Validation of a nomogram for predicting the risk of lymphedema following contemporary treatment for breast cancer: a large multi-institutional study (KROG 20-05).

PURPOSE: We previously constructed a nomogram for predicting the risk of arm lymphedema following contemporary breast cancer treatment. This nomogram should be validated in patients with different background characteristics before use. Therefore, we aimed to externally validate the nomogram in a large multi-institutional cohort. METHODS: Overall, 8835 patients who underwent breast cancer surgery during 2007-2017 were identified. Data of variables in the nomogram and arm lymphedema were collected. The nomogram was validated externally using C-index and integrated area under the curve (iAUC) with 1000 bootstrap samples and by calibration plots. RESULTS: Overall, 1377 patients (15.6%) developed lymphedema. The median time from surgery to lymphedema development was 11.4 months. Lymphedema rates at 2, 3, and 5 years were 11.2%, 13.1%, and 15.6%, respectively. Patients with lymphedema had significantly higher body mass index (median, 24.1 kg/m2 vs. 23.4 kg/m2) and a greater number of removed nodes (median, 17 vs. 6) and more frequently underwent taxane-based chemotherapy (85.7% vs. 41.9%), total mastectomy (73.1% vs. 52.1%), conventionally fractionated radiotherapy (71.9% vs. 54.2%), and regional nodal irradiation (70.7% vs 22.4%) than those who did not develop lymphedema (all P < 0.001). The C-index of the nomogram was 0.7887, and iAUC was 0.7628, indicating good predictive accuracy. Calibration plots confirmed that the predicted lymphedema risks were well correlated with the actual lymphedema rates. CONCLUSION: This nomogram, which was developed using factors related to multimodal breast cancer treatment and was validated in a large multi-institutional cohort, can well predict the risk of breast cancer-related lymphedema.

Risk of Lymphedema Following Contemporary Treatment for Breast Cancer: An Analysis of 7617 Consecutive Patients From a Multidisciplinary Perspective.

OBJECTIVE: The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making. SUMMARY BACKGROUND DATA: Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear. METHODS: We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients. RESULTS: Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients). CONCLUSIONS: Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk.

Intraoperative radiation therapy induces immune response activity after pancreatic surgery.

BACKGROUND: Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment. METHODS: Among 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes. RESULTS: Levels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response. CONCLUSIONS: Based on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence. CLINICAL TRIAL REGISTRATION: NCT03273374 .

Magnetic resonance imaging-based validation of the 2018 FIGO staging system in patients treated with definitive radiotherapy for locally advanced cervix cancer.

OBJECTIVE: To validate the revised 2018 International Federation of Gynecologic and Obstetrics (FIGO) staging system in patients who underwent diagnostic magnetic resonance imaging (MRI) and radiotherapy (RT) for locally advanced cervix cancer. METHODS: We analyzed 677 patients who were diagnosed with pelvic MRI and treated with definitive (chemo-)RT for locally advanced cervix cancer (stage IB2/IIA2-IVA or N+) between 1992 and 2018. Patients were classified according to 2009 and 2018 FIGO staging, and survival outcomes were compared. We developed a nomogram to improve prediction of progression-free survival (PFS). RESULTS: Pelvic and paraaortic lymph nodes were positive in 331 (48.9%) and 78 (11.5%) patients, respectively. At a median follow-up of 77.9 months, the 5-year PFS was 83.5%, 65.2%, 71.0%, 60.6%, 37.6% and 38.9% for IB, IIA, IIB, IIIA, IIIB and IVA according to FIGO 2009 and 88.9%, 60.0%, 73.8%, 66.7%, 36.3%, 68.9%, 43.6%, and 38.9% for IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA according to FIGO 2018, respectively. Survival of stage IIIC cervix cancer depended on the local extent of the tumor: the 5-year PFS of T1, T2, and T3 stages were 80.3%, 73.9%, and 45.5% for IIIC1 and 100%, 44.9%, and 23.4% for IIIC2. Histology, tumor size, node metastasis, FIGO 2009, and treatment modality were independent prognostic factors in the Cox regression analysis, and the nomogram incorporating these factors outperformed FIGO 2009 and FIGO 2018 (AUC 0.718 vs. 0.616 vs. 0.594). CONCLUSIONS: FIGO 2018 revision was associated with heterogenous outcomes among stage III cervix cancer patients. Our nomogram can assist the FIGO system in predicting PFS after definitive RT.

A phase II study investigating the acute toxicity of targeted intraoperative radiotherapy as tumor-bed boost plus whole breast irradiation after breast-conserving surgery in Korean patients.

BACKGROUND: There are concerns regarding local toxicity when IORT is applied in Asian women with a smaller breast volume than that of Western women. Trials are required to develop safety profiles for this technique. The aim of this trial was to evaluate acute toxicity after intra-operative radiotherapy (IORT) with low-energy X-ray plus whole breast irradiation (WBI) in Asian patients with breast cancer. METHODS: This single-arm, single-institute, phase II trial investigated acute toxicity after completion of radiotherapy (targeted IORT followed by WBI) in Korean patients treated with breast-conserving surgery (BCS). In the conventional WBI arm from the TARGIT-A trial, the incidence of acute toxicity within 6 months was 15%. To prove the non-inferiority of the acute toxicity rate, 215 patients were required. This trial is registered with ClinicalTrials.gov (NCT02213991). RESULTS: Two-hundred and fifteen women were enrolled, and 198 underwent IORT. In 33 patients, clinically significant complications during the acute period were noted. The incidence of acute toxicity was 16.7% (95% CI 11.5-21.9%). There were 29 patients with seroma needing more than 3 aspirations, 4 with wound infection, and 2 with skin breakdown. There was no difference in the rate of complications according to the tumor volume or the tumor-breast volume ratio. Advanced age and high BMI were risk factors for acute complications. CONCLUSIONS: Targeted intra-operative radiotherapy using Intrabeam® is a safe procedure for Korean patients with breast cancer with an acceptable toxicity profile in the acute period.

Redefining Eligibility by Analyzing Canceled Intraoperative Radiotherapy as a Boost for Patients Undergoing Breast-Conserving Treatment.

BACKGROUND: Intraoperative radiotherapy (IORT) with a 50-kV x-ray is used for a tumor bed boost during breast-conserving surgery. This study evaluated the anatomicosurgical factors associated with cancellation of planned IORT. METHODS: Patient eligibility for the study included age of 20 years or older, compatibility for lumpectomy, and ductal carcinoma in situ or stages 1-3 invasive carcinoma. All the patients underwent magnetic resonance imaging (MRI) and multidisciplinary team evaluations. Resection margins were assessed by frozen pathology. Pre- and intraoperative variables were compared between the IORT and IORT-cancellation groups. RESULTS: A total of 434 patients underwent surgeries for IORT between August 2014 and December 2017. For 90 of these patients, IORT was canceled because of repeated positive margins leading to a large cavity or total mastectomy (n = 27), insufficient cavity-skin distance (n = 14), satellite lesions leading to a large cavity or total mastectomy (n = 12), MRI findings of a large primary tumor or uncertain margins leading to a large cavity (n = 6), cavity geometry unsuitable for IORT (n = 6), subareolar tumor extension (n = 6), tumor abutting the pectoralis muscle (n = 3), patient refusal (n = 5), intraoperative confirmation of bilateral breast cancer (n = 3) or benign pathology (n = 3), device malfunction (n = 3), or scheduling difficulty (n = 2). A tumor larger than 2 cm (P = 0.014) and the presence of satellite lesions (P = 0.014) were independent predictors of IORT cancellation. CONCLUSIONS: Surgical procedures resulting in large cavities were the leading cause of IORT cancellation. Multidisciplinary evaluations using MRI were critical for completion of IORT procedures.

Lung Adenocarcinoma Invasiveness Risk in Pure Ground-Glass Opacity Lung Nodules Smaller than 2 cm.

BACKGROUND: We aimed to identify clinicopathologic characteristics and risk of invasiveness of lung adenocarcinoma in surgically resected pure ground-glass opacity lung nodules (GGNs) smaller than 2 cm. METHODS: Among 755 operations for lung cancer or tumors suspicious for lung cancer performed from 2012 to 2016, we retrospectively analyzed 44 surgically resected pure GGNs smaller than 2 cm in diameter on computed tomography (CT). RESULTS: The study group was composed of 36 patients including 11 men and 25 women with a median age of 59.5 years (range, 34-77). Median follow-up duration of pure GGNs was 6 months (range, 0-63). Median maximum diameter of pure GGNs was 8.5 mm (range, 4-19). Pure GGNs were resected by wedge resection, segmentectomy, or lobectomy in 27 (61.4%), 10 (22.7%), and 7 (15.9%) cases, respectively. Pathologic diagnosis was atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA) in 1 (2.3%), 18 (40.9%), 15 (34.1%), and 10 (22.7%) cases, respectively. The optimal cutoff value for CT-maximal diameter to predict MIA or IA was 9.1 mm. In multivariate analyses, maximal CT-maximal diameter of GGNs ≥10 mm (odds ratio, 24.050; 95% confidence interval, 2.6-221.908; p = 0.005) emerged as significant independent predictor for either MIA or IA. Estimated risks of MIA or IA were 37.2, 59.3, 78.2, and 89.8% at maximal GGN diameters of 5, 10, 15, and 20 mm, respectively. CONCLUSION: Pure GGNs were highly associated with lung adenocarcinoma in surgically resected cases, while estimated risk of GGNs invasiveness gradually increased as maximal diameter increased.

A phase II study of intraoperative radiotherapy using a low-energy x-ray source for resectable pancreatic cancer: a study protocol.

BACKGROUND: The current standard treatment for resectable pancreatic cancer is surgical resection followed by adjuvant chemotherapy. Local recurrence rates are high even after curative resection; thus, the long-term outcome of locally advanced pancreatic cancer remains poor. Intraoperative radiotherapy (IORT) uses a low-energy x-ray source to deliver a single fraction of high-dose radiation to the tumor bed during a surgical procedure, while effectively sparing the surrounding normal tissues. IORT has the potential to improve the efficacy of radiation therapy for pancreatic cancer. METHODS/DESIGN: This prospective, one-armed, phase II study will investigate the role of IORT in improving local control in patients with resectable pancreatic adenocarcinoma. The patients will receive surgery and IORT of 10 Gy prescribed at a 5-mm depth of the tumor bed, followed by adjuvant gemcitabine chemotherapy according to the current standard of care. The aim is to enroll 42 patients. DISCUSSION: The primary endpoint of this trial is to evaluate the feasibility of IORT and the local recurrence rate after one year. The secondary endpoints include the acute and late toxicities, and disease-free survival and overall survival rates. TRIAL REGISTRATION: The trial was prospectively registered at Clinicaltrials.gov NCT03273374 on September 6, 2017.

Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial.

OBJECTIVE: This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC. SUMMARY BACKGROUND DATA: Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC), no high-level evidence exists to support the role of such treatment. METHODS: This phase 2/3 multicenter randomized controlled trial was designed to enroll 110 patients with BRPC who were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment (54 Gray external beam radiation) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea. The primary endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at the time of 50% case enrollment. RESULTS: After excluding the patients who withdrew consent (n = 8) from the 58 enrolled patients, 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups. The overall 2-YSR was 34.0% with a median survival of 16 months. In the intention-to-treat analysis, the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [40.7%, 21 months vs 26.1%, 12 months, hazard ratio 1.495 (95% confidence interval 0.66-3.36), P = 0.028]. R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery (n = 14, 51.8% vs n = 6, 26.1%, P = 0.004). The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy. CONCLUSION: This is the first prospective randomized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC. Compared to upfront surgery, neoadjuvant chemoradiation provides oncological benefits in patients with BRPC.

Multi-institutional study of treatment patterns in Korean patients with WHO grade II gliomas: KNOG 15-02 and KROG 16-04 intergroup study.

INTRODUCTION: We performed this study to identify the treatment patterns of patients with low-grade gliomas (LGG) in Korea. METHODS: A total of 555 patients diagnosed as WHO grade II gliomas between 2000 and 2010 at 14 Korean institutions were included. The patients were divided into four adjuvant treatment groups: adjuvant fractionated radiotherapy (RT, N = 204), adjuvant chemotherapy (N = 20), adjuvant fractionated RT and chemotherapy (N = 65), and non-adjuvant treatment (N = 266) groups. We examined differences among the groups and validated patient/tumor characteristics associated with the adjuvant treatments. RESULTS: Astrocytoma was diagnosed in 210 patients (38%), oligoastrocytoma in 85 patients (15%), and oligodendroglioma in 260 patients (47%). Gross total resection was performed in 200 patients (36%), subtotal resection in 153 (28%), partial resection in 71 patients (13%), and biopsy in 131 patients (24%). RT was most commonly applied as an adjuvant treatment. The use of chemotherapy with or without RT decreased after 2008 (from 38 to 4%). The major chemotherapeutic regimen was procarbazine, lomustine, and vincristine (PCV); however, the proportion of temozolomide increased since 2005 (up to 69%). Patient/tumor characteristics related with RT were male gender, non-seizure, multiple lobes involvement, and non-gross total resection. Chemotherapy was associated with non-gross total resection and non-astrocytoma. CONCLUSIONS: A preference for RT and increased use of temozolomide was evident in the treatment pattern of LGG. The extent of resection was associated with a decision to perform RT and chemotherapy. To establish a robust guideline for LGG, further studies including molecular information are needed.

Impact of adjuvant treatments on survival in Korean patients with WHO grade II gliomas: KNOG 15-02 and KROG 16-04 intergroup study.

INTRODUCTION: Optimal treatment strategies for low-grade glioma (LGG) remain controversial. We analyzed treatment outcomes and evaluated prognostic factors of adult LGG patients in Korea. METHODS: We reviewed the medical records of 555 patients diagnosed with WHO grade II LGG (astrocytoma 37.8%, oligoastrocytoma 15.3%, and oligodendroglioma 46.8%) at 14 institutions between 2000 and 2010. Primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS). Propensity-score matching (PSM) analyses were performed to correct imbalances in patient/tumor characteristics among adjuvant treatment groups. RESULTS: The median follow-up time was 83.4 months, and the 5-year PFS and OS rates were 52.2% and 83.0%, respectively. Male, older age, poorer performance status, multiple lobe involvement, and astrocytoma histology were associated with poorer survival. Among the treatment factors, gross total resection (GTR) was associated with better PFS and OS, and adjuvant chemotherapy with improved PFS. Interestingly, adjuvant radiotherapy (RT) did not improve PFS; rather, it was related with poorer OS. Regarding patient/tumor characteristics, the RT group had poorer characteristics than the non-RT group. After PSM, we detected a tendency for improved PFS in the matched RT group, and no significant difference in OS compared with the matched non-RT group. CONCLUSIONS: The achievement of GTR is important to improve survival in LGG patients. Adjuvant chemotherapy may enhance PFS, but adjuvant RT did not improve survival outcomes. After PSM, we observed potential impacts of adjuvant RT on PFS. Our results may reflect real-world practice and consequently may help to optimize treatment strategies for LGG.

Mechanistic insights into the interaction between energetic oxygen ions and nanosized ZnFe2O4: XAS-XMCD investigations.

The interactions of energetic ions with multi-cation compounds and their consequences in terms of changes in the local electronic structure, which may facilitate intriguing hybridization between O 2p and metal d orbitals and magnetic ordering, are the subject of debate and require a deep understanding of energy transfer processes and magnetic exchange mechanisms. In this study, nanocrystals of ZnFe2O4 were exposed to O7+ ions with an energy of 100 MeV to understand, qualitatively and quantitatively, the metal-ligand field interactions, cation migration and magnetic exchange interactions by employing X-ray absorption fine structure measurements and X-ray magnetic circular dichroism to get deeper mechanistic insights. Nanosized zinc ferrite nanoparticles (NPs) with a size of ∼16 nm synthesized in the cubic spinel phase exhibited deterioration of the crystalline phase when 100 MeV O7+ ions passed through them. However, the size of these NPs remained almost the same. The behaviour of crystal deterioration is associated with the confinement of heat in this interaction. The energy confined inside the nanoparticles promotes cation redistribution as well as the modification of the local electronic structure. Prior to this interaction, almost 42% of Zn2+ ions occupied AO4 tetrahedra; however, this value increased to 63% after the interaction. An inverse effect was observed for metal ion occupancies in BO6 octahedra. The L-edge spectra of Fe and Zn reveal that the spin and valence states of the metal ions were not affected by this interaction. This effect is also supported by K-edge measurements for Fe and Zn. The t2g/eg intensity ratio in the O K-edge spectra decreased after this interaction, which is associated with detachment of Zn2+ ions from the lattice. The extent of hybridization, as estimated from the ratio of the post-edge to the pre-edge region of the O K-edge spectra, decreased after this interaction. The metal-oxygen and metal-metal bond lengths were modified as a result of this interaction, as determined from extended X-ray absorption fine structure measurements. These measurements further support the observation of cation migration from AO4 tetrahedra to AO6 octahedra and vice versa. The Fe L-edge magnetic circular dichroism spectra indicate that Fe3+ ions occupying sites in AO4 tetrahedra and BO6 octahedra exhibited antiferromagnetic-like ordering prior to this interaction. The NPs that interacted with energetic O ions displayed a different kind of magnetic ordering.

Maximum surgical resection and adjuvant intensity-modulated radiotherapy with simultaneous integrated boost for skull base chordoma.

BACKGROUND: Local recurrence is common after surgical resection of clivus chordoma. We report the results of maximum surgical resection followed by intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB). METHODS: We reviewed 14 consecutive clivus chordoma cases undergoing postoperative IMRT-SIB using the institutional protocol between 2005 and 2013. Total and near-total resections were achieved in 11 patients (78.6 %), partial in 2 patients (14.3 %), and 1 patient (7.1 %) received RT for recurrent tumor after total resection. Gross residual or the high-risk area defined the planning target volume (PTV)1; PTV2 was the postoperative tumor bed plus a 3-5-mm margin, and PTV3 was PTV2 plus a 5-10 mm margin. A moderate hypofractionation schedule was used: doses to PTV1, PTV2 and PTV3 were 3.9 Gy, 3.15 Gy and 2.8 Gy through 15 fractions for the first two patients, and the rest received 2.5 Gy, 2.2 Gy and 1.8 Gy through 25 fractions. The biologically equivalent dose in 2-Gy fractions (EQD2) was 65-68 Gy for PTV1, 52-56 Gy for PTV2, and 44.3-44.8 Gy for PTV3. RESULTS: Median follow-up was 41 months. Eight patients were free of disease for median 42.5 months (range 23-91 months), four patients had stable disease for median 60.5 months (range 39-113 months), and 1 patient showed partial response for 38 months after RT. Local progression was seen in one patient who received EQD2 67.8 Gy after partial resection. Estimated 5-year progression-free and overall survival rates were 92.9 %. Surgery improved the neurologic deficit in six patients, and IMRT-SIB was well tolerated without lasting toxicity. CONCLUSION: Our experience suggests that maximum resection and high-dose IMRT-SIB can achieve local control without significant morbidities.

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.

Radiological-pathological correlation study of hepatocellular carcinoma undergoing local chemoradiotherapy and surgery.

BACKGROUND AND AIMS: Optimal response criteria and assessment timing were investigated through radiologic-pathologic correlation in hepatocellular carcinoma (HCC) treated with localized chemoradiotherapy (CRT). METHODS: We reviewed 19 consecutive HCC patients who underwent surgical resection after radiotherapy and concurrent hepatic arterial infusion chemotherapy. Patients who received transarterial chemoembolization before RT or surgery were excluded from evaluation. Tumor diameters and total and enhancing tumor volumes were measured from CT images obtained 1, 3, 6, and 9 months after CRT. Percent changes calculated using size (RECIST and WHO) and enhancement criteria (mRECIST and EASL) were correlated with percent changes in total and enhancing tumor volumes, and with percent viable tumor in surgical specimens. RESULTS: Median time between CRT and resection was 4.1 months (range, 1.5-15.4 months). CR and PR rates were 0 and 68% by RECIST, 0 and 63% by WHO, 53% and 37% by mRECIST, and 53% and 42% by EASL. Pathologic CR (pCR) rate was 52.6%. Radiologic criteria showed strong correlation with tumor volumes at 1 and 3 months after CRT; at 6 months, however, size and enhancement criteria showed strong correlation only with total and enhancing tumor volumes, respectively. Enhancement criteria were better predictors of pathologic response at all times including preoperative evaluation (RECIST: R(2) = 0.303, P = 0.015 and WHO: R(2) = 0.366, P = 0.006 vs. mRECIST: R(2) = 0.760, P < 0.0001 and EASL: R(2) = 0.768, P < 0.0001). Time interval >6 months before resection showed significant correlation with pCR (P = 0.013). CONCLUSIONS: We recommend using enhancement criteria in assessing tumor viability, especially if the tumor was to be resected <6 months after CRT.

A sub-micrometer resolution hard X-ray microprobe system of BL8C at Pohang Light Source.

A microprobe system has been installed on the nanoprobe/XAFS beamline (BL8C) at PLS-II, South Korea. Owing to the reproducible switch of the gap of the in-vacuum undulator (IVU), the intense and brilliant hard X-ray beam of an IVU can be used in X-ray fluorescence (XRF) and X-ray absorption fine-structure (XAFS) experiments. For high-spatial-resolution microprobe experiments a Kirkpatrick-Baez mirror system has been used to focus the millimeter-sized X-ray beam to a micrometer-sized beam. The performance of this system was examined by a combination of micro-XRF imaging and micro-XAFS of a beetle wing. These results indicate that the microprobe system of the BL8C can be used to obtain the distributions of trace elements and chemical and structural information of complex materials.

Characteristics of a tapered undulator for the X-ray absorption fine-structure technique at PLS-II.

An in-vacuum undulator (IVU) with a tapered configuration was installed in the 8C nanoprobe/XAFS beamlime (BL8C) of the Pohang Light Source in Korea for hard X-ray nanoprobe and X-ray absorption fine-structure (XAFS) experiments. It has been operated in planar mode for the nanoprobe experiments, while gap-scan and tapered modes have been used alternatively for XAFS experiments. To examine the features of the BL8C IVU for XAFS experiments, spectral distributions were obtained theoretically and experimentally as functions of the gap and gap taper. Beam profiles at a cross section of the X-ray beam were acquired using a slit to visualize the intensity distributions which depend on the gap, degree of tapering and harmonic energies. To demonstrate the effect of tapering around the lower limit of the third-harmonic energy, V K-edge XAFS spectra were obtained in each mode. Owing to the large X-ray intensity variation around this energy, XAFS spectra of the planar and gap-scan modes show considerable spectral distortions in comparison with the tapered mode. This indicates that the tapered mode, owing to the smooth X-ray intensity profile at the expense of the highest and most stable intensity, can be an alternative for XAFS experiments where the gap-scan mode gives a considerable intensity variation; it is also suitable for quick-XAFS scanning.

High-dose versus standard-dose radiotherapy with concurrent chemotherapy in stages II-III esophageal cancer.

OBJECTIVE: In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. METHODS: A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. RESULTS: The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. CONCLUSIONS: High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials.

Intensive nutritional counseling improves PG-SGA scores and nutritional symptoms during and after radiotherapy in Korean cancer patients.

PURPOSE: This study was conducted for the nutritional assessment of cancer patients undergoing radiotherapy (RT) and to investigate the changes in nutrition status, oral intake, morbidity and quality of life (QOL) in cancer patients after intensive nutrition counseling. METHODS: Eighty-seven cancer patients were randomized to either a nutrition counseling group (n = 44, age 58.0 ± 2.2 years) or a control group (n = 43, 62.0 ± 1.8 years). Nutrition counseling accompanied RT, and the subjects received at least three sessions of individualized dietary counseling over the duration of RT. Assessment parameters were nutritional intake (24-h recall method), nutritional status Patient-Generated Subjective Global Assessment (PG-SGA), QOL and blood parameters including albumin. All parameters were measured at baseline, at the end of RT, and 1 month after the termination of RT. RESULTS: Body weight, body mass index (BMI), and energy and protein intake for the intervention and control groups did not differ significantly between baseline and the end of RT. However, at 1 month follow-up, protein intake was significantly decreased in the control group (p < 0.05). Blood albumin, total protein (TP), total lymphocyte count (TLC) were not different between the two groups. According to PG-SGA stage, at 1 month follow-up, patients in the intervention group showed increased number of patients with stage A status (well nourished). In addition, insomnia and nausea was significantly improved in the intervention group assessed by QOL. CONCLUSION: We suggest that repetitive and intensive nutritional counseling is necessary to improve QOL and to prevent deterioration of nutritional status in cancer patients receiving RT.

Local control may be the key in improving treatment outcomes of esophageal squamous cell carcinoma undergoing concurrent chemoradiation.

BACKGROUND/AIM: Little is known about the patterns of treatment failure following definitive chemoradiotherapy (CCRT), especially in esophageal squamous cell carcinoma (SCC). We evaluated definitive CCRT failure patterns and determined the predictive factors for treatment response in esophageal SCC. METHODS: We evaluated 136 consecutive patients with esophageal SCC treated with definitive CCRT. We evaluated the factors associated with complete remission (CR) after CCRT and analyzed the pattern of treatment failure of recurred patients and incomplete remission patients. The failures were categorized as either within (locoregional failure) or outside the radiation field (out-field failure). RESULTS: Fifty-seven patients achieved CR after CCRT. Consolidation chemotherapy was significantly associated with CR. Only 4 (7.0%) patients had CR after CCRT in patients with M1a node (Celiac or subclavian lymph nodes involvement by 6th AJCC). During follow-up, 74 patients (54.4%) experienced locoregional failure, 26 (19.1%) out-field failure, and 35 (25.7%) no failure. Esophageal obstruction prior to CCRT, residual tumor according to the first follow-up endoscopy, and poor follow-up computed tomography responses were significantly associated with locoregional failure. CONCLUSION: Approximately 70% of treatment failures were local failures. Future therapeutic strategies need to focus on improving local control to increase treatment outcomes of CCRT.