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BACKGROUND: The quality of life of patients is an important consideration when selecting treatments for localized prostate cancer (PCa). We retrospectively compared sexual function after robot-assisted radical prostatectomy (RARP) and carbon-ion radiotherapy (CIRT) using propensity score matching. METHODS: In total, 127 Japanese PCa patients treated with RARP and 190 treated with CIRT monotherapy were evaluated. We evaluated the Expanded Prostate Cancer Index Composite (EPIC) score before treatment and 12 and 24 months after treatment. After propensity score matching, data from 101 patients from each group were analyzed. The study protocol was approved by the Institutional Review Board of Gunma University Hospital (no. IRB2020-050, 1839). RESULTS: After propensity score matching, the mean EPIC sexual function summary scores in the RARP and CIRT groups were 46.4 and 48.2, respectively. At 12 and 24 months after treatment, these scores were 27.9 (39.9% decrease) and 28.2 (39.2% decrease) in the RARP group and 41.4 (14.1% decrease) and 41.6 (13.7% decrease) in the CIRT group, respectively. Both groups demonstrated significantly decreased scores after 12 and 24 months of treatment compared to before treatment (all p < 0.05). At 12 and 24 months, the sexual function summary score was significantly higher in the CIRT group than in the RARP group (p < 0.001). CONCLUSIONS: There was a smaller decrease in the EPIC sexual function score in the CIRT group than in the RARP group. These results provide useful information for treatment decision-making of Japanese PCa patients.
Subject(s)
Prostatic Neoplasms , Robotics , Male , Humans , Japan , Propensity Score , Quality of Life , Retrospective Studies , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Prostatectomy/adverse effects , CarbonABSTRACT
Reports on the therapeutic efficacy and safety of carbon-ion radiotherapy (C-ion RT) for oligometastatic liver disease are limited, with insufficient evidence. This study aimed to evaluate the clinical outcomes of C-ion RT for oligometastatic liver disease at all Japanese facilities using the nationwide cohort data. We reviewed the medical records to obtain the nationwide cohort registry data on C-ion RT between May 2016 and June 2020. Patients (1) with oligometastatic liver disease as confirmed by histological or diagnostic imaging, (2) with ≤3 synchronous liver metastases at the time of treatment, (3) without active extrahepatic disease, and (4) who received C-ion RT for all metastatic regions with curative intent were included in this study. C-ion RT was performed with 58.0-76.0 Gy (relative biological effectiveness [RBE]) in 1-20 fractions. In total, 102 patients (121 tumors) were enrolled in this study. The median follow-up duration for all patients was 19.0 months. The median tumor size was 27 mm. The 1-year/2-year overall survival, local control, and progression-free survival rates were 85.1%/72.8%, 90.5%/78.0%, and 48.3%/27.1%, respectively. No patient developed grade 3 or higher acute or late toxicity. C-ion RT is a safe and effective treatment for oligometastatic liver disease and may be beneficial as a local treatment option in multidisciplinary treatment.
Subject(s)
Heavy Ion Radiotherapy , Liver Neoplasms , Radiation Oncology , Humans , Heavy Ion Radiotherapy/adverse effects , Heavy Ion Radiotherapy/methods , Japan , Liver Neoplasms/radiotherapy , Multicenter Studies as Topic , Progression-Free Survival , Retrospective Studies , Treatment OutcomeABSTRACT
Perfluorooctane sulfonate (PFOS) has been used in a wide variety of industrial and commercial products. The adverse effects of PFOS on the developing brain are becoming of a great concern. However, the molecular mechanisms of PFOS on brain development have not yet been clarified. We investigated the effect of early-life exposure to PFOS on brain development and the mechanism involved. We investigated the change in thyroid hormone (TH)-induced dendrite arborization of Purkinje cells in the primary culture of newborn rat cerebellum. We further examined the mechanism of PFOS on TH signaling by reporter gene assay, quantitative RT-PCR, and type 2 iodothyronine deiodinase (D2) assay. As low as 10-7 M PFOS suppressed thyroxine (T4)-, but not triiodothyronine (T3)-induced dendrite arborization of Purkinje cells. Reporter gene assay showed that PFOS did not affect TRα1- and TRß1-mediated transcription in CV-1 cells. RT-PCR showed that PFOS suppressed D2 mRNA expression in the absence of T4 in primary cerebellar cells. D2 activity was also suppressed by PFOS in C6 glioma-derived cells. These results indicate that early-life exposure of PFOS disrupts TH-mediated cerebellar development possibly through the disruption of D2 activity and/or mRNA expression, which may cause cerebellar dysfunction.
Subject(s)
Cerebellum , Iodide Peroxidase , Animals , Rats , Iodide Peroxidase/genetics , Purkinje Cells , RNA, MessengerABSTRACT
Carbon-ion radiotherapy (CIRT) for clinical stage I non-small-cell lung cancer (NSCLC) is used as an advanced medical treatment regimen in Japan. Carbon-ion radiotherapy reportedly aids in achieving excellent treatment outcomes, despite its high medical cost. We aimed to compare CIRT with stereotactic body radiotherapy (SBRT) in terms of cost-effectiveness for treating clinical stage I NSCLC. Data of patients with clinical stage I NSCLC treated with CIRT or SBRT at Gunma University between 2010 and 2015 were analyzed. The CIRT and SBRT groups included 62 and 27 patients, respectively. After propensity-score matching, both groups comprised 15 patients. Life year (LY) was used as an indicator of outcome. The CIRT technical fee was 3 140 000 JPY. There was no technical fee for the second CIRT carried out on the same organ within 2 years. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental cost by the incremental LY for 5 years after treatment. Sensitivity analysis was applied to evaluate the impact of LY or costs of each group on ICER. The ICERs were 7 491 017 JPY/LY and 3 708 330 JPY/LY for all patients and matched patients, respectively. Hospitalization and examination costs were significantly higher in the CIRT group, and the impact of the CIRT technical costs was smaller than other costs and LY. Carbon-ion radiotherapy is a cost-effective treatment approach. However, our findings suggest that reducing excessive costs by considering the validity and necessity of examinations and hospitalizations would make CIRT a more cost-effective approach.
Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Heavy Ion Radiotherapy/economics , Lung Neoplasms/radiotherapy , Radiosurgery/economics , Carcinoma, Non-Small-Cell Lung/economics , Carcinoma, Non-Small-Cell Lung/pathology , Cost-Benefit Analysis , Health Care Costs , Humans , Japan , Lung Neoplasms/economics , Lung Neoplasms/pathology , Treatment OutcomeABSTRACT
AIM: The treatment of hepatocellular carcinoma in the caudate lobe (HCCCL) is technically challenging. We aimed to investigate the efficacy and toxicity of carbon ion radiotherapy (C-ion RT) for HCCCL. METHODS: Patients with HCCCL treated with C-ion RT at our hospital between January 2011 and December 2018 were evaluated. The total dose was 52.8 or 60 Gy (relative biological effectiveness) in four or 12 fractions depending on the distance between the tumor and the gastrointestinal tract. The survival outcome, the presence or absence of recurrence (local recurrence, intrahepatic recurrence outside the irradiation field, or extrahepatic recurrence), and acute/late adverse events were evaluated. RESULTS: Nine patients were included. The median tumor size was 3.4 cm, and the median follow-up duration was 18.3 months for all patients. No patient developed local recurrence during follow-up. Five patients subsequently developed intrahepatic recurrence outside the irradiation field and two had extrahepatic metastasis. Five patients died of hepatocellular carcinoma. No acute adverse events of grade ≥2 were observed. Two patients experienced grade 2 or 3 late adverse events, including obstructive jaundice, hepatic encephalopathy, ascites, and edema. CONCLUSION: Carbon ion radiotherapy for HCCCL achieved excellent local control with acceptable adverse events and can thus be a curative treatment option for HCCCL.
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BACKGROUND: The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy. METHODS: Between March 2010 and December 2016, a total of 1337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, seven patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event version 5.0. RESULTS: At the completion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only one patient. Regarding late toxicities, only one patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity, and gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT. CONCLUSIONS: Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.
Subject(s)
Adenocarcinoma/radiotherapy , Heavy Ion Radiotherapy , Prostatic Neoplasms/radiotherapy , Urinary Bladder Neoplasms/radiotherapy , Urinary Bladder/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Androgen Antagonists/therapeutic use , Combined Modality Therapy , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Invasiveness , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Retrospective Studies , Salvage Therapy , Urinary Bladder/diagnostic imaging , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathologyABSTRACT
OBJECTIVE: To elucidate tumor mutation profiles associated with outcomes of uterine cervical cancer (UCC) patients treated with definitive radiotherapy. METHODS: Ninety-eight patients with newly diagnosed and pathologically confirmed UCC (82 squamous cell carcinomas, 12 adenocarcinomas, and four adenosquamous carcinomas) who were treated with definitive radiotherapy were analyzed. DNA was extracted from pre-treatment tumor biopsy specimens. The exons of 409 cancer-related genes were sequenced using a next-generation sequencer. Genetic mutations were identified and analyzed for correlations with clinical outcome. RESULTS: Recurrent mutations were observed in PIK3CA (35.7%), ARID1A (25.5%), NOTCH1 (19.4%), FGFR3 (16.3%), FBXW7 (19.4%), TP53 (13.3%), EP300 (12.2%), and FGFR4 (10.2%). The prevalence of mutations in FGFR family genes (i.e., FGFR1-4) was almost as high (24.5%) as that in PIK3CA and ARID1A, both of which are well-studied drivers of UCC. Fifty-five percent (21 of 38) of the identified FGFR mutations were located in the FGFR protein tyrosine kinase domain. Five-year progression-free survival (PFS) rates for FGFR mutation-positive patients (n = 24) were significantly worse than those for FGFR mutation-negative patients (n = 74) (43.9% vs. 68.5%, respectively; P = 0.010). Multivariate analysis identified FGFR mutations as significant predictors of worse 5 year PFS (P = 0.005), independent of clinicopathological variables. CONCLUSIONS: FGFR mutations are associated with worse PFS in UCC patients treated with definitive radiotherapy. These results warrant further validation in prospective studies.
Subject(s)
Adenocarcinoma/genetics , Carcinoma, Adenosquamous/genetics , Carcinoma, Squamous Cell/genetics , Uterine Cervical Neoplasms/genetics , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Adenosquamous/pathology , Carcinoma, Adenosquamous/radiotherapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Female , High-Throughput Nucleotide Sequencing , Humans , Middle Aged , Mutation , Progression-Free Survival , Receptors, Fibroblast Growth Factor/metabolism , Retrospective Studies , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapyABSTRACT
Proton and carbon ion radiotherapy for the treatment of prostate cancer is associated with a lower incidence of adverse events than conventional radiotherapy. There are few reports on the quality of life of patients treated with particle therapy, and limited patient-reported outcomes. Analysis of quality of life is important for patients treated with radiotherapy alone or in combination with hormonal therapy, and long-term results, dose fractionation and costs need to be included in the analysis. This information might help both clinical decision-making and selection of appropriate treatments according to the individual needs of patients. This study reviews the literature on the quality of life and outcomes of patients treated with particle therapy, and discusses future directions.
Subject(s)
Prostatic Neoplasms/radiotherapy , Quality of Life , Humans , Male , Proton Therapy , Radiotherapy/methods , Treatment OutcomeABSTRACT
Purpose: Treatment outcomes of definitive photon radiation therapy for nonmetastatic castration-resistant prostate cancer (nmCRPC) are reportedly unsatisfactory. Carbon ion radiation therapy (CIRT) has shown favorable tumor control in various malignancies, including radioresistant tumors. Therefore, we retrospectively evaluated the clinical outcomes of CIRT for nmCRPC. Methods and Materials: Patients with nmCRPC (N0M0) treated with CIRT at a total dose of 57.6 Gy (relative biologic effectiveness) in 16 fractions or 51.6 Gy (relative biologic effectiveness) in 12 fractions were included. The castration-resistant status received a diagnosis based on prostate-specific antigen kinetics showing a monotonic increase during primary androgen deprivation therapy or the need to change androgen deprivation therapy. Clinical factors associated with patient prognosis were explored. Twenty-three consecutive patients were identified from our database. The median follow-up period was 63.6 months (range, 14.1-120). Results: Seven patients developed biochemical relapse, 6 had clinical relapse, and 4 died of the disease. The 5-year overall survival, local control rate, biochemical relapse-free survival, and clinical relapse-free survival were 87.5%, 95.7%, 70.3%, and 75.7%, respectively. One patient with diabetes mellitus requiring insulin injections and taking antiplatelet and anticoagulant drugs developed grade 3 hematuria and bladder tamponade after CIRT. None of the patients developed grade 4 or worse toxicity. Conclusions: The present findings indicate the acceptable safety and favorable efficacy of CIRT, encouraging further research on CIRT for nmCRPC.
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PURPOSE: This retrospective study aimed to evaluate the safety and efficacy of repeated carbon-ion radiation therapy (CIRT) in patients with intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS AND MATERIALS: We reviewed patients who underwent repeated CIRT for intrahepatic recurrent HCC between 2010 and 2020. RESULTS: Forty-one patients received multiple CIRT courses for HCC. During the second course, 17 (41.5%) and 24 (58.5%) of 41 patients underwent CIRT for local recurrence (LR) and intrahepatic recurrence after the first irradiation, respectively. The median age at the first course was 76 years, and the median tumor size in all the courses was 25 mm. Throughout all CIRT courses, the prescribed dose was 52.8 to 60.0 Gy (relative biological effectiveness), which was delivered in 4 to 12 fractions. The median follow-up period after the first and second CIRT was 40 and 21 months. Median overall survival (OS) after the first and second CIRT were 80 and 27 months, respectively. The 2- and 5-year OS after the first CIRT were 87.8% and 50.1%, and the 2-year OS rate after the second CIRT was 56.0%. The 1- and 2-year local control (LC) after the second CIRT was 93.4% and 83.0%, respectively. The median progression-free survival (PFS) after the second CIRT was 11 months. There were no significant differences in the LC and PFS between patients with LR and out-of-field recurrence (P = .83; 0.28, respectively). The albumin-bilirubin scores at 3 and 6 months after the second CIRT were not significantly different from those before irradiation. According to the Common Terminology Criteria for Adverse Events version 4.0, grade 4 or greater toxicities were not observed. CONCLUSIONS: Repeated CIRT for intrahepatic recurrent HCC was safe and effective, including reirradiation for LR. OS, LC, and PFS were satisfactory, and liver function was preserved. Repeated CIRT could be considered a treatment option for intrahepatic recurrent HCC.
Subject(s)
Carcinoma, Hepatocellular , Heavy Ion Radiotherapy , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/pathology , Retrospective Studies , Liver Neoplasms/radiotherapy , Liver Neoplasms/pathology , Progression-Free Survival , Heavy Ion Radiotherapy/adverse effects , CarbonABSTRACT
Systemic chemotherapy has significantly improved in recent years. In this study. the clinical impact of carbon-ion radiotherapy (CIRT) with concurrent chemotherapy for locally advanced unresectable pancreatic cancer (URPC) was evaluated. METHODS: Patients with URPC who were treated with CIRT between January 2016 and December 2020 were prospectively registered and analyzed. The major criteria for registration were (1) diagnosed as URPC on imaging; (2) pathologically diagnosed adenocarcinoma; (3) no distant metastasis; (4) Eastern Cooperative Oncology Group performance status of 0-2; (5) tumors without gastrointestinal tract invasion; and (6) available for concurrent chemotherapy. Patients who received neoadjuvant chemotherapy (NAC) for more than one year prior to CIRT were excluded. RESULTS: Forty-four patients met the inclusion criteria, and thirty-seven received NAC before CIRT. The median follow-up period of living patients was 26.0 (6.0-68.6) months after CIRT. The estimated two-year overall survival, local control, and progression-free survival rates after CIRT were 56.6%, 76.1%, and 29.0%, respectively. The median survival time of all patients was 29.6 months after CIRT and 34.5 months after the initial NAC. CONCLUSION: CIRT showed survival benefits for URPC even in the multiagent chemotherapy era.
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BACKGROUND/AIM: Prognostic factors, including CD8-positive tumor-infiltrating lymphocytes (CD8+TILs), in definitive radiotherapy (RT) for squamous cell carcinoma (SqCC) of the uterine cervix need to be studied. This study aimed to explore these factors in a retrospective cohort. PATIENTS AND METHODS: Patients with SqCC who underwent definitive RT comprising external beam RT and intracavitary brachytherapy at our facility between April 2006 and November 2013 were evaluated. CD8 immunohistochemistry was performed in pre-treatment biopsy samples to analyze the prognostic significance of CD8+TILs in the tumor nest. Positive staining was defined as at least one CD8+ lymphocyte infiltrating the tumor area in the specimen. RESULTS: In total, 150 consecutive patients were included. Among them, 66 (43.7%) patients had International Federation of Gynecology and Obstetrics (FIGO, 2008 edition) stage IIIA or higher progressive disease. The median follow-up period was 61 months. In the entire cohort, the 5-year cumulative rates of overall survival (OS), progression-free survival (PFS), and pelvic recurrence-free rate (PRFR) were 75.6%, 69.6%, and 84.8%, respectively. Of the 150 patients, 120 (80.0%) patients were CD8+TIL positive. The independent favorable prognostic factors were FIGO stage I or II disease, administration of concurrent chemotherapy, and CD8+TILs for OS (p=0.028, 0.005, and 0.038, respectively); FIGO stage I or II disease and CD8+TILs for PFS (p=0.015 and <0.001, respectively); and CD8+TILs for PRFR (p=0.017). CONCLUSION: The presence of CD8+TILs in the tumor nest may be a favorable prognostic factor of survival after definitive RT in patients with SqCC of the uterine cervix.
Subject(s)
Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Female , Humans , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/pathology , CD8-Positive T-Lymphocytes/pathology , Lymphocytes, Tumor-Infiltrating/pathology , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/pathologyABSTRACT
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.
Subject(s)
Neoplasm Metastasis , Radiosurgery , Humans , Cohort Studies , East Asian People , Liver , Retrospective Studies , Treatment Outcome , X-Rays , Neoplasm Metastasis/radiotherapyABSTRACT
Hepatocellular carcinoma (HCC) often recurs in the liver and requires multiple rounds of treatment. Thus, less-invasive multidisciplinary approaches are essential for preserving liver function, especially in elderly patients. Here, we report a case of an 86 year-old Japanese male patient with HCC who was successfully treated with repeated carbon ion radiotherapy (C-ion RT) and transarterial chemoembolization (TACE). The patient had alcoholic liver cirrhosis with a 60 mm HCC lesion and a satellite lesion in segment 6. The patient underwent initial C-ion RT but developed primary tumor recurrence (segment 6) and a new lesion (segment 2) 24 months later. The patient received TACE for each lesion, followed by an increased dose of C-ion RT for the recurrent primary tumor. Although the primary tumor lesion was well controlled, the patient subsequently developed new lesions, and TACE was repeated. The patient died of bacterial pneumonia 88 months after the initial treatment. His general condition and liver function were well preserved, and no severe adverse events were observed throughout the course of treatment. These results suggest that a less-invasive multidisciplinary approach involving repeated C-ion RT combined with TACE enables preservation of liver function, which may contribute to long-term survival in elderly patients with HCC.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Heavy Ion Radiotherapy , Liver Neoplasms , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Humans , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Male , Retrospective Studies , Survivors , Treatment OutcomeABSTRACT
BACKGROUND/AIM: Previous evaluation of the safety and clinical efficacy of re-irradiation for pelvic recurrence of rectal cancer after preoperative chemoradiotherapy (PCRT) and rectal surgery is insufficient. We evaluated the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for pelvic recurrence of rectal cancer after PCRT. PATIENTS AND METHODS: We reviewed the medical records of patients treated with C-ion RT between August 2011 and December 2021 and analyzed the data of seven consecutive patients. The probabilities of overall survival (OS), local control (LC), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: The median follow-up duration after C-ion RT initiation was 30.9 months. Five patients received 73.6 Gy [relative biological effectiveness (RBE)] in 16 fractions, and two patients received 57.6 Gy (RBE) in 12 fractions. All patients completed C-ion RT as scheduled. Two-year estimated OS, LC, and PFS rates after C-ion RT initiation were 100%, 83.3%, and 28.6%, respectively. No patients developed grade ≥3 acute toxicity. Regarding late toxicities, one patient who received Gore-Tex sheets as a spacer before C-ion RT developed grade 3 colon perforation, and then developed a grade 3 urinary tract disorder. One patient developed grade 2 peripheral neuropathy. CONCLUSION: C-Ion RT showed favorable local efficacy with minimal toxicity. C-Ion RT might be an effective treatment option for pelvic recurrence of rectal cancer after PCRT even when re-irradiation of the pelvis is required.
Subject(s)
Re-Irradiation , Rectal Neoplasms , Carbon , Chemoradiotherapy , Humans , Pelvis , Re-Irradiation/adverse effects , Re-Irradiation/methods , Rectal Neoplasms/radiotherapy , Retrospective StudiesABSTRACT
BACKGROUND: Curative treatment of inoperable post-irradiation sarcoma is often challenging, especially using radiotherapy, wherein curative dose administration is difficult because the organs around the tumor have already been irradiated during the first cancer treatment. Carbon-ion radiotherapy (C-ion RT) might be useful in the treatment of post-irradiation sarcomas because it allows re-irradiation with high-dose localization properties and also demonstrates higher cytotoxic effects on radioresistant tumors compared with X-rays. This study presents the long-term survival of two patients with inoperable post-irradiation pelvic osteosarcoma treated with C-ion RT after uterine cervical cancer treatment. CASE PRESENTATION: The durations from prior radiotherapy to the diagnosis of post-irradiation osteosarcoma were 112.8 and 172.2 months, respectively. Both patients received 70.4 Gy (relative biological effectiveness) in 16 fractions of C-ion RT, and chemotherapy was performed before and after C-ion RT. Both patients achieved a complete response 1 year after the initiation of C-ion RT. However, one patient developed single lung metastasis 12.6 months after the initiation of C-ion RT and underwent thoracoscopic lobectomy. After 63.7 and 89.0 months from the initiation of C-ion RT, respectively, the patients were alive with no evidence of local recurrence, other distant metastasis, or fatal toxicities. CONCLUSIONS: The study findings suggest that C-ion RT is a suitable treatment option for inoperable post-irradiation osteosarcoma.
Subject(s)
Bone Neoplasms , Heavy Ion Radiotherapy , Osteosarcoma , Bone Neoplasms/radiotherapy , Carbon , Female , Humans , Osteosarcoma/radiotherapy , Treatment OutcomeABSTRACT
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.
Subject(s)
Fractures, Stress , Proton Therapy , Uterine Neoplasms , Humans , Middle Aged , Female , Linear Energy Transfer , Retrospective Studies , Fractures, Stress/etiology , Relative Biological Effectiveness , Uterine Neoplasms/radiotherapy , Carbon , Radiotherapy Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
BACKGROUND AND PURPOSE: In radiotherapy (RT) for pancreatic cancer, the pancreas is considered an important organ at risk. However, there are insufficient reports on pancreatic function deterioration after X-ray RT as organ at risk, and there are no reports on those after carbon ion (C-ion) RT. Here, we evaluated pancreatic exocrine insufficiency (PEI) after C-ion RT using dose-volume histogram (DVH) analysis. MATERIALS AND METHODS: Data were retrospectively collected from patients who had undergone C-ion RT for pancreatic cancer between July 2013 and June 2019. The prescribed C-ion doses were 55.2 Gy (relative biological effectiveness) in 12 fractions. Serum pancreatic amylase and lipase values were measured before and after C-ion RT. In DVH analysis, we assessed V5Gy-50Gy and V<5 Gy-50Gy of pancreatic volume and analyzed whether these DVH parameters involved PEI. RESULTS: Thirty-three patients were included in the analysis. The median follow-up duration after the initiation of C-ion RT in these patients was 15.8 months (range, 4.3-64.8). During and after treatment, 57.6% of patients developed PEI within 13.6 months, defined as pancreatic amylase and lipase deficiencies. In DVH analysis, V<5Gy was the most effective factor for the PEI, and the cutoff value for developing PEI in V<5Gy was 4.57 cm3. CONCLUSION: We showed that pancreatic exocrine function declined after C-ion RT for pancreatic cancer and that PEI was initiated early in the course of C-ion RT. Additionally, a low dose of DVH parameters, such as V<5Gy, was a prognostic factor of PEI.
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Lung cancer is a leading cause of cancer-related deaths worldwide despite advances in treatment. In the past few decades, radiotherapy has achieved outstanding technical advances and is being widely used as a definitive, prophylactic, or palliative treatment of patients with lung cancer. The anti-tumor effects of radiotherapy are considered to result in DNA damage in cancer cells. Moreover, recent evidence has demonstrated another advantage of radiotherapy: the induction of anti-tumor immune responses, which play an essential role in cancer control. In contrast, radiotherapy induces an immunosuppressive response. These conflicting reactions after radiotherapy suggest that maximizing immune response to radiotherapy by combining immunotherapy has potential to achieve more effective anti-tumor response than using each alone. Immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1/programmed death-ligand 1, and their inhibitors, have attracted significant attention for overcoming the immunosuppressive conditions in patients with cancer. Therefore, the combination of immune checkpoint inhibitors and radiotherapy is promising. Emerging preclinical and clinical studies have demonstrated the rationale for these combination strategies. In this review, we outlined evidence suggesting that combination of radiotherapy, including particle therapy using protons and carbon ions, with immunotherapy in lung cancer treatment could be a promising treatment strategy.
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Radical treatments of hepatocellular carcinoma (HCC) with hepatic encephalopathy (HE) can be often difficult due to poor liver function or disturbance of consciousness. An effective treatment requires a combinatorial approach incorporating a treatment for HE and radical therapy for HCC that does not compromise liver function. Here, we report a case of a 78-year-old Japanese male with HCC and HE caused by splenorenal shunt. Serum ammonia levels were high. He was not suitable for surgery, percutaneous radiofrequency ablation, or transarterial chemoembolization due to the location of the tumor and poor liver function, which included HE. Thus, he underwent BRTO, with an immediate improvement in both HE and serum ammonia levels. After BRTO, he received C-ion RT as a radical treatment for HCC. After treatment, HCC was well controlled; however, at 35 months post-initiation of C-ion RT, he developed local recurrence without a further reduction in liver function status. Therefore, we repeated C-ion RT. The patient remains alive at 3 months post-treatment, with no evidence of local recurrence, distant metastasis, or toxicity. Although this is a single case report, it suggests that a combinatorial treatment consisting of BRTO and C-ion RT may increase survival rates of patients with HCC and HE.