Reactivation of the hepatitis B virus (HBV) is a well-recognized complication in patients with chronic HBV infection who receive cytotoxic or other immunosuppressive therapy. In cases of patients treated by radiotherapy however, only a few of such reports exist and most of these include the patients previously treated by chemotherapy or transarterial chemoembolization. The results of this study point to a case of a patient with reactivation of HBV after radiotherapy alone. This study shows the possibility of HBV reactivation by partial hepatic irradiation alone hence, special attention should be paid to patients with HBV disease.
Hepatitis ; Hepatitis B ; Hepatitis B virus ; Humans ; Liver

PURPOSE: To develop the dose volume histogram (DVH) management software which guides the evaluation of radiotherapy (RT) plan of a new case according to the biological consequences of the DVHs from the previously treated patients. MATERIALS AND METHODS: We determined the radiation pneumonitis (RP) as an biological response parameter in order to develop DVH management software. We retrospectively reviewed the medical records of lung cancer patients treated with curative 3-dimensional conformal radiation therapy (3D-CRT). The biological event was defined as RP of the Radiation Therapy Oncology Group (RTOG) grade III or more. RESULTS: The DVH management software consisted of three parts (pre-existing DVH database, graphical tool, and Pinnacle3 script). The pre-existing DVH data were retrieved from 128 patients. RP events were tagged to the specific DVH data through retrospective review of patients' medical records. The graphical tool was developed to present the complication histogram derived from the pre-existing database (DVH and RP) and was implemented into the radiation treatment planning (RTP) system, Pinnacle3 v8.0 (Phillips Healthcare). The software was designed for the pre-existing database to be updated easily by tagging the specific DVH data with the new incidence of RP events at the time of patients' follow-up. CONCLUSION: We developed the DVH management software as an effective tool to incorporate the phenomenological consequences derived from the pre-existing database in the evaluation of a new RT plan. It can be used not only for lung cancer patients but also for the other disease site with different toxicity parameters.
Humans ; Incidence ; Lung Neoplasms ; Medical Records ; Radiation Pneumonitis ; Retrospective Studies

The funding acknowledgment in this article was partially omitted as published.

PURPOSE: Definitive high dose thoracic radiation therapy (TRT) alone in stage III non-small cell lung cancer (NSCLC) has resulted in only modest survival gains that are far from satisfaction. When using conventional fractionation schedules, which usually last for about 7 weeks, issues relating to the cost versus the benefit ratio are raised, including the treatment costs, protracted side effects and inconvenience to patients and family, especially if they reside in a remote district from the hospital. A retrospective analyses on the stage III NSCLC patients who received definitive high dose TRT alone, in 3 Gy per fractions lasting less than 4 weeks, were performed. MATERIALS AND METHODS: Between October 1994 and June 2001, 82 NSCLC patients were given definitive high dose TRT alone, in 3 Gy fractions, at Samsung Medical Center. Of these patients 37 (45.1%) had a stage IIIA and 45 (54.9%) had a IIIB disease. Squamous cell carcinomas were the most common (65.9%) pathology followed by adenocarcinomas (23.2%). External beam radiation therapy (ERT) alone was employed in 61 patients (74.4%), with additional high dose rate endobronchial brachytherapy (EBB) in 21 patients (25.6%). The TRT was typically started with the AP/PA technique using 10 MV X-rays for 30 Gy, and then a computerized CT plan was performed to keep the total spinal cord dose below 40 Gy. The median total TRT dose was 54 Gy/18 fractions (range: 39-60 Gy). RESULTS: The median age was 68 years (43-84), with a male to female ratio of 4.9/1. After a median follow-up of 10 months (1~72), 31 (37.8%) and 24 (29.3%) developed local in-field failures and distant metastases, respectively, with the lung being the most common site (12, 38.7%). The median and overall survivals at 1-, 2-, 3- and 4-year were 10 months and 45.9, 19.4, 12.9 and 9.7%, respectively. The median relapse-free survival was 13.0 months, and relapse-free survival rates at 1-, 2-, 3-, and 4-year were 51.9, 23.3, 11.6 and 7.3%, respectively. From a univariate analysis, the performance status (p= 0.0366) and radiotherapy response (p=0.0323) were significant on the overall survival, gender (p=0.0329) and response (p=0.0107) on the relapse free survival, and histology (p=0.0466) on the local relapse. From a multivariate analysis, the nodal status, radiotherapy response and mediastinal radiation dose were significant prognostic factors on both the relapse free survival and local control. Treatment related morbidities were observed in 75 patients (91.5%), 10 of whom had grade 3 or 4 complications (12.2%), with esophagitis being the most common (73 patients). Symptomatic radiation pneumonitis occurred in 20 patients (24.4%), with 17 requiring steroid medication and a further 1 each required mechanical dilatation for an esophageal stricture and tracheal stenosis. CONCLUSION: Based on the above results, definitive high dose TRT in 3.0 Gy per fractions was adjudged to be comparable to TRT using the conventional fractionation schedules reported in the literature, with the advantages of shorter treatment duration and less overall cost
Adenocarcinoma ; Appointments and Schedules ; Brachytherapy ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Dilatation ; Esophageal Stenosis ; Esophagitis ; Female ; Follow-Up Studies ; Health Care Costs ; Humans ; Lung ; Male ; Multivariate Analysis ; Neoplasm Metastasis ; Pathology ; Radiation Pneumonitis ; Radiotherapy ; Recurrence ; Retrospective Studies ; Spinal Cord ; Survival Rate ; Tracheal Stenosis

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

PURPOSE: This study was conducted to evaluate clinical outcomes following definitive concurrent chemoradiotherapy (CCRT) for patients with N3-positive stage IIIB (N3-IIIB) non-small cell lung cancer (NSCLC), with a focus on radiation therapy (RT) techniques. MATERIALS AND METHODS: From May 2010 to November 2012, 77 patients with N3-IIIB NSCLC received definitive CCRT (median, 66 Gy). RT techniques were selected individually based on estimated lung toxicity, with 3-dimensional conformal RT (3D-CRT) and intensity-modulated RT (IMRT) delivered to 48 (62.3%) and 29 (37.7%) patients, respectively. Weekly docetaxel/paclitaxel plus cisplatin (67, 87.0%) was the most common concurrent chemotherapy regimen. RESULTS: The median age and clinical target volume (CTV) were 60 years and 288.0 cm3, respectively. Patients receiving IMRT had greater disease extent in terms of supraclavicular lymph node (SCN) involvement and CTV > or = 300 cm3. The median follow-up time was 21.7 months. Fortyfive patients (58.4%) experienced disease progression, most frequently distant metastasis (39, 50.6%). In-field locoregional control, progression-free survival (PFS), and overall survival (OS) rates at 2 years were 87.9%, 38.7%, and 75.2%, respectively. Although locoregional control was similar between RT techniques, patients receiving IMRT had worse PFS and OS, and SCN metastases from the lower lobe primary tumor and CTV > or = 300 cm3were associated with worse OS. The incidence and severity of toxicities did not differ significantly between RT techniques. CONCLUSION: IMRT could lead to similar locoregional control and toxicity, while encompassing a greater disease extent than 3D-CRT. The decision to apply IMRT should be made carefully after considering oncologic outcomes associated with greater disease extent and cost.
Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy* ; Cisplatin ; Disease Progression ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Incidence ; Lung ; Lymph Nodes ; Neoplasm Metastasis ; Radiotherapy, Intensity-Modulated

PURPOSE: This study was conducted to evaluate the treatment outcomes following definitive bimodality concurrent chemoradiotherapy (CCRT) in patients with inoperable N2-positive stage IIIA (N2-IIIA) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From May 1997 to December 2012, 65 out of 633 patients with N2-IIIA NSCLC received bimodality therapy. The treatment modality was selected during/after neoadjuvant CCRT in 21 patients or primarily at diagnosis in 44 through a multidisciplinary consensus meeting. The median age was 65 years (range, 36 to 76 years). Sixty patients (92.3%) had clinically evident N2 disease, while 22 (33.8%) had multi-station N2 involvement. The median radiation therapy dose was 66 Gy in 33 fractions, while the dose was elevated to 72 Gy in 13 patients who had a treatment break due to delayed decision regarding resectability. The most frequent chemotherapy regimen was weekly paclitaxel or docetaxel plus cisplatin or carboplatin (54, 83.1%). RESULTS: During the median follow-up of 18.8 months (range, 1.6 to 173.1 months), 34 patients (52.3%) experienced disease progression, with distant metastasis being the most common first treatment failure pattern (23, 34.8%). The median and 2-year rates of progression-free survival were 18.8 months and 45.9%, respectively. The median and 2-year rates of overall survival were 28.6 months and 50.1%, respectively. CONCLUSION: Definitive bimodality therapy in patients with N2-IIIA NSCLC demonstrated favorable outcomes, while trimodality therapy could be considered for candidates for less than pneumonectomy.
Carboplatin ; Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy* ; Cisplatin ; Consensus ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Paclitaxel ; Pneumonectomy ; Treatment Failure