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To evaluate the therapeutic efficacy of cyclin-dependent kinase (CDK) inhibition in combination with ionizing radiation for lung cancer.Human lung adenocarcinoma (A549) and squamous cell carcinoma (H520) cells were used to evaluate the therapeutic efficacy of CDK inhibition in combination with ionizing radiation in vitro using colony formation assay, γH2AX immunofluorescence staining, western blotting, and cell cycle phase analysis. We also performed in vivo evaluations of ectopic tumor growth.In vitro pretreatment with the CDK inhibitor, seliciclib, before irradiation significantly decreased the survival of A549 and H520 cells in a dose-dependent manner. Although CDK inhibition alone did not increase the intensity of γH2AX foci, its combination with ionizing radiation increased DNA double-strand breaks, as shown by γH2AX immunofluorescence staining and western blotting. The combination of CDK inhibition and ionizing radiation-induced G2/M arrest and increased apoptosis, as evidenced by the increased proportion of cells in G2/M arrest, subG1 apoptotic population, and expression of apoptotic markers (cleaved PARP-1 and cleaved caspase-3). Mechanistic studies showed reduced expression of cyclin A with combined treatment, indicating cell cycle shifting effects. An in vivo xenograft model showed that the combination of CDK inhibition and ionizing radiation delayed xenograft tumor growth, and increased the proportion of cleaved PARP-1- and cleaved caspase-3-positive cells, compared to either treatment alone.We provide preclinical tumoricidal evidence that the combination of CDK inhibition and ionizing radiation is an efficacious treatment for lung cancer.

BACKGROUND Extended-field (EF) bone marrow-sparing (BMS) radiotherapy is attracting interest for cervical cancer patients with para-aortic lymphadenopathy. OBJECTIVE To compare dosimetric quality of volumetric-modulated arc therapy (VMAT) vs. helical tomotherapy (HT) during EF BMS radiotherapy. METHODS HT dose-volume histogram parameters including (1) coverage, homogeneity, and conformity of target volumes, (2) sparing of organs-at-risk, (3) monitor units, and (4) estimated treatment time were compared with those of VMAT in 20 cervical cancer patients who underwent EF BMS radiotherapy. The pelvic and para-aortic regions received 45-Gy dose (25 fractions), with simultaneous integrated boost of 55 Gy (25 fractions) for pelvic and para-aortic lymphadenopathy, followed by a parametrial boost of 9 Gy (5 fractions). RESULTS The HT-based and VMAT techniques achieved adequate and similar target volume coverage with good dose homogeneity and conformity, while sparing all organs-at-risk, including the rectum, bladder, bowel, bone marrow, femoral head, kidney, and spinal cord. The HT treatment plan had significantly higher monitor units (p

This phase 2 trial aimed to determine whether xenon-enhanced ventilation computed tomography (XeCT)-guided functional-lung-avoidance radiation therapy could reduce the radiation pneumonitis (RP) rate in patients with lung cancer undergoing definitive chemoradiation therapy.Functional lung ventilation was measured via pulmonary function testing (PFT) and XeCT. A standard plan (SP) without reference to XeCT and a functional-lung-avoidance plan (fAP) optimized for lowering the radiation dose to the functional lung at the guidance of XeCT were designed. Dosimetric parameters and predicted RP risks modeled by biological evaluation were compared between the 2 plans in a treatment planning system (TPS). All patients received the approved fAP. The primary endpoint was the rate of grade ≥2 RP, and the secondary endpoints were the survival outcomes. The study hypothesis was that fAP could reduce the rate of grade ≥2 RP to 12% compared with a 30% historical rate.Thirty-six patients were evaluated. Xenon-enhanced total functional lung volumes positively correlated with PFT ventilation parameters (forced vital capacity, P = .012; forced expiratory volume in 1 second, P = .035), whereas they were not correlated with the diffusion capacity parameter. We observed a 17% rate of grade ≥2 RP (6 of 36 patients), which was significantly different (P = .040) compared with the historical control. Compared with the SP, the fAP significantly spared the total ventilated lung, leading to a reduction in predicted grade ≥2 RP (P = .001) by TPS biological evaluation. The median follow-up was 15.2 months. The 1-year local control (LC), disseminated failure-free survival (DFFS), and overall survival (OS) rates were 88%, 66%, and 91%, respectively. The median LC and OS were not reached, and the median DFFS was 24.0 months (95% confidence interval, 15.7-32.3 months).This report of XeCT-guided functional-lung-avoidance radiation therapy provided evidence showing its feasibility in clinical practice. Its benefit should be assessed in a broader multicenter trial setting.

BACKGROUND We hypothesized that patients with head and neck squamous cell carcinoma (HNSCC) with smoking cessation during curative chemoradiotherapy (CRT) had fewer complications and lower tumor progression risks. METHODS Sixty-three patients with nonmetastatic HNSCC who were smokers at diagnosis (carbon monoxide [CO] breath concentrations ≥3 ppm) and underwent curative CRT were prospectively enrolled. Successful smoking cessation throughout CRT was confirmed by CO breath concentrations

Background Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC. Methods This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), reverse reflux rate constant (kep), volume transfer constant (Ktrans), blood plasma volume fraction (vp), extracellular extravascular volume fraction (ve), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC60). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously. Results Serum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p Ktrans, and kep, showed strong linear correlations (p p = 0.004), MTV values (p kep values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm3 (p = 0.046), Ktrans > 200 10− 3/min (p = 0.069), and kep > 900 10− 3/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival. Conclusions The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI), low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS), patients with age &gt, 60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.

Stereotactic body radiation therapy (SBRT) has been proved to be effective in refractory ventricular arrhythmia (VA). We report the first Asian series of SBRT for refractory VA in a group of Taiwanese. This study included patients with treatment-failure VA. 3D electroanatomic maps, delayed enhancement magnetic resonance imaging (DE-MRI) and dual energy computed tomography (CT) were used to identify scar substrates. The target volume was treated with a single radiation dose of 20 Gy delivered by Varian TrueBeam System. Efficacy was assessed by VA events recorded by implantable cardioverter defibrillator (ICD) or 24-hour Holter. Pre- and post-radiation therapy image studies were also performed. Adverse events were monitored during follow-up. From February 2019 to December 2019, 7 patients were enrolled. Six male and one female patients, mean age 55 years, received the treatment. Among the 7 patients with variety of cardiomyopathy, one patient died of hepatic failure. For the other 6 patients, at a median follow-up of 14.5 months, the burden of VA decreased significantly. Increased intensity of DE-MRI might be associated with lower risk of VA recurrence while the dual energy CT had lower sensitivity in the detection. No acute and minimal late adverse events were reported. We conclude that, in patients with refractory VA, SBRT was associated with a marked reduction in the burden of VA and DE-MRI might be useful to monitor treatment effect.

BackgroundHippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT is better for preserving neurocognitive function.MethodsThis single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned to receive HA-WBRT or conformal WBRT. Primary end point is the decline of Hopkins Verbal Learning Test–Revised (HVLT-R) Delayed Recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression free survival (BPFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsPatients were enrolled from March 2015 to December 2018 with a median follow-up of 12.4 months. A total of 70 patients were randomized. No differences in baseline neurocognitive function existed between the two arms. There were no differences in any neurocognitive assessments at four months. At six months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, p = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, p = 0.019) and memory score (mean difference = 4.38, p = 0.020) compared with patients undergoing conformal WBRT. There were no differences in TMT part A, part B, or the COWA test between the two arms at any time point. There were no differences in BPFS or OS between arms as well.ConclusionsPatients receiving HA-WBRT without Memantine showed better preservation in late verbal memory, but not in verbal fluency or executive function.

We investigated whether radiologic parameters by dynamic contrast-enhanced (DCE) integrated magnetic resonance–positron-emission tomography (MR-PET) predicts tumor response to treatment and survival in non-metastatic non-small-cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT). Patients underwent DCE integrated MR-PET imaging 1 week before CRT. The following parameters were analyzed: primary tumor size, gross tumor volume, maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), volume transfer constant (Ktrans), reverse reflux rate constant (kep), extracellular extravascular volume fraction (ve), blood plasma volume fraction (vp), and initial area under the time-concentration curve defined over the first 60 s post-enhancement (iAUC60). CRT responses were defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Thirty patients were included. Non-responders demonstrated higher baseline TLG (p = 0.012), and lower baseline Ktrans (p = 0.020) and iAUC60 (p = 0.016) compared to responders, indicating the usefulness of DCE integrated MR-PET to predict treatment responses. Receiver operating characteristic curve indicated that TLG has the best differentiation capability to predict responders. By setting the threshold of TLG to 277, the sensitivity, specificity, and accuracy were 66.7%, 83.3%, and 75.0%, respectively, with an area under the curve of 0.776. The median follow-up time was 19.6 (range 7.8–32.0) months. In univariate analyses, baseline TLG >277 (p = 0.005) and baseline Ktrans 277 remained the significant factor in predicting progression (p = 0.012) and death (p = 0.031). The radiologic parameters derived from DCE integrated MR-PET scans are useful for predicting treatment response in NSCLC patients treated with CRT; furthermore, these parameters are correlated with clinical and survival outcomes including tumor progression and death.

Background The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. Methods We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. Results One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. Conclusions Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. Trial registration ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.

Purpose To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). Materials and Methods We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, Ktrans, kep, ve, vp, and iAUC60. Chest computed tomography (CT) was performed at 3 months after SBRT. Results SBRT treatment led to tumor changes including significant decreases in the SUVmax (–61%, P 10 (P = 0.083). Conclusion In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

C57BL/6 mice implanted in the flank with murine Lewis lung carcinoma cells were randomized into control, anti-angiogenic, anti-PD-L1, radiotherapy (RT), RT + anti-angiogenic, RT + anti-PD-L1, and RT + anti-PD-L1 + anti-angiogenic therapy groups. Immune response and immunophenotyping were determined by flow cytometry. Vasculature analysis after RT and anti-angiogenic therapy was assessed by quantified power Doppler sonography. Antitumor response, survival, and rechallenged tumor growth were evaluated. RT increased PD-L1 expression on CD8+ T, CD4+ T, dendritic, myeloid-derived suppressor cells (MDSCs), and tumor cells and increased PD-1 expression on CD8+ and CD4+ T cells. Anti-angiogenic therapy insignificantly decreased the RT-induced PD-1 expression on CD8+ and CD4+ T cells, implying a weak reversal of the immune-suppressive environment. Transient vessel collapse was observed within days after RT, and blood flow recovered at 1 week after RT. RT + anti-PD-L1 suppressed the tumor growth, improved survival, and prolonged immune memory capable of protecting against tumor recurrence, evidenced by local accumulation of CD8+ T cells and reduction in MDSCs in microenvironment. Similar and more prominent effects were observed when anti-VEGF was added to RT + anti-PDL1 therapies, implying an additive, rather than synergistic, antitumor immunity. Phenotypic analyses revealed that anti-cancer treatments increased the proportion of effector memory T cells in TILs and splenocytes, and RT, alone or in combination with other treatments, further increased the proportion of central memory T cells in splenocytes. These results provide evidence on operating the immunosuppressive tumor environment and offer insights into the design of the new combination treatment.

This study examined the efficacy of polo-like kinase 1 (PLK1) inhibition on radiosensitivity in vitro and in vivo by a pharmacologic approach using the highly potent PLK1 inhibitor volasertib. Human esophageal squamous cell carcinoma (ESCC) cell lines KYSE 70 and KYSE 150 were used to evaluate the synergistic effect of volasertib and irradiation in vitro using cell viability assay, colony formation assay, cell cycle phase analysis, and western blot, and in vivo using ectopic tumor models. Volasertib decreased ESCC cell proliferation in a dose- and time-dependent manner. Combination of volasertib and radiation caused G2/M cell cycle arrest, increased cyclin B levels, and induced apoptosis. Volasertib significantly enhanced radiation-induced death in ESCC cells by a mechanism involving the enhancement of histone H3 phosphorylation and significant cell cycle interruption. The combination of volasertib plus irradiation delayed the growth of ESCC tumor xenografts markedly compared with either treatment modality alone. The in vitro results suggested that targeting PLK1 might be a viable approach to improve the effects of radiation in ESCC. In vivo studies showed that PLK1 inhibition with volasertib during irradiation significantly improved local tumor control when compared to irradiation or drug treatment alone.

We evaluated the prognostic significance of immunologic inhibitory biomarkers in head and neck squamous cell carcinoma (HNSCC) patients undergoing definitive chemoradiotherapy (CRT). Thirty patients were prospectively enrolled. Plasma levels of soluble MHC class I polypeptide-related sequence A (sMICA) and transforming growth factor-β1 (TGF-β1) were measured before and 2 weeks after CRT. The median follow-up was 32.9 months (range: 12.4-40.6 months). The pre-treatment sMICA (p < 0.001) and TGF-β1 (p < 0.001) levels were significantly increased in HNSCC patients, compared to healthy controls. In HNSCC patients, the median pre-CRT and post-CRT sMICA levels were 43.1 pg/mL and 65.3 pg/mL, respectively, while the median pre-CRT and post-CRT TGF-β1 levels were 57.7 ng/mL and 36.0 ng/mL, respectively. After CRT, 19 patients (63.3%) exhibited persistently elevated sMICA, six patients (20.0%) exhibited persistently elevated TGF-β1, and five patients (16.7%) exhibited persistently elevated sMICA and TGF-β1. Patients with persistently elevated sMICA and TGF-β1 after CRT experienced an earlier tumor progression (p = 0.030), and poor overall survival (p = 0.010). Our results suggest that HNSCC patients who exhibit persistently elevated sMICA and TGF-β1 levels after CRT are at higher risk of tumor progression or death.

To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC).We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, KSBRT treatment led to tumor changes including significant decreases in the SUVIn patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome.2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199.

Since December 2009, after breast-conserving surgery for Stage 0–I cancer of the left breast, 21 women with relatively pendulous breasts underwent computed tomography prone and supine simulations. The adjuvant radiotherapy was 50 Gy in 25 fractions to the left breast alone. Four plans—conventional wedged tangents and forward intensity-modulated radiotherapy (fIMRT) in supine and prone positions—were generated. fIMRT generated better homogeneity in both positions. Prone position centralized the breast tissue by gravity and also shortened the breast width which led to better conformity in both planning techniques. Prone fIMRT significantly reduced doses to left lung, Level I and Level II axilla. The mean cardiac doses did not differ between positions. Among the four plans, prone fIMRT produced the best target dosimetry and normal organ sparing. In subgroup analysis, patients with absolute breast depth > 7 cm in the prone position or breast depth difference > 3 cm between positions had significant cardiac sparing with prone fIMRT. Sixteen patients with significant cardiac sparing in prone position were treated using prone fIMRT and the others using supine fIMRT. All patients received a supine electron tumor bed boost of 10 Gy in 5 fractions. No patients developed Grade 2 or worse acute or late toxicities. There was no difference in the number of segments or beams, monitor units, treatment time, or positioning reproducibility between prone and supine positions. At a median follow-up time of 26.8 months, no locoregional or distant recurrence or death was noted.

// Jenny Ling-Yu Chen 1,2 , Yu-Sen Huang 3,4 , Sung-Hsin Kuo 1,5 , Ruey-Long Hong 1 , Jenq-Yuh Ko 6 , Pei-Jen Lou 6 and Chun-Wei Wang 1 1 Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 2 Department of Radiation Oncology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan 3 Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 4 Department of Medical Imaging, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan 5 Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan 6 Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Correspondence to: Chun-Wei Wang, email: // Keywords : intensity-modulated radiation therapy; conformal radiation therapy; nasopharyngeal carcinoma; survival outcomes; late toxicities Received : May 23, 2016 Accepted : October 12, 2016 Published : October 18, 2016 Abstract Purpose: To examine the survival outcomes and late toxicity profiles of three-dimensional conformal radiation therapy (3DCRT) vs . intensity-modulated radiation therapy (IMRT) for patients with nasopharyngeal carcinoma (NPC). Methods: Three hundred and seventy-four patients with newly diagnosed, non-metastatic, NPC who were curatively treated with 3DCRT between 2004 and 2006 and 481 patients treated with IMRT between 2007 and 2009 were analyzed. Patients were categorized as having advanced-stage disease (stage III, IVA, and IVB disease; n = 709) or early-stage disease (stage I and II; n = 146). The median follow-up time was 90.3 months for patients treated with 3DCRT and 86.3 months for patients treated with IMRT. Results: For early-stage patients, the outcomes of IMRT vs . 3DCRT were similar considering locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). For advanced-stage patients, IMRT was associated with better LRC compared with 3DCRT (5-year LRC rate: 85.6% vs . 76.6%, respectively; p = 0.035) and OS (5-year OS rate: 82.3% vs . 71.8%, respectively; p = 0.002), whereas DMFS was similar for both treatments (5-year DMFS rate: 80.9% vs . 79.0%, respectively; p = 0.324). Furthermore, the IMRT technique was more beneficial for patients with T4 disease. Late toxicities occurred more frequently in patients treated with 3DCRT than in those treated with IMRT (grade ≥3 neck fibrosis: 6.7% vs . 3.7%, respectively, p = 0.036; radiographic temporal lobe necrosis: 10.2% vs . 4.4%, respectively, p < 0.001). Conclusions: Compared with 3DCRT, IMRT offered better LRC in patients with advanced-stage non-metastatic NPC, which corresponded with better OS.

A 46-year-old man with a history of alcohol abuse was admitted to the emergency department with drowsiness, septic shock and chronic back pain that had exacerbated quickly over the past 2 days. His medical history was limited to alcoholic liver cirrhosis without regular medical attention. Physical and laboratory examinations revealed leukocytosis, thrombocytopenia, coagulopathy and deteriorated …

To evaluate the clinical, pathologic, and imaging findings of solid pseudopapillary neoplasm (SPN) of the pancreas in order to differentiate benign from malignant pancreatic neoplasms.We retrospectively identified 23 patients with 24 SPNs confirmed by pathology at National Taiwan University Hospital between January, 2001 and March, 2012. All computed tomography and magnetic resonance imaging were reviewed by two radiologists in consensus. Each tumor was analyzed for location of tumor, tumor margin, proportion of solid component, capsule morphology, growth pattern, presence of calcification, presence of upstream pancreatic duct dilatation, and enhancement pattern.SPN of the pancreas demonstrated variable degrees of hemorrhagic degeneration and calcification. Focal discontinuity of capsule was consistently observed in five malignant tumors (p = 0.004). There were no statistical differences between benign and malignant tumors based on location of tumor, tumor margin, proportion of solid component, growth pattern, presence of calcification, presence of upstream pancreatic duct dilatation, or enhancement patternAmong the various imaging features, we found that focal discontinuity of the capsule may suggest malignancy.

Resistance of cancer stem cells to radiotherapy remains a major obstacle to successful cancer management. Prominin-1 (PROM1) is a cancer stem cell marker. Nanoparticle (NP) chemotherapeutics preferentially accumulate in tumors and are able to target cancer and cancer stem-like cells through cancer cell-specific ligands, making them uniquely suited as radiosensitizers for chemoradiation therapy. Using a biocompatible apoferritin NP, a PROM1-targeted NP carrying irinotecan (PROM1-NP) is engineered. The synergistic effect of the NP and irradiation is evaluated in PROM1-overexpressing HCT-116 colorectal cancer cell lines in vitro and in vivo. PROM1-NP has a size of 17.2 ± 0.2 nm and surface charge of −13.5 ± 0.2 mV. It demonstrates higher intracellular uptake than nontargeted NP or irinotecan alone. Treatment with PROM1-NPs decreases HCT-116 cell proliferation in a dose- and time-dependent manner. In vitro radiosensitization reveals that PROM1-NP is significantly more effective as a radiosensitizer than nontargeted NP or irinotecan. HCT-116 tumor xenograft growth is markedly slower following treatment with PROM1-NP plus irradiation, suggesting that PROM1-NP is more effective as a radiosensitizer than irinotecan and nontargeted NP in vivo. This study provides the first preclinical evidence of the effectiveness of PROM1-targeted NP formulation of irinotecan as a radiosensitizer.

Objective To compare tumor characteristics and clinical outcome of patients with cervical locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) and squamous cell carcinoma (SCC). Design Retrospective study. Setting National Taiwan University Hospital, Taipei, Taiwan. Population All patients with cervical SCC (n = 35), AC or ASC (n = 194) with FIGO stage ≥IIB who received definitive radiotherapy or concurrent chemoradiotherapy (CCRT) from January 1995 to December 2009. Method Medical and histopathological record review. Main outcome measures Progression-free survival (PFS), local recurrence-free survival, distant metastasis-free survival, and overall survival (OS). Results Compared with the SCC subgroup, patients with AC/ASC were significantly younger (p = 0.007), more of them without clinical symptoms were diagnosed by abnormal Pap smear findings (p = 0.043), and less responded to treatment (p = 0.018). After a median follow-up of 59.3 months, patients with AC/ASC had worse 5-year PFS (30.0% vs. 47.6%, p = 0.044), worse 5-year distant metastasis-free survival (41.5% vs. 69.9%, p = 0.005), and trends toward worse 5-year local recurrence-free survival (64.4% vs. 76.2%, p = 0.165) and worse 5-year OS (41.3% vs. 58.1%, p = 0.090) than patients with SCC. In univariate analysis, early FIGO stage and complete treatment response were significantly associated with PFS and OS. Histology of non-AC/ASC and Point A biologically equivalent doses in 2-Gy fractions >85 Gy were significantly associated with better PFS, and CCRT was significantly associated with better OS. In multivariate analysis, complete treatment response and early FIGO stage remained significant factors for predicting better PFS and OS. Conclusions Cervical AC/ASC may be more aggressive than is SCC. For cervical AC/ASC, more comprehensively effective treatments are warranted.

To compare survival between patients with cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC).Retrospective study.National Taiwan University Hospital, Taipei, Taiwan.All patients with cervical AC or ASC who received definitive treatment from January 1995 to December 2009.Medical and histopathological record review.Overall and recurrence-free survival.A total of 170 women received a histological diagnosis of AC and 42 of ASC. The median follow-up was 56.7 months. There were no significant differences in age, International Federation of Gynecology and Obstetrics (FIGO) stage, gravidity or treatment modality between women with AC and ASC. Patients with ASC had a higher percentage of poorly differentiated tumors than those with AC (33.3 vs. 15.3%, respectively; p= 0.014). Five year overall and recurrence-free survival was 66.8 and 58.9%, respectively, for women with AC and 69.5 and 61.9%, respectively, for those with ASC (p= 0.795 and p= 0.892, respectively). Survival outcomes in patients with early or advanced stage disease did not differ between the histological groups. No differences in failure patterns were found between the two groups. The FIGO stage and treatment modality were factors which affected overall and recurrence-free survival.We did not find evidence to suggest that ASC subtypes indicate worse outcome. Cervical ASC could be categorized as one subtype of AC. The FIGO stage and treatment modalities have greater influence on outcomes than histological subtype.

e16503 Background: To compare tumor characteristics, treatment response, failure patterns, and clinical outcome of patients with cervix locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) and squamous cell carcinoma (SCC). Methods: Medical records for 36 patients with stage IIB–IVA histologically proven cervix AC/ASC and 199 patients with SCC who received definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) between 1995 and 2009 were retrospectively reviewed. The clinicopathologic features, radiation dose, treatment response, recurrent pattern, metastases pattern, and survival outcome between histologic groups were evaluated. Results: Compared with the SCC subgroup of patients, patients with AC/ASC were significantly younger (mean age, 56 vs. 62 years, p=0.007), more of them without clinical symptoms were diagnosed by abnormal Papanicolaou smear findings (16.7% vs. 5.5%, p = 0.019), and less responded to treatment (complete response, 72.2% vs. 86.9%, p = 0.024). After a median follow-up of 59.3 months, patients with AC/ASC had worse 5-year recurrence-free survival (RFS) (33.7% vs. 58.7%, p = 0.046), worse 5-year distant metastasis-free survival (40.2% vs. 70.3%, p = 0.002), and trends toward worse 5-year local recurrence-free survival (62.4% vs. 75.7%, p = 0.127) and worse 5-year overall survival (OS) (40.1% vs. 58.0%, p = 0.062) than those with SCC. In univariate analysis, early FIGO stage and complete treatment response were found to be significantly associated with both RFS and OS. Histology of non-AC/ASC and Point A biologically equivalent doses in 2-Gy fractions >85Gy were significantly associated with better RFS, and CCRT was significantly associated with better OS. In multivariate analysis, complete treatment response remained significant factor for predicting better RFS, and early FIGO stage, CCRT and complete treatment response remained significant factors for predicting better OS. Conclusions: Cervix AC/ASC may behave more aggressively than does SCC. For this subgroup of cervical cancer, more comprehensively effective treatment is warranted.

We aimed to evaluate the influence of mammographic breast density at diagnosis on the risk of cancer recurrence and survival outcomes in patients with invasive breast cancer after modified radical mastectomy. This case-control study included 121 case-control pairs of women diagnosed with invasive breast cancer between 2004 and 2009, and who had undergone modified radical mastectomy and had mammographic breast density measured before or at diagnosis. Women with known locoregional recurrence or distant metastasis were matched by pathological disease stage, age, and year of diagnosis to women without recurrence. Locoregional recurrence was defined as recurrence in the ipsilateral chest wall, or axillary, internal mammary, or supraclavicular nodes. The median follow-up duration was 84.0 months for case patients and 92.9 months for control patients. Patients with heterogeneously dense (50–75% density) and extremely dense (>75% density) breasts had an increased risk of locoregional recurrence (hazard ratios 3.1 and 5.7, 95% confidence intervals 1.1–9.8 and 1.2–34.9, p = 0.043 and 0.048, respectively) than did women with less dense breasts. Positive margins after surgery also increased the risk of locoregional recurrence (hazard ratio 3.3, 95% confidence interval 1.3–8.3, p = 0.010). Multivariate analysis that included dense breasts (>50% density), positive margin, no adjuvant radiotherapy, and no adjuvant chemotherapy revealed that dense breasts were significant factors for predicting locoregional recurrence risk (hazard ratio 3.6, 95% confidence interval 1.2–11.1, p = 0.025). Our results demonstrate that dense breast tissue (>50% density) increased the risk of locoregional recurrence after modified radical mastectomy in patients with invasive breast cancer. Additional prospective studies are necessary to validate these findings. The study is retrospectively registered with ClinicalTrials.gov, number NCT02771665 , on May 11, 2016.