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There are no clinical reports of long‐term follow‐up after carbon‐ion radiotherapy (CIRT) using a dose of 51.6 Gy (relative biological effectiveness [RBE]) in 12 fractions for localized prostate cancer, or of a comparison of clinical outcomes between passive and scanning beam irradiation. A total of 256 patients with localized prostate cancer who received CIRT at a dose of 51.6 Gy (RBE) in 12 fractions using two different beam delivery techniques (passive [n = 45] and scanning [n = 211]), and who were followed for more than 1 year, were analyzed. The biochemical relapse‐free (bRF) rate was defined by the Phoenix definition, and the actuarial toxicity rates were evaluated using the Kaplan‐Meier method. Of the 256 patients, 41 (16.0%), 111 (43.4%), and 104 (40.6%) were classified as low, intermediate, and high risk, respectively, after a median follow‐up of 7.0 (range 1.1‐10.4) years. Androgen deprivation therapy was performed in 212 patients (82.8%). The 5‐year bRF rates of the low‐, intermediate‐, and high‐risk patients were 95.1%, 90.9%, and 91.1%, respectively. The 5‐year rates of grade 2 late gastrointestinal and genitourinary toxicities in all patients were 0.4% and 6.3%, respectively. No grade ≥3 toxicities were observed. There were no significant differences in the rates of bRF or grade 2 toxicities in patients who received passive irradiation versus scanning irradiation. Our long‐term follow‐up results showed that a CIRT regimen of 51.6 Gy (RBE) in 12 fractions for localized prostate cancer yielded a good therapeutic outcome and low toxicity rates irrespective of the beam delivery technique. A 51.6 Gy (relative biological effectiveness) carbon‐ion radiotherapy regimen in 12 fractions for localized prostate cancer with long‐term follow‐up yielded a good therapeutic outcome and low toxicity rates in both passive and scanning beam irradiation without significant difference.

PurposeThe Working Group of the Gynecological Tumor Committee of the Japanese Radiation Oncology Study Group (JROSG) published recommendations for contouring high-risk clinical target volumes (HR-CTV) on CT for 3-dimentional image-guided brachytherapy for cervical cancer. The purpose of this study was to compare HR-CTV delineated on CT, referencing recommendations from JROSG, with HR-CTV delineated on MRI, referencing consensus guidelines from the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC ESTRO).Material and methodsFourteen patients were evaluated. After the insertion of the CT/MR applicator into the patient, CT and MRI were performed. HR-CTVMR was delineated on MRI for clinical examination and HR-CTVCT was delineated on CT retrospectively referencing the MRI just before brachytherapy within a week. The volume and dosimetry of HR-CTV based on a 6 Gy dose of the Manchester system were evaluated.ResultsThe median volumes of HR-CTVMR and HR-CTVCT were 24.4 ml (range, 13.6–50.4 ml) and 29.9 ml (range, 13.2–49.2 ml), respectively. Median D90 of HR-CTVMR and HR-CTVCT were 6.7 Gy (range, 5.8–10.1 Gy) and 6.8 Gy (range, 5.1–10.4 Gy), respectively.ConclusionSomewhat difference could be seen between HR-CTVMR and HR-CTVCT.

The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, we screened 12 fullerene derivatives using an in vitro PA endonuclease inhibition assay. We identified 8 fullerene derivatives that inhibited the endonuclease activity of the PA N-terminal domain or full-length PA protein in vitro. We also performed in silico docking simulation analysis of the C60 fullerene and PA endonuclease, which suggested that fullerenes can bind to the active pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza A viral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate that fullerene derivatives are possible candidates for the development of novel anti-influenza drugs.

The H1N1 influenza A virus of swine-origin caused pandemics throughout the world in 2009 and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. The threat of influenza A thus remains a serious global health issue and novel drugs that target these viruses are highly desirable. Influenza A possesses an endonuclease within its RNA polymerase which comprises PA, PB1 and PB2 subunits. To identify potential new anti-influenza compounds in our current study, we screened 33 different types of phytochemicals using a PA endonuclease inhibition assay in vitro and an anti-influenza A virus assay. The marchantins are macrocyclic bisbibenzyls found in liverworts, and plagiochin A and perrottetin F are marchantin-related phytochemicals. We found from our screen that marchantin A, B, E, plagiochin A and perrottetin F inhibit influenza PA endonuclease activity in vitro. These compounds have a 3,4-dihydroxyphenethyl group in common, indicating the importance of this moiety for the inhibition of PA endonuclease. Docking simulations of marchantin E with PA endonuclease suggest a putative \"fitting and chelating model\" as the mechanism underlying PA endonuclease inhibition. The docking amino acids are well conserved between influenza A and B. In a cultured cell system, marchantin E was further found to inhibit the growth of both H3N2 and H1N1 influenza A viruses, and marchantin A, E and perrotein F showed inhibitory properties towards the growth of influenza B. These marchantins also decreased the viral infectivity titer, with marchantin E showing the strongest activity in this assay. We additionally identified a chemical group that is conserved among different anti-influenza chemicals including marchantins, green tea catechins and dihydroxy phenethylphenylphthalimides. Our present results indicate that marchantins are candidate anti-influenza drugs and demonstrate the utility of the PA endonuclease assay in the screening of phytochemicals for anti-influenza characteristics.

Background To evaluate the clinical relative biological effectiveness (RBE) of carbon‐ion radiotherapy (C‐ion RT) for prostate cancer. Methods The records of 262 patients with low‐risk prostate cancer (median age, 65 [47–80] years) treated with C‐ion RT at QST Hospital, National Institutes for Quantum Science and Technology in Japan during 2000–2018 were reviewed retrospectively. Four different protocol outcomes and prostate‐specific antigen (PSA) responses were evaluated. The median follow‐up was 8.4 years. The Kaplan–Meier method was used to estimate the biochemical or clinical failure‐free rate (BCFFR). Clinical RBE was calculated using the tumor control probability model. Results The 5‐, 7‐, and 10‐year BCFFRs were 91.7%, 83.8%, and 73.2%, respectively. The 10‐year BCFFRs of patients who received C‐ion RT at 66 Gy (RBE) in 20 fractions, 63 Gy (RBE) in 20 fractions, and 57.6 Gy (RBE) in 16 fractions were 81.4%, 70.9%, and 68.9%, respectively. The PSA level and density during follow‐up were better in the patients treated with the lower fraction size. A higher PSA nadir and shorter time to PSA nadir were risk factors for biochemical or clinical failure by multivariate Cox regression. The tumor control probability analysis showed that the estimated clinical RBE values to achieve an 80% BCFFR at 10 years for 20, 16, and 12 fractions were 2.19 (2.18–2.24), 2.16 (2.14–2.23), and 2.12 (2.09–2.21), respectively. Conclusions Using clinical data from low‐risk prostate cancer patients, we showed the clinical RBE of C‐ion RT decreased with increasing dose per fraction. This is the first study to use clinical data of carbon‐ion radiotherapy from low‐risk prostate cancer to evaluate the clinical relative biological effectiveness (RBE). Our results showed that the RBE of carbon‐ion decreased when the dose per fraction increased.

There are no studies on the risk factors of radiation pneumonitis (RP) after carbon-ion radiotherapy at a dose of 50 Gy (relative biological effectiveness (RBE)) in a single fraction. The objective of this study was to identify factors associated with RP after radiotherapy, including dose–volume parameters. Ninety-eight patients without a history of thoracic radiotherapy who underwent treatment for solitary lung tumors between July 2013 and April 2016 were retrospectively analyzed. Treatment was planned using Xio-N. The median follow-up duration was 53 months, and the median clinical target volume was 32.3 mL. Three patients developed grade 2 RP, and one patient developed grade 3 interstitial pneumonitis. None of the patients developed grade 4 or 5 RP. The dose-volume parameters of the normal lung irradiated at least with 5–30 Gy (RBE), and the mean lung dose was significantly lower in patients with grade 0–1 RP than in those with grade 2–3 RP. Pretreatment with higher SP-D and interstitial pneumonitis were significant factors for the occurrence of symptomatic RP. The present study showed a certain standard for single-fraction carbon-ion radiotherapy that does not increase the risk of RP; however, further validation studies are needed.

Background Three‐dimensional image‐guided brachytherapy is the standard of care in cervical cancer radiotherapy. In addition, the usefulness of the so‐called “hybrid brachytherapy (HBT)” has been reported, which involves the addition of needle applicators to conventional intracavitary brachytherapy for interstitial irradiation. Aim To evaluate the clinical outcomes of CT‐based HBT consisting of transvaginal insertion of needle applicators (CT‐based transvaginal HBT) and only intravenous sedation without general or saddle block anesthesia. Methods and results This is a retrospective chart review of patients who received definitive radiotherapy, including CT‐based transvaginal HBT, between February 2012 and July 2019. The inclusion criteria were as follows: (i) histologically diagnosed disease, (ii) untreated cervical cancer, (iii) International Federation of Gynecology and Obstetrics (FIGO) stage IB1–IVA disease in the 2008 FIGO staging system, and (iv) patients who underwent CT‐based transvaginal HBT at least once in a series of intracavitary brachytherapy. Overall, 54 patients fulfilled the eligibility criteria in the present study. The median follow‐up period was 32 (IQR, 19–44) months. No patient complained of symptoms such as persistent bleeding or abdominal pain after the treatment. The 3‐year local control (LC), disease‐free survival, and overall survival rates for all 54 patients were 86.6%, 60.3%, and 90.7% (95% CI [81.3%–100.0%]), respectively. The 3‐year LC rate was 87.7% in patients with FIGO III–IVA and 90.4% in tumor size >6.0 cm. The incidence rate of late adverse events, grade ≥3, in the rectum and bladder was 0% and 1.8%, respectively. In the dose‐volume histogram analyses, transvaginal HBT increased the dose of HR‐CTVD90 by ~7.5% without significantly increasing the dose of organs at risk. Conclusion Considering the favorable clinical outcomes, CT‐based transvaginal HBT may be a good option for treating cervical cancer.

Carbon-ion radiotherapy (CIRT) is a high-dose intensive treatment, whose safety and efficacy have been proven for prostate cancer. This study aims to evaluate the outcomes of CIRT in elderly patients with prostate cancer. Patients aged 75 years or above at the initiation of CIRT were designated as the elderly group, and younger than 75 years as the young group. The overall survival (OS), disease-specific survival (DSS), biochemical control rate (BCR), biochemical relapse-free survival (BRFS), and adverse events were compared between the elderly and young patients with high-risk prostate cancer treated with CIRT. The elderly group comprised 173 of 927 patients treated for high-risk prostate cancer between April 2000 and May 2018. The overall median age was 69 (range: 45–92) years. The median follow-up period was 91.9 (range: 12.6–232.3) months. The 10-year OS, DSS, BCR, and BRFS rates in the young and elderly groups were 86.9%/71.5%, 96.6%/96.8%, 76.8%/88.1%, and 68.6%/64.3%, respectively. The OS (p < 0.001) was longer in the younger group and the BCR was better in the elderly group (p = 0.008). The DSS and BRFS did not differ significantly between the two groups. The rates of adverse events between the two groups did not differ significantly and no patient had an adverse event of Grade 4 or higher during the study period. CIRT may be as effective and safe in elderly patients as the treatment for high-risk prostate cancer.

To investigate outcomes of patients with cervical cancer who received radiation therapy for extrapelvic lymph node recurrence after initial pelvic radiotherapy. The treatment charts of 20 patients were retrospectively reviewed, and factors influencing patient's prognosis were statistically analyzed. The three-year in-field tumor control rate was 55% and overall survival (OS) at 2, 3, and 5 years was 55%, 45%, and 37.5%, respectively. The rate of the three-year OS in patients with recurrence within and after 9 months was 20% and 70%, respectively (p=0.016). None of the 4 patients who were diagnosed with supraclavicular lymph node recurrence alone at more than 9 months after initial treatment experienced further recurrence. Five-year survival of the remaining 16 patients was only 21% (p=0.021). Time to recurrence significantly influenced survival in patients with cervical cancer who received radiotherapy for extra-pelvic lymph node recurrence. Supraclavicular lymph node recurrence alone had a favorable impact on patient's prognosis.

Purpose We propose a method of image-guided brachytherapy (IGBT) that combines MRI-based target volume delineation for the first fraction with CT datasets of subsequent fractions, using an automatic, applicator-based co-registration, and report our preliminary experience. Materials and methods The MRI of the first fraction was used for the first brachytherapy planning. For each subsequent brachytherapy fraction, after the same applicator insertion, a new CT scan with the applicator in place was obtained. The MR image set was registered to the subsequent brachytherapy treatment planning CT using the applicator for rigid body registration. To demonstrate the registration quality, we used here the Dice index as a measurement of tandem delineation overlap between CT and MRI. Results The median Dice index was 0.879 (range 0.610–0.932), which indicated that the contours on CT and MRI fitted well. With this combination method, the median D90 of HR CTV and the calculated D2 cm 3 of the bladder, rectum, and sigmoid in each fraction were 7.2 (4.0–10.4), 5.9 (2.3–7.7), 4.0 (1.9–6.7), and 3.8 (0.6–7.2) Gy, respectively. Conclusion Our described method of MRI-guided IGBT offers a practical option for the benefits of target delineation.