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Purpose: Satisfactory treatment options for advanced leiomyosarcoma and liposarcoma are limited. The LEADER study (NCT03526679) investigated the safety and efficacy of lenvatinib plus eribulin., Methods: LEADER is a multicenter phase Ib/II study for advanced leiomyosarcoma or liposarcoma. The phase Ib part enrolled 6 patients to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) with the starting dose of lenvatinib 18 mg/day and eribulin 1.1 mg/m2 D1, D8 every 21 days. The primary endpoint of the phase II part was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors 1.1, with phase Ib patients preplanned to be included in the efficacy analysis. Translational analyses were based on the transcriptomic data obtained from the NanoString nCounter platform., Results: Thirty patients were enrolled (leiomyosarcoma 21, liposarcoma 9); the median age was 59. One patient had to temporarily stop lenvatinib due to grade 2 arthritis in the first cycle, meeting DLT criteria. Four of 6 patients had to decrease the dose of lenvatinib to 14 mg between cycles two and three. RP2D was determined at lenvatinib 14 mg/day and eribulin 1.1 mg/m2. The confirmed ORR was 20%, and the ORR was not significantly different between phase Ib/II cohorts (P = 0.23). The median progression-free survival was 8.56 months (95% confidence interval, 4.40-not reached). Translational studies suggested increased dendritic cells in the tumor microenvironment (TME) after treatment., Conclusions: Lenvatinib plus eribulin has a manageable safety profile and exhibits promising efficacy for treating advanced leiomyosarcoma and liposarcoma., (©2022 American Association for Cancer Research.)

Objectives: The optimal duration of anti-PD-1 for cancer therapy has not been tested, especially when using combination therapy. Epidermal growth factor receptor (EGFR) pathway blocker was the top compound that enhanced T-cell killing of tumor cells in a high-throughput immune-oncology screen, possibly by stimulate the antigen presentation machinery and other mechanisms. We explored the effect of combination of EGFR inhibition with a short course of anti-PD-1 therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC)., Method: We analyzed the effect of a short course of anti-PD-1 with continuous afatinib on the survival of a real-world cohort of R/M HNSCC patients. Patient characteristics, treatments, efficacies, and toxicities were reviewed and recorded for analysis., Results: From November 2016 to May 2018, 51 consecutive patients received pembrolizumab and afatinib. The cutoff date was June 30, 2022. The most common toxicities (all grades) were diarrhea (62.7%), skin rash (43.1%), mucositis (31.4%), and paronychia (23.5%). The objective response rate was 54.9% (95% confidence interval [CI] 40.3-68.9%). Median progression-free survival was 5.9 months (95% CI: 4.4-7.6 months), and the median overall survival was 10.5 months (95% CI: 6.8-16.5 months). The 12-month, 24-month, 36-month, and 48-month survival rate was 47.0%, 22.5%, 17.7%, and 12.6% respectively., Conclusions: This retrospective study showed that short course pembrolizumab with afatinib therapy has acceptable efficacy in R/M HNSCC patients. The durable response and long-term survival rates were similar to prospective clinical trials. Short course anti-PD-1 therapy, especially in combination with EGFR blocker, is worth for further prospective study., (© 2022. The Author(s).)

Objectives: To assess health-related quality of life (HRQoL) with first-line pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the phase 3 KEYNOTE-048 trial (NCT02358031)., Materials and Methods: HRQoL was measured using the European Organisation for Research and Treatment of Cancer 30-question quality-of-life (EORTC QLQ-C30), the EORTC 35-question quality-of-life head and neck cancer-specific module (EORTC QLQ-H&N35), and the EuroQol 5-dimension 3-level instruments (EQ-5D-3L). Secondary endpoints included mean change from baseline in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) at week 15 and time to deterioration (TTD) in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing., Results: Of 882 enrolled participants, 844 received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment; adherence was ≥ 79% at week 15 across treatment groups. At week 15, EORTC QLQ-C30 GHS/QoL scores remained stable; no clinically meaningful between-group differences were observed (least squares mean difference, pembrolizumab vs cetuximab-chemotherapy, 0.24; 95% CI, -3.34 to 3.82; pembrolizumab-chemotherapy vs cetuximab-chemotherapy, 0.40; 95% CI, -3.46 to 4.26). Median TTD in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing scores was not reached over 51 weeks across groups, showing stable HRQoL. TTD was similar between groups for EORTC QLQ-C30 GHS/QoL (pembrolizumab vs cetuximab-chemotherapy: HR, 1.38; 95% CI, 0.95-2.00; pembrolizumab-chemotherapy vs cetuximab-chemotherapy: HR, 1.37; 95% CI, 0.94-2.00), as was TTD in EORTC QLQ-H&N35 pain and swallowing scores., Conclusions: Pembrolizumab monotherapy and pembrolizumab-chemotherapy extended OS while maintaining HRQoL, further supporting first-line use for R/M HNSCC., (Copyright © 2022 Merck Sharp & Dohme Corp, The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: EGFR pathway inhibition may promote anti-programmed cell death protein 1 (PD-1) responses in preclinical models, but how EGFR inhibition affects tumor antigen presentation during anti-PD-1 monotherapy in humans remain unknown. We hypothesized that afatinib, an irreversible EGFR tyrosine kinase inhibitor, would improve outcomes in patients treated with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) by promoting antigen presentation and immune activation in the tumor microenvironment., Patients and Methods: The ALPHA study (NCT03695510) was a single-arm, Phase II study with Simon's 2-stage design. Afatinib and pembrolizumab were administered to patients with platinum-refractory, recurrent, or metastatic HNSCC. The primary endpoint was the objective response rate (ORR). The study applied gene expression analysis using a NanoString PanCancer Immune Profiling Panel and next-generation sequencing using FoundationOne CDx., Results: From January 2019 to March 2020, the study enrolled 29 eligible patients. Common treatment-related adverse events were skin rash (75.9%), diarrhea (58.6%), and paronychia (44.8%). Twelve patients (41.4%) had an objective partial response to treatment. The median progression-free survival was 4.1 months, and the median overall survival was 8.9 months. In a paired tissue analysis, afatinib-pembrolizumab were found to upregulate genes involved in antigen presentation, immune activation, and natural killer cell-mediated cytotoxicity. Unaltered methylthioadenosine phosphorylase and EGFR amplification may predict the clinical response to the therapy., Conclusions: Afatinib may augment pembrolizumab therapy and improve the ORR in patients with HNSCC. Bioinformatics analysis suggested the enhancement of antigen presentation machinery in the tumor microenvironment., (©2022 The Authors; Published by the American Association for Cancer Research.)

Polatuzumab vedotin (PoV) has recently shown promising activity when combined with rituximab-bendamustine (BR) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, few studies have described the prognostic factors predicting response. Here, we aimed to evaluate the efficacy and safety profile of PoV-based chemotherapy, including regimens other than BR, as third-line or beyond treatment for patients with R/R DLBCL and to explore prognostic factors. Overall, 40 patients, including 37 with de novo and 3 with transformed DLBCL, were enrolled. The overall response rate was 52.5%, and 25% and 27.5% of patients showed a complete response and partial response, respectively. With a median follow-up of 18.8 months, the median overall survival (OS) of the total cohort was 8.5 months, and that of those receiving subsequent hematopoietic stem cell transplantation (HSCT) was 24 months. Low/intermediate risk according to the revised International Prognostic Index score at diagnosis and before PoV treatment predicted better OS. Furthermore, a normal lactate dehydrogenase level and an absolute lymphocyte count/absolute monocyte count ratio > 1.5 were favorable OS prognostic factors. The most common adverse event was cytopenia, with 42.5% of patients developing febrile neutropenia. Grade 1-3 peripheral neuropathy associated with PoV was reported in 25% of patients and resolved in most patients after the cessation of treatment. In summary, we demonstrated that PoV combined with either BR or other intensive chemotherapy is an effective and well-tolerated salvage option for patients with R/R DLBCL. Subsequent HSCT has the potential to further improve survival outcomes in this high-risk population. Clinicaltrials.gov number: NCT05006534., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Histopathological characteristics of cytomegalovirus (CMV) lymphadenitis have been well described. Rare studies have reported the immune status and clinical features. Clinically, experts believed that CMV lymphadenitis develops in immunocompromised and immunocompetent patients. Infectious mononucleosis (IM)-like syndrome is the most well-known clinical presentation., Methods: We reviewed archived CMV immunohistochemical stains on lymphoid tissues. The clinicopathological features of CMV-positive cases were studied., Results: For lymph nodes, we detected CMV in 29% (5/17) allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) recipients, 29% (4/14) post-autologous PBSCT patients, 13% (6/47) patients treated with intravenous chemotherapy, and 9% (9/96) immunocompetent patients. We detected CMV in 7% (2/24) of tonsils but not in the nasopharynx, tongue base, or spleen specimens. The patients with iatrogenic immunodeficiency ranged from 37 to 76 years old. CMV infections developed a few years after lymphoma treatment (median duration after allogeneic PBSCT, 932 days; after autologous PBSCT, 370 days; and after chemotherapy, 626 days). The most common clinical presentation was neck mass (13/25, 42%), followed by asymptomatic image finding (10/25, 40%). Positron emission tomography/computed tomography (PET/CT) scan showed increased uptake compared to the liver in all patients (11/11, 100%). Of 10 lymphoma patients, 8 (80%) had a Deauville score of 4-5; they accounted for 30% (8/27) of lymphoma patients with false-positive PET/CT scan results. All cases were self-limiting. 96% (23/25) cases had Epstein-Barr virus coinfection, and EBER-positive cells were predominantly in a few germinal centers., Conclusions: Cytomegalovirus (CMV) lymphadenitis and tonsillitis were subclinical infections, not primary CMV infection with IM-like syndrome. The lymphadenopathy typically developed a few years after lymphoma treatments in the middle-aged and the elderly. The lesions mimicked lymphoma relapse in PET scans. Therefore, recognizing CMV infection in lymphoid tissues is of clinical importance., (© 2021. The Author(s).)

Purpose: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC., Methods: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified., Results: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect., Conclusion: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: For locally advanced head and neck cancers, intra-arterial (IA) chemotherapy is utilized for locoregional control with favorable results. The study aimed to evaluate the surgical outcomes of microsurgical reconstruction in head and neck cancer patients with IA chemotherapy METHODS: This cohort study retrospectively reviewed patients who underwent head and neck microsurgical reconstruction from January 2014 to August 2018. Patients with prior history of chemotherapy were included and categorized into two groups according to history of IA chemotherapy (IA group)/intravenous chemotherapy (IV group). Flap survival was evaluated along with microsurgical revision rates and complications. Recipient vessel specimens were analyzed by histological examination. A 1:1 propensity score matched analysis was performed., Results: The study cohort included 45 patients with IA chemotherapy and 201 patients with IV chemotherapy. After propensity score matching, the difference in total flap loss and microsurgical revision rates were nonsignificant between two groups. However, the IA group had significantly higher rates of arterial thrombosis (Odds ratio [OR] 4.98; 95%CI, 1.28-19.38; p = 0.021), wound-related complications (OR 3.30; 95%CI, 1.21-9.02; p = 0.02) and revision surgery within one month (OR 3.73; 95%CI, 1.10-12.64; p = 0.035). Based on histology, IA group vessels showed a higher intima/media ratio than the IV group (0.45 ± 0.06 versus 0.23 ± 0.03, p = 0.02) CONCLUSION: Despite treating local advanced head and neck cancers with good results, IA chemotherapy may cause subsequent deleterious effects on local tissue due to the high concentration of cytotoxic chemotherapeutic agents. Surgeons should be cautious in selection of recipient vessels when performing microvascular reconstruction., (Copyright © 2019. Published by Elsevier B.V.)

Background: The present study evaluated the 2-year survival of the Asian population in the CheckMate 141 trial., Methods: The CheckMate 141 trial included patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). In the present study, 34 Asian patients (nivolumab group: 23 patients; investigator's choice of therapy [IC] group: 11 patients) were analyzed., Results: The median overall survival (OS) was 12.1 and 6.2 months for the nivolumab and IC groups, respectively. The estimated 2-year OS rates were 22.7% and 0% for the nivolumab and IC groups, respectively. In the nivolumab group, the patients with any treatment-related adverse events (TRAEs), including skin-related disorders, showed better OS than the patients without any TRAEs., Conclusions: Nivolumab demonstrated prolonged OS benefits in the Asian population with platinum-refractory R/M SCCHN and a favorable safety profile. TRAEs, including skin-related disorders, may be favorable prognostic factors for nivolumab efficacy., Clinical Trial Registration: NCT02105636., (© 2020 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Mesenchymal chondrosarcoma (MCS) is a rare malignant variant of chondrosarcoma with a high tendency of recurrence and metastasis. Intradural extramedullary spinal MCS is exceedingly rare and usually found in pediatric patients. Herein, we present an elderly patient with primary intradural extramedullary spinal MCS. Relevant literatures are reviewed to disclose characteristics of intradural extramedullary spinal MCS., Case Presentation: A 64-year-old female presented with urinary difficulty and tightness of upper back preceding progressive weakness of right lower extremity. Magnetic resonance imaging revealed an intradural extramedullary tumor at the level of 3rd thoracic vertebra. This patient underwent total tumor resection and then received adjuvant radiotherapy. Histopathological examination showed that the tumor composed of spindle and round cells with high nucleocytoplasmic ratio accompanied by scattered eosinophilic chondroid matrix. Along with immunohistochemical findings and the existence of HEY1-NCOA2 fusion transcript, the diagnosis of MCS was confirmed. Neurologic deficit recovered nearly completely after surgery. No evidence of local recurrence or distant metastasis was found 5 years after treatments. Including the current case, a total of 18 cases have been reported in the literature with only one case with local recurrence and one case of mortality. The current case was the eldest patient diagnosed with primary intraspinal MCS in the literature., Conclusions: MCS rarely appears in the intradural space of the spine. In contrast to classic MCS, treatment outcome of primary intradural extramedullary spinal MCS is usually excellent as total tumor resection is commonly achievable. Adjuvant radiotherapy may reduce local recurrence and chemotherapy may be associated with fewer recurrences especially for unresectable tumors.

Objectives: Treatment options for patients with unresectable or metastatic salivary gland carcinoma (SGC) are limited. Safety and efficacy of pembrolizumab for SGC expressing programmed death ligand 1 (PD-L1) were explored., Materials and Methods: A cohort of patients with advanced, PD-L1-positive SGC was enrolled in the nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors (KEYNOTE-028; NCT02054806). Key inclusion criteria included recurrent or metastatic disease, failure of prior systemic therapy, and PD-L1 expression on ≥1% of tumor or stroma cells (per a prototype immunohistochemistry assay). Patients received pembrolizumab 10 mg/kg every 2 weeks for ≥2 years or until confirmed disease progression or unacceptable toxicity. Primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator review., Results: Twenty-six patients with PD-L1-positive SGC were enrolled and treated; median age was 57 years, 88% were men, and 74% had received prior therapy for recurrent/metastatic disease. Confirmed objective response rate after median follow-up of 20 months was 12% (95% confidence interval, 2%-30%), with 3 patients achieving partial response; there were no complete responses. Median duration of response was 4 months (range, 4 to 21 mo). Treatment-related adverse events occurred in 22 patients (85%), resulting in discontinuation in 2 patients and death in 1 (interstitial lung disease); those occurring in ≥15% of patients were diarrhea, decreased appetite, pruritus, and fatigue., Conclusions: Pembrolizumab demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, PD-L1-positive SGC.

Objectives: To assess efficacy and safety of nivolumab versus investigator's choice of therapy (IC) in Asian patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)., Materials and Methods: Thirty-four patients from Japan, Taiwan, Hong Kong, and Korea received nivolumab 3mg/kg (n=23) every 2weeks or IC (n=11), as part of a global trial (n=361), until intolerable toxicity or disease progression. The primary endpoint was overall survival (OS)., Results: Median OS was 9.5months (95% confidence interval [CI] 9.1-NR) with nivolumab and 6.2months (95% CI 2.6-NR) with IC. Seven (30.4%) patients receiving nivolumab and six (54.5%) receiving IC died. The hazard ratio (HR) for risk of death (nivolumab vs. IC) was 0.50 (95% CI 0.17-1.48). Median progression-free survival was 1.9months (95% CI 1.6-7.5) with nivolumab and 1.8months (95% CI 0.4-6.1) with IC (HR 0.57 [95% CI 0.25-1.33]). Objective response rates (complete+partial responses) were 26.1% (6/23 patients; 95% CI 10.2-48.4) for nivolumab and 0% (0/11 patients; 95% CI 0.0-28.5) for IC. Sixteen (69.6%) nivolumab-treated patients and 10 (90.9%) patients receiving IC had a treatment-related adverse event, most commonly decreased appetite (21.7%), pruritus, rash, and fatigue (17.4% each) with nivolumab, and nausea, stomatitis, and decreased appetite (27.3% each) with IC., Conclusion: Nivolumab demonstrated a survival advantage compared with conventional treatments in Asian patients with platinum-refractory recurrent or metastatic SCCHN, and was well tolerated. Clinical trial registration NCT02105636., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context/objective: Temporal changes have not been examined in patient-caregiver agreement on life-sustaining treatment (LST) preferences at end of life (EOL). We explored the extent of and changes in patient-caregiver agreement on LST-preference patterns for two independent cohorts of Taiwanese cancer patient-family caregiver dyads recruited a decade apart., Methods: We surveyed preferences for cardiopulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, tube feeding, and dialysis among 1049 and 1901 dyads in 2003-2004 and 2011-2012, respectively. LST-preference patterns were examined by multi-group latent class analysis. Extent of patient-caregiver agreement on LST-preference patterns was determined by percentage agreement and kappa coefficients., Results: For both patients and family caregivers, we identified seven distinct LST-preference classes. Patient-caregiver agreement on LST-preference patterns was poor to fair across both study cohorts, indicated by 24.4%-43.5% agreement and kappa values of 0.06 (95% CI: 0.04, 0.09) to 0.27 (0.23, 0.30), and declined significantly over time. Agreement on LST-preference patterns was most likely when both patients and caregivers uniformly rejected LSTs. When patients disagreed with caregivers on LST-preference patterns, discrepancies were most likely when patients totally rejected LSTs but caregivers uniformly preferred LSTs or preferred nutritional support but rejected other treatments., Conclusion: Patients and family caregivers had poor-to-fair agreement on LST-preference patterns, and agreement declined significantly over a decade. Encouraging an open dialogue between patients and their family caregivers about desired EOL care would facilitate patient-caregiver agreement on LST-preference patterns, thus honoring terminally ill cancer patients' wishes when they cannot make EOL-care decisions., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Thymic tumors are epithelial tumors of the thymus for which multimodal therapies are often ineffective because of a lack of standardized regimens. Due to the low incidence, the molecular pathology and genomic abnormalities of thymic epithelial tumors are largely unknown. In this study, we report our comprehensively genomic study on a case of metastatic thymic tumor. Using next generation deep DNA sequencing technology, we sequenced 190 segments of 46 cancer genes of the cancer genome to cover 739 COSMIC mutations in 604 loci. Among these sequenced cancer genes, we identified that three low frequency (~10% of cells) mutations in the TP53 gene (c.782+1G>T), ALK gene (c.3551C>T), and RET gene (c.2651A>T). To the best of our knowledge, this is the first study to show those mutations in thymic tumor. Of note, our study further indicates comprehensive molecular analysis may facilitate development of novel diagnostic and therapeutic strategies for thymic tumors., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Adenoid cystic carcinoma (ACC), commonly from salivary glands, is known for its insidious local growth and usually protracted clinical course. ACC developing from non-salivary glands (i.e., non-salivary ACC) is heterogeneous, and its clinicopathological features remain poorly defined. Patients treated for ACC in a single institution between 1995 and 2007 were included in this study. Immunohistochemical evaluation of Ki-67, E-cadherin, p16, and cyclinD1 was performed. The prognostic significance of clinical and immunophenotypic markers was evaluated. 83 cases of salivary ACC and 24 cases of non-salivary ACC were included. The expression levels of Ki-67 (54.8%), E-cadherin (90.4%), p16 (32.9%), and cyclinD1 (19.2%) between ACCs present at various sites were not different. Sinonasal, lacrimal, and tracheobronchial ACCs had significantly worse outcomes than those of ACC of the major salivary glands. Postoperative radiotherapy reduced the recurrence rate of patients with a negative resection margin (P=0.028). Older age (age >60 years), advanced stage, positive resection margin, high histological grade, and high expression of Ki-67 were significantly correlated with poor prognosis. In conclusion, the site of origin plays a role in the prognosis of ACC, in which positive resection margin and advanced stage are possible factors underlying the differences in outcomes., (Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: This study was designed to compare (201)Tl single photon emission computed tomography (SPECT)/CT with 18-fluoro-2-deoxyglucose ((18)F-FDG) PET/CT in diagnosing recurrent skull base nasopharyngeal carcinoma (NPC)., Methods: Twenty-seven patients were recruited. Both (201)Tl SPECT/CT and (18)F-FDG PET/CT for each patient were performed at least 4 months later after initial therapy., Results: The sensitivity and specificity for (201)Tl SPECT/CT were 66.7% and 100%, and those for (18)F-FDG PET/CT were 86.7% and 75.0%. Lesion/background ratios were obtained for the 10 lesions that were both SPECT and PET true positive. For the 8 patients with recurrences in nasopharyngeal regions, PET lesion/background ratios were all higher than SPECT lesion/background ratios. For the 2 patients with intracranial metastases, SPECT lesion/background ratios were higher than PET lesion/background ratios., Conclusion: (201)Tl SPECT/CT is as effective as (18)F-FDG PET/CT in detecting recurrent NPC. For intracranial recurrence, (201)Tl SPECT, because of its high intracranial lesion/background ratio, is probably better than (18)F-FDG PET., ((c) 2009 Wiley Periodicals, Inc.)

Oxaliplatin-related thrombocytopenia is considered rare and mostly self-limited. We present the first reported fatal case due to this complication. A 64-year-old patient with metastatic colon cancer was admitted for his 24th course of chemotherapy with oxaliplatin and 24-hour infusion of fluorouracil and leucovorin. Consciousness changed on the next evening and deteriorated to deep coma within hours. Computed tomography revealed large intracranial hemorrhage with brain herniation. Hemogram showed severe thrombocytopenia, which was considered to be associated with oxaliplatin. The patient died six days later. The incidence of oxaliplatin-related thrombocytopenia may have been underestimated and its severity long neglected. Other hypersensitivity reactions may precede its onset. Early hemogram examination during hypersensitivity reaction to oxaliplatin may provide early diagnosis and the prevention of the possible fatal consequences.

Unlabelled: The aim of this retrospective study was to evaluate the sensitivity and prognostic significance of whole-body (18)F-FDG PET for nasopharyngeal carcinoma (NPC) patients for whom there was a suspicion of recurrence or metastasis by conventional radiologic or clinical findings during their follow-up examinations., Methods: Whole-body (18)F-FDG PET examinations were performed on 64 Taiwanese NPC patients (14 female, 50 male; mean age +/- SD, 45.8 +/- 13.0 y; age range, 16-75 y) 4-70 mo (mean +/- SD, 14.1 +/- 13.5 mo) after radiotherapy or induction chemotherapy followed by concurrent chemoradiotherapy from February 1997 to May 2001. The accuracy of (18)F-FDG PET detection for each patient was determined by the histopathologic results or other clinical evidence., Results: The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of (18)F-FDG PET images in the diagnosis of NPC recurrence or metastases and secondary primary cancers were 92%, 90%, 92%, 90%, and 91%, respectively. Furthermore, the presence of (18)F-FDG hypermetabolism was highly correlated with the survival time of NPC patients., Conclusion: Whole-body (18)F-FDG PET is a sensitive follow-up diagnostic tool for the evaluation of NPC recurrences and metastases. It is also an effective prognostic indicator for NPC patients. To determine the optimized utilization of (18)F-FDG PET in the follow-up for NPC patients, further cost-effectiveness analysis of (18)F-FDG PET in combination with conventional management is necessary.

The outcome of nasopharyngeal carcinoma (NPC) treatment has greatly improved as advances in imaging techniques increase the accuracy of tumor mapping. Radiotherapy remains a common treatment for early disease, while concurrent chemoradiotherapy is being increasingly accepted as the standard treatment for advanced disease. Intensity modulation radiotherapy (IMRT) delivers a more conformal radiation dose to the target area and may spare normal organs such as parotid gland for patients with early stage disease. IMRT in conjunction with concurrent chemotherapy offers excellent tumor control with fewer complications. These benefits suggest it will become the mainstay of radiotherapy treatment for NPC. Prevention of distant metastasis remains a crucial objective. The potential of induction chemotherapy to reduce distant metastasis has gained increased attention. Adjuvant chemotherapy has been unsuccessful due to poor tolerability. For metastatic NPC, cisplatin-based chemotherapy is effective but limited by cumulative toxicities. Newer drugs such gemcitabine and vinorelbine have been shown to be active in salvage therapy when cisplatin-containing combinations have failed. Due to their advantageous toxicity profiles, new drugs may replace cisplatin-based combinations as first-line treatment for metastatic NPC in the near future. Signal transduction manipulation is promising but has not been shown to be an essential therapy. Immunotherapy, such as mini-transplant, may offer the chance for durable control without long-term treatment, but its efficacy remains to be demonstrated.

Unlike conventional liposomes, sterically stabilized liposomes, with their smaller volume of distribution and reduced clearance, preferentially convey encapsulated drugs into tumor sites. Despite these improvements, intracellular delivery is hampered by the stable drug retention of the liposomes, which diminishes the efficacy of the liposomal drug. To facilitate uptake of liposomal drugs into cells, two cell-penetrating peptides, penetratin (PEN) and TAT, derived from the HIV-1 TAT protein, were studied. In contrast to control peptides, both TAT and PEN enhanced the translocation efficiency of liposomes in proportion to the number of peptides attached to the liposomal surface. A peptide number of as few as five could enhance the intracellular delivery of liposomes. The kinetics of uptake was peptide- and cell-type dependent. Intracellular accumulation of TAT-liposomes increased with incubation time, but PEN-liposomes peaked at 1 h and then declined gradually. After treatment with 1 microg/ml doxorubicin equivalents of liposome for 2 h, TAT increased the doxorubicin uptake of A431 cells by 12-fold. However, the improvement of uptake of liposomal doxorubicin was not reflected by cytotoxicity in vitro or tumor control in vivo. Our results demonstrated that merely adding CPP to a liposome encapsulating anticancer drug was inadequate in improving its antitumor activity. An additional approach to enhance the intracellular release of the encapsulated drug is obviously necessary.

Objective: Nasopharyngeal carcinoma (NPC) is one of the dominant cancers in South China and Taiwan. Although NPC is highly chemosensitive, the use of chemotherapy for treating patients with recurrent or metastatic NPC has not been very successful. The emergence of drug resistance may be one of the major reasons. However, the mechanisms of drug resistance of NPC have never been addressed before. In this study, we sought to clarify the role of classical drug resistance markers in predicting the chemosensitivity and the prognosis of patients with advanced NPC., Methods: In a cohort of 202 consecutive patients diagnosed at the Department of Pathology of the National Taiwan University Hospital, 44 patients with adequately preserved pretreatment tumor tissues and complete clinical information regarding the details of chemotherapy and tumor response were identified. The expression of multidrug resistance (MDR1), glutathione-S-transferase-pi (GSTpi), and p53 were determined by immunohistochemistry. Tumor response to chemotherapy and survival of the patients were the endpoints of this analysis., Results: Thirty-four patients received cisplatin-based regimens, and 28 of them were enrolled in a prospective trial using a doxorubicin-containing regimen. The overall response rate was 70%. Expression of MDR1 was seen in only 5 cases (11%) and was associated with a significantly worse overall survival, yet did not appear to predict chemoresistance to the doxorubicin-containing regimen. Overexpression of p53 was seen in 22 patients, and surprisingly, was correlated with chemoresponse and a trend towards better survival. GSTpi expression was demonstrated in 13 cases (30%) and was not correlated with chemoresistance to cisplatin-containing regimens and overall survival., Conclusion: In this relatively small cohort, positive MDR1 immunostaining predicted a poor overall survival for recurrent or metastatic NPC patients receiving chemotherapy. Overexpression of p53 by immunohistochemical staining, however, was associated with a better response rate to systemic chemotherapy and a trend towards better survival., (Copyright 2002 S. Karger AG, Basel)

Background/aims: Gastrointestinal tumors with microsatellite instability represent a replication error-positive phenotype. BAT-26, a repeat of 26 deoxyadenosine localized in intron 5 of hMSH2 gene, has been reported as a reliable indicator of replication error phenotype in colorectal cancers. This study investigated whether BAT-26 is a useful marker for a mutator phenotype with distinct clinicopathologic features in gastric cancer., Methodology: One hundred and nineteen gastric cancer tissues and matched non-tumor tissue were examined by polymerase chain reactions with electrophoresis for 9 dinucleotide microsatellites and BAT-26, and frameshift mutations of transforming growth factor-beta type II receptor. The relation between BAT-26 alterations and relevant clinicopathological or genetic parameters were analyzed., Results: Gastric cancer with BAT-26 alterations was highly correlated with multiple microsatellite alterations (> or = 3 loci) and frameshift mutations of transforming growth factor-beta type II receptor, and predominantly showed antral location, intestinal histologic subtype, advanced stage, a higher rate of Helicobacter pylori infection, a better postoperative survival and less lymph node metastasis., Conclusions: These results show testing of BAT-26 alterations is a convenient and rapid screening method for identifying a subset of gastric cancer with a mutator phenotype and better prognosis.