC. Data from nine patients (aged 52–79 years) with large HCC treated with patch-field PBT were investigated. The cranial–caudal diameters of the clinical target volumes (CTVs) were 15.0–18.6 cm (median 15.9). The CTV was divided cranially and caudally while both isocenters were aligned along the cranial–caudal axis and overlap of the cranial and caudal irradiation fields was set at 0–0.5 mm. Multileaf collimators were used to eliminate hot or cold spots. Total irradiation doses were 60–76.4 Gy equivalents. Irradiation doses as a percentage of the prescription dose (from the treatment planning system) around the junction were a minimum of 93–105%, a mean of 99–112%, and a maximum of 105–120%. Quality assurance (QA) was assessed in the cranial and caudal irradiation fields using imaging plates. Acute adverse effects of Grade 3 were observed in one patient (hypoalbuminemia), and a late adverse effect of Grade 3 was observed in one patient (liver abscess). Child–Pugh class elevations were observed in four patients (A to B: 3; B to C: 1). Overall survival rates at 1 and 2 years were 55 and 14%, respectively, with a median overall survival of 13.6 months. No patients showed local recurrence. Patch-field PBT supported by substantial QA therefore is one of the treatment options for large HCC

Long-term follow-up after proton beam therapy for pediatric tumors: a Japanese national survey

Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long-term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0–19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow-up period was 8.1 years (5.0–31.2 years). The 5-, 10- and 20-year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10- and 20-year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow-up is needed to confirm the benefits of PBT for pediatric tumors

Proton beam therapy for liver metastases from gastric cancer

Liver metastases from gastric cancer (LMGC) is a non-curable, fatal disease with a 5-year survival rate of <10%. Although various local treatments have been applied, their clinical utility has not been established. The purpose of this study was to investigate the safety and effectiveness of proton beam therapy (PBT) for the treatment of patients with LMGC. A total of nine patients (seven men, two women; aged 56–78 years) with LMGC who received PBT between 2002 and 2012 were retrospectively reviewed. Patients who had tumors confined to the liver were investigated, and patients who had extrahepatic tumors were excluded. Six of the patients had solitary tumors, and three patients had multiple tumors. The total irradiation dose was 64–77 Gy relative biological effectiveness (RBE), and three patients received concurrent chemotherapy. The overall and progression-free survival (OS and PFS) rates, local control (LC) rate, and adverse effects were investigated. All patients completed treatment without interruption, and late adverse effects of higher than Grade 3 were not observed. The OS rates at 1, 3 and 5 years were 100%, 78% and 56%, respectively (median, 5.5 years); the PFS rates were 67%, 40% and 40% (median, 2.6 years); and the LC rates were 89%, 71% and 71%. PBT was demonstrated to be a safe treatment, and the OS and PFS rates were not inferior to those for other types of local treatment. Therefore, PBT should be considered as an effective local treatment option for patients with LMGC

Registration error of the liver CT using deformable image registration of MIM Maestro and Velocity AI

BackgroundUnderstanding the irradiated area and dose correctly is important for the reirradiation of organs that deform after irradiation, such as the liver. We investigated the spatial registration error using the deformable image registration (DIR) software products MIM Maestro (MIM) and Velocity AI (Velocity).MethodsImage registration of pretreatment computed tomography (CT) and posttreatment CT was performed in 24 patients with liver tumors. All the patients received proton beam therapy, and the follow-up period was 4–14 (median: 10) months. We performed DIR of the pretreatment CT and compared it with that of the posttreatment CT by calculating the dislocation of metallic markers (implanted close to the tumors).ResultsThe fiducial registration error was comparable in both products: 0.4–32.9 (9.3 ± 9.9) mm for MIM and 0.5–38.6 (11.0 ± 10.0) mm for Velocity, and correlated with the tumor diameter for MIM (r = 0.69, P = 0.002) and for Velocity (r = 0.68, P = 0.0003). Regarding the enhancement effect, the fiducial registration error was 1.0–24.9 (7.4 ± 7.7) mm for MIM and 0.3–29.6 (8.9 ± 7.2) mm for Velocity, which is shorter than that of plain CT (P = 0.04, for both).ConclusionsThe DIR performance of both MIM and Velocity is comparable with regard to the liver. The fiducial registration error of DIR depends on the tumor diameter. Furthermore, contrast-enhanced CT improves the accuracy of both MIM and Velocity

Long-term outcomes of proton beam therapy in patients with previously untreated hepatocellular carcinoma

Long-term efficacy of proton beam therapy (PBT) remains unclear for patients with previously untreated hepatocellular carcinoma (HCC). We aimed to study the long-term outcomes of PBT according to Barcelona Clinic Liver Cancer (BCLC) staging classifications in patients with previously untreated HCC. The major eligibility criteria of this observational study were an Eastern Cooperative Oncology Group performance status (PS) 0–2, Child–Pugh grade A or B, previously untreated HCC covered within an irradiation field, and no massive ascites. A total of 66.0–77.0 GyE was administered in 10–35 fractions. Local tumor control (LTC), defined as no progression in the irradiated field, progression-free survival (PFS), and overall survival (OS) were assessed according to BCLC staging. From 2002 to 2009 at our institution, 129 patients were eligible. The 5-year LTC, PFS, and OS rates were 94%, 28%, and 69% for patients with 0/A stage disease (n = 9/21), 87%, 23%, and 66% for patients with B stage disease (n = 34), and 75%, 9%, and 25% for patients with C stage disease (n = 65), respectively. The 5-year LTC and OS rates of 15 patients with tumor thrombi in major vessels were 90% and 34%, respectively. Multivariate analyses revealed that PS (0 versus 1–2) was a significant prognostic factor for OS. No grade 3 or higher adverse effects were observed. PBT showed favorable long-term efficacies with mild adverse effects in BCLC stage 0 to C, and can be an alternative treatment for localized HCC especially when accompanied with tumor thrombi. This study was registered with UMIN Clinical Trials Registry (UMIN000025342)

Proton beam therapy for a patient with a giant thymic carcinoid tumor and severe superior vena cava syndrome

Surgical resection is the first choice for treatment of a thymic carcinoid tumor and radiotherapy is often performed as adjuvant therapy. Here, we report a case of an unresectable and chemoresistant thymic carcinoid tumor that was treated successfully using standalone proton beam therapy (PBT). The patient was a 66-year-old woman in whom surgical resection of the tumor was impossible because of cardiac invasion. Therefore, chemotherapy was administered. However, the tumor grew to 15 cm in diameter and she developed severe superior vena cava (SVC) syndrome. She was referred to our hospital and received PBT at a dose of 74 GyE in 37 fractions. PBT was conducted without severe early toxicities. After PBT, the tumor mildly shrunk to 13 cm in diameter and SVC syndrome almost disappeared. Subsequently, the tumor has continued to decrease in size slowly over the last 2 years and late toxicities have not been observed. Our experience with this case suggests that PBT may be effective for an unresectable thymic carcinoid tumor

Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi‑institutional study

Purpose To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). Materials and methods From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) orcarbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy.Results Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196).ConclusionDifferences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy