Increased Screening Rates for Thyroid Cancer Among Residents Living Near Nuclear Power Plants.

Frequent screening for thyroid cancer has been suggested as a probable explanation for the observed high risk of thyroid cancer in nuclear power plant (NPP) areas. We aimed to compare thyroid cancer screening rates of residents living near NPPs to those of the general population. This study utilized data from two national survey-based studies in 2016 and in 2014, respectively, for residents (n = 1,200) living in administrative districts within 5 km of NPP sites as the interest group, and the general population (n = 228,712) including distant-living residents (n = 19,100) in administrative districts within 30 km of NPP sites as reference groups. We observed an increase in screening rates in residents near NPPs, which may lead to a higher possibility of thyroid cancer detection. Therefore, further epidemiological studies investigating radiation-induced thyroid cancer risk among residents near NPPs should be carefully designed and interpreted considering possible detection bias.

Prognostic impact of neutrophilia and lymphopenia on survival in anal cancer treated with definitive concurrent chemoradiotherapy: a retrospective multicenter study.

PURPOSE: This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy. RESULTS: Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/µl) and neutrophilia (> 7500/µl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/µl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/µl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively. CONCLUSION: The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer.

Metformin Protects the Intestinal Barrier by Activating Goblet Cell Maturation and Epithelial Proliferation in Radiation-Induced Enteropathy.

Radiotherapy or accidental exposure to high-dose radiation can cause severe damage to healthy organs. The gastrointestinal (GI) tract is a radiation-sensitive organ of the body. The intestinal barrier is the first line of defense in the GI tract, and consists of mucus secreted by goblet cells and a monolayer of epithelium. Intestinal stem cells (ISCs) help in barrier maintenance and intestinal function after injury by regulating efficient regeneration of the epithelium. The Wnt/ß-catenin pathway plays a critical role in maintaining the intestinal epithelium and regulates ISC self-renewal. Metformin is the most widely used antidiabetic drug in clinical practice, and its anti-inflammatory, antioxidative, and antiapoptotic effects have also been widely studied. In this study, we investigated whether metformin alleviated radiation-induced enteropathy by focusing on its role in protecting the epithelial barrier. We found that metformin alleviated radiation-induced enteropathy, with increased villi length and crypt numbers, and restored the intestinal barrier function in the irradiated intestine. In a radiation-induced enteropathy mouse model, metformin treatment increased tight-junction expression in the epithelium and inhibited bacterial translocation to mesenteric lymph nodes. Metformin increased the number of ISCs from radiation toxicity and enhanced epithelial repair by activating Wnt/ß-catenin signaling. These data suggested that metformin may be a potential therapeutic agent for radiation-induced enteropathy.

Combined Administration of Pravastatin and Metformin Attenuates Acute Radiation-Induced Intestinal Injury in Mouse and Minipig Models.

Radiation-induced gastrointestinal (GI) damage is one of the critical factors that serve as basis for the lethality of nuclear accidents or terrorism. Further, there are no Food and Drug Administration-approved agents available to mitigate radiation-induced intestinal injury. Although pravastatin (PS) has been shown to exhibit anti-inflammatory and epithelial reconstructive effects following radiation exposure using mouse and minipig models, the treatment failed to improve the survival rate of high-dose irradiated intestinal injury. Moreover, we previously found that metformin (MF), a common drug used for treating type 2 diabetes mellitus, has a mitigating effect on radiation-induced enteropathy by promoting stem cell properties. In this study, we investigated whether the combined administration of PS and MF could achieve therapeutic effects on acute radiation-induced intestinal injury in mouse and minipig models. We found that the combined treatment markedly increased the survival rate and attenuated histological damage in a radiation-induced intestinal injury mouse model, in addition to epithelial barrier recovery, anti-inflammatory effects, and improved epithelial proliferation with stem cell properties. Furthermore, in minipig models, combined treatment with PS and MF ameliorates gross pathological damage in abdominal organs and attenuated radiation-induced intestinal histological damage. Therefore, the combination of PS and MF effectively alleviated radiation-induced intestinal injury in the mouse and minipig models. We believe that the combined use of PS and MF is a promising therapeutic approach for treating radiation-induced intestinal injury.

Zileuton Alleviates Radiation-Induced Cutaneous Ulcers via Inhibition of Senescence-Associated Secretory Phenotype in Rodents.

Radiation-induced cutaneous ulcers are a challenging medical problem for patients receiving radiation therapy. The inhibition of cell senescence has been suggested as a prospective strategy to prevent radiation ulcers. However, there is no effective treatment for senescent cells in radiation ulcers. In this study, we investigated whether zileuton alleviated radiation-induced cutaneous ulcer by focusing on cell senescence. We demonstrate increased cell senescence and senescence-associated secretory phenotype (SASP) in irradiated dermal fibroblasts and skin tissue. The SASP secreted from senescent cells induces senescence in adjacent cells. In addition, 5-lipoxygenase (5-LO) expression increased in irradiated dermal fibroblasts and skin tissue, and SASP and cell senescence were regulated by 5-LO through p38 phosphorylation. Finally, the inhibition of 5-LO following treatment with zileuton inhibited SASP and mitigated radiation ulcers in animal models. Our results demonstrate that inhibition of SASP from senescent cells by zileuton can effectively mitigate radiation-induced cutaneous ulcers, indicating that inhibition of 5-LO might be a viable strategy for patients with this condition.

Atorvastatin Inhibits Endothelial PAI-1-Mediated Monocyte Migration and Alleviates Radiation-Induced Enteropathy.

Intestinal injury is observed in cancer patients after radiotherapy and in individuals exposed to radiation after a nuclear accident. Radiation disrupts normal vascular homeostasis in the gastrointestinal system by inducing endothelial damage and senescence. Despite advances in medical technology, the toxicity of radiation to healthy tissue remains an issue. To address this issue, we investigated the effect of atorvastatin, a commonly prescribed hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor of cholesterol synthesis, on radiation-induced enteropathy and inflammatory responses. We selected atorvastatin based on its pleiotropic anti-fibrotic and anti-inflammatory effects. We found that atorvastatin mitigated radiation-induced endothelial damage by regulating plasminogen activator inhibitor-1 (PAI-1) using human umbilical vein endothelial cells (HUVECs) and mouse model. PAI-1 secreted by HUVECs contributed to endothelial dysfunction and trans-endothelial monocyte migration after radiation exposure. We observed that PAI-1 production and secretion was inhibited by atorvastatin in irradiated HUVECs and radiation-induced enteropathy mouse model. More specifically, atorvastatin inhibited PAI-1 production following radiation through the JNK/c-Jun signaling pathway. Together, our findings suggest that atorvastatin alleviates radiation-induced enteropathy and supports the investigation of atorvastatin as a radio-mitigator in patients receiving radiotherapy.

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.

Ultrasonographic Thyroid Nodule Classification Using a Deep Convolutional Neural Network with Surgical Pathology.

Ultrasonography with fine-needle aspiration biopsy is commonly used to detect thyroid cancer. However, thyroid ultrasonography is prone to subjective interpretations and interobserver variabilities. The objective of this study was to develop a thyroid nodule classification system for ultrasonography using convolutional neural networks. Transverse and longitudinal ultrasonographic thyroid images of 762 patients were used to create a deep learning model. After surgical biopsy, 325 cases were confirmed to be benign and 437 cases were confirmed to be papillary thyroid carcinoma. Image annotation marks were removed, and missing regions were recovered using neighboring parenchyme. To reduce overfitting of the deep learning model, we applied data augmentation, global average pooling. And 4-fold cross-validation was performed to detect overfitting. We employed a transfer learning method with the pretrained deep learning model VGG16. The average area under the curve of the model was 0.916, and its specificity and sensitivity were 0.70 and 0.92, respectively. Positive and negative predictive values were 0.90 and 0.75, respectively. We introduced a new fine-tuned deep learning model for classifying thyroid nodules in ultrasonography. We expect that this model will help physicians diagnose thyroid nodules with ultrasonography.

Feasibility of split-course stereotactic ablative radiotherapy for oligometastases.

BACKGROUND: There is growing interest in the use of stereotactic ablative radiotherapy (SABR) for oligometastases. However, extreme caution should be exercised in treating tumors closely located to organs at risk (OARs) with SABR. To reduce complications, we have applied split-course SABR to oligometastases closely located to OARs or to those being retreated with radiotherapy. METHODS: We retrospectively reviewed the records of patients with oligometastases who were treated with planned split-course SABR between January 2012 and December 2016. RESULTS: A total of 23 patients with 29 oligometastatic lesions were enrolled. The primary diagnoses were bone and soft tissue cancers in 13 lesions, liver cancers in 12 lesions, and colorectal cancers in four lesions. The median tumor volume was 78 cm3 (range, 4-1781 cm3). The lesions were treated with 1-3 fractions in the first stage of SABR (first SABR), and one or two fractions in the second stage of SABR (second SABR). The time interval between the two stages was about 4 weeks. A partial response was noted in 16 lesions (55%) after the first SABR, and practical reductions in the doses to OARs were observed in the second SABR compared with the first SABR. The 1-, 2- and 3-year local control rates were 92%, 65% and 43%, respectively. No Grade 4 or 5 toxicities were observed during or after treatment. CONCLUSION: Split-course SABR appeared to be feasible for the treatment of oligometastases closely located to OARs.

Role of HIF-1α in response of tumors to a combination of hyperthermia and radiation in vivo.

PURPOSE: Mild temperature hyperthermia (MTH) increases blood flow and oxygenation in tumours. On the other hand, high-dose-per-fraction irradiation damages blood vessels, decreases blood flow and increases hypoxia in tumours. The radiation-induced hypoxia in tumours activates hypoxia-inducible factor-1α (HIF-1α) and its target genes, such as vascular endothelial growth factor (VEGF), promoting revascularization and recurrence. In the present study, we examined the hypothesis that MTH inhibits radiation-induced upregulation of HIF-1α and its target genes by increasing tumour oxygenation. MATERIALS AND METHODS: FSaII fibrosarcoma tumours grown subcutaneously in the legs of C3H mice were used. Tumours were irradiated with 15 Gy using a 60Co irradiator or heated at 41 °C for 30 min using an Oncothermia heating unit. Blood perfusion and hypoxia in tumours were assessed with Hoechst 33342 and pimonidazole staining, respectively. Expression levels of HIF-1α and VEGF were determined using immunohistochemical techniques. Apoptosis of tumour cells was quantitated via TUNEL staining and the effects of treatments on tumour growth rate were assessed by measuring tumour diameters. RESULTS: Irradiation of FSaII tumours with a single dose of 15 Gy led to significantly decreased blood perfusion, increased hypoxia and upregulation of HIF-1α and VEGF. On the other hand, MTH at 41 °C for 30 min increased blood perfusion and tumour oxygenation, thereby suppressing radiation-induced HIF-1α and VEGF in tumours, leading to enhanced apoptosis of tumour cells and tumour growth delay. CONCLUSION: MTH enhances the anti-tumour effect of high-dose irradiation, at least partly by inhibiting radiation-induced upregulation of HIF-1α.

Quality assurance for a multicenter Phase II study of stereotactic ablative radiotherapy for hepatocellular carcinoma ≤5 cm: a planning dummy run.

OBJECTIVE: The Korean Radiation Oncology Group (12-02) investigated the outcome of stereotactic ablative radiotherapy for hepatocellular carcinoma ≤5 cm using 60 Gy in three fractions. To evaluate dosimetric differences and compliance in a multicenter trial, a planning dummy run procedure was performed. METHODS: All six participating institutions were provided the contours of two dummy run cases. Plans were performed following the study protocol to cover the planning target volume with a minimum of 90% of the prescription dose and to satisfy the constraints for organs at risk. We assessed the institutional variations in plans using dose-volume histograms. RESULTS: Different planning techniques were applied: static intensity-modulated radiotherapy in two institutions, CyberKnife in two institutions and RapidArc in two institutions. The conformity index of all 12 plans was ≤1.2. In terms of the planning target volume coverage, all participants followed our study protocol. For the second dummy run case, located in Segment 8 near the heart, the minimum dose of the planning target volume (D99%: dose covering 99% of the planning target volume) was variable because there was no mention of constraints of D99% of the planning target volume in the study protocol. As an important organ at risk, the normal liver volumes receiving <17 Gy in all 12 plans were >700 ml. CONCLUSIONS: Dosimetric parameters showed acceptable compliance with the study protocol. However, we found the possibility of underdose to the planning target volume if the hepatocellular carcinoma lesion was located near organs at risk such as the heart. Based on this dummy run, we will conduct individual case reviews to minimize the effects of study protocol deviation.

Practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea: a survey of the Korean Stereotactic Radiosurgery Group.

OBJECTIVE: To investigate practical patterns for stereotactic body radiotherapy to hepatocellular carcinoma in Korea. METHODS: In June 2013, the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation Oncology conducted a national patterns-of-care survey about stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma, consisting of 19 questions and 2 clinical scenarios. RESULTS: All 208 radiation oncologists (100%), who are regular members of Korean Society for Radiation Oncology, responded to this survey. Among these, 95 radiation oncologists were specialists for hepatology; 64 physicians did not use stereotactic body radiotherapy for hepatocellular carcinoma, and 31 physicians used stereotactic body radiotherapy. Most physicians (52%) performed stereotactic body radiotherapy to hepatocellular carcinoma in ≤5 cases per year. Physicians applied stereotactic body radiotherapy according to tumour size and baseline Child-Pugh class. All physicians agreed the use of stereotactic body radiotherapy to 2.8-cm hepatocellular carcinoma with Child-Pugh class of A, while 23 physicians (74%) selected stereotactic body radiotherapy for Child-Pugh class of B. Nineteen physicians (61%) selected stereotactic body radiotherapy to 5-cm hepatocellular carcinoma with Child-Pugh class of A, and only 14 physicians (45%) selected stereotactic body radiotherapy for Child-Pugh class of B. On the other hand, the preferred dose scheme was same as 60 Gy in three fractions. CONCLUSIONS: Among radiation oncologists in Korea, there was diversity in the practice for stereotactic body radiotherapy to the liver lesion in hepatocellular carcinoma. Additional prospective studies are necessary to standardize the practice and establish Korea-specific practice guidelines for hepatocellular carcinoma stereotactic body radiotherapy.

Stereotactic body radiotherapy for oligometastases confined to the para-aortic region: clinical outcomes and the significance of radiotherapy field and dose.

We retrospectively reviewed 88 patients with oligometases in the para-aortic region from any controlled primary tumor site who were treated with stereotactic body radiotherapy (SBRT). The 5-year local control, disease-free survival, and overall survival rates were 83%, 31%, and 41%, respectively. A 90% tumor-control probability was predicted at a biological effective dose of 90 Gy. Severe gastrointestinal toxicities (grade ≥3) were observed in 2 of 88 patients (1%). The results of this study are limited by the retrospective nature of the study but could serve as the background and rationale for future prospective trials on SBRT-based treatment for oligometastses.

Nomogram prediction of survival in patients with brain metastases from hepatocellular carcinoma treated with whole-brain radiotherapy: a multicenter retrospective study.

The incidence of brain metastasis from hepatocellular carcinoma (HCC) is increasing because of the improved survival outcome of HCC patients, but the prognosis of these patients is extremely poor. HCC patients with brain metastasis were investigated to identify their prognostic factors for overall survival. Patients with brain metastasis from HCC who had been treated with whole-brain radiotherapy (WBRT) in five hospitals were enrolled in the study. The medical records of the patients were reviewed, and the clinical factors were analyzed to identify the prognostic factors for overall survival. Of the total of 97 patients who were enrolled in the study, 83 were male and the median age at the brain metastases was 56.6 years. Motor weakness (43.3 %) and headache (41.2 %) were common presenting symptoms. The median AFP level was 4180 ng/ml, and 81 patients were assessed as belonging to Child-Pugh classification A upon the diagnosis of brain metastasis. WBRT alone in 71 patients, surgery or radiosurgery combined with WBRT as the adjuvant setting in 18 patients, and WBRT as salvage treatment in 8 patients were performed. The median overall survival of the patients was 3.5 months. In the multivariate analysis, the ECOG performance status (PS), Child-Pugh classification, AFP, and treatment aim showed significant association with the overall survival of the patients. Based on these factors, a nomogram predicting the prognosis was developed. The concordance index of the nomogram was 0.74, and the prediction was well calibrated. In conclusion, the survival outcome of patients with brain metastasis from HCC can be predicted with the nomogram constructed from the ECOG PS, Child-Pugh classification, AFP, and treatment aim.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions.

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity≥grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV5Gy-rV35Gy: normal liver volume receiving

Recent update of proton beam therapy for hepatocellular carcinoma: A systematic review and meta-analysis.

Backgrounds/Aims: Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and meta-analysis to investigate the updated evidence of PBT for HCC. Methods: The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024. Results: A total of 1858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range: 41-100%), and the median tumor size was 3.6 cm (range: 1.2-9 cm). The median total dose ranged from 55 GyE to 76 GyE (median, 69 GyE). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91%) and 86% (95% CI, 82-90%), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66%) and 46% (95% CI, 38-54%), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiation-induced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively. Conclusions: The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

Five-Day Spacing of Two Fractionated Ablative Radiotherapies Enhances Antitumor Immunity.

PURPOSE: This study aimed to enhance tumor control and abscopal effects by applying diverse stereotactic ablative radiation therapy (SABR) schedules. METHODS AND MATERIALS: FSaII, CT-26, and 4T1 cells were used for tumor growth delay and lung metastases analysis after 1- or 5-day intervals radiation therapy (RT) with 40, 20, and 20 Gy, respectively. Immunodeficient BALB/c-nude, immunocompetent C3H, and BALB/c mouse models were used. For immune monitoring, FSaII tumors were analyzed using flow cytometry, immunofluorescence staining, and real-time quantitative reverse transcription polymerase chain reaction. The spleens were used for the ELISpot assay and flow cytometry to determine effector CD8 T cells. For abscopal effect analysis in CT-26 tumors, the volume of the nonirradiated secondary tumors was measured after primary tumors were irradiated with 1-day or 5-day intervals. RESULTS: Contrary to the high-dose 1-day interval RT, the 5-day interval RT significantly delayed tumor growth in immunocompetent mice, which was not observed in immunodeficient mice. In addition, the 5-day interval RT significantly reduced the number of lung metastases in FSaII and CT-26 tumors. Five-day spacing was more effective than 1-day interval in enhancing the antitumor immunity via increasing the secretion of tumor-specific IFN-γ, activating the CD8 T cells, and suppressing the monocytic myeloid-derived suppressor cells. The 5-day spacing inhibited nonirradiated secondary tumor growth more effectively than did the 1-day interval. CONCLUSIONS: Compared with the 1-day interval RT, the 5-day interval RT scheme demonstrated enhanced antitumor immunity of CD8 T cells associated with inhibition of myeloid-derived suppressor cells. Enhancing antitumor immunity leads to significant improvements in both primary tumor control and the abscopal effect.

Prognostic Significance of Bulky Nodal Disease in Anal Cancer Management: A Multi Institutional Study.

Purpose: This study aimed to assess the prognostic significance of bulky nodal involvement in patients with anal squamous cell carcinoma treated with definitive chemoradiotherapy. Materials and Methods: We retrospectively analyzed medical records of patients diagnosed with anal squamous cell carcinoma who underwent definitive chemoradiotherapy at three medical centers between 2004 and 2021. Exclusion criteria included distant metastasis at diagnosis, 2D radiotherapy, and salvage treatment for local relapse. Bulky N+ was defined as nodes with a long diameter of 2 cm or greater. Results: A total of 104 patients were included, comprising 51 with N0, 46 with non-bulky N+, and 7 with bulky N+. The median follow-up duration was 54.0 months (range, 6.4-162.2 months). Estimated 5-year progression-free survival (PFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS) rates for patients with bulky N+ were 42.9%, 42.9%, and 47.6%, respectively. Bulky N+ was significantly associated with inferior PFS, LRRFS and OS compared to patients without or with non-bulky N+, even after multivariate analysis. We proposed a new staging system incorporating bulky N+ as N2 stage, with estimated 5-year LRRFS, PFS, and OS rates of 81.1%, 80.6%, and 86.2% for stage I, 67.7%, 60.9%, and 93.3% for stage II, and 42.9%, 42.9%, and 47.6% for stage III disease, enhancing the predictability of prognosis. Conclusion: Patients with bulky nodal disease treated with standard chemoradiotherapy experienced poor survival outcomes, indicating the potential necessity for further treatment intensification.

CXCL10 upregulation in radiation-exposed human peripheral blood mononuclear cells as a candidate biomarker for rapid triage after radiation exposure.

PURPOSE: In case of a nuclear accident, individuals with high-dose radiation exposure (>1-2 Gy) should be rapidly identified. While ferredoxin reductase (FDXR) was recently suggested as a radiation-responsive gene, the use of a single gene biomarker limits radiation dose assessment. To overcome this limitation, we sought to identify reliable radiation-responsive gene biomarkers. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from mice after total body irradiation, and gene expression was analyzed using a microarray approach to identify radiation-responsive genes. RESULTS: In light of the essential role of the immune response following radiation exposure, we selected several immune-related candidate genes upregulated by radiation exposure in both mouse and human PBMCs. In particular, the expression of ACOD1 and CXCL10 increased in a radiation dose-dependent manner, while remaining unchanged following lipopolysaccharide (LPS) stimulation in human PBMCs. The expression of both genes was further evaluated in the blood of cancer patients before and after radiotherapy. CXCL10 expression exhibited a distinct increase after radiotherapy and was positively correlated with FDXR expression. CONCLUSIONS: CXCL10 expression in irradiated PBMCs represents a potential biomarker for radiation exposure.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).