Salvage robotic-assisted radical prostatectomy in a patient with recurrence after two sessions of heavy ion radiotherapy.

Salvage radical prostatectomy is a postradiation treatment for patients with localized prostate cancer. In 2016, Ozu et al. (Ozu C, Aoki K, Nakamura K, Yagi Y, Muro Y, Nishiyama T, et al. The initial case report: salvage robotic assisted radical prostatectomy after heavy ion radiotherapy. Urol Case Rep 2016;7:45-7) first reported salvage robotic-assisted radical prostatectomy (sRARP) after heavy-ion radiotherapy (HIRT). Thereafter, sRARP has been performed in >100 cases. However, it is currently avoided owing to some difficulties. Herein, we report about sRARP in a 67-year-old man who received two sessions of HIRT despite some expected challenges. He was initially treated with HIRT for prostate cancer in 2009 and received the second HIRT as salvage treatment for local recurrence in 2016. In 2019, he had biochemical recurrence and underwent sRARP. There were no significant peri- or postoperative complications. Subsequently, 12 months after sRARP, hormonal therapy was introduced after the diagnosis of biochemical recurrence. The patient's prostate-specific antigen level is currently undetectable.

Development and promotion of a 3D-printed phantom model for ultrasound-guided caudal block followed by intracavitary/interstitial brachytherapy for gynecological cancer.

PURPOSE: We developed a 3D-printed phantom model for ultrasound-guided caudal block for educational or training purposes because there have been no reports of the 3D-printed phantom model for ultrasound-guided caudal block. This study aimed to identify the needs for the phantom model in a lecture and demonstration at hands-on training (HoT) to promote the use of caudal block for sufficient pain control during high-dose-rate intracavitary/interstitial brachytherapy for gynecological cancers. MATERIALS AND METHODS: The sacrum and formwork were designed by computed tomography imaging. A 3D-modeling software program was used to create the sacrum and formwork. The phantom was solidified by injecting a gelatin-based gel. Ultrasonography was performed to visualize the sacral hiatus and puncture needle in the phantom. In October 2023, 10 radiation oncologists who did not perform caudal block in daily clinical practice from ten Japanese facilities participated in HoT on ultrasound-guided caudal block. After the HoT, questionnaires were distributed to each participant, and feedback was obtained through online channels. RESULTS: After receiving a lecture and demonstration on ultrasound-guided caudal block, 90% of the respondents would like to practice the procedure in their daily clinical practice. Moreover, 100% of the respondents would like to use the 3D-printed phantom model for ultrasound-guided caudal block for educational or training purposes. CONCLUSION: The 3D-printed phantom model for ultrasound-guided caudal block can be used in training and is in demand for facilities introducing caudal block.

Dose Contribution to the Regional Lymph-Node Metastases and Point B from Intracavity and Interstitial Hybrid Brachytherapy in Locally Advanced Cervical Cancer.

PURPOSE: Analyzing dose distributions to regional lymph-node metastases (RLNMs) in locally advanced cervical cancer (LACC) patients undergoing intracavitary and interstitial hybrid brachytherapy (IC/IS). METHODS: Dose distributions of eleven LACC patients with 38 RLNMs, and who received 38 IC/IS sessions were analyzed in EQD2, considering RLNM positions and ipsilateral interstitial needles; these RLNMs, excepting the para-aortic region, were classified into four groups. RESULTS: RLNMs had a median of two ipsilateral interstitial needles per session. Significant differences were observed in total RLNM D90, depending on whether the position was cranial or caudal of the uterine base (85.5 vs. 378.9 cGy, p < 0.0001), and whether the RLNM D90 was associated with a number of ipsilateral interstitial needles between 0-1 or 2 or more (68.4 vs. 112.2 cGy, p = 0.006) per session. At each session, Group 1 RLNMs (cranial of the uterine base, 0-1 ipsilateral interstitial needle) had a mean D90 of 21.1 cGy; Group 2 (cranial, 2 or more), 73.8; Group 3 (caudal, 0-1), 94.7; and Group 4 (caudal, 2 or more), 136.1. CONCLUSION: RLNMs located caudal of the uterine base associated with two or more ipsilateral interstitial needles in IC/IS had a higher dose contribution, which should be considered when calculating the RLNMs' dose of external beam boost irradiation.

Changes in Intratumor Blood Flow After Carbon-Ion Radiation Therapy for Early-Stage Breast Cancer.

Purpose: This study aimed to quantify the changes in intratumoral blood flow after carbon-ion radiation therapy (CIRT) for early-stage breast cancer and analyze their clinical significance. Patients and Methods: We included 38 patients with early-stage breast cancer who underwent CIRT. Dynamic imaging was performed using a 3T superconducting magnetic resonance scanner to quantify the washin index (idx), which reflects contrast uptake, and washout idx, which reflects the rate of contrast washout from tumor tissue. The changes in the apparent diffusion coefficient, washin idx, and washout idx were examined before CIRT and at 1 and 3 months after treatment. Clinical factors and imaging features were examined using univariate and receiver operating characteristic curve analyses to identify factors predicting clinical complete response (cCR). Results: The median observation period after CIRT was 51 (range: 12-122) months. During the observation period, 31 of the 38 patients achieved cCR, and 22 achieved cCR within 12 months. Tumor size (P < .001), washin idx (P = .043), and washout idx (P < .001) decreased significantly 1-month after CIRT. In contrast, the apparent diffusion coefficient values (P < .001) increased significantly 1-month after CIRT. Univariate analysis suggested that the washin idx after 1 and 3 months of CIRT was associated with cCR by 12 months post-CIRT (P = .028 and .021, respectively). No other parameters were associated with cCR by 12 months post-CIRT. Furthermore, receiver operating characteristic curve analyses showed that the area under the curve values of washin idx after 1 and 3 months of CIRT was 0.78 (specificity 75%, sensitivity 80%) and 0.73 (specificity 75%, sensitivity 71%), respectively. Conclusion: Tumor changes can be quantified early after CIRT using contrast-enhanced magnetic resonance imaging in patients with breast cancer. Washin idx values 1 and 3 months after CIRT were associated with cCR within 12 months post-CIRT.

The first real-world study on the role of carbon ion radiotherapy for oligo-metastatic, persistent, or recurrent (MPR) ovarian/fallopian tube cancer.

Introduction: In the multidisciplinary management of oligometastatic, persistent, or recurrent (MPR) ovarian cancer, radiotherapy (RT) is becoming a more and more worthwhile treatment to potentially improve the chronicity of the disease. Particle beam RT has proved to be effective in several gynecological malignancies, but so far no data are available for ovarian cancer. Material and Methods: This is a real-world, retrospective, bi-institutional, single-arm study aimed to assess the effectiveness and the safety of carbon ion RT (CIRT) in this setting. The co-first endpoints are 1-year and 2-year actuarial local control (LC) rates and the objective response rate (ORR) defined on a "per lesion" basis. The secondary endpoint was toxicity. Actuarial outcomes were evaluated using the Kaplan-Meier method while potential predictors were explored using the Log-rank test. Bi-variable logistic regression was employed in the analysis of factors predicting the complete response on a per-lesion basis. Results: 26 patients accounting for a total of 36 lesions underwent CIRT with a total median dose of 52.8 Gy[RBE] (range: 39-64 Gy[RBE]). Five patients received CIRT for re-irradiation. No concomitant systemic therapies were administered during CIRT. Within 12 months after the treatment, 17 lesions (47 %) achieved complete response while 18 (50 %) obtained a partial response with an ORR of 97 %. The achievement of a complete response is related to the dose per fraction (>4.2 Gy[RBE], p = 0.04) and total dose (>52,8 Gy[RBE], p = 0.05). The 1-year LC was 92 % and the 2-year LC was 83 %, according to the achievement of a CR (p = 0.007) and GTV ≤ 14 cm3 (p = 0.024). No grade > 3 toxicities were recorded both in naïve and re-irradiated patients. PARP-i and anti-VEGF seemed not to exacerbate the risk of severe toxicities. Conclusions: CIRT was effective and safe in MPR ovarian cancers, even in the case of re-irradiation. Largest cohort studies and longer follow-up are needed to confirm these data.

Inter-fractional error and intra-fractional motion of prostate and dosimetry comparisons of patient position registrations with versus without fiducial markers during treatment with carbon-ion radiotherapy.

A few reports have discussed the influence of inter-fractional position error and intra-fractional motion on dose distribution, particularly regarding a spread-out Bragg peak. We investigated inter-fractional and intra-fractional prostate position error by monitoring fiducial marker positions. In 2020, data from 15 patients with prostate cancer who received carbon-ion beam radiotherapy (CIRT) with gold markers were investigated. We checked marker positions before and during irradiation to calculate the inter-fractional positioning and intra-fractional movement and evaluated the CIRT dose distribution by adjusting the planning beam isocenter and clinical target volume (CTV) position. We compared the CTV dose coverages (CTV receiving 95% [V95%] or 98% [V98%] of the prescribed dose) between skeletal and fiducial matching irradiation on the treatment planning system. For inter-fractional error, the mean distance between the marker position in the planning images and that in a patient starting irradiation with skeletal matching was 1.49 ± 1.11 mm (95th percentile = 1.85 mm). The 95th percentile (maximum) values of the intra-fractional movement were 0.79 mm (2.31 mm), 1.17 mm (2.48 mm), 1.88 mm (4.01 mm), 1.23 mm (3.00 mm), and 2.09 mm (8.46 mm) along the lateral, inferior, superior, dorsal, and ventral axes, respectively. The mean V95% and V98% were 98.2% and 96.2% for the skeletal matching plan and 99.5% and 96.8% for the fiducial matching plan, respectively. Fiducial matching irradiation improved the CTV dose coverage compared with skeletal matching irradiation for CIRT for prostate cancer.

Efficacy and safety of FDG-PET for determining target volume during intensity-modulated radiotherapy for head and neck cancer involving the oral level.

PURPOSE: To determine the efficacy and safety of target volume determination by 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) for intensity-modulated radiation therapy (IMRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) extending into the oral cavity or oropharynx. METHODS: We prospectively treated 10 consecutive consenting patients with HNSCC using IMRT, with target volumes determined by PET-CT. Gross tumor volume (GTV) and clinical target volume (CTV) at the oral level were determined by two radiation oncologists for CT, magnetic resonance imaging (MRI), and PET-CT. Differences in target volume (GTVPET, GTVCT, GTVMRI, CTVPET, CTVCT, and CTVMRI) for each modality and the interobserver variability of the target volume were evaluated using the Dice similarity coefficient and Hausdorff distance. Clinical outcomes, including acute adverse events (AEs) and local control were evaluated. RESULTS: The mean GTV was smallest for GTVPET, followed by GTVCT and GTVMRI. There was a significant difference between GTVPET and GTVMRI, but not between the other two groups. The interobserver variability of target volume with PET-CT was significantly less than that with CT or MRI for GTV and tended to be less for CTV, but there was no significant difference in CTV between the modalities. Grade ≤ 3 acute dermatitis, mucositis, and dysphagia occurred in 55%, 88%, and 22% of patients, respectively, but no grade 4 AEs were observed. There was no local recurrence at the oral level after a median follow-up period of 37 months (range, 15-55 months). CONCLUSIONS: The results suggest that the target volume determined by PET-CT could safely reduce GTV size and interobserver variability in patients with locally advanced HNSCC extending into the oral cavity or oropharynx undergoing IMRT. Trial registration UMIN, UMIN000033007. Registered 16 jun 2018, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037631.

Significance of definitive concurrent chemoradiotherapy for vulvar cancer: a Japanese Gynecologic Oncology Group nationwide survey study.

OBJECTIVE: This study aimed to show the results of radical radiation therapy (RT) and concurrent chemoradiotherapy (CCRT) for vulvar cancer (VC) based on data from a Japanese nationwide survey. MATERIALS AND METHODS: We collected data from 108 institutions on cases of VC diagnosed between January 2001 and December 2010. Patients with histologically proven squamous cell carcinoma and adenocarcinoma with curative intent were selected, and 172 patients with VC were included in this study. The collected data were analyzed for overall survival (OS) using the Kaplan-Meier method. Univariate and multivariate analyses were performed to examine the prognostic factors for patients with VC. RESULTS: The median follow-up period was 16.8 (range; 3.2-154.8) months. Fifty-five patients received CCRT, and 117 patients received RT alone. The 2-year OS rates (95% confidence interval [CI]) for stages I, II, III, and IV were 77.9% (55.8-100.0), 71.9% (53.8-89.9), 55.4% (42.5-68.3), and 41.5% (27.3-55.7) respectively. Univariate analyses showed that the FIGO stage (p = 0.001), tumor diameter (p = 0.005), and lymph node (LN) status (p = 0.001) were associated with OS. The concurrent use of chemotherapy resulted in a significantly longer OS in Stage III (p = 0.013). Multivariate analysis showed that the hazard ratios (95% CI) for tumor diameter, positivity for LN metastasis, and RT alone (no concurrent chemotherapy) were 1.502 (1.116-2.021), 1.801 (1.287-2.521), and 1.936 (1.187-3.159), respectively. CONCLUSIONS: Our analysis revealed that CCRT should be recommended, especially for Stage III VC patients. Further studies are warranted to determine who benefits from CCRT, considering primary tumor size and LN status. The study was registered at the University Hospital Medical Information Network (protocol number: UMIN000017080) on April 8th, 2015.

Long-Term Outcomes of Ablative Carbon-Ion Radiotherapy for Central Non-Small Cell Lung Cancer: A Single-Center, Retrospective Study.

The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006-2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments.

Hands-on-training tailored in response to pre-questionnaire-based survey on image-guided brachytherapy effectively reduces anxiety about its implementation.

This study assessed the significance of hands-on-training (HoT) and questionnaire-based surveys on 3D image-guided brachytherapy (3D-IGBT) and a combination of intracavitary and interstitial brachytherapy, the so-called 'hybrid' BT (HBT), in uterine cervical cancer. In October 2023, 29 radiation oncologists, nurses, radiologic technologists and medical physicists from 10 Japanese facilities participated in an HoT on 3D-IGBT and HBT. Questionnaires were distributed to each participant before and after the HoT, and feedback was obtained through online channels. The questionnaire response rate was 83% (24/29), with at least one participant responding from each facility. 'Insertion of applicators and needles', 'human resource shortage' and 'pain relief and sedation' were the primary concerns of radiation oncologists. 'Applicator reconstruction', ' optimization of dwell positions', ' treatment planning' and ' human resource shortages ' were the primary concerns of radiological technologists and medical physicists. The HoT content was adjusted according to the results of preliminary surveys. The concerns expressed by the participants were addressed during the lectures and practical training. Significant reductions in anxiety were observed toward all items of the 10-point self-assessment after the HoT, regardless of the profession. The average score on satisfaction with the HoT (on a 10-point scale) was 9.52 (minimum of 8 and maximum of 10). In conclusion, HoT tailored in response to a pre-questionnaire-based survey effectively reduced participants' anxiety regarding the implementation of 3D-IGBT and HBT.

Identification of Early Biochemical Recurrence Predictors in High-Risk Prostate Cancer Patients Treated with Carbon-Ion Radiotherapy and Androgen Deprivation Therapy.

The aim of this retrospective study was to identify clinical predictors of early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). A total of 670 high-risk PCa patients treated with CIRT and ADT were included in the study. Early BCR was defined as recurrence occurring during adjuvant ADT after CIRT or within 2 years after completion of ADT. Univariate and multivariate analyses were performed to identify clinical predictors of early BCR. Patients were also classified according to the Systemic Therapy in Advancing or Metastatic Prostate cancer (STAMPEDE) PCa classification. Early BCR was observed in 5.4% of the patients. Multivariate analysis identified clinical T3b stage and ≥75% positive biopsy cores as clinical predictors of early BCR after CIRT and ADT. The STAMPEDE PCa classification was also significantly associated with early BCR based on univariate analysis. These predictors can help clinicians identify patients who are at risk of early BCR. In the future, combination therapy of ADT with abiraterone may be an option for high-risk PCa patients who are at risk of early BCR, based on the results of the STAMPEDE study.

A Phase Ib Study of Durvalumab (MEDI4736) in Combination with Carbon-Ion Radiotherapy and Weekly Cisplatin for Patients with Locally Advanced Cervical Cancer (DECISION Study): The Early Safety and Efficacy Results.

We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.

Comprehensive analysis of Japanese nationwide cohort data of particle beam therapy for pulmonary, liver and lymph node oligometastases: particle beam therapy versus high-precision X-ray radiotherapy.

Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e. X-SBRT/X-IMRT) and PT for P-OM, L-OM and LN-OM; and [3] a statistical comparison between LC and OS of the cohort data set in PT and that of the extracted historical data set in X-SBRT/X-IMRT from the preceding systematic review. Safety was evaluated as the incidence of grade ≥ 3 adverse events, while statistical comparisons of LC and OS were conducted by estimating the incidence rate ratios (IRR) for local progression and mortality, respectively. This study demonstrated that PT provided durable LC (3-year LC rate: 72.8-83.2%) with acceptable OS (3-year OS rate: 38.5-68.1%) and risk of severe toxicity incidence of 0.8-3.5% in radical metastasis-directed therapy for P-OM, L-OM and LN-OM. Compared to LC with X-SBRT or X-IMRT, LC with PT was potentially superior for P-OM; superior for L-OM; and equivalent for LN-OM. In particular, this study demonstrated that PT may be a new treatment option for L-OM tumors measuring > 5 cm.

A 211At-labelled mGluR1 inhibitor induces cancer senescence to elicit long-lasting anti-tumor efficacy.

Metabotropic glutamate receptor 1 (mGluR1), a key mediator of glutamatergic signaling, is frequently overexpressed in tumor cells and is an attractive drug target for most cancers. Here, we present a targeted radiopharmaceutical therapy strategy that antagonistically recognizes mGluR1 and eradicates mGluR1+ human tumors by harnessing a small-molecule alpha (α)-emitting radiopharmaceutical, 211At-AITM. A single dose of 211At-AITM (2.96 MBq) in mGluR1+ cancers exhibits long-lasting in vivo antitumor efficacy across seven subtypes of four of the most common tumors, namely, breast cancer, pancreatic cancer, melanoma, and colon cancers, with little toxicity. Moreover, complete regression of mGluR1+ breast cancer and pancreatic cancer is observed in approximate 50% of tumor-bearing mice. Mechanistically, the functions of 211At-AITM are uncovered in downregulating mGluR1 oncoprotein and inducing senescence of tumor cells with a reprogrammed senescence-associated secretory phenotype. Our findings suggest α-radiopharmaceutical therapy with 211At-AITM can be a useful strategy for mGluR1+ pan-cancers, regardless of their tissue of origin.

Phase I/II prospective clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer.

OBJECTIVE: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. METHODS: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. RESULTS: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. CONCLUSION: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

The clinical relative biological effectiveness and prostate-specific antigen kinetics of carbon-ion radiotherapy in low-risk prostate cancer.

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.

Effects of dose and dose-averaged linear energy transfer on pelvic insufficiency fractures after carbon-ion radiotherapy for uterine carcinoma.

BACKGROUND AND PURPOSE: The correlation between dose-averaged linear energy transfer (LETd) and its therapeutic or adverse effects, especially in carbon-ion radiotherapy (CIRT), remains controversial. This study aimed to investigate the effects of LETd and dose on pelvic insufficiency fractures after CIRT. MATERIAL AND METHODS: Among patients who underwent CIRT for uterine carcinoma, 101 who were followed up for > 6 months without any other therapy were retrospectively analyzed. The sacrum insufficiency fractures (SIFs) were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. The correlations between the relative biological effectiveness (RBE)-weighted dose, LETd, physical dose, clinical factors, and SIFs were evaluated. In addition, we analyzed the association of SIF with LETd, physical dose, and clinical factors in cases where the sacrum D50% RBE-weighted dose was above the median dose. RESULTS: At the last follow-up, 19 patients developed SIFs. Receiver operating characteristic curve analysis revealed that the sacrum D50% RBE-weighted dose was a valuable predictor of SIF. Univariate analyses suggested that LETd V10 keV/µm, physical dose V5 Gy, and smoking status were associated with SIF. Cox regression analysis in patients over 50 years of age validated that current smoking habit was the sole risk factor for SIF. Therefore, LETd or physical dose parameters were not associated with SIF prediction. CONCLUSION: The sacrum D50% RBE-weighted dose was identified as a risk factor for SIF. Additionally, neither LETd nor physical dose parameters were associated with SIF prediction.

An Asian multi-national, multi-institutional, retrospective study on image-guided brachytherapy in cervical adenocarcinoma and adenosquamous carcinoma.

Purpose: There are limited reports on outcomes of three-dimensional image-guided brachytherapy (3D-IGBT) for cervical adenocarcinoma in Asia. In a multi-institutional retrospective study, we assessed the clinical outcomes of three-dimensional image-guided brachytherapy for cervical adenocarcinoma or adenosquamous carcinoma (CA/CAC) in Asian countries. Material and methods: Patients who had undergone definitive radiation therapy/concurrent chemoradiotherapy for untreated cervical cancer between 2000 and 2016 were registered. Those who had undergone 3D-IGBT for histologically proven CA/CAC were included. Data on patients' characteristics and treatment were collected, including tumor reduction rate (defined as a percentage of reduction in tumor size before brachytherapy compared with that at diagnosis) and high-risk clinical target volume D90. Overall survival (OS), local control (LC), and progression-free survival (PFS) rates were calculated using Kaplan-Meier method. Late toxicities were assessed using common terminology criteria for adverse events version 4.0. Results: Anonymized data of 498 patients were collected. Of the 498 patients, 36 patients met inclusion criteria. The median follow-up period was 39 months. The 3-year OS, LC, and PFS rates were 68.4%, 68.5%, and 44.4%, respectively. After treatment, five patients had tumor re-growth without complete disappearance of the tumor. Two patients developed grade 3 vaginal toxicity or grade 4 rectal toxicity; none developed other severe late toxicities. A tumor reduction rate of > 26.3% was the only significant factor in multivariate analyses, and was associated with significantly better OS (p = 0.018), LC (p = 0.022), and PFS (p = 0.013). There were no significant trends in local control or dose to high-risk clinical target volume D90. Conclusions: LC rate of CA/CAC was insufficient despite 3D-IGBT. Meanwhile, tumor reduction rate was associated with LC, OS, and PFS rates. Therefore, CA/CAC may require a different treatment strategy than that applied in cervical squamous cell carcinoma.

Risk of secondary malignancy after radiotherapy for breast cancer: long-term follow-up of Japanese patients with breast cancer.

PURPOSE: There have been very few reports of secondary malignancies after breast cancer treatment in Asia, particularly in Japan. This study aimed to evaluate the risk of secondary malignancies after radiotherapy (RT) in Japanese breast cancer patients. METHODS: This single-center retrospective study included patients who underwent RT between July 1961 and September 2006 for postoperative breast cancer. A total of 702 patients with a follow-up period of more than 5 years were analyzed. All malignancies observed at more than 5 years after the start of RT were defined as secondary malignancies. To calculate the relative risk (RR) of secondary malignancies, we applied data from the National Cancer Center in Japan. RESULTS: The median observation period was 9.7 (interquartile range 7.1-18.2) years. The cumulative person-years of observation were 6879.4. The RR of contralateral breast cancer increased by 1.85-fold (95% confidence interval [CI] 1.05-3.26) among patients compared with that among the general population; however, the difference was not significant (p = 0.053). The RR of secondary malignancies other than breast cancer increased by 2.71-fold (95% CI 1.99-3.70, p < 0.001) among the patients compared with the general population. Even when only malignancies detected more than 10 years after RT were defined as secondary malignancies, the RR of secondary malignancies other than breast cancer was 1.91 (95% CI 1.33-2.73, p < 0.001). CONCLUSION: The incidence of secondary malignancies after RT may be somewhat higher in Japanese patients with breast cancer than in the general population.

An Asian multi-national multi-institutional retrospective study comparing intracavitary versus the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical carcinoma.

This study is an international multi-institutional retrospective study comparing the clinical outcomes between intracavitary brachytherapy (ICBT) and the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients treated with definitive radiation therapy. Locally advanced cervical cancer, the initial size of which is larger than 4 cm and treated by concurrent chemoradiotherapy and image-guided adaptive brachytherapy, were eligible for this retrospective study. Patients who received HBT at least once were included in the HBT group, and patients who received only ICBT were included in the ICBT group. Anonymized data from 469 patients from 13 institutions in Japan, one from Korea and one from Thailand, were analyzed. Two hundred eighty and 189 patients were included in the ICBT group and the HBT group, respectively. Patients in the HBT group had more advanced stage, non-Scc histopathology, a higher rate of uterine body involvement, larger tumor at diagnosis, larger tumor before brachytherapy and a lower tumor reduction ratio. With a median follow-up of 51.3 months (2.1-139.9 months), 4-y local control (LC), progression-free survival (PFS) and overall survival (OS) for the entire patient population were 88.2%, 64.2% and 83%, respectively. The HBT group received a higher HR-CTV D90 than that of the ICBT group (68.8 Gy vs 65.6 Gy, P = 0.001). In multivariate analysis, the non-Scc histological subtype, HR-CTV D95 ≤ 60 Gy, reduction ratio ≤ 29% and total treatment time (TTT) ≥ 9 weeks were identified as the independent adverse prognostic factors for LC. Regarding LC, no difference was found between ICBT and HBT (4-y LC 89.3% vs 86.8%, P = 0.314). After adjustment for confounding factors by propensity score matching, no advantage of applying HBT was demonstrated regarding LC, PFS, or OS. Despite the fact that HBT patients had more adverse clinical factors than ICBT patients, HBT delivered a higher dose to HR-CTV and resulted in comparable LC.