Safety and Efficacy of Moderate-Intensity Stereotactic Body Radiation Therapy for Ultra-Central Lung Tumor.

Background and Objectives: Ultra-central (UC) lung tumors are defined as those abutting the proximal bronchial tree. Stereotactic body radiation therapy (SBRT) for UC tumors is difficult because of concerns about severe toxicities. Therefore, we report the safety and efficacy of moderate-intensity SBRT for UC tumors at our institution. Materials and Methods: From January 2017 to May 2021, we treated 20 patients with UC tumors with SBRT at a dose of 45-60 Gy in 10 fractions. The primary endpoints were local control (LC) and overall survival (OS). Results: The median follow-up time was 15.8 months (range: 2.7-53.8 months). Ten of the 20 patients (50.0%) showed a complete response, five (25.0%) had a partial response, two (10.0%) had stable disease, and three (15.0%) showed progressive disease (PD). The response and disease control rates were 75.0% and 85.0%, respectively. Patients with PD showed local progression at median 8.3 months (range: 6.8-19.1 months) after SBRT. One-year and 2-year OS rates were 79.4% and 62.4%, respectively. One-year and 2-year LC rates are 87.1% and 76.2%, respectively. Eight patients died due to a non-radiation therapy related cause. One patient experienced grade 5 massive hemoptysis 6 months after SBRT, resulting in death. One patient experienced grade 2 esophageal pain and two experienced grade 2 radiation pneumonitis. Otherwise, no grade 3 or higher toxicities were reported. Conclusions: Moderate-intensity SBRT offers effective control of UC tumors and is a well-tolerated treatment for such tumors.

A Potential Radiomics-Clinical Model for Predicting Failure of Lymph Node Control after Definite Radiotherapy in Locally Advanced Head and Neck Cancer.

Background and Objectives: To optimally predict lymph node (LN) failure after definite radiotherapy (RT) in head and neck cancer (HNC) with LN metastases, this study examined radiomics models extracted from CT images of different periods during RT. Materials and Methods: This study retrospectively collected radiologic and clinical information from patients undergoing definite RT over 60 Gy for HNC with LN metastases from January 2010 to August 2021. The same largest LNs in each patient from the initial simulation CT (CTpre) and the following simulation CT (CTmid) at approximately 40 Gy were indicated as regions of interest. LN failure was defined as residual or recurrent LN within 3 years after the end of RT. After the radiomics features were extracted, the radiomics alone model and the radiomics plus clinical parameters model from the set of CTpre and CTmid were compared. The LASSO method was applied to select features associated with LN failure. Results: Among 66 patients, 17 LN failures were observed. In the radiomics alone model, CTpre and CTmid had similar mean accuracies (0.681 and 0.697, respectively) and mean areas under the curve (AUC) (0.521 and 0.568, respectively). Radiomics features of spherical disproportion, size zone variance, and log minimum 2 were selected for CTpre plus clinical parameters. Volume, energy, homogeneity, and log minimum 1 were selected for CTmid plus clinical parameters. Clinical parameters including smoking, T-stage, ECE, and regression rate of LN were important for both CTpre and CTmid. In the radiomics plus clinical parameters models, the mean accuracy and mean AUC of CTmid (0.790 and 0.662, respectively) were more improved than those of CTpre (0.731 and 0.582, respectively). Conclusions: Both models using CTpre and CTmid were improved by adding clinical parameters. The radiomics model using CTmid plus clinical parameters was the best in predicting LN failure in our preliminary analyses.

Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Stereotactic ablative radiotherapy for pulmonary oligometastases from primary hepatocellular carcinoma: a multicenter and retrospective analysis (KROG 17-08).

OBJECTIVE: Hypofractionated radiotherapy has recently been applied to treat pulmonary metastases of hepatocellular carcinoma. However, there is no definite evidence on its safety and efficacy. We evaluate the clinical outcomes of hypofractionated radiotherapy for oligo pulmonary metastases of hepatocellular carcinoma in the multicenter and retrospective study. METHODS: From March 2011 to February 2018, 58 patients with fewer than five pulmonary metastases of hepatocellular carcinoma who underwent hypofractionated radiotherapy in nine tertiary university hospitals were analyzed retrospectively. The primary endpoint was the local control rate. The secondary endpoints were overall survival, progression-free survival, prognostic factors affecting the treatment outcomes and treatment-related side effects. RESULTS: The local tumor response rate including complete and partial response was 77.6% at 3 months after hypofractionated radiotherapy. The median survival and progression-free survival times were 20.9 and 5.3 months, respectively. The 1-year overall survival and progression-free survival rates were 65.5 and 22.4%, respectively. The good treatment response after hypofractionated radiotherapy (P = 0.001), the absence of intrahepatic tumor (P = 0.004) and Child-Pugh class A (P = 0.010) were revealed as significant prognostic factors for overall survival in the multivariate analysis. A progression-free interval of <6 months (P = 0.009) was a negative prognostic factor for overall survival in the multivariate analysis. Of 58 patients, five (8.6%) had grade 2 or higher radiation pneumonitis after hypofractionated radiotherapy. CONCLUSIONS: The favorable local control rate and acceptable toxicity indicate the clinical usefulness of hypofractionated radiotherapy for hepatocellular carcinoma patients who have less than five pulmonary metastases.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

Implications of Radiotherapy Utilization in Korea from 2010 to 2019.

BACKGROUND: This study was to assess the rate of radiotherapy (RT) utilization according to the modality in South Korea to identify the implications of contemporary RT patterns. METHODS: We collected information from claims and reimbursement records of the National Health Insurance Service from 2010 to 2019. We classified the location of each institution as capital (Seoul, Incheon, and Gyeonggi-do) and non-capital areas. RESULTS: The rate of RT utilization in total cancer patients nationwide was 24.5% in 2010, which consistently has increased to 36.1% in 2019 (annual increase estimate [AIE], 4.5%). There was an abrupt increase in patients receiving intensity-modulated RT (IMRT), with an AIE of 33.5%, and a steady decline in patients receiving three-dimensional conformal RT (3DCRT), with an AIE of -7.1%. The commonest RT modality was IMRT (44.5%), followed by 3DCRT and stereotactic RT (SRT) (37.2% and 13.5%) in 2019. An increasing trend of advanced RT (such as IMRT and SRT) utilization was observed regardless of the region, although the AIE in the capital areas was slightly higher than that in non-capital areas. CONCLUSION: The utilization of overall RT application and especially of advanced modalities remarkably increased from 2010 to 2019. We also found gaps in their AIEs between capital and non-capital areas. We should ensure that advanced RT is accessible to all cancer patients across South Korea.

Clinical Impact of Supraclavicular Lymph Node Involvement of Stage IIIC Non-Small Cell Lung Cancer Patients.

Background and Objective: Investigations on the clinical impact of supraclavicular lymph node (SCN) involvement in stage IIIC non-small cell lung cancer (NSCLC) remain scarce. We evaluated the oncological outcomes of definitive radiochemotherapy and the clinical significance of SCN involvement. Materials and Methods: Between November 2009 and June 2019, a total of 40 patients with N3-positivity and NSCLC were evaluated. Most patients received concomitant chemotherapy, but six patients who received radiotherapy (RT) alone were also included. Twenty-one patients (52.5%) received 3D-conformal RT (3DCRT), and the remainder received intensity-modulated RT (IMRT). Results: The median follow-up duration was 10.7 months (range: 1.7-120.6 months). Median overall survival (OS) and cause-specific survival (CSS) times were 10.8 months and 16.3 months, respectively. Among the 40 patients, 17 (42.5%) had SCN involvement. SCN involvement negatively affected progression-free survival (hazard ratio (HR): 2.08, 95% confidence interval (CI): 1.04-4.17, p = 0.039) and local control (HR: 3.05, 95% CI: 1.09-8.50, p = 0.034). However, IMRT use was correlated with higher local control (HR: 0.28, 95% CI: 0.09-0.86, p = 0.027). Grade ≥3 esophagitis and pneumonitis accounted for 7.5% and 15.0% of all cases, respectively. A higher RT dose (mean dose: 66.6 vs. 61.7 Gy) was significantly correlated with grade ≥3 pneumonitis (p = 0.001). RT modality was a significant factor (p = 0.042, five of six cases occurred in the IMRT group). Conclusions: SCN involvement could negatively affect oncologic outcomes of stage IIIC NSCLC patients. High-dose irradiation with IMRT could increase local control but may cause lung toxicities.

Salvage External Beam Radiotherapy after Incomplete Transarterial Chemoembolization for Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review.

Background and objective: Although transarterial chemoembolization (TACE) has been the commonest local modality for hepatocellular carcinoma (HCC), incomplete repsonse occurs especially for tumors with a large size or difficult tumor accessment. The present meta-analysis assessed the efficacy and feasibility of external beam radiotherapy (EBRT) as a salvage modality after incomplete TACE. Materials and Methods: We systematically searched the PubMed, Embase, Medline, and Cochrane databases. The primary endpoint was overall survival (OS), and the secondary endpoints included the response ratem toxicity of grade 3, and local control. Results: Twelve studies involving 757 patients were included; the median of portal vein thrombosis rate was 25%, and the pooled median of tumor size was 5.8 cm. The median prescribed dose ranged from 37.3 to 150 Gy (pooled median: 54 Gy in *EQD2). The pooled one- and two-year OS rates were 72.3% (95% confidence interval (CI): 60.2-81.9%) and 50.5% (95% CI: 35.6-65.4%), respectively; the pooled response and local control rates were 72.2% (95% CI: 65.4-78.1%) and 86.6 (95% CI: 80.1-91.2%) respectively. The pooled rates of grade ≥3 gastrointestinal toxicity, radiation-induced liver disease, hepatotoxicity, and hematotoxicity were 4.1%, 3.5%, 5.7%, and 4.9%, respectively. Local control was not correlated with intrahepatic (p = 0.6341) or extrahepatic recurrences (p = 0.8529) on meta-regression analyses. Conclusion: EBRT was feasible and efficient in regard to tumor response and control; after incomplete TACE. Out-field recurrence, despite favorable local control, necessitates the combination of EBRT with systemic treatments. *Equivalent dose in 2 Gy per fraction scheme.

Physical activity status in relation to quality of life and dietary habits in breast cancer survivors: subset analyses of KROG 14-09 nationwide questionnaire study.

PURPOSE: We investigated the relationship of physical activity with dietary habits and quality of life (QoL) in breast cancer survivors in accordance with the recommendations of the American Cancer Society. METHODS: Data of 928 breast cancer survivors were obtained from the KROG 14-09 study to measure QoL in early phase after adjuvant radiotherapy. According to the extent of physical activity, survivors were divided into four groups: inactivity (0-149 min/week, N = 144), regular activity (150-450 min/week, N = 309), moderate activity (451-900 min/week, N = 229), and marked activity (901-1800 min/week, N = 164) excluding hyperactivity (> 1800 min/week, N = 82) as it is a difficult condition to recommend to survivors. Global physical activity questionnaire, 5-dimensional questionnaire by EuroQoL (EQ-5D-3L), QoL Questionnaire-breast cancer (QLQ-BR23) from EORTC, and dietary habits were surveyed. A linear-to-linear association test for EQ-5D-3L and Kruskal-Wallis analysis for QLQ-BR23 and dietary habit were conducted. RESULTS: Overall, 15.5% respondents (144/928) were classified as physically inactive. The trends of frequent intake of fruits (p = 0.001) and vegetable (p = 0.005) and reluctance toward fatty food (p < 0.001) were observed in physically active groups. Mobility (p = 0.021) and anxiety (p = 0.030) of EQ-5D-3L, and systemic therapy side effect (p = 0.027) and future perspective (p = 0.008) of QLQ-BR23 were better in physically active groups besides body image (p = 0.003) for the survivors with breast-conserving surgery. However, moderate and marked activities did not further improve QoL than regular activity. CONCLUSION: Physicians and care-givers have to pay attention to inactive survivors to boost their physical activity, thereby facilitating a better QoL and dietary habit.

Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review.

PURPOSE: Non-surgical treatment including stereotactic body radiation therapy (SBRT) have been used practically as alternative modalities for unresectable or recurrent cholangiocarcinoma (CC). We performed a systematic review and meta-analysis to examine the efficacy of SBRT for such patients. METHODS: Embase, PubMed, MEDLINE, and Cochrane library databases were searched systematically until October 2017. Primary endpoint was 1­year local control (LC) rate; 1­year overall survival (OS), response rates, and grade ≥3 toxicities were assessed as secondary endpoints. RESULTS: Eleven studies (226 patients) were included. The prescribed median SBRT dose was 45 (range 30-55) Gy in 3-5 fractions. The pooled 1­year LC rate was 81.8% (95% confidence interval [CI] 69.4-89.9%) in the studies using an equivalent dose in 2 Gy per fraction (EQD2) ≥71.3 Gy2 and 74.7% (95% CI 57.1-86.7%) in the studies using an EQD2 <71.3 Gy2. The median OS was 13.6 (range 10-35.5) months. The pooled 1­year OS rate was 53.8% (95% CI 44.9-62.5%) and the pooled 1­year LC rate was 78.6% (95% CI 69.0-85.8%). Most common toxicity was duodenal ulcer and gastric ulcer in available studies, with the acute incidence of grade ≥3 of less than 10% and the late incidence of 10-20%. CONCLUSIONS: SBRT was a feasible treatment option with respect to achieving a high LC for unresectable or recurrent CC. Gastrointestinal toxicity is acceptable, but remains an obstacle related to dose escalation.

Questionnaire study of the dietary habits of breast cancer survivors and their relationship to quality of life (KROG 14-09).

We evaluated the dietary habits of breast cancer survivors and investigated the relationship with quality of life (QoL), with 1,156 survivors recruited from 17 institutions. We used the Questionnaire Survey of Dietary Habits of Korean Adults (Q-DH-KOR) comprising 25 questions. The following indices were derived as follows: (1) quality of healthy dietary habits (Q-HD)-eight questions on number of meals, regularity, quantity, duration, skipping breakfast, dinner with companion(s), overeating and late-night snacks; (2) habits of nutritional balance (H-NB)-questions on consuming five food categories (grains, fruits, proteins, vegetables and dairy products); and (3) habits of unhealthy foods (H-UF)-questions on consuming three food categories (fatty, instant and fast foods). The times and regularity of meals, frequency of skipping breakfast, dinner with companion(s) and overeating were better in groups with high symptomatic and functional QoL. Symptomatic QoL positively affected Q-HD and H-NB (p < 0.001 and p = 0.024 respectively) and negatively affected H-UF (p = 0.02). Breast cancer survivors more frequently ate from the fruit, protein and vegetable categories than did the control group, with lower H-UF and higher Q-HD values (p < 0.001 and p < 0.001 respectively). Our findings supported the relationship between QoL and dietary habit and showed healthier dietary habits of breast cancer survivors than controls.

Factors predicting intolerance to definitive conventional radiotherapy in geriatric patients.

PURPOSE: Although radiotherapy can be administered with a relatively low therapeutic burden, many elderly patients do not complete radiotherapy. In order to predict intolerance during radiotherapy, this study retrospectively analyzed the frequency of and risk factors for radiotherapy interruption among geriatric patients. METHODS: From September 2009 to December 2016, 353 patients aged ≥70 years received definitive radiotherapy with a conventionally fractionated schedule. "Total interruption" included completion of ≤90% of a planned radiotherapy, temporary discontinuation, and treatment-related mortality within 2 months. "Early-phase incompletion" and "mid-phase incompletion" represented completion of ≤50 and ≤80% of a planned radiotherapy, respectively. RESULTS: The median age of patients was 74 years. Early- and mid-phase incompletions and total interruption occurred in 4.2, 9.3, and 19.3% of patients, respectively. Total interruption occurred frequently in cancers involving the thorax (27.4%), head and neck (23.1%), abdomen (20.0%), pelvis (17.4%), and breast/extremity (8.1%). The Eastern Cooperative Oncology Group (ECOG) performance score (P = 0.004 and 0.002), serum albumin level (P = 0.016 and 0.002), and the expected 5­year survival (P = 0.033 and 0.034) were significant factors for mid-phase incompletion and total interruption. Age ≥ 75 years (P = 0.008), concurrent chemotherapy (P = 0.017), and the extent of radiation field (P = 0.027) were factors associated with total interruption. CONCLUSION: Overall, 19.3% of the elderly patients showed treatment intolerance during conventional radiotherapy. Serum albumin level and ECOG performance score should be considered as surrogate markers for radiotherapy interruption prior to the decision regarding definite conventional radiotherapy.

A Survey of Radiation Therapy Utilization in Korea from 2010 to 2016: Focusing on Use of Intensity-Modulated Radiation Therapy.

BACKGROUND: This study aimed to assess the recent changes of radiation therapy (RT) modalities in Korea. In particular, we focused on intensity-modulated radiation therapy (IMRT) utilization as the main index, presenting the application status of advanced RT. METHODS: We collected information from the Korean Health and Insurance Review and Assessment Service data based on the National Health Insurance Service claims and reimbursements records by using treatment codes from 2010 to 2016. We classified locating region of each institution as capital vs. non-capital areas and metropolitan vs. non-metropolitan areas to assess the regional difference in IMRT utilization in Korea. RESULTS: IMRT use has been steadily increased in Korea, with an annual increase estimate (AIE) of 37.9% from 2011 to 2016 (P < 0.001) resulting in IMRT being the second most common RT modality following three-dimensional conformal radiotherapy. In general, an increasing trend of IMRT utilization was observed, regardless of the region. The rate of AIE in the capital areas or metropolitan areas was higher than that in non-capital areas or non-metropolitan areas (40.7% vs. 31.9%; P < 0.001 and 39.7% vs. 29.4%; P < 0.001, respectively). DISCUSSION: The result of our survey showed that IMRT has become one of the most common RT modalities. IMRT is becoming popular in both metropolitan and non-metropolitan areas, while metropolitan area has faster AIE possibly due to concentration of medical resources and movement of advanced patients.

Radiotherapeutic strategies for hepatocellular carcinoma with portal vein tumour thrombosis in a hepatitis B endemic area.

BACKGROUND & AIMS: This nationwide, multicenter study investigated treatment outcomes as well as the optimal radiotherapeutic strategy in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT). METHODS: We retrospectively reviewed the records of 985 patients who received radiotherapy (RT) for PVTT. The median equivalent RT dose was 48.75 Gy. Combined treatment, defined as liver-directed treatments performed within a month of RT, was administered to 657 patients (66.7%). The PVTT and primary tumour were irradiated in 413 patients (41.9%), and PVTT only was targeted in 572 patients (58.1%). RESULTS: The response rate of the PVTT was 51.8%, and RT responders had a significantly longer survival than non-responders (15.2 vs. 6.9 months). Equivalent RT dose and combined treatment predicted response of PVTT. The median overall survival (OS) was 10.2 months. Multivariate analysis revealed the equivalent RT dose ˃45 Gy and combined treatment as significant positive factors for OS. In the propensity score matching analysis, the combined treatment group had better OS than the no combined treatment group, whereas the OS of the PVTT + primary tumour group did not differ significantly from that of the PVTT only group. CONCLUSION: The equivalent RT dose ˃45 Gy, given in combination with other treatments, provided better PVTT control and OS. The optimal RT volume is suggested for either PVTT + primary or PVTT only. Taken together, multimodal treatment with equivalent RT dose higher than 45 Gy is recommended for patients with HCC and PVTT.

An assessment of quality of life for early phase after adjuvant radiotherapy in breast cancer survivors: a Korean multicenter survey (KROG 14-09).

BACKGROUNDS: Quality of life (QoL) has become a major concern as the survival time of breast cancer increases. We investigated the changes in QoL through comprehensive categorical analysis, for the first three years after breast cancer treatment including radiotherapy. METHODS: A total of 1156 patients were enrolled from 17 institutions. All survivors were grouped according to a surveillance period of 9-15 months (first year), 21-27 months (second year), and 33-39 months (third year) from the end of radiotherapy. The 5-dimensional questionnaire by the EuroQol group (EQ-5D) and the EORTC Quality of Life Questionnaire; breast cancer specific module (QLQ-BR23) were checked by self-administrated method. RESULTS: First, second and third year groups comprised 51.0, 28.9, and 21.0%. In EQ-5D-3 L (3-Likert scale) analysis, pain/discomfort and anxiety/depression categories showed lower QoL. In multivariate analyses of EQ-5D-VAS (visual-analogue scale), categories of pain/discomfort and self-care were improved with time; axillary dissection was a significant clinical factor deteriorates pain/discomfort, self-care and usual activities. In QLQ-BR23 analysis, the lowest scored category was sexual activity, followed by sexual enjoyment, future perspective, and hair loss, and the best scored category was breast symptoms. In multivariate analyses, arm symptoms, breast symptoms and body image were improved with time. CONCLUSIONS: Categories of pain/discomfort and self-care in EQ-5D-VAS, arm/breast symptoms and body image in QLQ-BR23 were improved, while categories of anxiety/depression and future perspective BR23 were not, suggesting necessity of psychosocial support. This research provides comprehensive information on the categorical aspects of QoL and changes during early follow-up after breast cancer treatment.

Oncologic Outcomes After Adjuvant Radiotherapy for Stage II Endometrial Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-10).

OBJECTIVE: The aim of this study was to investigate the survival, patterns of failure, and prognostic factors in patients with stage II endometrial carcinoma treated with adjuvant radiotherapy. METHODS: We reviewed the medical records of patients who underwent total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection followed by adjuvant radiotherapy in 10 participating hospitals of the Korean Radiation Oncology Group. Most patients received adjuvant external beam radiation therapy, with a median dose of 50.4 Gy; approximately 50% of these patients received an additional brachytherapy boost, with a median dose of 18 Gy. Adjuvant chemotherapy was administered to 19 patients. RESULTS: A total of 122 patients were examined. Over a median follow-up period of 62.7 months (range, 1.9-158.8 months), the 5-year overall survival (OS) and disease-free survival rates were found to be 91.1% and 85.1%, respectively. Recurrence was observed in 14 patients (11.5%), including 3 with local recurrence and 11 with distant metastases as the first site of recurrence. Univariate analysis indicated that lymphovascular invasion was related to an unfavorable OS. An age of 60 years or above, histologic grade 3, and lymphovascular invasion were identified as risk factors for OS. Because there were several risk factors related to OS, we assigned patients to a high-risk group (defined as cases with ≥1 risk factors) and a low-risk group. The 5-year OS rate of the high-risk group was significantly inferior to that of the low-risk group (82.9% vs 100%, P = 0.003). CONCLUSIONS: The high-risk group had a significantly poorer survival rate than the low-risk group, and distant metastasis was the main pattern of recurrence, thus indicating that further adjuvant chemotherapy should be considered in high-risk patients.

Interobserver variability in gross tumor volume delineation for hepatocellular carcinoma : Results of Korean Radiation Oncology Group 1207 study.

PURPOSE: There has been increasing use of external beam radiotherapy for localized treatment of hepatocellular carcinoma (HCC) with both palliative and curative intent. Quality control of target delineation in primary HCC is essential to deliver adequate doses of radiation to the primary tumor while preserving adjacent healthy organs. We analyzed interobserver variability in gross tumor volume (GTV) delineation for HCC. PATIENTS AND METHODS: Twelve radiation oncologists specializing in liver malignancy participated in a multi-institutional contouring dummy-run study of nine HCC cases and independently delineated GTV on the same set of provided computed tomography images. Quantitative analysis was performed using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE) with kappa statistics calculating agreement between physicians. To quantify the interobserver variability of GTV delineations, the ratio of the actual delineated volume to the estimated consensus volume (STAPLE), the ratio of the common and encompassing volumes, and the coefficient of variation were calculated. RESULTS: The median kappa agreement level was 0.71 (range 0.28-0.86). The ratio of the actual delineated volume to the estimated consensus volume ranged from 0.19 to 1.93 (median 0.94) for all cases. The ratio of the common and encompassing volumes ranged from 0.001 to 0.56 (median 0.25). The coefficient of variation for GTV delineation ranged from 8 to 57 % (median 26 %). CONCLUSION: The interobserver variability in target delineation of HCC GTV in this study is noteworthy. Multi-institution studies involving radiotherapy for HCC require appropriate quality assurance programs for target delineation.

A multicenter analysis of adjuvant therapy after surgery for stage IIIC endometrial adenocarcinoma: A Korean Radiation Oncology Group study (KROG 13-17).

OBJECTIVE: To investigate whether combined chemoradiotherapy (CTRT) confers a benefit for survival outcome over radiotherapy (RT) alone after primary surgery in patients with FIGO stage IIIC endometrial adenocarcinoma. METHODS: We conducted a multicenter retrospective study of patients with surgical stage IIIC endometrial cancer from 1990 to 2011. Adjuvant RT alone was performed in 85 patients (40.3%) and adjuvant CTRT in 126 patients (59.7%). Disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Stage IIIC1 and stage IIIC2 accounted for 63% and 37%, respectively. FIGO IIIC2 had a higher recurrence rate than FIGO IIIC1 (38.5% vs. 29.3%, p=0.172). Five-year OS and DFS were lower in FIGO IIIC2 than FIGO IIIC1 (85.1% vs. 76.9%, p=0.417; 71.0% vs. 59.2%, p=0.108, respectively). Eighteen patients (13.5%) in stage IIIC1 developed PALN recurrence, whereas only one (3.3%) in stage IIIC2 had PALN recurrence (p=0.001). In multivariate analysis, predictors of DFS were parametrial invasion (HR, 3.49; 95% CI, 1.83-6.64; p<0.001), higher grade (HR, 2.78; 95% CI, 1.31-5.89; p=0.008), and >3 positive pelvic nodes (HR, 1.84; 95% CI, 1.11-3.05; p=0.019). Combined CTRT did not affect DFS or OS in IIIC1 and IIIC2 compared with RT alone. CONCLUSION: CTRT showed comparable survival outcome to RT alone. Half of relapses (46%) in stage IIIC1 occurred in PALN region, whereas relapse in stage IIIC2 primarily occurred in distant metastasis (90%). Future randomized studies are needed to determine which subgroup may be most likely to benefit from CCRT.

Quantitative analysis of tumor volume reduction after three-dimensional conformal radiation therapy for intracranial meningiomas.

To provide radiobiological information on the inherent response of intracranial meningiomas after three-dimensional conformal radiation therapy. Quantitative tumor volume measurements were generated from 120 magnetic resonance images of a total of 24 patients. Gross tumor volumes were delineated on a series of contrast-enhanced T1-weighted magnetic resonance images by using commercial software. The percentage of tumor volume reduction at each follow-up was determined and compared to the baseline tumor volume. The median follow-up time was 103.5 months (range 30-137 months). The mean pre-radiation therapy tumor volume was 30.0 cm(3) (range 1.3-167.4 cm(3)). Tumor volume reduction was observed in 96 % of the study population. The mean absolute and relative tumor volume reduction were 14.0 cm(3) (range -0.6-84.5 cm(3)) and 40.8 % (range -6.8-82.9 %), respectively. The mean relative tumor volume reduction was 15.9, 28.9, 40.5, 50.3, and 52.6 % at 2, 4, 6, 8, and 10 years after irradiation. The quantitative volumetric analysis of the pattern of tumor volume reduction in response to irradiation gives an insight into the radiobiological nature of intracranial meningiomas after conventionally fractionated radiation therapy.

Comparison of clinical outcomes of adenocarcinoma and adenosquamous carcinoma in uterine cervical cancer patients receiving surgical resection followed by radiotherapy: a multicenter retrospective study (KROG 13-10).

OBJECTIVE: To evaluate the prognostic influence of adenocarcinoma (AC) and adenosquamous carcinoma (ASC) in patients with FIGO stage IB-IIA cervical cancer who received radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: We analyzed 1323 patients who satisfied the following criteria: histologically proven squamous cell carcinoma (SCC), AC, or ASC of the uterine cervix; FIGO stage IB-IIA disease; no history of neoadjuvant chemotherapy; and a history of radical hysterectomy with pelvic lymph node (PLN) dissection, followed by postoperative pelvic RT at a dose ≥ 45 Gy. The median age was 50 years. Median RT dose delivered to the whole pelvis was 50.4 Gy, and 219 (16.6%) patients received brachytherapy at a median dose of 24 Gy. Concurrent chemotherapy was delivered to 492 (37.2%) patients. RESULTS: Pathologic risk factors were not different according to pathologic subtype. The median follow-up duration was 75.7 months. Locoregional recurrence-free survival, relapse-free survival (RFS), and overall survival were significantly affected by histology, tumor size, PLN metastasis, parametrial invasion, lymphovascular invasion, and deep stromal invasion. The 5-year RFS rates were 83.7%, 66.5%, and 79.6% in patients with SCC, AC, and ASC histology, respectively (P<0.0001). By multivariate analysis, AC histology was the only significant prognostic factor affecting all survival outcomes. CONCLUSIONS: AC histology was associated with poor survival outcomes in patients with FIGO stage IB-IIA cervical cancer who received adjuvant RT or CCRT. Prognosis of ASC histology was closer to that of SCC histology than that of AC histology.