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Purpose@#Glioblastoma (GBM) is a malignant brain tumor with poor prognosis. Radioresistance is a major challenge in the treatment of brain tumors. The development of several types of tumors, including GBM, involves the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. Upon activation, this pathway induces radioresistance. In this study, we investigated whether additional use of selective inhibitors of PI3K isoforms would enhance radiosensitivity in GBM. @*Materials and Methods@#We evaluated whether radiation combined with PI3K isoform selective inhibitors can suppress radioresistance in GBM. Glioma 261 expressing luciferase (GL261-luc) and LN229 were used to confirm the effect of combination of radiation and PI3K isoform inhibitors in vitro. Cell viability was confirmed by clonogenic assay, and inhibition of PI3K/AKT signaling activation was observed by Western blot. To confirm radiosensitivity, the expression of phospho-γ-H2AX was observed by immunofluorescence. In addition, to identify the effect of a combination of radiation and PI3K-α isoform inhibitor in vivo, an intracranial mouse model was established by implanting GL261-luc. Tumor growth was observed by IVIS imaging, and survival was analyzed using Kaplan–Meier survival curves. @*Results@#Suppression of the PI3K/AKT signaling pathway increased radiosensitivity, and PI3K-α inhibition had similar effects on PI3K-pan inhibition in vitro. The combination of radiotherapy and PI3K-α isoform inhibitor suppressed tumor growth and extended survival in vivo. @*Conclusion@#This study verified that PI3K-α isoform inhibition improves radiosensitivity, resulting in tumor growth suppression and extended survival in GBM mice.
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Purpose@#We evaluated the safety, feasibility, and early treatment outcomes of intraoperative radiotherapy (IORT) using a lowenergy X-ray source. @*Materials and Methods@#Patients with resectable pancreatic cancer were enrolled in this single-institution, prospective, singlearm, phase II trial. Patients underwent surgery and IORT with 10 Gy prescribed at a 5-mm depth from the tumor bed using a 50 kV X-ray source (Intrabeam, Carl Zeiss). Six cycles of adjuvant gemcitabine-based chemotherapy were administered 8–12 weeks after surgery. @*Results@#A total of 41 patients were included. Thirty-one patients (75.6%) underwent wide R0 resection, while 5 (12.2%) underwent R1 resection and 5 (12.2%) underwent narrow R0 resection (retroperitoneal margin <1 mm). Grade 3 postoperative complications were reported in only one patient (4.9%) who needed additional surgery due to ulcer perforation. At a median follow-up of 9 months, four patients showed local-only recurrence, nine had distant metastases, and two showed both local and distant recurrence. The 1-year local control rate was 76.4%. @*Conclusion@#Our preliminary report suggests that IORT is well-tolerated and feasible in patients with resectable pancreatic cancer. Further follow-up is needed to confirm the clinical benefits of IORT in terms of local control and overall survival.Trial Registration: Clinical trial registration No. (NCT03273374).
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Purpose@#This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT. @*Materials and Methods@#This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively. @*Results@#The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3. @*Conclusion@#PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.
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Purpose@#To evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomy @*Materials and Methods@#Medical records of 274 patients from 18 institutions treated with mastectomy between January 2000 and December 2016 were retrospectively reviewed. Among these, 202 patients underwent PMRT, while 72 did not. Two hundred and forty-one patients (88.0%) received systemic chemotherapy, and 172 (62.8%) received hormonal therapy. Patients receiving PMRT were younger, more likely to have progesterone receptor-positive tumors, and received adjuvant chemotherapy more frequently compared with those without PMRT (p <0.001, 0.018, and <0.001, respectively). Other characteristics were not significantly different between the two groups. @*Results@#With a median follow-up of 95 months (range, 1-249), there were 9 locoregional recurrences, and 20 distant metastases. The 8-year locoregional recurrence-free survival rates were 98.0% with PMRT and 91.3% without PMRT (p=0.133), and the 8-year disease-free survival (DFS) rates were 91.8% with PMRT and 73.9% without PMRT (p=0.008). On multivariate analysis incorporating age, histologic grade, lymphovascular invasion, hormonal therapy, chemotherapy, and PMRT, the absence of lymphovascular invasion and the receipt of PMRT were associated with improved DFS (p=0.025 and 0.009, respectively). @*Conclusion@#Locoregional recurrence rate was very low in node-negative breast cancer of 5cm or larger tumors treated with mastectomy regardless of the receipt of PMRT. However, PMRT was significantly associated with improved DFS. Further investigation is needed to confirm these findings.
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Purpose@#The details of breast reconstruction and radiation therapy (RT) vary between institutions; therefore, we sought to investigate the practice patterns of radiation oncologists who specialize in breast cancer. @*Materials and Methods@#We identified the practice patterns and inter-hospital variations from a multi-center cohort of women with breast cancer who underwent post-mastectomy RT (PMRT) to the reconstructed breast at 16 institutions between 2015 and 2016. The institutions were requested to contour the target volume and produce RT plans for one representative case with five different clinical scenarios and answer questionnaires which elicited infrastructural information. We assessed the inter-institutional variations in RT in terms of the target, normal organ delineation, and dose-volume histograms. @*Results@#Three hundred fourteen patients were included; 99% of them underwent immediate reconstruction. The most irradiated material was tissue expander (36.9%) followed by transverse rectus abdominis musculocutaneous flap (23.9%) and silicone implant (12.1%). In prosthetic-based reconstruction with tissue expander, most patients received PMRT following partial deflation. Conventional fractionation and hypofractionation RT were used in 66.6% and 33.4% patients, respectively (commonest: 40.05 Gy in 15 fractions [17.5%]). Furthermore, 15.6% of the patients received boost RT and 53.5% were treated with bolus. Overall, 15 physicians responded to the questionnaires and six submitted their contours and RT plans. There was a significant variability in target delineations and RT plans between physicians, and between clinical scenarios. @*Conclusion@#Adjuvant RT following post-mastectomy reconstruction has become a common practice in Korea. The details vary significantly between institutions, which highlights an urgent need for standard protocol in this clinical setting.
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Purpose@#The details of breast reconstruction and radiation therapy (RT) vary between institutions; therefore, we sought to investigate the practice patterns of radiation oncologists who specialize in breast cancer. @*Materials and Methods@#We identified the practice patterns and inter-hospital variations from a multi-center cohort of women with breast cancer who underwent post-mastectomy RT (PMRT) to the reconstructed breast at 16 institutions between 2015 and 2016. The institutions were requested to contour the target volume and produce RT plans for one representative case with five different clinical scenarios and answer questionnaires which elicited infrastructural information. We assessed the inter-institutional variations in RT in terms of the target, normal organ delineation, and dose-volume histograms. @*Results@#Three hundred fourteen patients were included; 99% of them underwent immediate reconstruction. The most irradiated material was tissue expander (36.9%) followed by transverse rectus abdominis musculocutaneous flap (23.9%) and silicone implant (12.1%). In prosthetic-based reconstruction with tissue expander, most patients received PMRT following partial deflation. Conventional fractionation and hypofractionation RT were used in 66.6% and 33.4% patients, respectively (commonest: 40.05 Gy in 15 fractions [17.5%]). Furthermore, 15.6% of the patients received boost RT and 53.5% were treated with bolus. Overall, 15 physicians responded to the questionnaires and six submitted their contours and RT plans. There was a significant variability in target delineations and RT plans between physicians, and between clinical scenarios. @*Conclusion@#Adjuvant RT following post-mastectomy reconstruction has become a common practice in Korea. The details vary significantly between institutions, which highlights an urgent need for standard protocol in this clinical setting.
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PURPOSE: There is limited data on radiotherapy (RT) for hepatocellular carcinoma (HCC) in patients with Child-Pugh classification B (CP-B). This study aimed to evaluate the treatment outcomes of fractionated conformal RT in HCC patients with CP-B. MATERIALS AND METHODS: We retrospectively reviewed the data of HCC patients with CP-B treated with RT between 2009 and 2014 at 13 institutions in Korea. HCC was diagnosed by the Korea guideline of 2009, and modern RT techniques were applied. Fraction size was ≤ 5 Gy and the biologically effective dose (BED) ≥ 40 Gy₁₀ (α/β = 10 Gy). A total of 184 patients were included in this study. RESULTS: Initial CP score was seven in 62.0% of patients, eight in 31.0%, and nine in 7.0%. Portal vein tumor thrombosis was present in 66.3% of patients. The BED ranged from 40.4 to 89.6 Gy₁₀ (median, 56.0 Gy₁₀). After RT completion, 48.4% of patients underwent additional treatment. The median overall survival (OS) was 9.4 months. The local progression-free survival and OS rates at 1 year were 58.9% and 39.8%, respectively. In the multivariate analysis, non-classic radiation-induced liver disease (RILD) (p < 0.001) and additional treatment (p < 0.001) were the most significant prognostic factors of OS. Among 132 evaluable patients without progressive disease, 19.7% experienced non-classic RILD. Normal liver volume was the most predictive dosimetric parameter of non-classic RILD. CONCLUSION: Fractionated conformal RT showed favorable OS with a moderate risk non-classic RILD. The individual radiotherapy for CP-B could be cautiously applied weighing the survival benefits and the RILD risks.
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Humans , Carcinoma, Hepatocellular , Classification , Disease-Free Survival , Korea , Liver , Liver Diseases , Multivariate Analysis , Portal Vein , Radiotherapy , Radiotherapy, Conformal , Retrospective Studies , Thrombosis , Treatment OutcomeABSTRACT
PURPOSE: Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. MATERIALS AND METHODS: We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. RESULTS: The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. CONCLUSION: RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.
Subject(s)
Humans , Breast Neoplasms , Breast , Diagnosis , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Lymph Nodes , Prognosis , Radiotherapy , Radiotherapy, Adjuvant , Radiotherapy, Intensity-Modulated , Recurrence , Retrospective StudiesABSTRACT
Cancer is the leading cause of death in the Republic of Korea and cancer death accounts for 27.8% of the total deaths, which is not only a social issue but also a concern for the public. Among the cancer death rates, lung cancer mortality account for 34 deaths per 100,000 populations, making it the number one cancer death rate. In a preliminary report on cancer death in 2012, the lung cancer mortality ratio showed the regional variation indicating that there were differences in the qualitative level and the structure among the medical care benefit agency and in the assessment of the treatment process. Therefore, the Health Insurance Review and Assessment Service (HIRA) had begun evaluation of the assessment of lung cancer treatment since 2014 to improve the quality of lung cancer care through evaluation and feeds back the results of lung cancer care process. In this report, authors described the current Indicators for the lung cancer adequacy assessment proposed by HIRA and results of the evaluation reported in 2017.
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Cause of Death , Evaluation Studies as Topic , Insurance, Health , Korea , Lung Neoplasms , Lung , Mortality , Quality Assurance, Health Care , Republic of KoreaABSTRACT
PURPOSE: Anaplastic thyroid cancer (ATC) is a rare tumor with a lethal clinical course despite aggressive multimodal therapy. Intensity-modulated radiotherapy (IMRT) may achieve a good therapeutic outcome in ATC patients, and the role of IMRT should be assessed. We retrospectively reviewed outcomes for ATC treated with three-dimensional conformal radiotherapy (3D-CRT) or IMRT to determine the optimal treatment option and explore the role of radiotherapy (RT). MATERIALS AND METHODS: Between December 2000 and December 2015, 41 patients with pathologically proven ATC received RT with a sufficient dose of ≥40 Gy. Among them, 21 patients (51%) underwent surgery before RT. Twenty-eight patients received IMRT, and 13 received 3D-CRT. Overall survival (OS) and progression-free survival (PFS), patterns of failure, and toxicity were examined. RESULTS: The median follow-up time for survivors was 38.0 months. The median and 1-year OS and PFS rates were 7.2 months and 29%, 4.5 months and 15%, respectively. Surgery significantly improved the prognosis (median OS: 10.7 vs. 3.9 months, p = 0.001; median PFS: 5.9 vs. 2.5 months, p = 0.007). IMRT showed significantly better PFS and OS than 3D-CRT, even in multivariate analysis (OS: hazard ratio [HR] = 0.30, p = 0.005; PFS: HR = 0.33, p = 0.005). Significantly higher radiation dose could be delivered with IMRT than 3D-CRT (EQD210 66 vs. 60 Gy, p = 0.005). Only 2 patients had grade III dermatitis after IMRT. No other severe toxicity ≥grade III occurred. CONCLUSION: Patients with ATC showed better prognosis through multimodal treatment. Furthermore, IMRT could achieve favorable survival rates by safely delivering higher dose than 3D-CRT.
Subject(s)
Humans , Combined Modality Therapy , Dermatitis , Disease-Free Survival , Follow-Up Studies , Multivariate Analysis , Prognosis , Radiotherapy , Radiotherapy, Conformal , Radiotherapy, Intensity-Modulated , Retrospective Studies , Survival Rate , Survivors , Thyroid Carcinoma, AnaplasticABSTRACT
Cancer is the leading cause of death in the Republic of Korea and cancer death accounts for 27.8% of the total deaths, which is not only a social issue but also a concern for the public. Among the cancer death rates, lung cancer mortality account for 34 deaths per 100,000 populations, making it the number one cancer death rate. In a preliminary report on cancer death in 2012, the lung cancer mortality ratio showed the regional variation indicating that there were differences in the qualitative level and the structure among the medical care benefit agency and in the assessment of the treatment process. Therefore, the Health Insurance Review and Assessment Service (HIRA) had begun evaluation of the assessment of lung cancer treatment since 2014 to improve the quality of lung cancer care through evaluation and feeds back the results of lung cancer care process. In this report, authors described the current Indicators for the lung cancer adequacy assessment proposed by HIRA and results of the evaluation reported in 2017.
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The Korean clinical practice guideline recently developed by the Korean Breast Cancer Society to address the national clinical situation is currently under revision ahead of a seventh recommendation. A second consensus conference was held to further develop this guideline by soliciting opinions regarding important issues related to surgery, radiotherapy, and medical oncology. Several issues were discussed, and the discussion progressed to pros and cons in the context of cases in various clinical situations. The panels discussed and voted on issues regarding surgical treatment for non-axillary regional lymph nodes, regional nodal irradiation of pN1 disease, and ovarian functional suppression (OFS) as an adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Regarding the surgical treatment of non-axillary regional lymph node, most panelists agreed with the recommendation of preoperative chemotherapy and postoperative radiotherapy for patients with biopsy-diagnosed metastases, whereas surgery or radiotherapy of non-axillary regional lymph nodes was suggested for clinical partial responders. Discussions on radiotherapy addressed the need for adjuvant radiotherapy and radiation field of regional lymph node in the context of various N1 breast cancer cases. The participants reached a consensus to recommend that N1 patients should receive regional nodal irradiation for a large tumor burden (e.g., three positive nodes, perinodal extension, or large primary tumor). Finally, the panels favored OFS in addition to endocrine therapy for premenopausal women with high risk factors such as a large tumor size, involvement of more than three nodes, and a high histologic grade.
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Female , Humans , Breast Neoplasms , Breast , Consensus , Drug Therapy , Interdisciplinary Communication , Korea , Lymph Nodes , Medical Oncology , Neoplasm Metastasis , Radiotherapy , Radiotherapy, Adjuvant , Risk Factors , Tumor BurdenABSTRACT
PURPOSE: To report the results of a correlation analysis of skin dose assessed by in vivo dosimetry and the incidence of acute toxicity. This is a phase 2 trial evaluating the feasibility of intraoperative radiotherapy (IORT) as a boost for breast cancer patients. MATERIALS AND METHODS: Eligible patients were treated with IORT of 20 Gy followed by whole breast irradiation (WBI) of 46 Gy. A total of 55 patients with a minimum follow-up of 1 month after WBI were evaluated. Optically stimulated luminescence dosimeter (OSLD) detected radiation dose delivered to the skin during IORT. Acute toxicity was recorded according to the Common Terminology Criteria for Adverse Events v4.0. Clinical parameters were correlated with seroma formation and maximum skin dose. RESULTS: Median follow-up after IORT was 25.9 weeks (range, 12.7 to 50.3 weeks). Prior to WBI, only one patient developed acute toxicity. Following WBI, 30 patients experienced grade 1 skin toxicity and three patients had grade 2 skin toxicity. Skin dose during IORT exceeded 5 Gy in two patients: with grade 2 complications around the surgical scar in one patient who received 8.42 Gy. Breast volume on preoperative images (p = 0.001), ratio of applicator diameter and breast volume (p = 0.002), and distance between skin and tumor (p = 0.003) showed significant correlations with maximum skin dose. CONCLUSIONS: IORT as a boost was well-tolerated among Korean women without severe acute complication. In vivo dosimetry with OSLD can help ensure safe delivery of IORT as a boost.
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Female , Humans , Breast Neoplasms , Breast , Cicatrix , Follow-Up Studies , Incidence , Luminescence , Mastectomy, Segmental , Radiotherapy , Seroma , SkinABSTRACT
PURPOSE: The purpose of this study was to evaluate the benefits of adjuvant treatment for curatively resected thoracic esophageal squamous cell carcinoma (ESCC) and determine the optimal adjuvant treatments. MATERIALS AND METHODS: One hundred ninety-five patients who underwent a curative resection for thoracic ESCC between 1994 and 2014 were reviewed retrospectively. Postoperatively, the patients received no adjuvant treatment (no-adjuvant group, n=68), adjuvant chemotherapy (AC group, n=62), radiotherapy (RT group, n=41), or chemoradiotherapy (CRT group, n=24). Chemotherapy comprised cisplatin and 5-fluorouracil administration every 3 weeks. The median RT dose was 45.0 Gy (range, 34.8 to 59.4 Gy). The overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and distant metastasis (DM) rates were estimated. RESULTS: At a median follow-up duration of 42.2 months (range, 6.3 to 215.2 months), the 5-year OS and DFS were 37.6% and 31.4%, respectively. After adjusting for other clinicopathologic variables, the AC and CRT groups had a significantly better OS and DFS compared to the no-adjuvant group (p < 0.05). The LRR rate was significantly lower in the RT and CRT groups than in the no-adjuvant group (p < 0.05), whereas no significant difference was observed in the AC group. In the no-adjuvant and AC groups, 25% of patients received high-dose salvage RT due to LRR. The DM rates were similar. The anastomotic stenosis and leakage were similar in the treatment groups. CONCLUSION: Adjuvant treatment might prolong survival after an ESCC resection, and RT contributes to a reduction of the LRR. Overall, the risks and benefits should be weighed properly when selecting the optimal adjuvant treatment.
Subject(s)
Humans , Carcinoma, Squamous Cell , Chemoradiotherapy , Chemotherapy, Adjuvant , Cisplatin , Constriction, Pathologic , Disease-Free Survival , Drug Therapy , Epithelial Cells , Esophageal Neoplasms , Fluorouracil , Follow-Up Studies , Neoplasm Metastasis , Radiotherapy , Recurrence , Retrospective Studies , Risk AssessmentABSTRACT
PURPOSE: The aim of this study was to evaluate whether hepatic arterial infusion concurrent chemoradiotherapy (CCRT) could improve overall survival (OS) in patients with locally advanced hepatocellular carcinoma (LAHCC). MATERIALS AND METHODS: Two databases were reviewed from Yonsei Cancer Center (YCC) and Korean Liver Cancer Study Group (KLCSG) nationwide multi-center hepatocellular carcinoma (HCC) cohort. The CCRT group included 106 patients, with stage III-IV, Child-Pugh classification A, Eastern Cooperative Oncology Group performance status 0 or 1, who underwent definitive CCRT as the initial treatment at YCC. We used propensity score matching to adjust for seven clinical factors, including age, tumor size, TNM stage by the Liver Cancer Study Group of Japan, T stage, Barcelona Clinic Liver Cancer (BCLC) staging system, etiology of HCC, and portal vein invasion, which all differed significantly in the two databases. From the KLCSG cohort enrolled at 32 institutions, 106 patients for the non-CCRT group were defined. RESULTS: After propensity score matching, all patient characteristics were balanced between the two groups. The CCRT group had better OS (median, 11.4) than the non-CCRT group (6.6 months, p=0.02). In multivariate analyses for all patients, CCRT (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.11 to 1.97; p=0.007), tumor size (HR, 1.08; 95% CI, 1.04 to 1.12; p < 0.001), and BCLC stage (HR, 0.54; 95% CI, 0.36 to 0.8; p=0.003) were independent prognostic factors for OS. CONCLUSION: CCRT showed better OS for LAHCC patients. In LAHCC patients with a good performance and normal liver function, CCRT could be a feasible treatment option. All of these findings need to be validated in prospective clinical trials.
Subject(s)
Humans , Carcinoma, Hepatocellular , Chemoradiotherapy , Classification , Cohort Studies , Japan , Liver , Liver Neoplasms , Multivariate Analysis , Portal Vein , Propensity Score , Prospective Studies , RadiotherapyABSTRACT
PURPOSE: This study analyzed the outcomes of patients with resected extrahepatic bile duct cancer (EHBDC) in order to clarify the role of adjuvant treatments in these patients. MATERIALS AND METHODS: A total of 336 patients with EHBDC who underwent curative resection between 2001 and 2010 were analyzed retrospectively. The treatment types were as follows: surgery alone (n=168), surgery with chemotherapy (CTx, n=90), surgery with radiotherapy (RT) alone (n=29), and surgery with chemoradiotherapy (CRT, n=49). RESULTS: The median follow-up period was 63 months. The 5-year rates of locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for all patients were 56.5%, 59.7%, 36.6%, and 42.0%, respectively. In multivariate analysis, surgery with RT and CRT was a significant prognostic factor for LRFFS, and surgery with CTx was a significant prognostic factor for DMFS, and surgery with CTx, RT, and CRT was a significant prognostic factor for PFS (p < 0.05). Surgery with CTx and CRT showed association with superior OS (p < 0.05), and surgery with RT had marginal significance (p=0.078). In multivariate analysis of the R1 resection patients, surgery with CRT showed significant association with OS (p < 0.05). CONCLUSION: Adjuvant RT and CTx may be helpful in improving clinical outcomes of patients with resected EHBDC who have a high risk of disease recurrence, particularly R1 resection patients. Conduct of additional prospective, larger-scale studies will be required in order to confirm the benefit of adjuvant RT and CTx in these patients.
Subject(s)
Humans , Bile Ducts, Extrahepatic , Biliary Tract Neoplasms , Chemoradiotherapy , Cholangiocarcinoma , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Multivariate Analysis , Prospective Studies , Radiotherapy , Radiotherapy, Adjuvant , Recurrence , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: This study was conducted to evaluate the biological features of murine hepatocarcinoma according to different tumor microenvironmental models and to determine the change in molecular and immunologic responses after radiation. MATERIALS AND METHODS: Tumor models were established in the liver (orthotopic) and thigh (heterotopic) of male C3H/HeN mice. Tumor growth and lung metastasis were assessed in these models. To evaluate the radiation effect, the tumors were irradiated with 10 Gy. Factors associated with tumor microenvironment including vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), transforming growth factor beta1 (TGF-β1), CD31, and serum interleukin-6 (IL-6) were evaluated. Tumor-infiltrating regulatory immune cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) were also analyzed. RESULTS: A higher number of lung metastases were observed in the orthotopic tumor model than in the heterotopic tumor model. VEGF, CD31, COX-2, and TGF-β1 expression was more prominent in the orthotopic tumor model than in the heterotopic tumor model. Expression of the angiogenic factor VEGF and key regulatory molecules (TGF-β1 and COX-2) decreased following radiation in the orthotopic tumor model, while the serum IL-6 level increased after radiation. In the orthotopic tumor model, the number of both Tregs and MDSCs in the tumor burden decreased after radiation. CONCLUSION: The orthotopic tumor model showed higher metastatic potential and more aggressive molecular features than the heterotopic tumor model. These findings suggest that the orthotopic tumor mouse model may be more reflective of the tumor microenvironment and suitable for use in the translational research of radiation treatment.
Subject(s)
Animals , Humans , Male , Mice , Angiogenesis Inducing Agents , Cyclooxygenase 2 , Interleukin-6 , Liver , Lung , Neoplasm Metastasis , Radiation Effects , T-Lymphocytes, Regulatory , Thigh , Transforming Growth Factor beta1 , Translational Research, Biomedical , Tumor Burden , Tumor Microenvironment , Vascular Endothelial Growth Factor AABSTRACT
PURPOSE: We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse. RESULTS: The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively). CONCLUSION: The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Diaphragm , Disease-Free Survival , Joints , Pleura , Prognosis , Radiotherapy, Adjuvant , Thoracic WallABSTRACT
PURPOSE: To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. MATERIALS AND METHODS: Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). RESULTS: The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (> or =50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). CONCLUSION: In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.
Subject(s)
Humans , Bile Duct Neoplasms , Bile Ducts , Bile , Disease-Free Survival , Multivariate Analysis , Palliative Care , Radiotherapy Dosage , Radiotherapy , Radiotherapy, Adjuvant , Recurrence , Retrospective StudiesABSTRACT
PURPOSE: For locally unresectable hepatocellular carcinoma (HCC) patients, concurrent chemoradiotherapy (CCRT) has been applied as a loco-regional treatment. After shrinkage of tumors in selected patients, surgical resection is performed. The aim of this study was to evaluate prognostic factors and long-term survivors in such patients. MATERIALS AND METHODS: From January 2000 to January 2009, 264 patients with HCC were treated with CCRT (45 Gy with fractional dose of 1.8 Gy), and intra-arterial chemotherapy was administered during radiotherapy. Eighteen of these patients (6.8%) underwent hepatic resection after showing a response to CCRT. Cases were considered resectable when tumor-free margins and sufficient remnant volumes were obtained without extrahepatic metastasis. Prior to operation, there were six patients with complete remission, 11 with partial remission, and six with stable disease according to modified Response Evaluation Criteria in Solid Tumors. RESULTS: In pathologic review, four patients (22.2%) showed total necrosis and seven patients (38.9%) showed 70-99% necrosis. A high level of necrosis (> or =80%) was correlated with low risk for extrahepatic metastasis and long-term survival. In univariate analyses, vessel invasion and capsular infiltration were significantly correlated with disease free survival (DFS) (p=0.017 and 0.013, respectively), and vessel invasion was significantly correlated with overall survival (OS) (p=0.013). In multivariate analyses, capsule infiltration was a significant factor for DFS (p=0.016) and vessel invasion was significant for OS (p=0.015). CONCLUSION: CCRT showed favorable responses and locally advanced HCC converted into resectable tumor after CCRT in selected patients. Long-term survivors showed the pathological features of near total necrosis, as well as negative capsule and vessel invasion.