Prognostic analysis of radiation-induced liver damage following carbon-ion radiotherapy for hepatocellular carcinoma.

BACKGROUND: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT. METHODS: We retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child-Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47-95 years), and the median tumor diameter was 41 mm (range 5-160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child-Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3-41.1 months), and RILD was observed in 11 patients (10.1%). RESULTS: Multivariate analysis showed that pretreatment Child-Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child-Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively. CONCLUSION: In conclusion, the pretreatment Child-Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.

Innovative Combination Treatment to Expand the Indications of Particle Therapy: Spacer Placement Surgery Using Bio-Absorbable Polyglycolic Acid Spacer.

BACKGROUND: Particle therapy has favorable dose distribution and high curability. However, radiotherapy for malignant tumors adjacent to the gastrointestinal tract is contraindicated owing to its low tolerance. To overcome this, combination treatment with surgery to make a space between the tumor and adjacent gastrointestinal tract followed by particle therapy has been developed. Several materials have been used for the spacer and recently, we developed the absorbable polyglycolic acid (PGA) spacer, which has been used since 2019. This study is the first report of consecutive case series of spacer placement surgery using the PGA spacer. STUDY DESIGN: Fifty consecutive patients undergoing spacer placement surgery with the PGA spacer were evaluated. Postoperative laboratory data, morbidity related to the treatment, and spacer volume after treatment were evaluated. RESULTS: There were no treatment-related deaths, and all but 2 patients completed combination treatment. The median ratios of postoperative PGA spacer volume to the pretreatment volume were 96.9%, 87.7%, and 74.6% at weeks 2, 4, and 8, respectively. The spacer volume was maintained at 80% at 7 weeks and was predicted to be 50% at 15 weeks and 20% in 24 weeks. CONCLUSIONS: Spacer placement surgery using the PGA spacer was feasible and tolerable. The PGA spacers maintained sufficient thickness during the duration of subsequent particle therapy. Combination treatment using the PGA spacer is innovative and has the potential to become a new standard curative local treatment.

Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.

BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. RESULTS: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. CONCLUSION: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.

Particle beam therapy for pelvic recurrence of colorectal cancer: a registry data analysis in Japan and a systematic review.

The aim of this study was to investigate the efficacy and safety of particle beam therapy (PBT) with proton or carbon ion beam for pelvic recurrence of colorectal cancer (PRCC) by comparing the clinical outcomes of a dataset of prospectively enrolled patients for PBT with those from the literature, which were collected by a systematic review of external X-ray radiotherapy (XRT) and PBT. Patients with PRCC treated at 14 domestic facilities between May 2016 and June 2019 and entered the database for prospective observational follow-up were analyzed. The registry data analyzed included 159 PRCC patients treated with PBT of whom 126 (79%) were treated with carbon ion radiation therapy (CIRT). The 3-year overall survival and local control rate were 81.8 and 76.4%, respectively. Among these PRCC patients, 5.7% had Grade 3 or higher toxicity. Systematic search of PubMed and Cochrane databases published from January 2000 to September 2020 resulted in 409 abstracts for the primary selection. Twelve studies fulfilled the inclusion criteria. With one additional publication, 13 studies were selected for qualitative analysis, including 9 on XRT and 4 on PBT. There were nine XRT studies, which included six on 3D conformal radiotherapy and three on stereotactic body radiation therapy, and four PBT studies included three on CIRT and one on proton therapy. A pilot meta-analysis using literatures with median survival time extractable over a 20-month observation period suggested that PBT, especially CIRT, may be a promising treatment option for PRCC not amenable to curative resection.

Safety and Efficacy of Carbon-ion Radiotherapy Alone for Stage III Non-small Cell Lung Cancer.

BACKGROUND/AIM: We evaluated the efficacy and safety of carbon-ion radiotherapy (CIRT) alone for Stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Data of 65 patients (median age=73 years) with Stage III NSCLC who underwent CIRT alone in the QST Hospital, Chiba, Japan, between 1997 and 2015 were retrospectively analysed. The median dose was 72.0 Gy (relative biological effectiveness). RESULTS: The median follow-up was 27.6 months (range=1.6-207.7 months). Two-year local control, progression-free survival (PFS), and overall survival (OS) rates were 73.9%, 38.6%, and 54.9%, respectively. Overall, 1 (2%), 4 (6%), and 1 (2%) patient developed Grade 4 (mediastinal haemorrhage), Grade 3 (radiation pneumonitis), and Grade 3 (bronchial fistula) toxicities, respectively. On univariate analysis, clinical T and N stage and CIRT timing were significant predictors of PFS and OS; clinical target volume was a significant predictor of PFS. CONCLUSION: CIRT alone is effective with acceptable toxicity for Stage III NSCLC.

Carbon-ion radiotherapy for non-small cell lung cancer with interstitial lung disease: a retrospective analysis.

BACKGROUND: Lung cancer is frequently complicated by interstitial lung disease (ILD). Treatment protocols for lung cancer patients with ILD have not been established; surgery, chemotherapy, and radiotherapy can all cause acute exacerbation of ILD. This study evaluated the toxicity and efficacy of carbon ion radiotherapy (CIRT) in patients with non-small cell lung cancer (NSCLC) and ILD. METHODS: Between June 2004 and November 2014, 29 patients diagnosed with NSCLC and ILD were treated with CIRT. No patient was eligible for curative surgery or conventional radiotherapy secondary to ILD. Owing to prior symptomology, radiation pneumonitis (RP) and symptom progression pre- and post-treatment were evaluated. The relationships between RP and clinical factors were investigated. RESULTS: Twenty-eight men and one woman, aged 62 to 90 years old, were followed for 2.7-77.1 months (median: 22.8 months). Single-grade symptomatic progression (grade 2-3) was observed in 4 patients, while 1 patient experiencedtwo-grade progression. Two patients experienced radiation-induced acute exacerbation. Local control at 3 years was 63.3% (72.2% for stage I disease); survival at 3 years was 46.3% (57.2% for stage I disease). Eighteen patients had died by the time of this writing, 10 of lung cancer progression. Radiation pneumonitis post-treatment progression correlated with dosimetric factors of the lungs (V5, V10) and a low pre-treatment serum surfactant protein-D. CONCLUSIONS: We found that CIRT may be useful as a low-risk, curative option for NSCLC patients with ILD, a population that is typically ineligible for conventional therapy. The DVH analysis showed that minimizing the low-dose region is important for reducing the risk of severe RP. TRIAL REGISTRATION: NIRS-9404 . Registered 1 March 1994.

Reirradiation using high-dose-rate interstitial brachytherapy for locally recurrent cervical cancer: a single institutional experience.

OBJECTIVES: This study aimed to evaluate the effectiveness and feasibility of reirradiation using high-dose-rate interstitial brachytherapy (HDR-ISBT) in patients with recurrent cervical cancer. METHODS: The records of 52 consecutive women with central pelvic recurrence who were salvaged with HDR-ISBT-based reirradiation were retrospectively reviewed. Data regarding the primary disease, follow-up findings, recurrence, the treatment outcome, and toxicities were collected. Multivariate analysis was performed using the Cox proportional hazards regression model to identify predictors of the response to HDR-ISBT. Survival rate was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 52 patients who had been treated with HDR-ISBT-based reirradiation were included in our database. The local control rate was 76.9% (40/52), and the median postrecurrence survival period was 32 months. Grade 3 or 4 late toxicities were observed in 13 patients (25%). Multivariate analysis revealed that tumor size and the treatment-free interval were significant poor prognostic factors of postrecurrence survival. In a comparison between the patients who were salvaged with HDR-ISBT-based reirradiation (ISBT group) and those who were treated with palliative therapy alone (palliative group), we found that among the patients who displayed 0 or 1 poor prognostic factors, the patients in the ISBT group survived significantly longer than those in the palliative group. In contrast, similar survival rates were seen in both groups among the patients with 2 or more poor prognostic factors. CONCLUSIONS: Reirradiation using HDR-ISBT is effective and feasible in patients with recurrent cervical cancer. Our 2-clinical variable prognostic model might enable physicians to identify patients who would not derive clinical benefit from HDR-ISBT and offer them the opportunity to receive other types of treatment.

A case of idiopathic basal ganglia calcification associated with membranoproliferative glomerulonephritis.

Idiopathic basal ganglia calcification (IBGC) is a syndrome in which bilateral cerebral calcification occurs despite the absence of abnormal calcium metabolism. A 17-year-old Japanese female was admitted for investigation of intermittent proteinuria from the age of 12 years. On admission, her blood pressure was 126/60 mmHg and her serum creatinine was 0.8 mg/dL. Although computed tomography revealed bilateral striopallidodentate calcinosis, her level of intelligence and neurological findings were normal, as were the results of endocrine tests including parathyroid hormone. Asymptomatic IBGC was diagnosed. Renal biopsy showed membranoproliferative glomerulonephritis. Peritoneal dialysis was started for end-stage renal failure when she was 24 years old. Pyramidal and extrapyramidal signs started to develop at the age of 27 years and progressed, resulting in death from aspiration pneumonia at the age of 32 years. Post-mortem revealed bilateral calcification of the basal ganglia, dentate nucleus, thalamus, and centrum semiovale. On light microscopy, there was circumferential calcification of the media and intima of affected vessels in the brain, including small arteries, small veins, and capillaries, and luminal narrowing was seen. On electron microscopy, layers of differing electron density were arranged in concentric laminae. This is the first report of IBGC with bilateral and symmetrical cerebral calcification accompanied by membranoproliferative glomerulonephritis resulting in end-stage renal failure.

[A case of pulmonary varices demonstrated by three-dimensional computed tomography].

We present a case of pulmonary varices in a 44-year-old man. The patient's chest X-ray films revealed well-delineated shadows in the right lower lung field. An enhanced chest CT scan with three-dimensional volumetric imaging demonstrated a vascular malformation in the right lower lobe. Both the arterial and parenchymal phases of digital subtraction of the right pulmonary angiography were normal. However, the venous phase showed serpiginous right lower pulmonary veins draining into the left atrium, and a delayed pooling of contrast in dilated pulmonary veins confirmed a diagnosis of pulmonary varices. No echocardiographic findings of valvular disease were recognized. He remained asymptomatic and returned to work, but radiological follow-up was continued annually.