Investigation of Stem Cell-Like Characteristics and Immune Cell Interaction of Tumor Cells Survived from Continuous Shear Flow Environment.

When tumor cells are released from a primary tumor into the bloodstream or lymphatic circulation system, they are exposed to a continuous shear flow environment. This environment exerts physical stresses on the tumor cells, which can activate apoptotic pathways. However, certain tumor cells have the ability to adapt to these mechanical stresses, enhancing their likelihood of survival and promoting metastasis. In this study, these tumor cells survived from shear flow environment are examined and revealed to closely link to stem cell-like characteristics. Higher gene expression levels of self-renewal and differentiation markers and enhanced abilities of migration, spheroid formation, and colony formation are shown. Moreover, the interaction between immune cells and the surviving cells is investigated. The results show that the surviving cells possess immune escape capabilities, implying their ability to evade immune surveillance. Additionally, these surviving cells display characteristics reminiscent of stem cells. This study holds great importance in advancing the understanding of tumor biology. By comprehending the behavior and properties of these surviving cells, new therapeutic strategies can be developed to specifically target circulating tumor cells (CTCs) and enhance cancer treatment outcomes.

Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study.

INTRODUCTION: Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). METHODS: We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2 h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. RESULTS: In mouse GBM model, the survival analysis showed RT-FUS (2 Gy) group was significantly longer than RT (2 Gy) group and control, but not RT (5 Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33 days after RT-FUS, while another three patients had at least stable disease (mean 323 days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. CONCLUSION: Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.

A Review on Microfluidics-Based Impedance Biosensors.

Electrical impedance biosensors are powerful and continuously being developed for various biological sensing applications. In this line, the sensitivity of impedance biosensors embedded with microfluidic technologies, such as sheath flow focusing, dielectrophoretic focusing, and interdigitated electrode arrays, can still be greatly improved. In particular, reagent consumption reduction and analysis time-shortening features can highly increase the analytical capabilities of such biosensors. Moreover, the reliability and efficiency of analyses are benefited by microfluidics-enabled automation. Through the use of mature microfluidic technology, complicated biological processes can be shrunk and integrated into a single microfluidic system (e.g., lab-on-a-chip or micro-total analysis systems). By incorporating electrical impedance biosensors, hand-held and bench-top microfluidic systems can be easily developed and operated by personnel without professional training. Furthermore, the impedance spectrum provides broad information regarding cell size, membrane capacitance, cytoplasmic conductivity, and cytoplasmic permittivity without the need for fluorescent labeling, magnetic modifications, or other cellular treatments. In this review article, a comprehensive summary of microfluidics-based impedance biosensors is presented. The structure of this article is based on the different substrate material categorizations. Moreover, the development trend of microfluidics-based impedance biosensors is discussed, along with difficulties and challenges that may be encountered in the future.

Neuropsychological performances in patients with infiltrative non-GBM gliomas after postoperative adjuvant photon or proton radiotherapy: A prospective and preliminary investigation.

Infiltrative non-GBM gliomas are common primary intracranial malignancies, and postoperative adjuvant radiotherapy is recommended for most adult patients diagnosed with this disease to enhance local control and prolong intracranial progression-free survival (PFS). However, RT-related neurocognitive function (NCF) consequences should not be ignored. Early neurocognitive decline principally includes episodic memory, associated significantly with functions of the hippocampus. This prospective study aims to investigate the impact of adjuvant brain irradiation on neurocognitive performances and relevant oncological outcomes.Twenty-five patients with intracranial infiltrative non-GBM gliomas were enrolled when postoperative adjuvant RT was recommended. All recruited patients should receive baseline brain magnetic resonance imaging, and neuropsychological assessments before and 4 months after the RT course. A battery of neuropsychological measures, mainly including executive functions, memory, psychomotor speed and visuoconstructive ability, was used to evaluate NCFs of interest.Analyzing the delta values between post-irradiation and baseline NCF scores, we observed a robust trend reflecting cognitive stabilization rather than deterioration in almost all NCF. Both verbal and visual memory functions exhibited significant differences in the corresponding scaled scores (Z = -2.722, p = .006, regarding verbal memory; Z = -2.246, p = .025, concerning non-verbal memory). Moreover, patients' neuropsychological performances associated with psychomotor speed and executive functions also disclosed a tendency toward stabilization/improvement.This prospective study demonstrated that patients with infiltrative non-GBM exhibited a marked tendency toward neurocognitive stabilization after receiving postoperative adjuvant RT. Clinical trial registration: Trial Registration with ClinicalTrials.gov identifier: NCT03534050.

Salvage Boron Neutron Capture Therapy for Malignant Brain Tumor Patients in Compliance with Emergency and Compassionate Use: Evaluation of 34 Cases in Taiwan.

Although boron neutron capture therapy (BNCT) is a promising treatment option for malignant brain tumors, the optimal BNCT parameters for patients with immediately life-threatening, end-stage brain tumors remain unclear. We performed BNCT on 34 patients with life-threatening, end-stage brain tumors and analyzed the relationship between survival outcomes and BNCT parameters. Before BNCT, MRI and 18F-BPA-PET analyses were conducted to identify the tumor location/distribution and the tumor-to-normal tissue uptake ratio (T/N ratio) of 18F-BPA. No severe adverse events were observed (grade ≥ 3). The objective response rate and disease control rate were 50.0% and 85.3%, respectively. The mean overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) times were 7.25, 7.80, and 4.18 months, respectively. Remarkably, the mean OS, CSS, and RFS of patients who achieved a complete response were 17.66, 22.5, and 7.50 months, respectively. Kaplan-Meier analysis identified the optimal BNCT parameters and tumor characteristics of these patients, including a T/N ratio ≥ 4, tumor volume < 20 mL, mean tumor dose ≥ 25 Gy-E, MIB-1 ≤ 40, and a lower recursive partitioning analysis (RPA) class. In conclusion, for malignant brain tumor patients who have exhausted all available treatment options and who are in an immediately life-threatening condition, BNCT may be considered as a therapeutic approach to prolong survival.

Characterization of stem cell-like property in cancer cells based on single-cell impedance measurement in a microfluidic platform.

Investigation of stem cell-like property in cancer cells is important for the development of new therapeutic drugs targeting at malignant tumors. Currently, the standard approach for identifying cancer stem cell-like cells relies on the recognition of stem cell surface markers. However, the reliability remains controversial among biologists. In the current work, a dielectrophoretic and impedimetric hybrid microfluidic platform was developed for capturing single cells and characterizing their stem cell-like property. Single cells were captured in 20 µm trapping wells by dielectrophoretic force and their impedance spectra were measured by an impedance analyzer. The result showed that different cancer cell lines could be differentiated by impedance magnitude ranging between 2 and 20 kHz. Moreover, cancer cells and cancer stem cell-like cells could be categorized by a 2-dimensional graph of the impedance magnitudes at 2 and 20 kHz. The stem cell-like property in cancer cells was verified by stem cell surface markers and single-cell derived colony assay. Comparing with bio-chemical approach, i.e., surface markers, bio-physical approach, i.e., cell impedance, is a label-free technique to identify cancer stem cell-like cells.

Oncological Outcomes After Hippocampus-Sparing Whole-Brain Radiotherapy in Cancer Patients With Newly Diagnosed Brain Oligometastases: A Single-Arm Prospective Observational Cohort Study in Taiwan.

BACKGROUND: Promisingly, the technique of hippocampus sparing during WBRT (HS-WBRT) might preserve NCFs. In this research, we examined oncological outcomes, with emphasis on neurologic/non-neurologic causes of death, CNS progression, and leptomeningeal disease (LMD) recurrence in cancer patients who underwent HS-WBRT. METHODS: One hundred and fourteen cancer patients with newly diagnosed brain oligometastases underwent HS-WBRT were consecutively enrolled. The cumulative incidence of cancer-specific deaths (neurologic or non-neurologic), LMD recurrence, and the composite endpoint of CNS progression (CNS-CE) as the first event were computed with a competing-risks approach to characterize the oncological outcomes after HS-WBRT. RESULTS: Patients with intact brain metastases had a significantly increased likelihood of dying from non-neurologic causes of death associated with early manifestation of progressive systemic disease (hazard ratio for non-neurologic death, 1.78; 95% CI, 1.08-2.95; p = 0.025; competing-risks Fine-Gray regression), which reciprocally rendered them unlikely to encounter LMD recurrence or any pattern of CNS progression (HR for CNS-CE as the first event, 0.13; 95% CI, 0.02-0.97; p = 0.047; competing-risks Fine-Gray regression). By contrast, patients with resection cavities post-craniotomy had reciprocally increased likelihood of CNS progression which might be associated with neurologic death eventually. CONCLUSIONS: Patterns of oncological endpoints including neurologic/non-neurologic death and cumulative incidence of CNS progression manifesting as LMD recurrence are clearly clarified and contrasted between patients with intact BMs and those with resection cavities, indicating they are clinically distinct subgroups. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02504788, NCT03223675.

Multi-Institutional Validation of Two-Streamed Deep Learning Method for Automated Delineation of Esophageal Gross Tumor Volume Using Planning CT and FDG-PET/CT.

BACKGROUND: The current clinical workflow for esophageal gross tumor volume (GTV) contouring relies on manual delineation with high labor costs and inter-user variability. PURPOSE: To validate the clinical applicability of a deep learning multimodality esophageal GTV contouring model, developed at one institution whereas tested at multiple institutions. MATERIALS AND METHODS: We collected 606 patients with esophageal cancer retrospectively from four institutions. Among them, 252 patients from institution 1 contained both a treatment planning CT (pCT) and a pair of diagnostic FDG-PET/CT; 354 patients from three other institutions had only pCT scans under different staging protocols or lacking PET scanners. A two-streamed deep learning model for GTV segmentation was developed using pCT and PET/CT scans of a subset (148 patients) from institution 1. This built model had the flexibility of segmenting GTVs via only pCT or pCT+PET/CT combined when available. For independent evaluation, the remaining 104 patients from institution 1 behaved as an unseen internal testing, and 354 patients from the other three institutions were used for external testing. Degrees of manual revision were further evaluated by human experts to assess the contour-editing effort. Furthermore, the deep model's performance was compared against four radiation oncologists in a multi-user study using 20 randomly chosen external patients. Contouring accuracy and time were recorded for the pre- and post-deep learning-assisted delineation process.

Analysis of a Cancer Stem Cell-Derived Single Colony Raised in a Microwell Array.

Cancer stem cells (CSCs) were reported to play important roles in cancer initialization, progression, and metastasis. In order to study the variation between CSCs and non-CSCs, single-cell analysis is conducted but technically complicated. In the current work, a microwell array made by an agarose hydrogel was developed for the study of a CSC-derived single colony. This approach is simple, convenient, and compatible with the setting and skill set of existing biological laboratories. Single cells, double cells, and multiple cells were distributed in the microwells. Isolation of CSCs could be achieved after a 5 day starvation culture course. Then, a CSC-derived single colony was formed by culturing the CSCs in a nutritious culture medium for another 5 days. The results revealed that a single CSC presented a high colony formation rate. Multiple cells containing CSCs and non-CSCs could raise a larger single colony than the multiple cells with CSCs only. Although CSCs possess an aggressive characteristic, development of a solid tumor requires the proactive involvement of non-CSCs. This work showed a practical demonstration of using a microwell array for the investigation of a CSC-derived single colony.

Treatment of Primary Central Nervous System Germinomas With Short-course Induction Chemotherapy Followed by Low-dose Radiotherapy Without a Tumor Bed Boost: Prognostic Impact of Human Chorionic Gonadotropin.

OBJECTIVE: To investigate the clinical utility of short-course induction chemotherapy followed by low-dose radiotherapy without a tumor bed boost in patients with primary central nervous system (CNS) germinomas. METHODS: We retrospectively reviewed the clinical records of patients with primary CNS germinomas who received short-course induction chemotherapy (2 cycles of cisplatin 20 mg/m2 plus etoposide 40 or 100 mg/m2 for 5 days) followed by low-dose radiotherapy (dose: 2340 cGy) without a tumor bed boost. Disease-free survival and overall survival served as the main outcome measures. RESULTS: Between February 2002 and June 2018, 24 patients (20 males and 4 females; median age: 14.1 y; age range: 7.9 to 21.2 y) with pathology-proven CNS germinomas were included. The median follow-up time was 106 months (range: 17 to 169 mo). Isolated and multifocal lesions were identified in 13 and 11 patients, respectively. Tumor location was as follows: pineal gland (n=17), suprasellar region (n=13), periventricular region (n=7), and basal ganglia (n=2). Five patients had increased levels (>5 mIU/mL) of beta-human chorionic gonadotropin (ß-hCG), whereas alpha-fetoprotein concentrations were within the reference range in all participants. A total of 16 patients achieved remission after induction chemotherapy. The complete response rates of patients with increased and normal ß-hCG levels were 40.0% and 72.2%, respectively (P=0.208). Low-dose radiotherapy without a tumor bed boost was subsequently delivered to either the whole ventricle (n=16) or the whole brain (n=8), resulting in complete remission in all participants. Compared with patients without increased ß-hCG levels, those with ß-hCG-secreting germinomas had less favorable 5-year disease-free survival rates (100% vs. 60%, respectively, P=0.000115). CONCLUSIONS: Some children with primary CNS germinoma may benefit from short-course induction chemotherapy followed by low-dose radiotherapy to the whole ventricle without a tumor bed boost. The validity of our findings needs to be confirmed in a randomized phase II study for children with ß-hCG levels <5 mIU/mL.

Clinical outcomes of fractionated stereotactic radiosurgery in treating perioptic meningiomas and schwannomas: A single-institutional experience.

Application of radiosurgery to the newly diagnosed or post-operative residual perioptic lesions has been proved to improve tumor control. However, risk of vision injury induced by radiosurgery may increase substantially if the radiation dose is too high or tumor is close to the optic apparatus. The purpose of this study was to evaluate the safety and the effectiveness of fractionated stereotactic radiosurgery (FSRS) for perioptic tumors. We retrospectively analyzed 60 consecutive patients with 53 meningiomas and 7 schwannomas treated with FSRS between October 2007 and February 2020. We administered a marginal dose of 6-7 Gy (mean 6.8 Gy) per fraction and delivered 3 fractions in 3 consecutive days. The median tumor volume was 6.31 cm3 (range 0.3-58.23 cm3). The mean minimum lesion-optic distance (MLOD) is 0.85 mm (range 0-3 mm). After mean follow-up period of 69.6 months (range 6.82-156.32 months; median 58.9 months), the tumor control rates at 1, 3, 5, 8 and 13 years were 98.3%, 93.4%, 90.60%, 88.4% and 88.4%, respectively. Four out of the 60 tumors (6.7%) experienced a transient volume increase after FSRS. None of the patients developed visual impairment related to radiation induced optic neuropathy (RION) after FSRS. In conclusion, FSRS offers an alternative treatment option in treating perioptic meningiomas and schwannomas with acceptable tumor control rates and good visual preservation in the present study.

Treatment of intracranial meningioma with single-session and fractionated radiosurgery: a propensity score matching study.

Single-session stereotactic radiosurgery (SSRS) is recognized as a safe and efficient treatment for meningioma. We aim to compare the long-term efficacy and safety of fractionated stereotactic radiotherapy (FSRT) with SSRS in the treatment of grade I meningioma. A total of 228 patients with 245 tumors treated with radiosurgery between March 2006 and June 2017were retrospectively evaluated. Of these, 147 (64.5%) patients were treated with SSRS. The remaining 81 patients (35.5%) were treated with a fractionated technique. Protocols to treat meningioma were classified as 12-16 Gy per fraction for SSRS and 7 Gy/fraction/day for three consecutive days to reach a total dose of 21 Gy for FSRT. In univariate and multivariate analyses, tumor volume was found to be associated with local control rate (hazard ratio = 4.98, p = 0.025). The difference in actuarial local control rate (LCR) between the SSRS and FSRT groups after propensity score matching (PSM) was not statistically significant during the 2-year (96.86% versus 100.00%, respectively; p = 0.175), 5-year (94.76% versus 97.56%, respectively; p = 0.373), and 10-year (74.40% versus 91.46%, respectively; p = 0.204) follow-up period. FSRT and SSRS were equally well-tolerated and effective for the treatment of intracranial benign meningioma during the10-year follow-up period.

Missed radiation therapy sessions in first three weeks predict distant metastasis and less favorable outcomes in surgically treated patients with oral cavity squamous cell carcinoma.

BACKGROUND: We sought to investigate the prognostic impact of missed RT sessions in patients who had undergone surgery for oral cavity squamous cell carcinoma (OCSCC). METHODS: The study sample consisted of 905 patients with surgically treated OCSCC who fulfilled criteria of RT course ≤8 weeks. The study participants were divided into three groups based on the characteristics of missed RT, as follows: 1) early missed RT, 2) late missed RT, and 3) RT as scheduled. RESULTS: The 5-year overall survival (OS) rates in the early missed RT, late missed RT, and RT as scheduled groups were 53.0, 58.1, and 64.5%, respectively (p = 0.046). In multivariate analysis, early missed RT was independently associated with both OS (hazard ratio (HR) = 1.486; 95% confidence interval (CI): 1.122-1.966; p = 0.006) and the occurrence of distant metastasis (HR = 1.644; 95% CI: 1.047-2.583; p = 0.031). CONCLUSION: Early missed RT was independently associated with a higher occurrence of distant metastasis and less favorable OS in patients who had undergone surgery for OCSCC.

Prognostic value of lymph node to primary tumor standardized uptake value ratio in unresectable esophageal cancer.

BACKGROUND: Unresectable esophageal cancer harbors high mortality despite chemoradiotherapy. Better patient selection for more personalized management may result in better treatment outcomes. We presume the ratio of maximum standardized uptake value (SUV) of metastatic lymph nodes to primary tumor (NTR) in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT) may provide prognostic information and further stratification of these patients. METHODS: The patients with non-metastatic and unresectable esophageal squamous cell carcinoma (SCC) receiving FDG PET/CT staging and treated by chemoradiotherapy were retrospectively reviewed. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off value for NTR. Kaplan-Meier method and Cox regression model were used for survival analyses and multivariable analyses, respectively. RESULTS: From 2010 to 2016, 96 eligible patients were analyzed. The median follow-up time was 10.2 months (range 1.6 to 83.6 months). Using ROC analysis, the best NTR cut-off value was 0.46 for prediction of distant metastasis. The median distant metastasis-free survival (DMFS) was significantly lower in the high-NTR group (9.5 vs. 22.2 months, p = 0.002) and median overall survival (OS) (9.5 vs. 11.6 months, p = 0.013) was also significantly worse. Multivariable analysis revealed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR] 1.81, p = 0.023) and OS (HR 1.77, p = 0.014). CONCLUSIONS: High pretreatment NTR predicts worse treatment outcomes and could be an easy-to-use and helpful prognostic factor to provide more personalized treatment for patients with non-metastatic and unresectable esophageal SCC.

Association of subcutaneous and visceral adipose tissue with overall survival in Taiwanese patients with bone metastases - results from a retrospective analysis of consecutively collected data.

BACKGROUND: Growing evidence indicates that measures of body composition may be related to clinical outcomes in patients with malignancies. The aim of this study was to investigate whether measures of regional adiposity-including subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI)-can be associated with overall survival (OS) in Taiwanese patients with bone metastases. METHODS: This is a retrospective analysis of prospectively collected data. We examined 1280 patients with bone metastases who had undergone radiotherapy (RT) between March 2005 and August 2013. Body composition (SATI, VATI, and muscle index) was assessed by computed tomography at the third lumbar vertebra and normalized for patient height. Patients were divided into low- and high-adiposity groups (for both SATI and VATI) according to sex-specific median values. RESULTS: Both SATI (hazard ratio [HR]: 0.696; P<0.001) and VATI (HR: 0.87; P = 0.037)-but not muscle index-were independently associated with a more favorable OS, with the former showing a stronger relationship. The most favorable OS was observed in women with high SATI (11.21 months; 95% confidence interval: 9.434-12.988; P<0.001). CONCLUSIONS: High SATI and VATI are associated with a more favorable OS in Taiwanese patients with bone metastases referred for RT. The question as to whether clinical measures aimed at improving adiposity may improve OS in this clinical population deserves further scrutiny.

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in older patients with metastatic cancer.

BACKGROUND: Treatment options for older patients with malignancies remain suboptimal. An accurate prognostic stratification could inform treatment decisions, which can potentially improve patient outcomes. Here, we sought to investigate whether the neutrophil-to-lymphocyte ratio (NLR) may have prognostic significance in patients with metastatic malignant tumors, with a special focus on older individuals. METHODS: We retrospectively reviewed the clinical records of 3981 patients with histology-proven metastatic cancer who underwent radiotherapy between 2000 and 2013. The pretreatment NLR was determined within 7 days before treatment initiation. Patients aged ≥65 years were considered as older. We analyzed the prognostic significance of NLR for overall survival (OS) across all age groups. RESULTS: Compared with their younger counterparts, older patients showed a higher NLR (P < 0.001) and a lower OS (P < 0.001). Multivariate analysis revealed that a pretreatment NLR below the median was an independent favorable predictor of OS in both older (hazard ratio [HR]: 0.669, 95.0% CI: 0.605-0.740; P < 0.001) and younger patients (HR: 0.704; 95.0% CI: 0.648-0.765; P < 0.001). Regardless of age, patients who underwent systemic therapy showed more favorable OS, especially when NLR was low. In the older subgroup, the OS of patients with a low pretreatment NLR who did not undergo systemic therapy and of those with high pretreatment NLR who underwent systemic therapy was similar. CONCLUSION: A low pretreatment NLR predicts a more favorable OS in older patients with metastatic cancer. The most favorable OS was observed in patients with a low pretreatment NLR who received systemic therapy.

Prognostic significance of combined pretreatment lymphocyte counts and body mass index in patients with head and neck cancer treated with radiation therapy.

We aimed to investigate the prognostic significance of combined pretreatment lymphocyte counts (LCs) and body mass index (BMI) in patients with head and neck cancer (HNC) treated with radiation therapy (RT). Nine hundred and twelve patients with HNC who were treated with RT were retrospectively reviewed. Survival was analyzed by stratifying the patients according to pretreatment LCs and BMI. Patients with low pretreatment LCs and BMI were characterized by a more advanced T stage, fewer nasopharyngeal subsites, less smoking and drinking, and fewer comorbidities. Patients with low pretreatment LCs and BMI had a significantly poorer overall and distant metastasis-free survival than those with high pretreatment LCs and BMI. No significant differences were observed in terms of local or regional recurrence-free survival. Combined pretreatment LCs and BMI may be more effective at predicting overall and distant metastasis-free survival in patients with HNC treated with RT.

Pretreatment subcutaneous adipose tissue predicts the outcomes of patients with head and neck cancer receiving definitive radiation and chemoradiation in Taiwan.

We aimed to determine whether body composition assessment before treatment can predict outcomes in patients with head and neck cancer (HNC). All 881 patients with locoregional head and neck cancer treated with curative intent radiotherapy (RT) between 2005 and 2012 were retrospectively investigated. Body composition was analyzed via pre-RT planning computed tomography (CT) images. Subcutaneous adipose tissue (SAT) and skeletal muscle (SM) indices were measured cross-sectionally at the level of the third thoracic vertebra. Overall survival (OS), locoregional control (LRC), and distant metastasis-free survival (MFS) were analyzed by body composition index and body mass index (BMI). Survivors were followed up for a median of 4.68 years. The SAT indices in female patients were significantly higher than those in males (P < 0.001). The median SAT and muscle indices were 18.6 and 34.3 cm2 /m2 for women and 6.19 and 51.74 cm2 /m2 for men, respectively. The 5- and 10-year MFS, LRC, and OS rates were 83% and 82.1%, 73.4% and 71.4%, and 66.4 and 57.6%, respectively. Higher pretreatment SAT index was associated with MFS (hazard ratio [HR]: 0.65; P = 0.015), LRC (HR: 0.758; P = 0.047), and OS (HR: 0.604; P < 0.001). Higher pretreatment BMI was associated with MFS (HR: 0.642; P = 0.031) and OS (HR: 0.615; P < 0.001). The pretreatment SM index had no significant effect on MFS, LRC, and OS. Multivariate analysis revealed that T-stage, N-stage, lesion sites, age, and RT treatment days are independent factors associated with OS; T-stage, N-stage, and lesion sites are independent factors associated with MFS; and N-stage, smoking history, and betel quid chewing history are independent factors associated with LRC. A higher CT-assessed SAT index predicts superior MSF, LCR, and OS in patients with curative HNC, whereas SM does not predict survival or locoregional control.

Development and Validation of a Nomogram for Assessing Survival in Patients With Metastatic Lung Cancer Referred for Radiotherapy for Bone Metastases.

Importance: A survival prediction model for patients with bone metastases arising from lung cancer would be highly valuable. Objective: To develop and validate a nomogram for assessing the survival probability of patients with metastatic lung cancer receiving radiotherapy for osseous metastases. Design, Setting, Participants: In this prognostic study, the putative prognostic indicators for constructing the nomogram were identified using multivariable Cox regression analysis with backward elimination and model selection based on the Akaike information criterion. The nomogram was subjected to internal (bootstrap) and external validation; its calibration and discriminative ability were evaluated with calibration plots and the Uno C statistic, respectively. The training and validation set cohorts were from a tertiary medical center in northern Taiwan and a tertiary institution in southern Taiwan, respectively. The training set comprised 477 patients with metastatic lung cancer who received radiotherapy for osseous metastases between January 2000 and December 2013. The validation set comprised 235 similar patients treated between January 2011 and December 2017. Data analysis was conducted May 2018 to July 2018. Main Outcomes and Measures: The nomogram end points were death within 3, 6, and 12 months. Results: Of 477 patients in the training set, 292 patients (61.2%) were male, and the mean (SD) age was 62.86 (11.66) years. Of 235 patients in the validating set, 113 patients (48.1%) were male, and the mean (SD) age was 62.65 (11.49) years. In the training set, 186 (39%), 291 (61%), and 359 (75%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 4.21 (95% CI, 3.68-4.90) months. In the validating set, 84 (36%), 120 (51%), and 144 (61%) patients died within 3, 6, and 12 months, respectively, and the median overall survival was 5.20 (95% CI, 4.07-7.17) months. Body mass index (18.5 to <25 vs ≥25: hazard ratio [HR], 1.42; 95% CI, 1.14-1.78 and <18.5 vs ≥25: HR, 2.31; 95% CI, 1.56-3.44), histology (non-small cell vs small cell lung cancer: HR, 0.59; 95% CI, 0.41-0.86), epidermal growth factor receptor mutation (positive vs unknown: HR, 0.66; 95% CI, 0.46-0.93 and negative vs unknown: HR, 0.98; 95% CI, 0.66-1.45), smoking status (ever smoker vs never smoker: HR, 1.50; 95% CI, 1.24-1.83), age, and neutrophil to lymphocyte ratio were incorporated. The HRs of age and neutrophil to lymphocyte ratio were modeled nonlinearly with restricted cubic splines (both P < .001). The nomogram's discriminative ability was good in the training set (C statistic, ≥0.77; P < .001) and was validated using both an internal bootstrap method (C statistic, ≥0.76; P < .001) and an external validating set (C statistic, ≥0.75; P < .001). The calibration plots for the end points showed optimal agreement between the nomogram's assessment and actual observations. Conclusions and Relevance: The nomogram (with web-based tool) can be useful for assessing the probability of survival at 3, 6, and 12 months in patients with metastatic lung cancer referred for radiotherapy to treat bone metastases, and it may guide radiation oncologists in treatment decision making and engaging patients in end-of-life discussions and/or hospice referrals at appropriate times.