Thirty-day mortality after palliative radiotherapy in advanced cancer patients: Optimizing end-of-life care in Asia.

INTRODUCTION: Evidence-based guidelines recommend hypofractionated palliative radiotherapy (PRT); nonetheless, many patients receive prolonged course of PRT. To identify patients with limited benefits from PRT in end-of-life care, we evaluated the pattern of PRT at an Asian institution and factors associated with 30-day mortality after PRT (30dM). METHODS: We retrospectively reviewed 228 patients who died after PRT in Yonsei Wonju Severance Christian hospital between October 2014 and March 2022. The associations between clinical factors and survival were assessed using the Cox proportional hazards method. Survival was analysed using the existing models to evaluate their performance in our cohort. RESULTS: The median PRT duration was 13 (IQR, 7-15) days. Only 11.4% of the patients were treated with hypofractionated radiotherapy. One-third of the patients (32.9%) could not complete PRT and 39 (17.1%) died during PRT. The 30dM was 31.6%. The median time from PRT to death was 17 (IQR, 11-23) days for the patients who died within 30 days. The number of involved organs (≤2 vs. >2; P < 0.001), albumin level (<3.3 vs. ≥3.3; P = 0.016), admission during PRT (P < 0.001), admission 3 months before PRT (P = 0.036) and ICU care during PRT (P < 0.001) were prognostic factors. A comparison of survival based on the existing models yielded unsatisfactory results in our cohort. CONCLUSION: Almost one-third of the patients received PRT in the last 30 days of life. The use of hypofractionation for PRT was low in this Asian population. Further research is necessary to develop a predictive model of early mortality, allowing tailored end-of-life care for Asian patients.

Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional study.

PURPOSE: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. METHODS AND MATERIALS: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. RESULTS: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. CONCLUSION: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Feasibility of artificial intelligence-driven interfractional monitoring of organ changes by mega-voltage computed tomography in intensity-modulated radiotherapy of prostate cancer.

PURPOSE: High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. MATERIALS AND METHODS: We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. RESULTS: Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. CONCLUSION: We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.

Long-Term Feasibility of 13.56 MHz Modulated Electro-Hyperthermia-Based Preoperative Thermoradiochemotherapy in Locally Advanced Rectal Cancer.

We evaluated the effect of 13.56 MHz modulated electro-hyperthermia (mEHT) boost in neoadjuvant treatment for cT3-4- or cN-positive rectal cancer. Sixty patients who completed the mEHT feasibility trial (ClinicalTrials.gov Identifier: NCT02546596) were analyzed. Whole pelvis radiotherapy of 40 Gy, mEHT boost twice a week during radiotherapy, and surgical resection 6-8 weeks following radiotherapy were performed. The median age was 59. The median follow-up period was 58 (6-85) months. Total/near total tumor regression was observed in 20 patients (33.3%), including nine cases of complete response. T- and N-downstaging was identified in 40 (66.6%) and 53 (88.3%) patients, respectively. The 5-year overall and disease-free survival were 94.0% and 77.1%, respectively. mEHT energy of ≥3800 kJ potentially increased the overall survival (p = 0.039). The ypN-stage and perineural invasion were possible significant factors in disease-free (p = 0.003 and p = 0.005, respectively) and distant metastasis-free (p = 0.011 and p = 0.034, respectively) survival. Tumor regression, resection margin status, and other molecular genetic factors showed no correlation with survival. Although a limited analysis of a small number of patients, mEHT was feasible considering long-term survival. A relatively low dose irradiation (40 Gy) plus mEHT setting could ensure comparable clinical outcomes with possible mEHT-related prognostic features.

Gastric Complications after Adjuvant Radiotherapy for Breast Cancer.

PURPOSE: In some patients who receive adjuvant radiotherapy (RT) for the left breast, the stomach is located inside the RT field. This study investigates the incidence of gastric complications following adjuvant RT for breast cancer using data of the Health Insurance Review and Assessment Service in South Korea. METHODS: We identified 37,966 women who underwent surgery and received adjuvant RT for breast cancer. The cumulative incidence rate of gastric hemorrhage and gastric cancer was calculated and compared for left and right breast cancers. RESULTS: Among 37,966 patients, 19,531 (51.4%) and 18,435 (48.6%) had right and left breast cancers, respectively. After a median follow-up duration of 6.3 years, the cumulative incidence of gastric cancer and gastric hemorrhage did not differ between right and left breast cancers (p = 0.414 and p = 0.166, respectively). The multivariable analysis revealed that old age was the only factor associated with the development of gastric cancer (p < 0.001) and gastric hemorrhage (p < 0.001). The incidence of gastric cancer and hemorrhage did not differ between patients who received adjuvant RT for right and left breast cancers. CONCLUSION: Irradiation-related chronic complications of the stomach in patients with breast cancer are minimal. A study with a longer follow-up duration might be needed to assess the risk of gastric cancer.

Para-aortic lymph node recurrence after curative radiotherapy for cervical cancer.

OBJECTIVE: The para-aortic lymph nodes are one of the most common sites in recurrent cervical cancer. However, treatment strategies for para-aortic lymph node recurrence have not yet been established.This study aimed to evaluate the prognostic factors and treatment outcomes in patients with para-aortic lymph node recurrence after curative radiotherapy for cervical cancer. METHODS: We retrospectively reviewed patients who developed para-aortic lymph node recurrence following curative radiation therapy for cervical cancer from January 2001 and December 2014 at the Samsung Medical Center. Prognostic factors for overall survival after recurrence were analyzed by univariate and multivariate analyses. RESULTS: A total of 67 patients were included in the analysis. After a median follow-up of 24.0 months (range 4-155), the 3-year overall survival rate was 42.7%. 32 patients had isolated para-aortic lymph node recurrence (group 1), 21 patients had para-aortic lymph node recurrence combined with other lymph node recurrence (group 2), and 14 patients developed para-aortic lymph node recurrence with distant organ metastasis (group 3). The 3-year overall survival rates in groups 1, 2, and 3 were 60.8%, 42.1%, and 7.7%, respectively (p<0.001). In multivariate analysis, histologic type of squamous cell carcinoma (p=0.028), non-symptomatic recurrence (p=0.024), isolated para-aortic lymph node recurrence (p=0.008), and disease-free interval (p=0.008) were significant factors for survival. Among the patients with isolated para-aortic lymph node recurrence, survival rates differed significantly according to disease-free interval; the 3-year overall survival in patients with disease-free interval ≥12 months and disease-free interval <12 months was 69.6% and 37.5%, respectively (p<0.001). CONCLUSIONS: In patients with para-aortic lymph node recurrence from cervical cancer, histologic type, presence of symptoms, extent of disease, and disease-free interval were the prognostic factors for survival. Patients with isolated para-aortic lymph node recurrence with disease-free interval ≥12 months had higher survival outcomes at 3 years.

Is higher dose radiation necessary for positive resection margin after breast-conserving surgery for breast cancer?

BACKGROUND: A positive resection margin after breast-conserving surgery (BCS) usually requires re-excision, which impairs cosmetic outcomes and causes considerable distress. This study aimed to evaluate the prognosis of patients with positive resection margin after BCS and the role of radiation therapy (RT) in these patients. MATERIALS AND METHODS: We analyzed 297 patients who underwent BCS for breast cancer and had invasive carcinoma or ductal carcinoma in situ (DCIS) within less than 1 mm from the resection margin in Samsung Medical Center from January 2000 to June 2012. The association between RT dose and the incidence rate of ipsilateral breast tumor recurrence (IBTR) was examined. RESULTS: After a median follow-up of 78 months, the incidence rate of IBTR in all patients was 4.6% after 5 years. In the multivariate analysis, the unfavorable factors associated with IBTR were age < 40 years (p = 0.019), RT dose (<60 Gy vs. > 66 Gy, p = 0.012; 60-66 Gy vs. > 66 Gy, p = 0.017), and discontinuation of hormone therapy (p = 0.001). CONCLUSIONS: Among the patients with invasive carcinoma or DCIS within less than 1 mm from the resection margin, adjuvant RT with higher dose > 66Gy EQD2 might improve local control. Further prospective studies are warranted to validate the benefit and risk of a high dose boost after BCS in patients with a positive resection margin.

Heart-sparing radiotherapy with three-dimensional printing technology after mastectomy for patients with left breast cancer.

The purpose of this study was to analyze the effectiveness of electron beam therapy (EBT) with patient-tailored bolus (PTB) using three-dimensional printing technology to reduce heart and lung doses during post-mastectomy radiotherapy (PMRT). For 28 patients with left breast cancer, we designed customized virtual bolus for PMRT to compensate for surface irregularities on computed tomography images and developed optimized plans for EBT. As comparison between the PTB and tangential plans, the PTB plan reduced unnecessary exposure to heart and ipsilateral lung with better target coverage compared with the tangential technique.

Adjuvant radiation therapy in small ductal carcinoma in situ.

BACKGROUND: The objective of this study was to evaluate ipsilateral breast tumor recurrence (IBTR) rates in patients with small (≤1 cm) ductal carcinoma in situ (DCIS) who were followed up for more than 15 years. METHODS: We identified 209 patients with primary small (≤1 cm) DCIS without invasion who received curative excision with and without adjuvant radiation therapy (RT) from 1996 to 2009. IBTR rates and prognostic factors in all patients were estimated by univariate and multivariate analyses. RESULTS: With a median follow-up of 104 months, eight (53.3%) had DCIS recurrence and seven (46.7%) had recurrence of invasive ductal carcinoma. IBTR rate of all patients was 7.5% at 10 years and 12.1% at 15 years. In univariate analysis, age and subtypes were significant factors for IBTR. In multivariate analysis, resection margin, adjuvant RT, and endocrine therapy were significant factors for IBTR. CONCLUSIONS: IBTR rate of small (≤1 cm) DCIS following excision with or without adjuvant RT was 12.1% at 15 years. Adjuvant RT and endocrine therapy were associated with lower IBTR rate in small DCIS.

Which Patients with Left Breast Cancer Should be Candidates for Heart-Sparing Radiotherapy?

PURPOSE: This study aimed to identify risk factors that have significant interaction with radiation exposure to the heart, and thus to determine candidates for heart-sparing radiotherapy (RT) among women with left breast cancer. METHODS: We identified 4,333 patients who received adjuvant RT following breast-conserving surgery for ductal carcinoma in situ or invasive breast cancer from 1996 to 2010. Incidence rates of cardiovascular disease were compared between left-sided and right-sided RT, and stratified by age and risk factors such as body mass index (BMI), smoking, hyperlipidemia, hypertension, diabetes, administration of anthracycline, and trastuzumab. RESULTS: In all patients, the cumulative incidence of cardiovascular disease was greater in patients treated with left-sided RT than in those treated with right-sided RT, but the difference was not significant (p=0.428). Smoking (hazard ratio [HR], 5.991; 95% confidence interval [CI], 2.109-17.022; p=0.002) and hyperlipidemia (HR, 5.567; 95% CI, 3.235-9.580; p<0.001) were the most powerful risk factors for cardiovascular disease. There was no significant factor that further increased the risk of cardiovascular disease after left breast RT compared to right breast RT. CONCLUSION: Although hyperlipidemia and smoking are risk factors for cardiovascular disease, they have not been proven to increase the risk of RT-related cardiovascular disease in Korean women.

Effect of Body Mass Index on Survival in Breast Cancer Patients According to Subtype, Metabolic Syndrome, and Treatment.

PURPOSE: To investigate the effect of body mass index (BMI) on survival in patients with breast cancer according to tumor subtype, metabolic syndrome, and systemic treatment. PATIENTS AND METHODS: We identified 5668 patients who underwent curative surgery for breast cancer between 1996 and 2013 from the clinical data of a single institution. Disease-free survival (DFS) and overall survival (OS) were calculated and compared between the patients with BMI ≥ 25 kg/m2 and < 25 kg/m2 in all patients and in specific subgroups, including tumor subtype, metabolic syndrome, and systemic treatment. RESULTS: In all patients, BMI ≥ 25 kg/m2 was an unfavorable factor for OS (P = .030) but not for DFS. In the HR+/HER2- subgroup, DFS and OS were longer in patients with BMI < 25 kg/m2 than ≥ 25 kg/m2 (P = .012 and .005, respectively). In patients with more than one metabolic syndrome, BMI was an unfavorable factor for OS (hazard ratio, 2.669; P < .001) CONCLUSION: BMI ≥ 25 kg/m2 was an unfavorable survival factor, particularly in patients with HR+/HER2- breast cancer.

Inter-alpha Inhibitor H4 as a Potential Biomarker Predicting the Treatment Outcomes in Patients with Hepatocellular Carcinoma.

PURPOSE: Early prediction of treatment outcomes represents an essential step towards increased treatment efficacy and survival in patients with hepatocellular carcinoma (HCC). In this study, we performed two-dimensional electrophoresis (2-DE) followed by protein profiling to identify biomarkers predictive of therapeutic outcomes in patients with HCC who received liver-directed therapy (LDTx) involving local radiotherapy (RT), and studied the underlying mechanisms of the identified proteins. MATERIALS AND METHODS: 2-DE analysis was conducted by pooling sera from patients with a good or poor prognosis; serum proteomic profiles of the two groups were compared and analyzed using matrixassisted laser desorption/ionization time-of-flight mass spectrometry. Identified proteins were confirmed via enzyme-linked immunosorbent assay. An invasion assay was performed after overexpression and knockdown of target protein in Huh7 cells. RESULTS: Levels of inter-alpha inhibitor H4 (ITIH4), fibrinogen gamma chain, keratin 9/1 complex, carbonic anhydrase I, and carbonmonoxyhemoglobin S were changed by more than 4-fold in response to LDTx. In particular, pre-LDTx ITIH4 expression was more than 5-fold higher in patients with a good prognosis, compared to patients with a poor prognosis. The migration ability of Huh7 cells was significantly suppressed and enhanced by ITIH4 overexpression and knockdown, respectively. The tumors of patients with HCC and a good prognosis expressed high levels of ITIH4, compared to those of patients with a poor prognosis. CONCLUSION: Taken together, ITIH4 may be a potential therapeutic target that could inhibit cancer metastasis, as well as a prognostic marker for patients with HCC who are receiving LDTx.

Multi-analyte analysis of cytokines that predict outcomes in patients with hepatocellular carcinoma treated with radiotherapy.

AIM: To analyze cytokine levels and to identify their association with outcome in patients with hepatocellular carcinoma (HCC) treated with radiotherapy (RT). METHODS: Patients with HCC who were treated with RT were eligible for this prospective study. Blood samples were collected before and after RT, and serum cytokine levels including interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α were analyzed. RESULTS: Between 2008 and 2009, 51 patients were enrolled in this study. Baseline IL-6 level was high in patients with a history of pre-RT treatment. Median survival was 13.9 mo with alpha-fetoprotein (AFP) as a significant factor (P = 0.020). Median failure-free survival (FFS) for infield, outfield-intrahepatic and extrahepatic failures were 23.3, 11.5 and 12.0 mo, respectively. Sex and baseline IL-6 level were associated with infield FFS, and baseline IL-10 level was correlated with outfield-intrahepatic FFS. For extrahepatic FFS, AFP was significant (P = 0.034). Patients with a baseline IL-6 level of ≥ 9.7 pg/mL showed worse infield FFS (P = 0.005), and this significance was observed only in treatment-non-naïve patients (P = 0.022). CONCLUSION: In addition to AFP, cytokines seem useful in predicting infield and outfield-intrahepatic failure. Serum cytokines could be useful biomarkers for predicting RT outcome in HCC.

Individual case review in a phase 3 randomized trial to investigate the role of internal mammary lymph node irradiation for breast cancer: Korean Radiation Oncology Group 08-06 study.

PURPOSE/OBJECTIVE: This study aimed to assess protocol compliance based on an individual case review (ICR) of the Korean Radiation Oncology Group-0806 trial. METHODS AND MATERIALS: For the ICR, 747 participants were divided into eight subgroups based on internal mammary node irradiation (IMNI), tumor laterality, and surgery type. Next, 15% of patients were randomly selected within each subgroup, and corresponding hospitals were subsequently requested to upload information related to radiation therapy (RT) planning. We reviewed the dose distributions of targets and organs at risk to determine protocol compliance. RESULTS: Data of 102 patients were collected. Overall, RT plans were found to be mostly protocol-compliant, with acceptability rates of 60-80% despite deviations in the ipsilateral lung in Arm 2 (IMNI group). However, despite few deviations, a subgroup analysis revealed significant differences in protocol compliance. Among RT techniques, plans using standard and partial wide tangents were most compliant in both Arms. In this ICR, the estimated survival benefits based on IMN doses were 7.7%, 8.4%, and 7.2% for all, breast-conserving surgery, and mastectomy cases, respectively. CONCLUSION: This ICR demonstrated overall protocol compliance, despite significant differences with regard to IMN irradiation and organs at risk according to subgroups and adopted field arrangements.

Clinical Practice Patterns of Radiotherapy in Patients with Hepatocellular Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-07).

PURPOSE: The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC). MATERIALS AND METHODS: We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions. RESULTS: The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy10 vs. 56.3 Gy10). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT. CONCLUSION: Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival.

Prognostic values of vascular endothelial growth factor and matrix metalloproteinase-2 in hepatocellular carcinoma after radiotherapy.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a highly vascularized tumor. In this study, we investigated the prognostic and predictive values of proangiogenic factors in HCC patients receiving radiotherapy. METHODS: Between September 2008 and December 2009, a total of 50 patients treated with radiotherapy were prospectively enrolled in this study. Serum and urine samples were collected <1 week before and after radiotherapy. RESULTS: After completion of radiotherapy, serum vascular endothelial growth factor (VEGF)/platelet (Plt) levels were significantly increased (p < 0.01). Patients who experienced hepatic tumor recurrence outside the radiation field showed higher VEGF-A/Plt levels before and after radiotherapy than patients who did not (p = 0.04), whereas patients who had hepatic tumor recurrence inside the radiation field showed significantly higher matrix metalloproteinase (MMP)-2 levels after radiotherapy (p = 0.04). On multivariate analyses, a high level of either VEGF/Plt or MMP-2 (≥median) before radiotherapy was a significant independent prognostic factor for a worse progression-free survival (p = 0.04). CONCLUSIONS: In HCC patients receiving radiotherapy, levels of VEGF/Plt and MMP-2 before radiotherapy can be useful to predict treatment outcome. This study also suggests the necessity of anti-angiogenic therapy, such as sorafenib, since radiotherapy increases VEGF/Plt levels, and higher levels of VEGF/Plt are associated with a poor outcome.

Overall response of both intrahepatic tumor and portal vein tumor thrombosis is a good prognostic factor for hepatocellular carcinoma patients receiving concurrent chemoradiotherapy.

This study investigated the prognostic significance of portal vein tumor thrombosis (PVTT) response in hepatocellular carcinoma (HCC) patients treated with localized concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 100 patients treated with CCRT for UICC Stage T2-4N0M0 HCC with PVTT between 2002 and 2011. The radiotherapy (RT) volume included both primary tumor and PVTT, and the median radiation dose was 45 Gy. Treatment response was evaluated for up to 6 months after RT. With respect to PVTT response to treatment, complete response (CR) and partial response (PR) were achieved in 14% and 48% of patients, respectively, yielding an objective response (OR) rate of 62%. PVTT size (≤3cm diameter) was associated with a higher rate of a CR (P = 0.001). The median overall survival (OS) was 11.6 months. Independent prognostic factors for OS were OR of the tumor to RT and a CR of the PVTT. Achieving an OR in both the tumor and the PVTT demonstrated a significant correlation with improved survival (P = 0.002). Progression of intrahepatic metastasis was affected not by CCRT but by the clinical features of the PVTT, particularly the initial PVTT site. PVTT response following CCRT seems prognostically significant. CR of the PVTT was associated with improved survival. Achieving an OR in both the tumor and PVTT was also associated with improved survival.

Clinical factors related to recurrence after hepatic arterial concurrent chemoradiotherapy for advanced but liver-confined hepatocellular carcinoma.

Before the sorafenib era, advanced but liver-confined hepatocellular carcinoma (HCC) was treated by liver-directed therapy. Hepatic arterial concurrent chemoradiotherapy (CCRT) has been performed in our group, giving substantial local control but frequent failure. The aim of this study was to analyze patterns of failure and find out predictive clinical factors in HCC treated with a liver-directed therapy, CCRT. A retrospective analysis was done for 138 HCC patients treated with CCRT between May 2001 and November 2009. Protocol-based CCRT was performed with local radiotherapy (RT) and concurrent 5-fluorouracil (5-FU) hepatic arterial infusion chemotherapy (HAIC), followed by monthly HAIC (5-FU and cisplatin). Patterns of failure were categorized into three groups: infield, intrahepatic-outfield and extrahepatic failure. Treatment failure occurred in 34.0% of patients at 3 months after RT. Infield, intrahepatic-outfield and extrahepatic failure were observed in 12 (8.6%), 26 (18.7%) and 27 (19.6%) patients, respectively. Median progression-free survival for infield, outfield and extrahepatic failure was 22.4, 18 and 21.5 months, respectively. For infield failure, a history of pre-CCRT treatment was a significant factor (P = 0.020). Pre-CCRT levels of alpha-fetoprotein and prothrombin induced by vitamin K absence or antagonist-II were significant factors for extrahepatic failure (P = 0.029). Treatment failures after CCRT were frequent in HCC patients, and were more commonly intrahepatic-outfield and extrahepatic failures than infield failure. A history of pre-CCRT treatment and levels of pre-CCRT tumor markers were identified as risk factors that could predict treatment failure. More intensified treatment is required for patients presenting risk factors.

Patterns of care and treatment outcomes for primary thyroid lymphoma: a single institution study.

PURPOSE: The aim of this study was to analyze the patterns of care and treatment outcomes in patients with primary thyroid lymphoma (PTL) in a single institution. MATERIALS AND METHODS: Medical records of 29 patients with PTL treated between April 1994 and February 2012 were retrospectively reviewed. Diagnosis was confirmed by biopsy (n = 17) or thyroidectomy (n = 12). Treatment modality and outcome were analyzed according to lymphoma grade. RESULTS: The median follow-up was 43.2 months (range, 3.8 to 220.8 months). The median age at diagnosis was 57 years (range, 21 to 83 years) and 24 (82.8%) patients were female. Twenty-five (86.2%) patients had PTL with stage IEA and IIEA. There were 8 (27.6%) patients with mucosa-associated lymphoid tissue (MALT) lymphoma and the remaining patients had high-grade lymphoma. Patients were treated with surgery (n = 2), chemotherapy (n = 7), radiotherapy (n = 3) alone, or a combination of these methods (n = 17). Treatment modalities evolved over time and a combination of modalities was preferred, especially for the treatment of high-grade lymphoma in recent years. There was no death or relapse among MALT lymphoma patients. Among high-grade lymphoma patients, 5-year overall survival (OS) and 5-year progression-free survival (PFS) were 75.6% and 73.9%, respectively. Complete remission after initial treatment was the only significant prognostic factor for OS (p = 0.037) and PFS (p = 0.003). CONCLUSION: Patients with PTL showed a favorable outcome, especially with MALT lymphoma. Radiotherapy alone for MALT lymphoma and chemotherapy followed by radiotherapy for high-grade lymphoma can be effective treatment options for PTL.