The prognostic effect of tumor volume, reduction ratio, and cumulative doses on external beam radiotherapy with central-shielding method and image-guided adaptive brachytherapy for cervical cancer.

Objective: To evaluate the prognostic effect of tumor volume at diagnosis, tumor reduction ratio during external beam radiotherapy (EBRT) with central-shielding method, and cumulative minimal dose to 90% of the high-risk clinical target volume (CTVHR D90) on combined EBRT and image-guided adaptive brachytherapy (IGABT) for cervical cancer. Methods: Consecutive patients who underwent definitive radiotherapy or concurrent chemoradiotherapy for cervical cancer at Gunma University Hospital between January 2010 and December 2019 were retrospectively reviewed. Tumor volume at diagnosis and reduction ratio were calculated using magnetic resonance imaging at diagnosis and before the first IGABT session. The cumulative dose of EBRT and IGABT was calculated as an equivalent dose in 2 Gy fractions (EQD2). Optimal cutoff values were determined according to a receiver operating characteristic curve. Treatment outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional hazards regression. Results: A total of 254 patients were included in the analysis. The median follow-up for all patients was 57 (2-134) months. The 5-year overall survival (OS) was 81.9%, progression-free survival (PFS) was 71.3%, and local control (LC) was 94.5%. The patients were divided into four groups according to tumor volume at diagnosis and reduction ratio. The group with tumor volume at diagnosis ≥ 34.1 cm3 and reduction ratio < 68.8% showed significantly worse OS, PFS, and LC than the other three groups (All p < 0.05). In this group, the patients with a cumulative CTVHR D90 < 69.6 GyEQD2 showed significantly worse PFS and LC (p = 0.042 and p = 0.027, respectively). In the multivariate analysis of OS, adenocarcinoma/adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage III/IV, and a reduction ratio of < 68.8% were independent significant poor prognostic factors (p = 0.045, p = 0.009 and p = 0.001, respectively). In the univariate analysis of LC, a reduction ratio of < 68.8% was the only poor prognostic factor (p = 0.041). Conclusion: The patients with large and poorly responding tumors had significantly worse prognoses in terms of OS, PFS, and LC, suggesting that dose escalation should be considered for such tumors.

Intensity-Modulated Radiation Therapy with Simultaneous Integrated Boost for Clinically Node-Positive Prostate Cancer: A Single-Institutional Retrospective Study.

This study aimed to evaluate clinical outcomes and the toxicity of intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) combined with androgen-deprivation therapy for clinically node-positive (cN1) prostate cancer. We retrospectively analyzed 97 patients with cN1 prostate cancer who received SIB-IMRT between June 2008 and October 2017 at our hospital. The prescribed dosages delivered to the prostate and seminal vesicle, elective node area, and residual lymph nodes were 69, 54, and 60 Gy in 30 fractions, respectively. Kaplan-Meier analysis was used to determine 5-year biochemical relapse-free survival (bRFS), relapse-free survival (RFS), overall survival (OS), and prostate cancer-specific survival (PCSS). Toxicity was evaluated using the Common Terminology Criteria for Adverse Events ver. 4.0. Over a median follow-up duration of 60 months, the 5-year bRFS, RFS, OS, and PCSS were 85.1%, 88.1%, 92.7% and 95.0%, respectively. Acute Grade 2 genito-urinary (GU) and gastro-intestinal (GI) toxicities were observed in 10.2% and 2.1%, respectively, with no grade ≥3 toxicities being detected. The cumulative incidence rates of 5-year Grade ≥2 late GU and GI toxicities were 4.7% and 7.4%, respectively, with no Grade 4 toxicities being detected. SIB-IMRT for cN1 prostate cancer demonstrated favorable 5-year outcomes with low incidences of toxicity.

Prospective Evaluation of Quality of Life and Functional Outcomes after Carbon Ion Radiotherapy for Inoperable Bone and Soft Tissue Sarcomas.

Carbon-ion radiotherapy (CIRT) represents a definitive treatment for inoperable bone and soft tissue sarcoma (BSTS). This prospective study analyzed 61 patients with inoperable BSTS who were treated with CIRT to evaluate QOL, functional outcomes, and predictive factors in patients with inoperable BSTS treated with definitive CIRT. The Musculoskeletal Tumor Society (MSTS) scoring system and the Short Form (SF)-8 questionnaire were completed before and at 1, 3, 6, 12, and 24 months after CIRT. The median follow-up period was 38 months. The main site of primary disease was the pelvis (70.5%), and the most common pathologic diagnosis was chordoma (45.9%). The 3-year overall survival and local control rates were 87.8% and 83.8%, respectively. The MSTS score and physical component score (PCS) of SF-8 did not change significantly between the baseline and subsequent values. The mental component score of SF-8 significantly improved after CIRT. Multivariate analysis showed that the normalized MSTS and normalized PCS of SF-8 at the final follow-up were significantly affected by performance status at diagnosis and sex. CIRT showed clinical efficacy, preserving the physical component of QOL and functional outcomes and improving the mental component of QOL, suggesting its potential value for the treatment of patients with inoperable BSTS.

Clinical features and dosimetric evaluation of carbon ion radiation-induced osteoradionecrosis of mandible in head and neck tumors.

BACKGROUND AND PURPOSE: Osteoradionecrosis (ORN) affects the patient's quality of life by making eating and maintaining oral hygiene painful. This study aimed to analyze carbon ion radiotherapy (C-ion RT)-induced ORN of the mandible. MATERIALS AND METHODS: A retrospective study of 199 patients with head and neck tumors treated with C-ion RT was performed from 2010 to 2019. Only 11 patients with tumors located in the oropharynx and floor of the mouth were analyzed. C-ion RT consisted of 57.6 Gy or 64.0 Gy (relative biological effectiveness) in 16 fractions. The mandible was analyzed for magnetic resonance imaging (MRI) changes and bone exposure. The relationship between the radiation dose and ORN of the mandible was analyzed. RESULTS: Five patients (45.5%) had ORN of the mandible. The median follow-up time was 68 months. The median onset times based on MRI changes and bone exposure were 9 and 15 months, respectively. Doses of 30 Gy (relative biological effectiveness) to the mandible and teeth showed the most significant effect, causing ORN at 29.5 ± 6.7 cc and 3.9 ± 1.8 cc, respectively, with cut-off values at 16.5 cc (p = 0.002) and 1.8 cc (p = 0.0059), respectively. CONCLUSION: This is the first study reporting the incidence, onset time, and risk-predictive dosimetry parameters of C-ion RT-induced ORN of the mandible. Our study will be useful for establishing clinical strategies for C-ion RT to the head and neck near the mandible.

Rectovaginal fistula in a cervical cancer patient treated with sequential radiotherapy and bevacizumab: A dose-volume analysis.

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor that exerts antitumor effect by preventing tumor angiogenesis. Gastrointestinal fistula is a common side effect of bevacizumab in combination with radiotherapy. This case of rectovaginal fistula indicates that the side effect may be unpredictable by the conventional dose-volume parameters for the rectum.

Carbon-ion Radiotherapy for Oligometastatic Colorectal Cancer in the Liver or Lung.

BACKGROUND/AIM: We aimed to evaluate the clinical outcomes of oligometastatic colorectal cancer in the liver and lung treated with carbon-ion radiotherapy (C-ion RT). PATIENTS AND METHODS: Nineteen consecutive patients with oligometastatic colorectal cancer in the liver or lung who received C-ion RT were analyzed. The doses of C-ion RT were 60.0 Gy [relative biological effectiveness (RBE)] in 4 fractions, 60.0 Gy (RBE) in 12 fractions, or 64.8 Gy (BRE) in 12 fractions. RESULTS: The median follow-up duration was 19 months. There were 23 tumors in 19 patients. The 2-year overall survival and local control rates for the whole patient cohort were 100% and 67%, respectively. None of the patients developed grade 2 or higher acute or late toxicities. CONCLUSION: C-ion RT for oligometastatic colorectal cancer in liver and lung provides favorable clinical outcomes. These outcomes suggest C-ion RT is a treatment option for oligometastatic colorectal cancer in liver and lung.

Analysis of radiotherapy-induced alteration of CD8+ T cells and PD-L1 expression in patients with uterine cervical squamous cell carcinoma.

Radiotherapy induces an immune response in the cancer microenvironment that may influence clinical outcome. The present study aimed to analyse the alteration of CD8+ T-cell infiltration and programmed death-ligand 1 (PD-L1) expression following radiotherapy in clinical samples from patients with uterine cervical squamous cell carcinoma. Additionally, the current study sought to analyse the association between these immune responses and clinical outcomes. A total of 75 patients who received either definitive chemoradiotherapy or radiotherapy were retrospectively analyzed. CD8+ T-cell infiltration and PD-L1 expression were determined by immunohistochemistry using biopsy specimens before radiotherapy (pre-RT) and after 10 Gy radiotherapy (post-10 Gy). The PD-L1+ rate was significantly increased from 5% (4/75) pre-RT to 52% (39/75) post-10 Gy (P<0.01). Despite this increase in the PD-L1+ rate post-10 Gy, there was no significant association between both pre-RT and post-10 Gy and overall survival (OS), locoregional control (LC) and progression-free survival (PFS). On the other hand, the CD8+ T-cell infiltration density was significantly decreased for all patients (median, 23.1% pre-RT vs. 16.9% post-10 Gy; P=0.038); however, this tended to increase in patients treated with radiotherapy alone (median, 17.7% pre-RT vs. 24.0% post-10 Gy; P=0.400). Notably, patients with high CD8+ T-cell infiltration either pre-RT or post-10 Gy exhibited positive associations with OS, LC and PFS. Thus, the present analysis suggested that CD8+ T-cell infiltration may be a prognostic biomarker for patients with cervical cancer receiving radiotherapy. Furthermore, immune checkpoint inhibitors may be effective in patients who have received radiotherapy, since radiotherapy upregulated PD-L1 expression in cervical cancer specimens.

Impact of Carbon Ion Radiotherapy on Inoperable Bone Sarcoma.

Management of patients with bone sarcoma who are unsuitable for surgery is challenging. We aimed to analyze the clinical outcomes among such patients who were treated with carbon ion radiotherapy (C-ion RT). We reviewed the medical records of the patients treated with C-ion RT between April 2011 and February 2019 and analyzed the data of 53 patients. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (Version 4.0). The median follow-up duration for all patients was 36.9 months. Histologically, 32 patients had chordoma, 9 had chondrosarcoma, 8 had osteosarcoma, 3 had undifferentiated pleomorphic sarcoma, and 1 had sclerosing epithelioid fibrosarcoma. The estimated 3-year overall survival (OS), local control (LC), and progression-free survival (PFS) rates were 79.7%, 88.6%, and 68.9%, respectively. No patients developed grade 3 or higher acute toxicities. Three patients developed both grade 3 radiation dermatitis and osteomyelitis, one developed both grade 3 radiation dermatitis and soft tissue infection, and one developed rectum-sacrum-cutaneous fistula. C-ion RT showed favorable clinical outcomes in terms of OS, LC, and PFS and low rates of toxicity in bone sarcoma patients. These results suggest a potential role for C-ion RT in the management of this population.

The effects of PSA kinetics on the outcome of hypofractionated salvage radiotherapy for biochemical recurrence of prostate cancer after prostatectomy.

The feasibility and efficacy of hypofractionated salvage radiotherapy (HS-RT) for prostate cancer (PC) with biochemical recurrence (BR) after prostatectomy, and the usefulness of prostate-specific antigen (PSA) kinetics as a predictor of BR, were evaluated in 38 patients who received HS-RT without androgen deprivation therapy between May 2009 and January 2017. Their median age, PSA level and PSA doubling time (PSA-DT) at the start of HS-RT were 68 (53-74) years, 0.28 (0.20-0.79) ng/ml and 7.7 (2.3-38.5) months, respectively. A total dose of 60 Gy in 20 fractions (three times a week) was three-dimensionally delivered to the prostate bed. After a median follow-up of 62 (30-100) months, 19 (50%) patients developed a second BR after HS-RT, but only 1 patient died before the last follow-up. The 5-year overall survival and BR-free survival rates were 97.1 and 47.4%, respectively. Late grade 2 gastrointestinal and genitourinary morbidities were observed in 0 and 5 (13%) patients, respectively. The PSA level as well as pathological T-stage and surgical margin status were regarded as significant predictive factors for a second BR by multivariate analysis. BR developed within 6 months after HS-RT in 11 (85%) of 13 patients with a PSA-DT < 10 months compared with 1 (17%) of 6 with a PSA-DT ≥ 10 months (median time to BR: 3 vs 14 months, P < 0.05). Despite the small number of patients, our HS-RT protocol seems feasible, and PSA kinetics may be useful for predicting the risk of BR and determining the appropriate follow-up schedule.

Oral Gastrografin Facilitates Delineation of Intestinal Tracts in CT-Based Brachytherapy for Uterine Cervical Cancer.

Three-dimensional image-guided brachytherapy (3D-IGBT) using computed tomography (CT) is an essential component of definitive radiation therapy for uterine cervical cancer (UCC). Treatment planning for CT-based 3D-IGBT requires delineating the high-risk clinical target volume (CTVHR) and the organs at risk (OARs), which is difficult when the small intestine is adjacent to those delineation targets. Uncertainty in target delineation threatens the validity of 3D-IGBT treatment plans. To address this issue, we introduce the use of diatrizoate meglumine and diatrizoate sodium (gastrografin), an orally administrable iodine-based radiopaque contrast agent. We present two cases of UCC treated with CT-based 3D-IGBT and describe how intraluminal enhancement of the small intestine by oral gastrografin pretreatment facilitated discrimination between the small intestine and the adjacent CTVHR (case no.1) or the rectosigmoid colon (case no. 2). Oral gastrografin pretreatment is a simple and cost-effective method that allows distinguishing the small intestine from the adjacent delineation target (i.e., CTVHR and the OARs) in CT-based 3D-IGBT for UCC.

FIGO 2018 Staging for Cervical Cancer: Influence on Stage Distribution and Outcomes in the 3D-Image-Guided Brachytherapy Era.

Recent widespread use of three-dimensional image-guided brachytherapy (3D-IGBT) has improved radiotherapy outcomes of cervical cancer dramatically. In 2018, the International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer was revised. However, the influence of the revisions on the stage distribution and outcomes of cervical cancers treated with 3D-IGBT remains unclear. Here, we retrospectively analyzed 221 patients with cervical squamous cell carcinoma treated with definitive radiotherapy using 3D-IGBT (median follow-up, 60 months). The stage distribution and outcomes were compared between the 2009 and 2018 schemas. Stage migration occurred in 52.9% of the patients. Patients classified with the 2018 criteria as stage IIICr had the highest proportion (43.8%) of migration, and were mainly from the 2009 stages IIB and IIIB. The 2009 and 2018 schemas showed comparable performance at stratifying 5-year overall survival (OS) and 5-year progression-free survival (PFS) for patients in stages IB-IVA. The 2018 criteria effectively stratified 5-year OS and PFS in the stage III substages. The 5-year OS and PFS for stage IIIC1r patients varied according to tumor T stage. These data provide evidence for the utility of the revised 2018 FIGO staging system in the clinical management of cervical cancers in the 3D-IGBT era.

Treatment outcomes of patients with adenocarcinoma of the uterine cervix after definitive radiotherapy and the prognostic impact of tumor-infiltrating CD8+ lymphocytes in pre-treatment biopsy specimens: a multi-institutional retrospective study.

The current study aimed to evaluate the outcomes of patients with adenocarcinoma (AC) of the uterine cervix after definitive radiotherapy (RT) and to evaluate prognostic factors, including immunity-related molecules. A total of 71 patients with AC of the uterine cervix from multiple Japanese institutions were retrospectively analysed. Histological subtypes were diagnosed according to the 2014 World Health Organization classification. All patients underwent definitive RT comprising external beam RT and intracavitary brachytherapy with or without concurrent chemotherapy. Immunohistochemical studies were performed to detect the expression of programmed cell death-ligand 1(PD-L1) and CD8. The 5-year locoregional control (LC), overall survival (OS) and progression-free survival (PFS) rates for all patients were 61.8, 49.7 and 36.1%, respectively. The LC, OS and PFS rates were not significantly different among the histological subtypes. Membranous PD-L1 expression was not significantly associated with prognosis. Patients with CD8-positive tumor-infiltrating lymphocytes (CD8+TILs) in the tumor nests had significantly better OS than patients without CD8+TILs in the tumor nests (5-year OS: 53.8 vs 23.8%, P = 0.038). As expected, the International Federation of Gynecology and Obstetrics (FIGO) stage (2008) III-IVA and maximum tumor diameter > 40 mm were significantly associated with worse prognosis. In summary, the presence of CD8+TILs in the tumor nests has the potential to be an independent favorable prognostic factor for patients with AC of the uterine cervix after definitive RT.

Comparison of Dose Distributions When Using Carbon Ion Radiotherapy Versus Intensity-modulated Radiotherapy for Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Retrospective Analysis.

BACKGROUND/AIM: This study compared the dose distributions of carbon ion radiotherapy (C-ion RT) and intensity-modulated radiotherapy (IMRT) in patients with locally advanced hepatocellular carcinoma (LAHCC). PATIENTS AND METHODS: A retrospective analysis was conducted in 10 consecutive patients with LAHCC who had undergone C-ion RT. The dose-volume histogram parameters of clinical plans using C-ion RT at 60 Gy and simulated plans using IMRT at 60 Gy and 50 Gy were compared. We measured the percentage of the normal liver volume that received at least 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), and 50 Gy (V50). RESULTS: The V5, V10, V20, and the mean liver dose were significantly lower in patients who received 60 Gy of C-ion RT than in those who received 50 or 60 Gy of IMRT. CONCLUSION: C-ion RT exhibits a better liver dose distribution than IMRT in patients with LAHCC.

FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy.

Radiotherapy is an essential component of cancer therapy. Carbon ion radiotherapy (CIRT) promises to improve outcomes compared with standard of care in many cancers. Nevertheless, clinicians often observe in-field recurrence after CIRT. This indicates the presence of a subset of cancers that harbor intrinsic resistance to CIRT. Thus, the development of methods to identify and sensitize CIRT-resistant cancers is needed. To address this issue, we analyzed a unique donor-matched pair of clinical specimens: a treatment-naïve tumor, and the tumor that recurred locally after CIRT in the same patient. Exon sequencing of 409 cancer-related genes identified enrichment of somatic mutations in FGFR3 and FGFR4 in the recurrent tumor compared with the treatment-naïve tumor, indicating a pivotal role for FGFR signaling in cancer cell survival through CIRT. Inhibition of FGFR using the clinically available pan-FGFR inhibitor LY2874455 sensitized multiple cancer cell lines to carbon ions at 3 Gy (RBE: relative biological effectiveness), the daily dose prescribed to the patient. The sensitizer enhancement ratio was 1.66 ± 0.17, 1.27 ± 0.09, and 1.20 ± 0.18 in A549, H1299, and H1703 cells, respectively. Our data indicate the potential usefulness of the analytical pipeline employed in this pilot study to identify targetable mutations associated with resistance to CIRT, and of LY21874455 as a sensitizer for CIRT-resistant cancers. The results warrant validation in larger cohorts.

Prospective Observational Study of High-Dose Carbon-Ion Radiotherapy for Pelvic Recurrence of Rectal Cancer (GUNMA 0801).

Background and purpose: Favorable clinical outcomes of carbon-ion radiotherapy for pelvic recurrence of rectal cancer have been described by previous prospective phase I/II and II studies; however, these studies were performed at a single institution. Therefore, we conducted a prospective observational study aimed at exploring whether carbon-ion radiotherapy for post-operative pelvic recurrence of rectal cancer provides a less invasive local treatment strategy with higher cure rates than other anticancer treatments. Materials and methods: Patients (1) with pelvic recurrence of rectal cancer, as confirmed by histology or diagnostic imaging; (2) without distant metastasis; (3) who had undergone curative resection of their primary disease and regional lymph nodes, without gross or microscopic residual disease; and (4) with radiographically measurable tumors were included in this study. The total carbon-ion radiotherapy dose for all patients was 73.6 Gy [relative biological effectiveness (RBE)] administered in 16 fractions once daily for 4 days a week (Tuesday to Friday). Results: A total of 28 patients were enrolled between October 2011 and July 2017. The median follow-up duration was 38.9 months. The 3-year overall survival, local control, and progression-free survival rates were 92, 86, and 31%, respectively. At the time of the analysis, 4 patients had local recurrence, and 7 had died of rectal cancer. None of the patients developed grade 3 or higher acute toxicities. Late toxicities occurred in 2 and 7 patients who developed grade 3 pelvic infection and grade 2 peripheral neuropathy, respectively. Conclusion: Carbon-ion radiotherapy for pelvic recurrence of rectal cancer showed favorable clinical outcomes and is a highly curative and less invasive local treatment.

Deep learning-assisted literature mining for in vitro radiosensitivity data.

BACKGROUND AND PURPOSE: Integrated analysis of existing radiosensitivity data obtained by the gold-standard clonogenic assay has the potential to improve our understanding of cancer cell radioresistance. However, extraction of radiosensitivity data from the literature is highly labor-intensive. To aid in this task, using deep convolutional neural networks (CNNs) and other computer technologies, we developed an analysis pipeline that extracts radiosensitivity data derived from clonogenic assays from the literature. MATERIALS AND METHODS: Three classifiers (C1-3) were developed to identify publications containing radiosensitivity data derived from clonogenic assays. C1 uses Faster Regions CNN with Inception Resnet v2 (fRCNN-IRv2), VGG-16, and Optical Character Recognition (OCR) to identify publications that contain semi-logarithmic graphs showing radiosensitivity data derived from clonogenic assays. C2 uses fRCNN-IRv2 and OCR to identify publications that contain bar graphs showing radiosensitivity data derived from clonogenic assays. C3 is a program that identifies publications containing keywords related to radiosensitivity data derived from clonogenic assays. A program (iSF2) was developed using Mask RCNN and OCR to extract surviving fraction after 2-Gy irradiation (SF2) as assessed by clonogenic assays, presented in semi-logarithmic graphs. The efficacy of C1-3 and iSF2 was tested using seven datasets (1805 and 222 publications in total, respectively). RESULTS: C1-3 yielded sensitivity of 91.2% ±â€¯3.4% and specificity of 90.7% ±â€¯3.6%. iSF2 returned SF2 values that were within 2.9% ±â€¯2.6% of the SF2 values determined by radiation oncologists. CONCLUSION: Our analysis pipeline is potentially useful to acquire radiosensitivity data derived from clonogenic assays from the literature.

A comparison of carbon ion radiotherapy and transarterial chemoembolization treatment outcomes for single hepatocellular carcinoma: a propensity score matching study.

BACKGROUND: We compared clinical outcomes of carbon ion radiotherapy and transarterial chemoembolization in the treatment of hepatocellular carcinoma. METHODS: Data of 477 patients with hepatocellular carcinoma who had undergone carbon ion radiotherapy or transarterial chemoembolization between April 2007 and September 2016 were retrospectively reviewed. Treatment naïve patients with single HCC, who underwent carbon ion radiotherapy or transarterial chemoembolization as a primary treatment were included. Clinical outcomes of the treatments were compared after utilizing propensity score matching. RESULTS: Of 124 patients who received carbon ion radiotherapy and 353 patients who received transarterial chemoembolization, 31 and 23 patients met our inclusion criteria, respectively. After utilizing propensity score matching, 17 matched pairs of patients from each treatment group were analyzed. The median follow-up durations after carbon ion radiotherapy and transarterial chemoembolization were 43 and 32 months, respectively. The 3-year overall survival, local control, and progression-free survival rates in the carbon ion radiotherapy versus transarterial chemoembolization groups were 88% versus 58% (p < 0.05), 80% versus 26% (p < 0.01), and 51% versus 15% (p < 0.05), respectively. CONCLUSIONS: Carbon ion radiotherapy showed more favorable clinical outcomes than did transarterial chemoembolization for patients with single hepatocellular carcinoma after matching patient characteristics utilizing propensity score matching. Further studies with larger patient numbers are required to confirm our results. TRIAL REGISTRATION: UMIN000036455 : date of registration 22 March 2019, retrospectively registered.

Carbon-ion radiotherapy for lymph node oligo-recurrence: a multi-institutional study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS).

BACKGROUND: The efficacy of carbon-ion radiotherapy (C-ion RT) for lymph node (LN) oligo-recurrence has only been evaluated in limited single-center studies. We aimed to investigate the benefit of C-ion RT for LN oligo-recurrence in a large multi-center study. METHODS: Patients who received C-ion RT between December 1996 and December 2015 at 4 participating facilities and who met the following eligibility criteria were included: (i) histological or clinical diagnosis of LN recurrence; (ii) controlled primary lesion; (iii) no recurrence other than LN; (iv) LN recurrence involved in a single lymphatic site; and (v) age ≥ 20 years. RESULTS: A total of 323 patients were enrolled. Median follow-up period was 34 months for surviving patients. The most common dose fractionation of C-ion RT was 48.0 Gy (relative biological effectiveness) in 12 fractions. Forty-seven patients had a history of RT at the recurrent site. The 2-year local control (LC) and overall survival (OS) rates after C-ion RT were 85% and 63%, respectively. Only 1 patient developed grade-3 toxicity. Factors such as LN diameter, histology, and history of previous RT did not correlate with LC. Smaller diameters (< 30 mm) and numbers (≤ 3) of LN metastases as well as longer disease-free intervals post-primary therapy (≥ 16 months) were associated with significantly better OS. CONCLUSIONS: C-ion RT for LN oligo-recurrence appeared to be effective and safe. C-ion RT may provide a survival benefit to patients with LN oligo-recurrence, particularly to those with few LN metastases, smaller LN diameters, and longer disease-free intervals.

Long-term outcome of hypofractionated intensity-modulated radiotherapy using TomoTherapy for localized prostate cancer: A retrospective study.

BACKGROUND: Recently, the clinical outcome of prostate cancer treated by hypofractionated radiation therapy has been reported. However, there are few reports from Japan. In Hidaka Hospital, hypofractionated intensity-modulated radiotherapy (HIMRT) for prostate cancer was initiated in 2007. The purpose of this study is to analyze the long-term outcome. METHODS: Ninety-two patients with localized prostate cancer treated with HIMRT at Hidaka Hospital between 2007 and 2009 were retrospectively analyzed. HIMRT was delivered using TomoTherapy. The prescription dose was 66 Gy at 95% of the PTV in 22 fractions performed 3 days a week over 7 weeks in all patients. The overall survival rate, biochemical relapse-free rate, and acute and late toxicities were evaluated. RESULTS: The median follow-up duration was 78 (range 14-100) months. The median age at the start of the HIMRT was 72 (range 46-84) years. The disease characteristics were as follows: stage T1c, 45; T2a, 20; T2b, 5; T2c, 1; T3a, 13; T3b, 6; T4, 2; Gleason score 6, 13; 7, 44; 8, 20; 9, 15; 10, 0; pretreatment PSA ≤10 ng/mL, 42; 10 to ≤20, 27; and >20, 23. According to the D'Amico classification system, 10, 37, and 45 patients were classified as low-risk, intermediate-risk, and high-risk. The overall survival rate, the cause-specific survival rate, and the biochemical relapse-free rate at 5 years was 94.7%, 100% and 98.9%, respectively. Severe acute toxicity (grade 3 or more) was not observed. The late urinary toxicity was 52.2% in grade 0, 28.3% in grade 1, 19.6% in grade 2, and 2.2% in grade 3. The late rectal toxicity was 78.3% in grade 0, 7.6% in grade 1, 9.8% in grade 2, and 4.3% in grade 3. CONCLUSIONS: The present study demonstrated that HIMRT using TomoTherapy for prostate cancer has a favorable outcome with tolerable toxicity.