Aerobic Exercise Improves Radiation Therapy Efficacy in Non-Small Cell Lung Cancer: Preclinical Study Using a Xenograft Mouse Model.

The "oxygen effect" improves radiation efficacy; thus, tumor cell oxygen concentration is a crucial factor for improving lung cancer treatment. In the current study, we aimed to identify aerobic exercise-induced changes in oxygen concentrations in non-small cell lung cancer (NSCLC) cells. To this end, an NSCLC xenograft mouse model was established using human A549 cells. Animals were subsequently subjected to aerobic exercise and radiation three times per week for 2 weeks. Aerobic exercise was performed at a speed of 8.0 m/m for 30 min, and the tumor was irradiated with 2 Gy of 6 MV X-rays (total radiation dose 12 Gy). Combined aerobic exercise and radiation reduced NSCLC cell growth. In addition, the positive effect of aerobic exercise on radiation efficacy through oxygenation of tumor cells was confirmed based on hypoxia-inducible factor-1 and carbonic anhydrase IX expression. Finally, whole-transcriptome analysis revealed the key factors that induce oxygenation in NSCLC cells when aerobic exercise was combined with radiation. Taken together, these results indicate that aerobic exercise improves the effectiveness of radiation in the treatment of NSCLC. This preclinical study provides a basis for the clinical application of aerobic exercise to patients with NSCLC undergoing radiation therapy.

Mitochondrial glutamate transporter SLC25A22 uni-directionally export glutamate for metabolic rewiring in radioresistant glioblastoma.

Glioblastoma Multiforme (GBM) is a malignant primary brain tumor. Radiotherapy, one of the standard treatments for GBM patients, could induce GBM radioresistance via rewiring cellular metabolism. However, the precise mechanism attributing to GBM radioresistance or targeting strategies to overcome GBM radioresistance are lacking. Here, we demonstrate that SLC25A22, a mitochondrial bi-directional glutamate transporter, is upregulated and showed uni-directionality from mitochondria to cytosol in radioresistant GBM cells, resulting in accumulating cytosolic glutamate. However, mitochondrial glutaminolysis-mediated TCA cycle metabolites and OCR are maintained constantly. The accumulated cytosolic glutamate enhances the glutathione (GSH) production and proline synthesis in radioresistant GBM cells. Increased GSH protects cells against ionizing radiation (IR)-induced reactive oxygen species (ROS) whereas increased proline, a rate-limiting substrate for collagen biosynthesis, induces extracellular matrix (ECM) remodeling, leading to GBM invasive phenotypes. Finally, we discover that genetic inhibition of SLC25A22 using miR-184 mimic decreases GBM radioresistance and aggressiveness both in vitro and in vivo. Collectively, our study suggests that SLC25A22 upregulation confers GBM radioresistance by rewiring glutamate metabolism, and SLC25A22 could be a significant therapeutic target to overcome GBM radioresistance.

The Current Evidence of Intensity-Modulated Radiotherapy for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Intensity-modulated radiotherapy (IMRT), an advanced RT technique, is a considerable treatment option for hepatocellular carcinoma (HCC). However, the distinguishing features of IMRT for HCC have not yet been clearly defined. A systematic review was performed according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The PubMed/MedLine, Embase, Cochrane Library, Web of Science, and KoreaMed were used to screen eligible studies focusing on treatment outcomes after IMRT for HCC until 18 April 2023. A total of 1755 HCC patients receiving IMRT among 29 studies from 2009 to 2023 were selected for the meta-analysis. The median proportion of Barcelona Clinic Liver Cancer stage C was 100% (range: 38-100%). Nineteen studies used combined treatment. Pooled rates of response and 1-year local control were 58% (95% confidence interval [CI], 50-65%) and 84% (95% CI, 70-94%), respectively. The median overall survival (OS) was 13 months (range: 5-45 months), and pooled 1- and 3-year OS rates were 59% (95% CI, 52-66%), and 23% (95% CI, 14-33%), respectively. Pooled rates of classic radiation-induced liver disease (RILD), nonclassic RILD, and hepatic toxicity ≥ grade 3 were 2%, 4%, and 4%, respectively. Although most patients had advanced-stage HCC and combined treatment was commonly used, IMRT for HCC showed similar survival to existing RT modalities and relatively low severe toxicity.

NRBF2-mediated autophagy contributes to metabolite replenishment and radioresistance in glioblastoma.

Overcoming therapeutic resistance in glioblastoma (GBM) is an essential strategy for improving cancer therapy. However, cancer cells possess various evasion mechanisms, such as metabolic reprogramming, which promote cell survival and limit therapy. The diverse metabolic fuel sources that are produced by autophagy provide tumors with metabolic plasticity and are known to induce drug or radioresistance in GBM. This study determined that autophagy, a common representative cell homeostasis mechanism, was upregulated upon treatment of GBM cells with ionizing radiation (IR). Nuclear receptor binding factor 2 (NRBF2)-a positive regulator of the autophagy initiation step-was found to be upregulated in a GBM orthotopic xenograft mouse model. Furthermore, ATP production and the oxygen consumption rate (OCR) increased upon activation of NRBF2-mediated autophagy. It was also discovered that changes in metabolic state were induced by alterations in metabolite levels caused by autophagy, thereby causing radioresistance. In addition, we found that lidoflazine-a vasodilator agent discovered through drug repositioning-significantly suppressed IR-induced migration, invasion, and proliferation by inhibiting NRBF2, resulting in a reduction in autophagic flux in both in vitro models and in vivo orthotopic xenograft mouse models. In summary, we propose that the upregulation of NRBF2 levels reprograms the metabolic state of GBM cells by activating autophagy, thus establishing NRBF2 as a potential therapeutic target for regulating radioresistance of GBM during radiotherapy.

18F-FDG PET/CT Parameters for Predicting Prognosis in Esophageal Cancer Patients Treated With Concurrent Chemoradiotherapy.

BACKGROUND AND AIMS: This study evaluated the prognostic value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) performed before and after concurrent chemoradiotherapy (CCRT) in esophageal cancer. METHODS: We analyzed the prognosis of 50 non-metastatic squamous cell esophageal cancer (T1-4N0-2) patients who underwent CCRT with curative intent at Inje University Busan Paik Hospital and Haeundae Paik Hospital from 2009 to 2019. Median total radiation dose was 54 Gy (range 34-66 Gy). Our aim was to investigate the relationship between PET/CT values and prognosis. The primary end point was progression-free survival (PFS). RESULTS: The median follow-up period was 9.9 months (range 1.7-85.7). Median baseline maximum standard uptake value (SUVmax) was 14.2 (range 3.2-27.7). After treatment, 29 patients (58%) showed disease progression. The 3-year PFS and overall survival (OS) were 24.2% and 54.5%, respectively. PFS was significantly lower (P = 0.015) when SUVmax of initial PET/CT exceeded 10 (n = 22). However, OS did not reach a significant difference based on maximum SUV (P = 0.282). Small metabolic tumor volume (≤14.1) was related with good PFS (P = 0.002) and OS (P = 0.001). Small total lesion of glycolysis (≤107.3) also had a significant good prognostic effect on PFS (P = 0.009) and OS (P = 0.025). In a subgroup analysis of 18 patients with follow-up PET/CT, the patients with SUV max ≤3.5 in follow-up PET/CT showed longer PFS (P = 0.028) than those with a maximum SUV >3.5. CONCLUSION: Maximum SUV of PET/CT is useful in predicting prognosis of esophageal cancer patients treated with CCRT. Efforts to find more effective treatments for patients at high risk of progression are still warranted.

Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas.

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.

Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma.

Radiotherapy is a standard treatment option for patients with glioblastoma (GBM). Although it has high therapeutic efficacy, some proportion of the tumor cells that survive after radiotherapy may cause side effects. In this study, we found that fructose 1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was downregulated upon treatment with ionizing radiation (IR). Ets1, which was found to be overexpressed in IR-induced infiltrating GBM, was suggested to be a transcriptional repressor of FBP1. Furthermore, glucose uptake and extracellular acidification rates were increased upon FBP1 downregulation, which indicated an elevated glycolysis level. We found that emodin, an inhibitor of phosphoglycerate mutase 1 derived from natural substances, significantly suppressed the glycolysis rate and IR-induced GBM migration in in vivo orthotopic xenograft mouse models. We propose that the reduced FBP1 level reprogrammed the metabolic state of GBM cells, and thus, FBP1 is a potential therapeutic target regulating GBM metabolism following 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.

Myeloid Sarcoma That Infiltrated a Preexisting Sebaceous Lymphadenoma in the Parotid Gland: Diagnostic Challenges and Literature Review.

Myeloid sarcoma (MS) is a rarely encountered extramedullary localized tumor that is composed of immature myeloid cells. We reported an extremely rare case of MS with concurrent bone marrow (BM) involvement that invaded into a preexisting sebaceous lymphadenoma in the parotid gland and neck lymph nodes. Prompted by this case, we also present a literature review of MS invasion into salivary glands. A 62-year-old man was initially diagnosed with carcinoma that arose in a sebaceous lymphadenoma in the parotid gland, through a total parotidectomy with neck dissection. After an extensive histopathological review that included immunohistochemistry, a pathologic diagnosis of MS with infiltration into the sebaceous lymphadenoma with concurrent BM involvement was confirmed. MS is difficult to diagnose accurately; herein, we analyzed the clinical presentations and effectiveness of the various diagnostic methods with a review of the literature. There are 17 cases, including our case, reported in 13 studies. Of the cases in which the salivary glands were affected, 10 involved the parotid gland, six involved the submandibular gland, and one involved both. Isolated invasion of the salivary gland was found in one case of parotid gland invasion and three cases of submandibular gland invasion. In 13 cases, the salivary glands were affected by various other lesions. Although there were no incidences of isolated MS, six patients were diagnosed with secondary MS and eight patients with MS with BM involvement, including this case. The diagnosis of MS is difficult given its rarity, and a high index of suspicion and integrated radiologic and careful histopathologic evaluation are required. Most cases of MS infiltrating the salivary gland might be indicated by the possibility of BM involvement. MS with BM involvement predicts poor prognosis and the need for intensive systemic treatment.

Port-Site Implantation Diagnosed by Iodine-131 Post-Ablation Single-Photon Emission Tomography-Computed Tomography After Robotic Thyroidectomy: A Case Report.

BACKGROUND Robotic thyroidectomy using remote access approaches is currently regarded as the optimal surgical protocol for highly selected patients. This approach has excellent cosmetic outcomes compared with conventional open transcervical thyroidectomy. Although the remote access approach offers significant benefits, it can cause complications associated with the large working space required for surgery. Such complications can lead to unusual imaging findings. CASE REPORT We report a case of a 37-year-old woman with thyroid cancer who underwent robotic thyroidectomy and demonstrated unusual port-site implantation findings on post-treatment iodine-131 whole-body scintigraphy and single-photon emission computed tomography-computed tomography. Evaluation of stimulated thyroglobulin and additional imaging studies did not reveal any remarkable findings. Through a multidisciplinary discussion, we discovered that the bag had developed a tear during specimen retrieval. Our patient was administered a therapeutic dose of radioiodine, which accumulated within the target area and successfully ablated the implanted tissue. Follow-up imaging and biochemical studies were normal after a follow-up period of 7 years. CONCLUSIONS Port-site seeding is a rare and unexpected surgical complication; however, it can be treated with radioiodine therapy involving a therapeutic dose. Meticulous surgical manipulation is essential to prevent port-site implantation related to spillage and tearing of thyroid or cancer tissue. Awareness and identification of these rare complications, which manifest as unusual imaging findings, are critical for improving the accuracy of interpretation.

Radiotherapy in combination with hyperthermia suppresses lung cancer progression via increased NR4A3 and KLF11 expression.

Purpose: Hyperthermia (HT), a clinical treatment involving delivery of heat to tumors, has been used in combination with traditional chemotherapy and radiotherapy to enhance their effects. However, the molecular mechanism underlying the high efficacy of combination therapy is not clear. This study was conducted to identify the molecular mechanism underlying the sensitization of lung cancer to radiotherapy by HT.Materials and methods: Nuclear receptor subfamily 4, group A, member 3 (NR4A3) and Krüppel-like factor 11 (KLF11) expression in non-small-cell lung cancer cells was confirmed by performing real-time quantitative reverse transcription-polymerase chain reaction. Tumor cell proliferation and apoptosis were assessed via a colony-forming assay and Annexin V/propidium iodide staining.Results and conclusions: Expression profile analysis revealed elevated levels of NR4A3 and KLF11 in A549 lung cancer cells after treatment with HT combined with radiation. We also confirmed that NR4A3 and KLF11 induced apoptosis and inhibited cell proliferation by elevating intracellular reactive oxygen species levels. Knockdown of NR4A3 or KLF11 using siRNA led to decreased effects of radiohyperthermia. Finally, the effect of these two factors on lung cancer progression was evaluated by in vivo xenograft studies. Taken together, the results suggest that NR4A3 and KLF11 are critical for increasing the efficacy of radiotherapy in combination with HT.

Diabetes as a prognostic factor in HER-2 positive breast cancer patients treated with targeted therapy.

PURPOSE: Recent studies revealed that metabolic stress influences the outcomes of breast cancer treatment. We sought to evaluate the prognostic effect of type 2 diabetes and find the molecular mechanism of relapses in postoperative HER-2+ breast cancer patients treated with HER-2 targeted therapy. MATERIALS AND METHODS: We evaluated 190 HER-2+ breast cancer patients (pT1-4N0-2M0) who were treated with surgical resection and trastuzumab (HER-2 targeted therapy) between 2006 and 2015. Survival outcomes and failure patterns were compared between such patients with (n = 12) and without (n = 178) type 2 diabetes. RESULTS: The median follow-up period was 42.4 months (range 12.0-124.7 months). Twenty-one patients (11.1%) showed relapse (including nine patients with locoregional failure), and three patients (1.6%) died as a result of cancer relapse. One-third of the patients with diabetes experienced relapse (4/12, 33.3%). The 3-year disease-free survival (DFS) and overall survival (OS) rates were 90.7% and 98.6%, respectively. Diabetic patients showed shorter DFS compared with non-diabetic patients (p = 0.006, 74.1% vs. 91.9%). OS was also shorter in diabetic patients compared with non-diabetic patients (p = 0.017, 91.7% vs. 99.1%). Of our interest, the levels of HER-3 and its ligand neuregulin-1 were significantly increased in the tumor specimen in HER-2+ breast cancer patients suffering with type 2 diabetes than that in the euglycemic control group. CONCLUSIONS: Type 2 diabetes was associated with detrimental effects on survival in postoperative HER-2+ breast cancer patients who were treated with trastuzumab. The poor prognostic effect of diabetes in HER-2+ breast cancer patients could be associated with the high levels of HER-3 and neuregulin 1, thus it should be considered and evaluated more.

Dummy Run of Quality Assurance Program before Prospective Study of Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases from Non-small Cell Lung Cancer: Korean Radiation Oncology Group (KROG) 17-06 Study.

PURPOSE: Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study. MATERIALS AND METHODS: Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated. RESULTS: In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol. CONCLUSION: The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.

Decreased Hepatic Lactotransferrin Induces Hepatic Steatosis in Chronic Non-Alcoholic Fatty Liver Disease Model.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging metabolic disease. Although it leads to severe hepatic diseases including steatohepatitis, cirrhosis, and hepatic cancer, little is known about therapy to prevent and cure hepatic steatosis, the first step of NAFLD. We conducted this investigation to unveil the mechanism of hepatic steatosis. METHODS: We established a novel chronic NAFLD mouse model through whole body irradiation and verified the model through histological and biochemical analysis. To find molecular mechanism for hepatic steatosis, we analyzed hepatic transcriptomic profiles in this model and selected target molecule. To induce the expression of lactotransferrin (Ltf) and regulate the NAFLD, growth hormone (GH) and coumestrol was introduced to hepatocyte and mice. The universal effect of coumestrol was confirmed by administration of coumestrol to NAFLD mouse model induced by high-fructose, high-fat, and MCD diet. RESULTS: It was observed that decreased hepatic Ltf expression led to excessive hepatic lipid accumulation in NAFLD mouse. Furthermore, we found that GH was decreased in irradiated mice and functioned as an upstream regulator of Ltf expression. It was observed that GH could stimulate Ltf expression and prevent uptake of dietary lipids in hepatocytes, leading to rescue of NAFLD. Finally, we suggested that coumestrol, a kind of isoflavonoid, could be used as an inducer of hepatic Ltf expression through cooperation with the GH signaling pathway both in vitro and in vivo. CONCLUSIONS: Hepatic Ltf prevents hepatic steatosis through inhibition of dietary lipid uptake in radiation-induced NAFLD mouse model. We also suggest coumestrol as a drug candidate for prevention of NAFLD.

Radiation-induced overexpression of transthyretin inhibits retinol-mediated hippocampal neurogenesis.

Cranial irradiation is the main therapeutic strategy for treating primary and metastatic brain tumors. However, radiation is well-known to induce several unexpected side effects including emotional disorders. Although radiation-induced depression may cause decreased quality of life after radiotherapy, investigations of its molecular mechanism and therapeutic strategies are still insufficient. In this study, we found that behavioral symptoms of depression on mice models with the decrease of BrdU/NeuN- and Dcx-positive populations and MAP-2 expression in hippocampus were induced by cranial irradiation, and transthyretin (TTR) was highly expressed in hippocampus after irradiation. It was shown that overexpression of TTR resulted in the inhibition of retinol-mediated neuritogenesis. PAK1 phosphorylation and MAP-2 expression were significantly reduced by TTR overexpression following irradiation. Moreover, we observed that treatment of allantoin and neferine, the active components of Nelumbo nucifera, interrupted irradiation-induced TTR overexpression, consequently leading to the increase of PAK1 phosphorylation, neurite extension, BrdU/NeuN- and Dcx-positive populations, and MAP-2 expression. Behavioral symptoms of depression following cranial irradiation were also relieved by treatment of allantoin and neferine. These findings demonstrate that TTR plays a critical role in neurogenesis after irradiation, and allantoin and neferine could be potential drug candidates for recovering the effects of radiation on neurogenesis and depression.

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.

Comparison of Treatment Outcomes between Breast Conserving Surgery Followed by Radiotherapy and Mastectomy Alone in Patients with T1-2 Stage and 1-3 Axillary Lymph Nodes in the Era of Modern Adjuvant Systemic Treatments.

PURPOSE: The role of postmastectomy radiotherapy in the treatment of T1-2 primary tumor with 1-3 positive lymph nodes is controversial. We compared treatment outcomes between breast conserving surgery followed by radiotherapy (BCS+RT) and total mastectomy alone (TM) in the setting of modern adjuvant systemic treatments. METHODS: Patients with T1-2 primary breast cancer and 1-3 positive lymph nodes who were treated between 2001 and 2011 were divided into 2 groups based on the treatment approach: BCS+RT (n = 169) and TM (n = 117). All patients received adjuvant chemotherapy including taxanes. Adjuvant endocrine therapy was administered to patients with positive hormone receptors according to their menstrual status. RESULTS: During a median follow-up of 76.5 months, 21 patients (7.3%) experienced locoregional recurrence as the first event, including 7 patients (4.1%) in the BCS+RT group and 14 patients (12.0%) in the TM group. The 5-year cumulative incidence rate of locoregional recurrence was 2.5% for BCS+RT versus 9.5% for TM (p = 0.016). Competing risk regression analysis revealed that TM was associated with a relative risk for locoregional recurrence of 5.347 (p = 0.003). TM was also associated with a significantly lower 5-year disease-free survival rate compared with BCS+RT (hazard ratio, 2.024; 95% confidence interval, 1.090-3.759; p = 0.026). CONCLUSION: To improve treatment outcomes for TM even after modern systemic treatments, postmastectomy radiotherapy might be required for patients with T1-2 primary breast cancer and 1-3 positive lymph nodes.

Efficacy of Dose-Escalated Radiotherapy for Recurrent Colorectal Cancer.

PURPOSE: This study aimed to evaluate the effects of radiotherapy (RT) on progression-free survival (PFS) for patients with recurrent colorectal cancer. METHODS: We reviewed the records of 22 patients with recurrent colorectal cancer treated with RT between 2008 and 2014. The median radiation dose for recurrent disease was 57.6 Gy (range, 45-75.6 Gy). Patients were divided into 2 groups according to the type of RT: patients underwent RT without previous history of irradiation (n = 14) and those treated with secondary RT (reirradiation: n = 8) at the time of recurrence. RESULTS: The median follow-up period was 24.9 months (range, 4.5-66.6 months). Progression was observed in 14 patients (including 8 with loco-regional failure and 9 with distant metastases). Distant metastases were related to the RT dose (<70 Gy, P = 0.031). The 2-year loco-regional control (LRC), PFS, and overall survival (OS) rates were 74.6%, 45.1%, and 82.0%, respectively. The LRC rate was not different between the patients treated with RT for the first time and those treated with reirradiation (P = 0.101, 2-year LRC 79.5% vs. 41.7%). However, reirradiation was related to poor PFS (P = 0.022) and OS (P = 0.002). An escalated RT dose (≥70 Gy) was associated with a higher PFS (P = 0.014, 2-year PFS 63.5% vs. 20.8%). CONCLUSION: Salvage RT for locally recurrent colorectal cancer can be offered when surgery is impossible. Dose-escalated RT shows a possible benefit in reducing the risk of progression.

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.

The anal canal as a risk organ in cervical cancer patients with hemorrhoids undergoing whole pelvic radiotherapy.

AIMS AND BACKGROUND: Tolerance of the anal canal tends to be ignored in patients with cervical cancer undergoing whole pelvic radiotherapy. However, patients with hemorrhoids may be troubled with low radiation dose. We tried to analyze the dose-volume statistics of the anal canal in patients undergoing whole pelvic radiotherapy. METHODS: The records of 31 patients with cervical cancer who received definite or postoperative radiotherapy at one institution were reviewed. Acute anal symptoms, such as anal pain and bleeding, were evaluated from radiotherapy start to 1 month after radiotherapy completion. Various clinical and dosimetric factors were analyzed to characterize relations with acute anal complications. RESULTS: The anal verge was located an average of 1.2 cm (range -0.6~3.9) below the lower border of the ischial tuberosity and an average of 2.7 cm (range -0.6~5.7) behind the sacral promontory level. The presence of hemorrhoids before radiotherapy was found to be significantly associated with acute radiation-induced anal symptoms (p = 0.001), and the mean induction dose for anal symptoms was 36.9 Gy. No patient without hemorrhoids developed an anal symptom during radiotherapy. Dosimetric analyses of V30 and V40 showed marginal correlations with anal symptoms (p = 0.07). CONCLUSIONS: The present study suggests a relation between acute anal symptoms following radiotherapy and acute hemorrhoid aggravation. Furthermore, the location of the anal verge was found to be variable, and consequently doses administered to the anal canal also varied substantially. Our results caution careful radiation treatment planning for whole pelvic radiotherapy, and that proper clinical management be afforded patients with hemorrhoids during radiotherapy.