Preventive and Therapeutic Effects of Lactiplantibacillus plantarum HD02 and MD159 through Mast Cell Degranulation Inhibition in Mouse Models of Atopic Dermatitis.

As the relationship between the gut microbiome and allergies becomes better understood, targeted strategies to prevent and treat allergies through gut microbiome modulation are being increasingly developed. In the study presented herein, we screened various probiotics for their ability to inhibit mast cell degranulation and identified Lactiplatibacillus plantarum HD02 and MD159 as effective candidates. The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE. In the house dust mite (HDM)-induced murine AD model, both L. plantarum HD02 and MD159 showed therapeutic effects, with L. plantarum HD02 demonstrating superior efficacy. Nevertheless, L. plantarum MD159 better suppressed transepidermal water loss (TEWL). Furthermore, L. plantarum HD02 and MD159 significantly increased the number of splenic Foxp3+ regulatory T cells, with L. plantarum MD159 having a more pronounced effect. However, only L. plantarum HD02 achieved a reduction in immune cells in the draining lymph nodes. Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications.

Reduced Risk of Severe Radiation-Induced Lymphopenia in Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer: A Comparative Analysis of Carbon Versus Photon Therapy.

PURPOSE: Radiation-induced lymphopenia (RIL) is associated with poor prognosis in patients with locally advanced pancreatic cancers. However, there are no reports comparing the effects of carbon ion radiation therapy (CIRT) and photon beam radiation therapy (RT) on the development of RIL. Differences in RIL after CIRT or photon beam RT and predictive factors for RIL in patients with locally advanced pancreatic cancer were investigated. MATERIALS AND METHODS: This retrospective study cohort included 834 patients who received concurrent chemoradiotherapy (CCRT) in 2 separate institutions: 337 and 497 in the CIRT and photon beam RT groups, respectively. Severe RIL was defined as an absolute lymphocyte count (ALC) <0.5 × 109 cells/L. A 1:1 propensity score-matching analysis was performed between the CIRT and photon beam RT groups. Patients were categorized into 3 groups according to the development of recovery from severe RIL: no severe RIL (Group A), recovery from severe RIL (Group B), and no recovery from severe RIL (Group C). Logistic regression analysis was performed to identify the predictive value of severe RIL. The prognostic factors of overall survival (OS) were determined using Cox regression analysis. RESULTS: After propensity score matching, the baseline ALC and planning target volume of the CIRT and photon beam RT groups were comparable. During CCRT, the ALC of the entire cohort decreased and was significantly lower in the photon beam RT group than in the CIRT group (P < .001). Multivariate logistic regression analysis showed that CIRT reduced severe RIL more than photon beam RT. After adjusting for other factors, the RT modality and RIL were significantly associated with OS. Photon beam RT showed a significantly worse OS than CIRT, and Group C showed a significantly worse OS than Group A. CONCLUSIONS: CIRT seems to reduce the development of severe RIL. The RT modality and development/recovery from severe RIL were associated with OS in patients who received CCRT for locally advanced pancreatic cancer. The reduction of severe RIL through optimized RT may be essential for improving treatment outcomes.

Experience of Implementing Deep Learning-Based Automatic Contouring in Breast Radiation Therapy Planning: Insights From Over 2000 Cases.

PURPOSE: This study evaluated the impact and clinical utility of an auto-contouring system for radiation therapy treatments. METHODS AND MATERIALS: The auto-contouring system was implemented in 2019. We evaluated data from 2428 patients who underwent adjuvant breast radiation therapy before and after the system's introduction. We collected the treatment's finalized contours, which were reviewed and revised by a multidisciplinary team. After implementation, the treatment contours underwent a finalization process that involved manual review and adjustment of the initial auto-contours. For the preimplementation group (n = 369), auto-contours were generated retrospectively. We compared the auto-contours and final contours using the Dice similarity coefficient (DSC) and the 95% Hausdorff distance (HD95). RESULTS: We analyzed 22,215 structures from final and corresponding auto-contours. The final contours were generally larger, encompassing more slices in the superior or inferior directions. Among organs at risk (OAR), the heart, esophagus, spinal cord, and contralateral breast demonstrated significantly increased DSC and decreased HD95 postimplementation (all P < .05), except for the lungs, which presented inaccurate segmentation. Among target volumes, CTVn_L2, L3, L4, and the internal mammary node showed increased DSC and decreased HD95 postimplementation (all P < .05), although the increase was less pronounced than the OAR outcomes. The analysis also covered factors contributing to significant differences, pattern identification, and outlier detection. CONCLUSIONS: In our study, the adoption of an auto-contouring system was associated with an increased reliance on automated settings, underscoring its utility and the potential risk of automation bias. Given these findings, we underscore the importance of considering the integration of stringent risk assessments and quality management strategies as a precautionary measure for the optimal use of such systems.

Efficacy of stereotactic ablative radiotherapy in patients with oligometastatic hepatocellular carcinoma: A phase II study.

BACKGROUND & AIMS: Stereotactic ablative radiotherapy (SABR) can extend survival and offers the potential for cure in some patients with oligometastatic disease (OMD). However, limited evidence exists regarding its use in oligometastatic hepatocellular carcinoma (HCC). We aimed to prospectively investigate the efficacy and safety of SABR in patients with oligometastatic HCC. METHODS: We enrolled patients with controlled primary HCC and one to five metastatic lesions amenable to SABR. The primary endpoint was treatment efficacy defined as overall survival (OS) and progression-free survival (PFS). The secondary endpoints included time to local progression, objective response rate, disease control rate, toxicities, and quality of life (QOL), assessed using the EORTC QLQ-C30 before, and 0, 1, and 3 months after SABR. RESULTS: Overall, 40 consecutive patients received SABR on 62 lesions between 2021 and 2022. The most common locations for OMD were the lungs (48.4%), lymph nodes (22.6%), and bone (17.7%). After a median follow-up of 15.5 months, the 2-year OS was 80%. Median PFS was 5.3 months, with 1- and 2-year PFS rates of 21.2% and 0%, respectively. A shorter time to OMD from the controlled primary independently correlated with PFS (p = 0.039, hazard ratio 2.127) alongside age, Child-Pugh class, and alpha-fetoprotein (p = 0.002, 0.004, 0.019, respectively). The 2-year time to local progression, objective response rate, and disease control rate were 91.1%, 75.8%, and 98.4%, respectively. Overall, 10% of patients experienced acute toxicity, and 7.5% experienced late toxicity, with no grade 3+ toxicity. All QOL scores remained stable, whereas the patients without systemic treatments had improved insomnia and social functioning scores. CONCLUSIONS: SABR is an effective and feasible option for oligometastatic HCC that leads to excellent local tumor control and improves survival without adversely affecting QOL. IMPACT AND IMPLICATIONS: Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment approach capable of efficiently ablating the target lesion; however, neither the oligometastatic disease concept nor the potential benefits of SABR have been well-defined in hepatocellular carcinoma (HCC). According to this study, SABR is an effective and safe treatment option for oligometastatic HCC, yielding excellent local tumor control and survival improvement without worsening patients' quality of life, regardless of tumor sites. We also demonstrated that patients with a later presentation of OMD from the controlled primary and lower alpha-fetoprotein levels achieved better survival outcomes. This is the first prospective study of SABR in oligometastatic HCC, providing insights for the development of novel strategies to improve oncologic outcomes. CLINICAL TRIAL NUMBER: NCT05173610.

Machine learning­based radiomics models for prediction of locoregional recurrence in patients with breast cancer.

Locoregional recurrence (LRR) is the predominant pattern of relapse after definitive breast cancer treatment. The present study aimed to develop machine learning (ML)-based radiomics models to predict LRR in patients with breast cancer by using preoperative magnetic resonance imaging (MRI) data. Data from patients with localized breast cancer that underwent preoperative MRI between January 2013 and December 2017 were collected. Propensity score matching (PSM) was performed to adjust for clinical factors between patients with and without LRR. Radiomics features were obtained from T2-weighted with and without fat-suppressed MRI and contrast-enhanced T1-weighted with fat-suppressed MRI. In the present study five ML models were designed, three base models (support vector machine, random forest, and logistic regression) and two ensemble models (voting model and stacking model) composed of the three base models, and the performance of each base model was compared with the stacking model. After PSM, 28 patients with LRR and 86 patients without LRR were included. Of these 114 patients, 80 patients were randomly selected to train the models, and the remaining 34 patients were used to evaluate the performance of the trained models. In total, 5,064 features were obtained from each patient, and 47-51 features were selected by applying variance threshold and least absolute shrinkage and selection operator. The stacking model demonstrated superior performance in area under the receiver operating characteristic curve (AUC), with an AUC of 0.78 compared to a range of 0.61 to 0.70 for the other models. An external validation study to investigate the efficacy of the stacking model of the present study was initiated and is still ongoing (Korean Radiation Oncology Group 2206).

Efficacy of Local Treatment in Lymph Node Metastasis from Hepatocellular Carcinoma.

Introduction: We aimed to investigate the significance of lymph node metastasis from hepatocellular carcinoma and the efficacy of local treatment. Methods: We included patients diagnosed hepatocellular carcinoma with lymph node metastasis. The pattern of lymph node metastasis was evaluated based on imaging examinations and stratified by three locations: regional (group A), beyond regional intra-abdomen (group B), and extra-abdomen (group C) lymph node metastasis. Results: Among 14,474 patients, 852 (5.8%) were identified as having lymph node metastasis. Regarding the location of presentation, group A showed the highest incidence, followed by groups B and C. The 1-year overall survival of patients was 31.7%. The survival significantly differed according to the location of lymph node metastasis. The 1-year overall survival rates were 39.8%, 25.5%, and 22.2% in groups A, B, and C, respectively. All patients underwent systemic treatment, with others receiving additional local treatment. Local treatment yielded superior overall survival compared with no local treatment. After propensity score matching, local treatment was associated with improved survival. Additionally, patients were stratified based on disease status at the time of diagnosis of lymph node metastasis: lymph node alone and combined extra-nodal metastasis. The survival benefits of local treatment were observed in both groups. Conclusions: Our findings demonstrated the clinical significance of lymph node metastasis from hepatocellular carcinoma, which was well discriminated according to location, favoring regional metastasis. In patients with hepatocellular carcinoma presenting lymph node metastasis, active application of local treatment for lymph node metastasis can improve oncologic outcomes.

Radiotherapy in recurrent ovarian cancer: updated results of involved-field radiation therapy.

OBJECTIVE: This study aimed to update the possible clinical benefits of radiation therapy in recurrent ovarian cancer. METHODS: The medical records of 495 patients with recurrent ovarian cancer after initially undergoing maximal cytoreductive surgery and adjuvant platinum-based chemotherapy based on the pathologic stage between January 2010 and December 2020 were analyzed: 309 and 186 patients were treated without and with involved-field radiation therapy, respectively. Involved-field radiation therapy is defined as radiation therapy only to the areas of the body involved by tumor. The prescribed doses were ≥45 Gy (equivalent dose in 2 Gy/fraction). Overall survival was compared between patients treated with and without involved-field radiation therapy. The favorable group was defined as patients who satisfied at least four of the following factors: good performance, no ascites, normal CA-125, platinum-sensitive tumor, and nodal recurrence. RESULTS: The median age of the patients was 56 years (range 49-63) and median time to recurrence was 11.1 months (range 6.1-15.5). 217 patients (43.8%) were treated at a single site. Radiation therapy, performance status, CA-125, platinum sensitivity, residual disease, and ascites were all significant prognostic factors. The 3-year overall survival of all patients, patients treated without radiation therapy, and patients treated with radiation therapy was 54.0%, 44.8%, and 69.3%, respectively. Radiation therapy was associated with higher overall survival rates in the unfavorable and favorable patient groups. Patient characteristics showed higher rates of normal CA-125, lymph node metastasis only, lower platinum sensitivity, and higher rates of ascites in the radiation therapy group. After propensity score matching, the radiation therapy group showed superior overall survival to the non-radiation therapy group. Normal CA-125, good performance status, and platinum sensitivity were associated with a good prognosis in patients treated with radiation therapy. CONCLUSION: Our study showed that higher overall survival was observed in patients treated with radiation therapy in recurrent ovarian cancer.

A Pulsed Electric Field Accelerates the Mass Transfer during the Convective Drying of Carrots: Drying and Rehydration Kinetics, Texture, and Carotenoid Content.

The pulsed electric field (PEF) is a non-thermal food processing technology that induces electroporation of the cell membrane thus improving mass transfer through the cell membrane. In this study, the drying and rehydration kinetics, microstructure, and carotenoid content of carrot (Daucus carota) pretreated by PEF during convective drying at 50 °C were investigated. The PEF treatment was conducted with different field strengths (1.0-2.5 kV/cm) using a fixed pulse width of 20 µs and at a pulse frequency of 50 Hz. The PEF 2.5 kV/cm showed the shortest drying time, taking 180 min, whereas the control required 330 min for the same moisture ratio, indicating a 45% reduction in drying time. The rehydration ability also increased as the strengths of PEF increased. PEF 2.5 kV/cm resulted in 27.58% increase in moisture content compared to the control after rehydration (1 h). Three mathematical models were applied to the drying and rehydration data; the Page and Peleg models were selected as the most appropriate models to describe the drying and rehydration kinetics, respectively. The cutting force of the sample was decreased as the strength of PEF increased, and a more homogeneous cellular structure was observed in the PEF pretreatment group. The reduction in drying time by PEF was beneficial to the carotenoid content, and PEF 2.5 kV/cm showed the highest preservation content of carotenoid. Overall, these results suggested that the pretreatment of PEF and the drying and rehydration rate influence the quality of products, functional components, and cellular structure.

High energy dissipation-based process to improve the rheological properties of bentonite drilling muds by reducing the particle size.

Drilling mud is a multi-phase fluid that is used in the petroleum drilling process. Bentonite is the most important constituent of drilling mud; it endows the drilling mud with its rheological behaviors, such as viscosity, yield stress, and shear thinning. The process of manufacturing microscale bentonite at the nanoscale level is very promising for commercializing nano-based drilling mud. In contrast to the conventional method using the impeller, bentonite was manufactured in its nanoparticle state in the present work through ultrasonic and homogenizer processes in the solution state. In case of the ultrasonic process, the viscosity increase in the low shear rate region before and after processing of the 5 wt% bentonite-based mud and the rheological properties in the presence of polymer additive were compared. In case of the homogenizer process, the rheological properties of 3 wt% bentonite-based mud employed through the homogenizer process and 5 wt% mud prepared generally were compared. Both processes reported improvement of rheological properties, in which shear thinning behavior strongly occurred when particle size decreased through FE-SEM, TEM image analysis, and particle size analyzer. A regularized Herschel-Bulkley model suitable for rheological quantitative explanation of drilling mud including yield stress was selected. The homogenizer process has the potential to be applied in the petroleum drilling industry for large-scale production, and the mechanism was confirmed by numerical analyses. In conclusion, we presented a simple and easy-to-apply process to rapidly produce nano-based drilling mud.

Importance of Local Ablative Therapies for Lung Metastases in Patients With Colorectal Cancer.

OBJECTIVE: To assess the effect of local ablative therapy (LAT) on overall survival in patients with lung metastases from colorectal cancer (CRC) compared with patients treated with systemic therapy. SUMMARY BACKGROUND DATA: CRC affects approximately 1.4 million individuals worldwide every year. The lungs are commonly affected by CRC, and there is no treatment standard for a secondary lung metastasis from CRC. METHODS: This longitudinal, retrospective cohort study (2010-2018) quantified the pulmonary and extrapulmonary tumor burden of 1143 patients by retrospectively reviewing computed tomography images captured at diagnosis. A comprehensive multidisciplinary approach informed how and when surgery and/or stereotactic body radiotherapy was administered. RESULTS: Among 1143 patients, 473 patients (41%) received LAT, with surgery first (n = 421) or stereotactic ablative radiation therapy first (n = 52) either at the time of diagnosis (n = 288), within 1 year (n = 132), or after 1 year (n = 53). LAT was repeated in 158 patients (33.4%, 384 total sessions) when new lung metastases were detected. The 5- and 10-year survival rates for patients treated with LAT (71.2% and 64.0%, respectively) were significantly higher than those of patients treated with systemic therapy alone (14.2% and 10.0%, respectively; P <0.001). The overall survival of patients who received LAT intervention increased as the total tumor burden decreased. CONCLUSIONS: A high long-term survival rate was achievable in a significant portion of patients with lung metastasis from CRC by the timely administrations of LAT to standard systemic therapy. The tumor burden and LAT feasibility should be included in a discussion during the follow-up period.

Automated Computer-Aided Detection of Lung Nodules in Metastatic Colorectal Cancer Patients for the Identification of Pulmonary Oligometastatic Disease.

PURPOSE: This study aimed to explore the possibility and clinical utility of existing artificial intelligence (AI)-based computer-aided detection (CAD) of lung nodules to identify pulmonary oligometastases. PATIENTS AND METHODS: The chest computed tomography (CT) scans of patients with lung metastasis from colorectal cancer between March 2006 and November 2018 were analyzed. The patients were selected from a database of 1395 patients and studied in 2 cohorts. The first cohort included 50 patients, and the CT scans of these patients were independently evaluated for lung-nodule (≥3 mm) detection by a CAD-assisted radiation oncologist (CAD-RO) as well as by an expert radiologist. Interobserver variability by 2 additional radiation oncologists and 2 thoracic surgeons were also measured. In the second cohort of 305 patients, survival outcomes were evaluated based on the number of CAD-RO-detected nodules. RESULTS: In the first cohort, the sensitivity and specificity of the CAD-RO for identifying oligometastatic disease (OMD) from varying criteria by ≤2 nodules, ≤3 nodules, ≤4 nodules, and ≤5 nodules were 71.9% and 88.9%, 82.9% and 93.3%, 97.1% and 73.3%, and 97.5% and 90.0%, respectively. The sensitivity of the CAD-RO in the nodule detection compared with the radiologist was 81.6%. The average (standard deviation) sensitivity in interobserver variability analysis was 80.0% (3.7%). In the second cohort, the 5-year survival rates of patients with 1, 2, 3, 4, or ≥5 metastatic nodules were 75.2%, 52.9%, 45.7%, 29.1%, and 22.7%, respectively. CONCLUSIONS: Proper identification of the pulmonary OMD and the correlation between the number of CAD-RO-detected nodules and survival suggest the potential practicality of AI in OMD recognition. Developing a deep learning-based model specific to the metastatic setting, which enables a quick estimation of disease burden and identification of OMD, is underway.

Significance of mid-radiotherapy 18F-fluorodeoxyglucose positron emission tomography/computed tomography in esophageal cancer.

BACKGROUND AND PURPOSE: Metabolic parameters evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) are known as prognostic markers in various cancers. We aimed to validate the predictive value of mid-radiotherapy (RT) FDG PET/CT parameters in esophageal cancer. MATERIALS AND METHODS: Eighty-three patients treated with RT with or without chemotherapy between 2015 and 2020 were included. PET parameters including metabolic tumor volume (MTV), total lesion glycolysis, and mean (SUVmean) and maximum standardized uptake value (SUVmax) were analyzed. Locoregional recurrence-free rate (LRFR) and distant metastasis-free rate (DMFR) were analyzed. RESULTS: The median follow-up period was 10.5 months. Mid-RT SUVmax was significantly associated with LRFR (HR 1.07, p = 0.009) and DMFR (HR 1.13, p = 0.047) while mid-RT MTV was associated with DMFR (HR 1.06, p = 0.007). Treatment response after RT was associated with overall survival (HR, 1.52, p = 0.025). Further, treatment response was significantly associated with mid-RT SUVmax. The optimal cutoff value for mid-RT SUVmax in predicting LRFR and DMFR was 11 while cutoff value for mid-RT MTV was 15. The patients with mid-RT SUVmax ≤ 11 showed superior LRFR and DMFR compared to SUVmax > 11 (1-year LRFR; 73.4% vs. 48.4%, p = 0.028, 1-year DMFR; 74.6% vs. 40.7%, p = 0.007). The 1-year DMFR was significantly different between patients with mid-RT MTV ≤ 15 and >15 (1-year DMFR; 78.2% vs. 31.9%, p = 0.002). CONCLUSION: Tumor metabolism changes during RT can be a useful predictive tool for treatment response and recurrence in patients with esophageal cancer. Clinicians may consider early response evaluation with PET during RT for predicting prognosis information about prognosis.

Association between Skeletal Muscle Loss and the Response to Neoadjuvant Chemotherapy for Breast Cancer.

There are no means to predict patient response to neoadjuvant chemotherapy (NAC); the impact of skeletal muscle loss on the response to NAC remains undefined. We investigated the association between response to chemotherapy and skeletal muscle loss in breast cancer patients. Patients diagnosed with invasive breast cancer who were treated with NAC, surgery, and radiotherapy were analyzed. We quantified skeletal muscle loss using pre-NAC and post-NAC computed tomography scans. The response to treatment was determined using the Response Evaluation Criteria in Solid Tumors. We included 246 patients in this study (median follow-up, 28.85 months). The median age was 48 years old (interquartile range 42-54) and 115 patients were less than 48 years old (46.7%). Patients showing a complete or partial response were categorized into the responder group (208 patients); the rest were categorized into the non-responder group (38 patients). The skeletal muscle mass cut-off value was determined using a receiver operating characteristic curve; it showed areas under the curve of 0.732 and 0.885 for the pre-NAC and post-NAC skeletal muscle index (p < 0.001 for both), respectively. Skeletal muscle loss and cancer stage were significantly associated with poor response to NAC in locally advanced breast cancer patients. Accurately measuring muscle loss to guide treatment and delaying muscle loss through various interventions would help enhance the response to NAC and improve clinical outcomes.

Radiotherapy as an immune checkpoint blockade combination strategy for hepatocellular carcinoma.

In the immune oncology era, the clinical efficacy of immune checkpoint inhibitors (ICIs) against most solid cancers is well known. In hepatocellular carcinoma, the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies. Radiotherapy (RT), an attractive modality, can be combined with ICIs, which act as strong modulators of the tumor immune microenvironment. Herein, we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.

Long-term survival after multimodal treatment involving radiotherapy for huge hepatocellular carcinoma with oligometastasis: a case report.

The clinical efficacy of local ablative treatment for oligometastasis is widely accepted in most cancers. However, due to limited data, this has not been the case for hepatocellular carcinoma (HCC). Here, we report a case of pulmonary oligometastasis of a huge HCC that was treated by multimodality with liver-directed concurrent chemoradiotherapy (CCRT) plus subsequent resection of the primary lesion and local ablative radiotherapy (RT) for subsequent lung oligometastatic lesions. In this patient, liver-directed CCRT induced significant tumor shrinkage with compensatory hypertrophy of the non-tumor liver, followed by curative resection. Surgical resection of the first and second pulmonary metastatic lesions as well as local ablative RT of the third lesion achieved complete tumor regression, which led to long-term survival of 6 years. Therefore, the active use of local ablative RT requires full consideration in cases of oligometastatic HCC.

Prognostic Significance of Sarcopenia in Advanced Biliary Tract Cancer Patients.

Background: Sarcopenia, systemic inflammation, and low muscularity significantly impact the survival of cancer patients. However, few studies have investigated how sarcopenia and systemic inflammation affect the prognosis of biliary tract cancer with distant metastasis. In this study, we investigated the association between sarcopenia with systemic inflammation and prognosis of metastatic biliary tract cancer. Materials and Methods: Data collected from 353 metastatic biliary tract cancer patients from 2007 to 2016 were analyzed. To evaluate the skeletal muscle mass, computed tomography images at the upper level of the third lumbar vertebra (L3) were used. Sarcopenia was defined using the Japan Society of Hepatology guideline; L3 muscle index <42 cm2/m2 for male and <38 cm2/m2 for female patients. Systemic inflammation was evaluated using the neutrophil lymphocyte ratio (NLR). Patients with NLR > 3 were categorized into the inflammatory category. The overall survival (OS) and progression free survival (PFS) were analyzed. Subgroup analysis was performed on those who received gemcitabine/cisplatin (GP) chemotherapy and depending on the presence of sarcopenia and inflammation. Results: Patients with sarcopenia showed lesser 1-year OS than those without (25.5 vs. 38.2%, p = 0.019). The patients with high NLR (NLR > 3) were associated with a shorter OS than were those with a low NLR (NLR ≤ 3) (21.0 vs. 52.8%, p < 0.001). Based on these results, we categorized the patients into three groups; sarcopenia accompanied by high NLR, no sarcopenia and low NLR, and either sarcopenia or high NLR. The OS of patients was well-stratified according to this grouping (1-year OS; 18.3 vs. 30.3 vs. 55.8%, p < 0.001). Concordant with OS results, the PFS was well-stratified based on the presence of either sarcopenia or high NLR (Sarcopenia; 9.5 vs. 19.4%, p < 0.001, NLR; 10.0 vs. 23.4%, p < 0.001). The PFS was significantly associated with high NLR and sarcopenia (1-year PFS; 7.8 vs. 13.0 vs. 27.9%, p < 0.001). Conclusion: Sarcopenia with inflammation was associated with inferior OS and PFS. In addition, sarcopenia accompanied by inflammation was associated with poor prognosis. Conservative treatments such as nutritional support, exercise, and pharmacologic intervention could help metastatic biliary tract cancer patients to overcome sarcopenia and the inflammatory status.

Significance of lymphocyte recovery from treatment-related lymphopenia in locally advanced pancreatic cancer.

BACKGROUND AND PURPOSE: Radiation-induced lymphopenia is associated with poor prognosis in resected pancreatic cancer and locally advanced pancreatic cancer. However, whether lymphocyte recovery contributes to pancreatic cancer prognosis has not been well-investigated. MATERIALS AND METHODS: We evaluated 497 locally advanced pancreatic cancer patients who underwent concurrent chemoradiotherapy (CCRT). Complete blood counts of patients were obtained before, during, and after CCRT until the 12-month follow-up visit. Patients were categorized into 3 groups according to the development of and recovery from acutte severe lymphopenia (ASL): no ASL (group A, n = 198), recovery from ASL (group B, n = 141), and no recovery from ASL (group C, n = 89). Prognostic factors of overall survival (OS) and progression-free survival (PFS) were determined using Cox regression analyses. RESULTS: In groups A, B, and C, the 2-year OS rates were 40.4%, 31.9%, and 14.6%, respectively, and the 2-year PFS rates were 23.7%, 18.4%, and 10.1%, respectively. OS and PFS were comparable between Groups A and B, while group C had poor OS and PFS (p < 0.001). Recovery from ASL was associated with superior OS (HR 0.42, 95% CI: 0.32-0.55, p < 0.001) and PFS (HR 0.53, 95% CI: 0.41-0.70, p < 0.001). The baseline lymphocyte counts and target volume independently predicted development and recovery from ASL. CONCLUSION: Recovery from ASL was associated with both superior OS and PFS in patients who received CCRT for locally advanced pancreatic cancer. Baseline lymphocyte counts and target volume were associated with both the development of and recovery from treatment-related ASL.

Hypofractionated Radiotherapy Dose Scheme and Application of New Techniques Are Associated to a Lower Incidence of Radiation Pneumonitis in Breast Cancer Patients.

Purpose: Radiation pneumonitis (RP) is one of the most severe toxicities experienced by patients with breast cancer after radiotherapy (RT). RT fractionation schemes and techniques for breast cancer have undergone numerous changes over the past decades. This study aimed to investigate the incidence of RP as a function of such changes in patients with breast cancer undergoing RT and to identify dosimetric markers that predict the risk of this adverse event. Methods and Materials: We identified 1,847 women with breast cancer who received adjuvant RT at our institution between 2015 and 2017. The RT technique was individually tailored based on each patient's clinicopathological features. Deep inspiration breath hold technique or prone positioning were used for patients who underwent left whole-breast irradiation for cardiac sparing, while those requiring regional lymph node irradiation underwent volumetric-modulated arc therapy (VMAT). Results: Of 1,847 patients who received RT, 21.2% received the conventional dose scheme, while 78.8% received the hypofractionated dose scheme (mostly 40 Gy in 15 fractions). The median follow-up period was 14.5 months, and the overall RP rate was 2.1%. The irradiated organ at risk was corrected concerning biologically equivalent dose. The ipsilateral lung V30 in equivalent dose in 2 Gy (EQD2) was the most significant dosimetric factor associated with RP development. Administering RT using VMAT, and hypofractionated dose scheme significantly reduced ipsilateral lung V30. Conclusions: Application of new RT techniques and hypofractionated scheme significantly reduce the ipsilateral lung dose. Our data demonstrated that ipsilateral lung V30 in EQD2 is the most relevant dosimetric predictor of RP in patients with breast cancer.

External validation of IBTR! 2.0 nomogram for prediction of ipsilateral breast tumor recurrence.

PURPOSE: IBTR! 2.0 nomogram is web-based nomogram that predicts ipsilateral breast tumor recurrence (IBTR). We aimed to validate the IBTR! 2.0 using an external data set. Materials and. METHODS: The cohort consisted of 2,206 patients, who received breast conserving surgery and radiation therapy from 1992 to 2012 at our institution, where wide surgical excision is been routinely performed. Discrimination and calibration were used for assessing model performance. Patients with predicted 10-year IBTR risk based on an IBTR! 2.0 nomogram score of <3%, 3%-5%, 5%-10%, and >10% were assigned to groups 1, 2, 3, and 4, respectively. We also plotted calibration values to observe the actual IBTR rate against the nomogram-derived 10-year IBTR probabilities. RESULTS: The median follow-up period was 73 months (range, 6 to 277 months). The area under the receiver operating characteristic curve was 0.607, showing poor accordance between the estimated and observed recurrence rate. Calibration plot confirmed that the IBTR! 2.0 nomogram predicted the 10-year IBTR risk higher than the observed IBTR rates in all groups. High discrepancies between nomogram IBTR predictions and observed IBTR rates were observed in overall risk groups. Compared with the original development dataset, our patients had fewer high grade tumors, less margin positivity, and less lymphovascular invasion, and more use of modern systemic therapies. Conclusions: IBTR! 2.0 nomogram seems to have the moderate discriminative ability with a tendency to over-estimating risk rate. Continued efforts are needed to ensure external applicability of published nomograms by validating the program using an external patient population.

The Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Are Prognostic Factors in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiotherapy.

BACKGROUND/AIMS: We investigated whether inflammatory markers such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) independently and in combination would be significant prognostic factors for survival in patients with locally advanced pancreatic cancer. METHODS: A total of 497 patients with locally advanced pancreatic cancer who received neoadjuvant or definitive chemoradiotherapy from 2005 to 2015 were evaluated. We divided the patients into groups according to the median values of NLR and PLR: NLR＜1.89 (n=156), NLR≥1.89 (n=341), PLR ＜149 (n=248) and PLR ≥149 (n=249). RESULTS: For NLR ＜1.89 and ≥1.89 groups, respectively, the 1-year overall survival (OS) rates were 73.2% and 60.8% (p＜0.001) and 1-year progression-free survival (PFS) rates were 43.9% and 31.3% (p＜0.001). For PLR ＜149 and ≥149 groups, respectively, the 1-year OS rates were 68.1% and 61.3% (p=0.029) and 1-year PFS rates were 37.9% and 32.5% (p=0.027). Patients with both high NLR and high PLR showed the worst OS and PFS rates compared with those with both lower NLR and lower PLR. CONCLUSIONS: Elevated pretreatment NLR and PLR independently and in combination significantly predicted poor OS and PFS.