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Post-transplant cyclophosphamide (PT-Cy) and calcineurin inhibitors used in peripheral blood haplo-identical stem cell transplantation (haploSCT) increase the risk of acute/chronic graft-versus-host disease (GVHD). Whether ATG/PT-Cy is feasible for Asian patients undergoing haploSCT is unclear, and an optimal strategy for GVHD prophylaxis is needed.We retrospectively analyzed 61 hematologic malignancy patients who underwent peripheral blood haploSCT using ATG/PT-Cy from January 2013 to December 2018. We also compared the effects of ATG/PT-Cy (ATG group; n = 61) with historical data from patients who underwent haploSCT using sirolimus/PT-Cy (non-ATG group; n = 22).Cumulative incidences of grades II-IV acute GVHD and moderate to severe chronic GVHD did not differ significantly. The ATG group had higher incidence of Epstein-Barr virus (EBV) reactivation, but neither group had post-transplant lymphoproliferative disorders. The ATG group also had a higher OS rate (2-year OS in ATG group vs. non-ATG group: 43.4% vs. 27.3%, respectively; P = 0.071).ATG/PT-Cy is an acceptable strategy for GVHD prophylaxis in Asian patients undergoing haploSCT.

Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase 3 trial (ClinicalTrials.gov identifier: NCT03581786), 289 patients with RM-NPC and no previous chemotherapy for recurrent or metastatic disease were randomized (1/1) to receive either toripalimab, a monoclonal antibody against human programmed death-1 (PD-1), or placebo in combination with GP every 3 weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee according to RECIST v.1.1. At the prespecified interim PFS analysis, a significant improvement in PFS was detected in the toripalimab arm compared to the placebo arm: median PFS of 11.7 versus 8.0 months, hazard ratio (HR) = 0.52 (95% confidence interval (CI): 0.36–0.74), P = 0.0003. An improvement in PFS was observed across key subgroups, including PD-L1 expression. As of 18 February 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.603 (95% CI: 0.364–0.997)). The incidence of grade ≥3 adverse events (AEs) (89.0 versus 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5 versus 4.9%) and fatal AEs (2.7 versus 2.8%) was similar between the two arms; however, immune-related AEs (39.7 versus 18.9%) and grade ≥3 infusion reactions (7.5 versus 0.7%) were more frequent in the toripalimab arm. In conclusion, the addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS compared to GP alone, and with a manageable safety profile. Interim analysis from the randomized phase 3 JUPITER-02 trial shows that the addition of anti-PD-1 toripalimab to standard gemcitabine/cisplatin as a first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma has manageable toxicity and improves progression-free survival, suggesting a potential new treatment standard in this setting.

Global vaccination against the coronavirus disease 2019 (COVID-19) is thought to be the most effective way to end or at least contain the COVID-19 pandemic. However, despite the good safety profiles and effectiveness of the available COVID-19 vaccines, rare but serious hematological complications have emerged, including thromboembolic outcomes with thrombocytopenia following the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and Ad26.COV.2.S (JohnsonJohnson/Janssen) vaccines. Moreover, COVID-19 vaccination may be linked to the development of aplastic anemia (AA). We discuss four cases of AA that arose after COVID-19 vaccination in our hospital and two other such cases identified in our literature review.

Background Randomized controlled trials had demonstrated local therapy, such as radiotherapy, can improve outcomes of patients with lung cancer with oligometastatic disease (OMD). However, the definition of OMD is not uniform and the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) proposed a new classification in 2020 comprising nine subtypes. Therefore, we aimed to investigate the prognostic significance of this European classification for patients with lung OMD treated with definitive radical radiotherapy. Patients and methods We identified eligible patients via an in-house database. Patient, disease, and treatment characteristics, as well as outcomes, were obtained via chart review plus peer review. Overall and progression-free survival were estimated via the Kaplan-Meier method. Log-rank test was used in univariate analysis and Cox regression in multivariable analyses to investigate the prognostic significance of the subtypes of OMD. Results We identified 35 eligible patients with six different OMD subtypes treated from 2011 to 2019. After a median follow-up of 23 (range=2-88) months, the median progression-free and overall survival were 11 and 38 months, respectively. The prognosis for patients with the subtype 'induced oligoprogression' was statistically worse than for those without in both univariate (p=0.02) and multivariate (adjusted hazard ratio for death=4.8, 95% confidence interval=1.4-16.2, p=0.01) analyses. Conclusion We found the subtype with induced oligoprogression in the European classification to be associated with worse survival. Further studies are needed to confirm our finding.

Docetaxel (DTX) combined with cisplatin and 5-fluorouracil has been used as induction chemotherapy for head and neck squamous cell carcinoma (HNSCC). However, the development of acquired resistance remains a major obstacle to treatment response. Tumor-associated macrophages are associated with chemotherapeutic resistance. In the present study, increased infiltration of macrophages into the tumor microenvironment (TME) was significantly associated with shorter overall survival and increased resistance to chemotherapeutic drugs, particularly DTX, in patients with HNSCC. Macrophage coculture induced expression of intercellular adhesion molecule 1 (ICAM1), which promotes stemness and the formation of polyploid giant cancer cells, thereby reducing the efficacy of DTX. Both genetic silencing and pharmacological inhibition of ICAM1 sensitized HNSCC to DTX. Macrophage secretion of IL-1β was found to induce tumor expression of ICAM1. IL-1β neutralization and IL-1 receptor blockade reversed DTX resistance induced by macrophage coculture. IL-1β activated superoxide dismutase 2 and inhibited catalase, thereby modulating intracellular levels of ROS and inducing ICAM1 expression. Arsenic trioxide (ATO) reduced macrophage infiltration into the TME and impaired IL-1β secretion by macrophages. The combinatorial use of ATO enhanced the in vivo efficacy of DTX in a mouse model, which may provide a revolutionary approach to overcoming acquired therapeutic resistance in HNSCC.

Mantle cell lymphoma (MCL) is a B-cell lymphoma featuring an aggressive course and a progressive relapsing pattern. International guidelines recommend early consolidative autologous stem cell transplant (auto-SCT) for eligible patients while reserving allogeneic SCT (allo-SCT) as second-line therapy for refractory cases. Since data describing the implementation of transplants in the Asian population with MCL are limited, we aimed to analyze post-SCT outcomes of 99 MCL patients from the Taiwan Bone Marrow Transplant Registry database. The median age was 56 years, and 11% of the patients had blastoid variant MCL. Ninety-four patients received auto-SCT, while 13 patients received allo-SCT, eight of which received allo-SCT after failing auto-SCT. Before auto-SCT, 52% of the patients were in their first complete remission (CR1). Overall, 37 patients (39%) relapsed after auto-SCT. The median post-auto-SCT progression-free survival and overall survival (OS) were 43.6 months and not reached, respectively. Blastoid variant MCL, transplant not received in CR1, and disease progression within 12 months post-auto-SCT independently predicted inferior OS in multivariate analysis. The median post-allo-SCT OS was 74 months. Two patients (15%) died of MCL recurrence post-allo-SCT. Three patients with refractory diseases were salvaged with ibrutinib or venetoclax to allo-SCT. Treatment strategies incorporating novel agents warrant further optimization.

Background The prognosis of advanced oral squamous cell carcinoma is poor. We investigated the effect of cetuximab-based sequential therapy as a primary treatment. Methods Forty-seven treatment-naive patients with advanced tumors originating from the oral cavity or oropharynx were enrolled. Neoadjuvant cetuximab, paclitaxel, and cisplatin were administered, followed by cetuximab-based radiotherapy. Immunohistochemical staining was applied to study the tissues. Results The best overall response rate was 70.2%, including 4 patients with a complete response and 29 with a partial response. The median progression-free and overall survival rates were 10.3 and 15.2 months, respectively. Patients with more than 50% tumor reduction with neoadjuvant therapy had better survival outcomes. Twenty-two patients had severe adverse events with mostly dermatological complications. Of the 16 patients who received operations, 9 had increased PD-L1 staining compared to pretreatment biopsy in the post hoc study. Conclusion The regimen was effective in selected patients. Increased PD-L1 suggested altered tumor features.

e18041 Background: PEP503 (aka NBTXR3), a novel radioenhancer composed of functionalized hafnium oxide nanoparticles, is designed for intratumoral injection to increase radiation energy deposition within solid tumors and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. PEP503 nanoparticles plus RT has been tested in elderly HNSCC patients and has demonstrated a good safety profile. The phase 1b part of the study aimed to test the feasibility and the recommended phase 2 dose (RP2D) of PEP503 intratumoral injection when added with low-dose (LD) weekly cisplatin-containing chemoradiation (CCRT) in HNSCC. Methods: Patients who had T3-4 locally advanced HNSCC suitable for CCRT were eligible. An intratumoral single injection of PEP503 was performed 24 to 72 hours before the start of CCRT: consisting of IMRT (70̃72 Gy, 2-2.12 Gy/fraction) and weekly cisplatin (low dose, 40 mg/m2) concurrently during IMRT. Traditional 3+3 design was planned for dose escalation and 5 levels of PEP503 were planned, including 5%, 10%, 15%, 22%, and 33% of the baseline GTV by MRI. PEP503 Intra-tumor dispersion was anayzed by CT-scan. Results: Twelve (12) patients (male/female: 11/1; oral cavity/oropharynx: 11/1) were enrolled, with 3, 6, and 3 patients at 5%, 10%, and 15% PEP503 dose levels, respectively, in combination with LD cisplatin CCRT. DLTs were observed in one patient at 10% dose level which were G3 ALT and G3 AST increased. Common G3 AEs observed across dose levels were stomatitis (50.0%), WBC decreased (33.3%), decreased appetite (16.7%), neutrophil count decreased (16.7%), and leukopenia (16.7%), and only one G4 AE (hyponatraemia) was observed. CT images demonstrated PEP503 within the tumor contour after injection throughout the CCRT period. Hafnium, for all patients, was either not detected or below the Lower Limit of Quantification (LLOQ) in the circulation 60 minutes after PEP503 intratumoral injection, and not found in urine. DCR was achieved in 100% of patients with responding patients for an ORR of 58.3%. No subjects received salvage surgery after study treatment. Study was terminated early before MTD and RP2D could be determined. Conclusions: Adding PEP503, a radioenhancer, via a single intratumoral injection to weekly cisplatin-containing CCRT was feasible and safe for patients with locally advanced or recurrent LA-HNSCC. RP2D was not reached due to study early termination. Clinical trial information: NCT02901483.

Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase 3 trial (ClinicalTrials.gov identifier: NCT03581786), 289 patients with RM-NPC and no previous chemotherapy for recurrent or metastatic disease were randomized (1/1) to receive either toripalimab, a monoclonal antibody against human programmed death-1 (PD-1), or placebo in combination with GP every 3 weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee according to RECIST v.1.1. At the prespecified interim PFS analysis, a significant improvement in PFS was detected in the toripalimab arm compared to the placebo arm: median PFS of 11.7 versus 8.0 months, hazard ratio (HR) = 0.52 (95% confidence interval (CI): 0.36-0.74), P = 0.0003. An improvement in PFS was observed across key subgroups, including PD-L1 expression. As of 18 February 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.603 (95% CI: 0.364-0.997)). The incidence of grade ≥3 adverse events (AEs) (89.0 versus 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5 versus 4.9%) and fatal AEs (2.7 versus 2.8%) was similar between the two arms; however, immune-related AEs (39.7 versus 18.9%) and grade ≥3 infusion reactions (7.5 versus 0.7%) were more frequent in the toripalimab arm. In conclusion, the addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS compared to GP alone, and with a manageable safety profile.

After the introduction of ICI treatment, data about feasibility and activity of a cetuximab-containing first-line therapy in patients with recurrent and/or metastatic head and neck cancer (R/M HNSCC) are still not available. We sought to analyze the clinical outcomes in the real-world setting.This retrospective study was conducted at two tertiary medical centers in Taiwan. Patients with R/M HNSCC receiving cetuximab-containing first-line therapy were included between January 2017 and July 2019. The study endpoints were the response, Progression-Free Survival (PFS), and Overall Survival (OS). Subgroup analyses were conducted to evaluate survival outcomes by platinum resistance and the use of immunotherapy.We identified 290 patients treated with cetuximab-containing first-line therapy. The most primary tumor site was oral cavity cancer (59.3%). 44% of patients were resistant to platinum. The median PFS and OS were 5.0 months and 9.1 months, respectively, for the total population. In patients with platinum resistance, the median OS was 10.4 months with ICIs versus 6.3 months without ICIs; p = 0.01. In patients with platinum sensitivity, the median OS was 20.6 months with ICIs versus 9.1 months without ICs; p 0.01. OS benefit with ICIs was similar between patients who received ICIs after progression on Cetuximab and receiving Cetuximab in combination with ICIs. Independent favorable prognostic factors for OS were platinum-sensitive, better response to cetuximab, and ICIs use.ICIs are indicated to improve OS in R/M HNSCC receiving cetuximab-containing first-line therapy, even in platinum-resistant populations. The reduction in risk of death with ICIs was similar regarding the combination or sequencing of cetuximab.

Background: Gemcitabine-Cisplatin (GP) chemotherapy is the standard first-line treatment for recurrent or metastatic (RM) Nasopharyngeal Carcinoma (NPC). Toripalimab, a humanized monoclonal antibody specific for human programmed death-1 (PD-1), provided durable responses in patients with RM-NPC in the second line+ setting. Methods: In this international phase III trial, 289 patients with RM-NPC with no prior chemotherapy in the RM setting were randomized (1:1) to receive either toripalimab or placebo in combination with GP every 3 weeks for up to 6 cycles, followed by monotherapy with toripalimab or placebo until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee per RECIST v1.1.RESULTSAt interim analysis, a significant improvement in PFS was detected in the toripalimab arm than the placebo arm, median PFS 11.7 vs. 8.0 months, HR=0.52 (95% CI: 0.36-0.74), p=0.0003. As of February 18, 2021, a 40% reduction in risk of death was observed in the toripalimab arm than the placebo arm, HR=0.603 (95% CI: 0.364 to 0.997). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%), and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS and OS than GP alone with a manageable safety profile. Trial Registration: NCT number NCT03581786. Funding: Shanghai Junshi Biosciences Co., LTD, Shanghai, China. Declaration of Interest: Hui Feng and Sheng Yao are employed by Shanghai Junshi Bioscience and TopAlliance Biosciences. Patricia Keegan is employed by TopAlliance Biosciences. Rui-hua Xu has served in a consulting or an advisory role for Bristol-Myers Squibb, Merck Serono, Roche, Astellas, AstraZeneca. The rest of authors have no disclosures of potential conflicts of interests. Ethical Approval: This trial was conducted in full conformance with the ICH E6 guideline for Good Clinical Practice (GCP) and the principles of the Declaration of Helsinki.

Background Phase 3 studies suggest that induction chemotherapy (ICT) of cisplatin and 5-fluorouracil plus docetaxel (TPF) is effective but toxic for patients with squamous-cell carcinoma of the head and neck (SCCHN). Dose-dense chemotherapy may yield favorable outcomes compared with standard-dose chemotherapy, yet the optimal induction regimen remains undefined. We assessed the efficacy and tolerability of biweekly dose-dense TPF ICT in patients with SCCHN. Methods In this prospective phase II study, We enrolled patients with stage III/IV (AJCC 7th edition) unresectable squamous cell carcinoma of head and neck cancer. Patients received dose-dense TPF (ddTPF) with cisplatin and docetaxel 50 mg/m2 on day 1, leucovorin 250 mg/m2 on day1, followed by 48-h continuous infusion of 2500 mg/m2 of 5-fluorouracil on day 1 and 2, every 2 weeks for 6 cycles followed by radiotherapy. The primary endpoint was the response rate (RR) after ICT. Results Fifty-eight patients were enrolled from June 2014 to September 2015. Overall RR after ICT was 89.6% [complete response (CR), 31%; partial response (PR), 58.6%]. Grade 3/4 neutropenia, mucositis, and diarrhea incidences were 25.9, 1.7, and 1.7%, respectively. 94.8% of patients completed all treatment courses of ICT without dose reduction. The 3-year overall survival (OS) was 54.3% (95%CI: 39.7 to 66.8%) and progression-free survival (PFS) was 34.3% (95%CI: 22.0 to 46.9%). Multivariate analysis showed that CR after ICT is an independent prognostic factor for OS and PFS. Conclusions Six cycles of ddTPF is an active, well-tolerated induction regimen for patients with SCCHN. The presence of CR after ICT predicted long-term survival. Trial registration ClinicalTrials.gov Identifier: NCT04397341, May 21, 2020, retrospectively registered.

Additional file 1: Table S1. Multivariate analysis of overall survival and progression-free survival.

Background Treatment options are limited for recurrent nasopharyngeal carcinoma (NPC). We report results from a phase II study of CC-486 (oral azacitidine) in advanced NPC. Patients and methods Patients with locally advanced or metastatic NPC and 1–2 prior treatment regimens received CC-486 300 mg daily on days 1–14 of 21-day cycles until disease progression or unacceptable toxicity. The first 6 patients of Asian-Pacific Islander (API) ethnicity received a reduced dose of 200 mg to preserve safety and tolerability; if well tolerated, subsequent API patients received CC-486 300 mg. The study could advance to stage 2 if > 4 patients achieved a response. Co-primary end-points were overall response rate (ORR) and progression-free survival (independent review). Key secondary end-points were overall survival and safety. Results Owing to faster-than-anticipated enrolment, 36 patients, including 13 of API ethnicity, were enrolled; the median age was 54.0 years. Most patients were male (81%) and had an Eastern Cooperative Oncology Group performance status ≤ 1 (97%). Among 25 efficacy-evaluable patients, the ORR was 12%; the median progression-free and overall survival were 4.7 and 18.0 months, respectively. The most common grade III/IV treatment-emergent adverse events were neutropenia (33%) and febrile neutropenia (11%). Twenty-one posttreatment deaths, primarily due to progressive disease or disease complications, and 1 on-treatment death (epistaxis, unrelated to study drug) occurred. The study did not advance to stage 2. Conclusion CC-486 did not show sufficient clinical activity to support further development as monotherapy in this patient population. The safety profile of CC-486 in NPC was consistent with that in other solid tumours.

6025 Background: Liposomal irinotecan (nal-IRI) + 5-FU/LV has been approved and used in treating patients with metastatic pancreatic cancer after gemcitabine-based therapy through the NAPOLI-1 study result. This phase 2 trial evaluated the activity of NAPOLI-1 regimen in patients with squamous cell carcinoma (SCC) of head and neck (H&N) or esophagus that progressed on or recur after platinum-based chemotherapy or concurrent chemoradiotherapy. Methods: Patients with histologically confirmed SCC of H&N or esophagus whose disease progressed while on or progressed/recurred within 6 months after platinum-based chemotherapy or chemoradiotherapy, and unsuitable for further surgical or radiation intervention were eligible. Prior anti-EGFR or anti-PD1/anti-PDL1 treatment was allowed. The regimen consisted of nal-IRI 70 mg/m2 (irinotecan free base) followed by LV 400 mg/m2 and 5-FU 2400 mg/m2, every 2 weeks. A Simon’s 2-stage design was used with planned 30 evaluable patients in the first stage and 52 evaluable patients in total. The primary endpoint is objective tumor response. Results: From December 2018 to April 2020, 59 subjects were enrolled, including 16 with esophagus cancer and 43 with H&N cancer. Thirty-seven (63%) patients had metastatic disease at enrollment. The mean of treatment cycles were 5 (range, 1-21). Among the total 59 enrolled subjects, 53 subjects (14 esophagus cancer, 39 H&N cancer) were evaluable for objective tumor response. The disease control rate in esophagus cancer was 50% (7 SD, intent-to-treat (ITT) population 43.8%). For H&N patients, 1 CR, 4 PR, and 23 SD resulted in the response rate 12.8% (11.6% in ITT population) and disease control rate 72% (65% in ITT population). The median progression free survival (N = 59) was 2.5 months (esophagus/H&N: 1.5/2.7 months) and the median overall survival was 5.9 months (esophagus/H&N: 4.2/7.3 months). Seventy-eight percent of patients had ≥grade 3 treatment-related adverse events. The most frequent ≥grade 3 toxicities were decreased lymphocyte count (50.8%), decreased neutrophil count (42.4%), and decreased white blood count (33.9%). Only 3 patients (5%) had grade 3 diarrhea during the treatment period. Conclusions: This study showed the modest efficacy and manageable toxicity profile of nal-IRI+5-FU/LV in platinum-refractory locally advanced or metastatic H&N or esophagus cancer patients. Clinical benefits including complete tumor response were noted in H&N patients. The role of this regimen in selective patients and the efficacy of combination with immunotherapeutic agents warrant further explorations. Clinical trial information: NCT03712397.

TPS6087 Background: Head and neck squamous cell carcinoma (HNSCC) accounts for more than 830,000 new cancer cases each year worldwide. The prognosis for recurrent and/or metastatic (R/M) HNSCC patients remains poor with an estimated median overall survival (mOS) of 7-15 months in the first line setting and 5-8 months in the second line setting and beyond. Approximately 4-8% of HNSCC tumors are driven by gain-of-function mutations in the HRAS (m HRAS) proto-oncogene. Tipifarnib is a potent and selective farnesyltransferase inhibitor that disrupts HRAS function by blocking required protein membrane localization, and subsequent cellular growth and survival. Data from a prior phase 2 study (RUN-HN; NCT02383927) of tipifarnib in R/M m HRAS HNSCC patients in the second line plus setting demonstrated encouraging efficacy, with an objective response rate (ORR) of 55% and mOS of 15.4 months for patients with mHRAS variant allele frequency (VAF) ≥ 20%, providing support for pursuing a pivotal trial in this patient population. Methods: AIM-HN (NCT03719690) is a global, open-label single-arm pivotal study evaluating the efficacy and tolerability of tipifarnib in second line plus R/M m HRAS HNSCC patients. The primary objective is to determine the ORR in patients with a m HRAS VAF ≥ 20% (High VAF population), as assessed using RECIST v1.1 by Independent Review Facility. Key secondary objectives include the ORR for patients of all VAF levels, and the duration of responses for both VAF≥ 20% and all VAF levels. Key inclusion criteria include: histologically confirmed head and neck cancer of squamous histology not amenable to local therapy with curative intent; known tumor missense HRAS mutation (with VAF determined and available) detected by Next Generation Sequencing; ECOG performance status of 0-1; measurable disease by RECIST v1.1; and adequate organ function. Key exclusion criteria include: salivary gland, thyroid, (primary) cutaneous squamous or non-squamous histologies; intolerable Grade 2 or ≥ Grade 3 neuropathy or unstable neurological symptoms within 4 weeks of Cycle 1 Day 1; or active, uncontrolled infections requiring systemic therapy. Tipifarnib is administered at a dose of 600 mg, orally with a meal twice a day for 7 days in alternating weeks (Days 1-7 and 15-21) of 28-day cycles until discontinuation criteria are met. All patients are being followed for safety through the End of Treatment visit, roughly 30 days after treatment discontinuation or immediately before the administration of another anticancer treatment, whichever occurs first. Upon therapy discontinuation, all patients are being followed approximately every 12 weeks for survival status, and the use of subsequent therapy. The IDMB last reviewed data in October 2020 and recommended the trial continue as planned. AIM-HN is continuing to enroll patients globally. Ho et al, JCO, accepted. Clinical trial information: NCT03719690.

In the foreland area of western Taiwan, some of the pre-orogenic basement-involved normal faults were reactivated during the subsequent compressional tectonics. The main purpose of this paper is to investigate the role played by the pre-existing normal faults in the recent tectonics of western Taiwan. In NW Taiwan, reactivated normal faults with a strike-slip component have developed by linkage of reactivated single pre-existing normal faults in the foreland basin and acted as transverse structures for low-angle thrusts in the outer fold-and-thrust belt. In the later stage of their development, the transverse structures were thrusted and appear underneath the low-angle thrusts or became tear faults in the inner fold-and-thrust belt. In SW Taiwan, where the foreland basin is lacking normal fault reactivation, the pre-existing normal faults passively acted as ramp for the low-angle thrusts in the inner fold-and-thrust belt. Some of the active faults in western Taiwan may also be related to reactivated normal faults with right-lateral slip component. Some main earthquake shocks related to either strike-slip or thrust fault plane solution occurred on reactivated normal faults, implying a relationship between the pre-existing normal fault and the triggering of the recent major earthquakes. Along-strike contrast in structural style of normal fault reactivation gives rise to different characteristics of the deformation front for different parts of the foreland area in western Taiwan. Variations in the degree of normal fault reactivation also provide some insights into the way the crust embedding the pre-existing normal faults deformed in response to orogenic contraction.

Background. The role of adjuvant chemotherapy for the treatment of nasopharyngeal carcinoma (NPC) is controversial, and the identification of adequate predictive factors is warranted. Therefore, we aimed to investigate whether the mean standardized uptake value (SUV) measured on [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) could predict the survival benefits for NPC patients that receive adjuvant chemotherapy. Materials and Methods. The data for 174 NPC patients who underwent PET/computed tomography before chemoradiation between January 2004 and January 2012 were reviewed. The SUV75% was recorded for primary tumors. All patients received intensity-modulated radiotherapy and cisplatin-based chemotherapy. Adjuvant chemotherapy consisted of 3 cycles of 75 mg/m2 cisplatin and 1,000 mg/m2 fluorouracil for 4 days. Results. The optimal cutoff value was 8.35 for SUV75%, with 112 (64.4%) patients having lower SUV75% and 62 (35.6%) having higher SUV75%. Patients with lower SUV75% had significantly better 5-year overall survival (OS) and distant metastasis-free survival. Multivariate analysis revealed that tumor stage, SUV75%, and adjuvant chemotherapy were significant prognostic factors for OS. Patients with higher SUV75% had significantly higher 5-year OS rates with adjuvant chemotherapy than without adjuvant chemotherapy (84.3% vs. 32.4%, respectively; p < .001). However, in the lower SUV75% group, no differences in 5-year OS were observed between patients who received and those who did not receive adjuvant chemotherapy (92.4% vs. 93.3%, respectively; p = .682). Conclusion. The SUV75% on FDG PET for primary tumors could successfully identify NPC patients who may benefit from adjuvant chemotherapy.

Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable‐risk groups; however, patients with intermediate‐risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next‐generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2,PHF6,KIT, and NPM1 mutation/FLT3‐ internal tandem duplication (ITD)negative were independent prognostic factors for the entire cohort. Among patients with intermediate‐risk cytogenetics, patients with mutations in CEBPA double mutation, IDH2, and NPM1 in the absence of FLT3‐ITD were associated with improved Overall survival (OS), similar to those with favorable‐risk cytogenetics; patients with mutations in TET2,RUNX1,ASXL1, and DNMT3A were associated with reduced OS, similar to those with unfavorable‐risk cytogenetics. We concluded that integration of cytogenetic and molecular profiling improves prognostic stratification of patients into three groups with more distinct prognoses (P

Despite good clinical results of current drugs, a good reason still exists to search for additional therapies for the management of Chronic Myeloid Leukemia (CML). Chinese Herbal Medicine (CHM) has thus far been overlooked by researchers and no data exists on the subject. We studied the impact of adjunctive CHM on the disease course of CML, using mortality as the major outcome measurement. We used the Taiwanese National Health Insurance Research Database to perform a nationwide population‐based cohort study. Our study included CML patients diagnosed between 2000 and 2010. We matched groups according to age, sex, Charlson Comorbidity Index (CCI) score and use of imatinib, and compared the Hazard Ratios (HR) of CHM group and non‐CHM users, as well as characterized trends of prescriptions used for treating CML. 1371 patients were diagnosed with CML in the years examined, of which 466 were included in to this study. We found that the HR of CHM group was significantly lower compared to non‐CHM groups (0.32, 95% CI 0.22–0.48, P

Pegylated liposomal doxorubicin (PLD) has been proven to be an effective antitumor drug for metastatic breast cancer, with less toxicity than conventional anthracycline. Our objective was to evaluate the efficacy and safety of PLD-based adjuvant chemotherapy compared to conventional chemotherapy for patients with stages I-III Triple-negative breast cancer (TNBC).A total of 162 patients, histologically proven to have TNBC at stages I-III between 2003 and 2010, were enrolled to evaluate the impact of PLD- and non-PLD-based adjuvant chemotherapy by using the end-pint of overall survival (OS) and relapse-free survival (RFS).Forty-nine (30.2%) patients received PLD-based adjuvant chemotherapy and 113 (69.8%) a non-PLD regimen, including 84 (52%) patients receiving non-PLD anthracycline. The Kaplan-Meier calculation indicated no differences in RFS and OS between the PLD and non-PLD groups. Multivariate analysis adjusted for tumor size and lymph node status also revealed similar RFS (HR=0.86, 95% CI=0.43-1.73, p=0.678) and OS (HR=0.86, 95% CI=0.41-1.79, p=0.692) for PLD-based chemotherapy compared with non-PLD-based. Patients receiving PLD-based chemotherapy had a relatively lower incidence of grade 3-4 neutropenia (25% vs. 41.6%, respectively; p=0.054) and significantly higher incidence of hand-foot syndrome (16.3% vs. 4.4%, respectively; p=0.010).PLD-based adjuvant chemotherapy was as effective as conventional chemotherapy for patients with TNBC. PLD is an alternative for patients with TNBC when conventional anthracycline is inappropriate.

Background: Concurrent chemoradiation has become the standard of treatment in locally advanced nasopharyngeal carcinoma. However, the exact magnitude of the benefits of adjuvant chemotherapy is still unclear. Materials & methods: This is a retrospective assessment of 181 patients with newly diagnosed, locally advanced nasopharygeal carcinoma who received concurrent chemoradiation followed by adjuvant chemotherapy with cisplatin plus fluorouracil in one institution between 2004 and 2010. Results: The median follow-up period was 40 months (range: 2.1–96.6 months). The estimated 5-year survival rate of patients with and without adjuvant chemotherapy were 83.6 and 66.7%, respectively (p = 0.027). Patients receiving two to three cycles of adjuvant chemotherapy had improved outcomes compared with those without adjuvant chemotherapy or who had received one cycle. Multivariate analysis showed that both advanced stage and suboptimal treatment of adjuvant chemotherapy were adverse risk factors in terms of overall survival and disease-specific survival. Conclusion: Adjuvant chemotherapy with two to three cycles of cisplatin plus fluorouracil improved the survival of nasopharyngeal carcinoma patients.

The primary aim of this study was to evaluate the efficacy of palonosetron combined with dexamethasone in the prevention of vomiting, and especially nausea, in patients receiving allogeneic stem cell transplantation.Palonosetron 0.25 mg was given to 27 patients receiving allogeneic transplantation on the first day of conditioning, and then every other day during the entire conditioning period. Dexamethasone was given daily also during conditioning. Vomiting and nausea were recorded daily according to CTCAE version 4.0 from the start of conditioning to Day 7 after transplantation. In addition, MASCC antiemetic tool (MAT) was also used in parallel to evaluate the intensity of nausea.The treatment was well tolerated; 25.9 and 40.7 % of the patients had grade 2/3 vomiting and nausea respectively during conditioning. The incidences of grade 2/3 vomiting and nausea were even higher in the first week after transplantation (40.7 and 51.8 %, respectively). The score of MAT correlated well with the grade of CTCAE. However, the difference in the mean intensity of nausea between period of conditioning and the first week after HSCT was significant only by using MAT (0.96 ± 1.829 vs. 3.81 ± 3.386, p=0.001) but not CTCAE (1.26 ± 0.903 vs. 1.63 ±0.967, p=0.152).Palonosetron combined with dexamethasone is effective in preventing vomiting during conditioning. However, more effort should be made to alleviate nausea during conditioning and both nausea and vomiting in the first week after transplantation. Furthermore, MAT has a higher discriminant power than CTCAE in assessing the intensity of nausea in patients receiving allogeneic transplantation.

6029Background: For pts with advanced NPC, no approved chemotherapy is available in the second-line setting or beyond, and treatment options are limited. Hypermethylation contributes to the initiat...

Utilization of Chinese Medicine (CM) is not uncommon in patients with chronic lymphocytic leukemia (CLL). However, the current knowledge of the usage and efficacy of CM among CLL patients is limited. The aim of this study was to determine the impact of integrative Chinese Herbal Medicine (CHM) on the disease course of CLL and ascertain the herbal products most commonly prescribed to patients with CLL. A Taiwanese nationwide population-based study involving the use of Western medicine and CM services provided by the National Health Insurance (NHI) was conducted. An NHI Research Database-based cohort study was performed; the timeframe of the study was January 2000 to December 2010. The end of the follow-up period was defined as December 31, 2011. A total of 808 patients were diagnosed with CLL in Taiwan within the defined study period. After randomly matching for age and sex and excluding patients younger than 18 years of age, data from 616 patients were analyzed. The 2 study groups both received standard of care treatment. In addition, 1 group also received CHM. Patients who were registered as receiving other forms of CM, such as acupuncture, were excluded. Hazard ratios of mortality were used to determine the influence of CHM and the therapeutic potential of herbal products. In total, 616 CLL patients were included in the analyses. We found that the HR associated with the adjunctive use of CHM was less than half when compared to the non-CHM group (0.43, 95% CI 0.33–0.55, P

The FLT3 gene with internal tandem duplication (ITD) is a poor prognostic factor in patients with acute myeloid leukemia (AML), and the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for AML patients with FLT3-ITD is controversial. We examined 122 AML patients; 34 patients had FLT3-ITD and 39 patients received allogeneic HSCT. The median overall survival (OS) of patients with wtFLT3/nonHSCT, wtFLT3/HSCT, FLT3-ITD/nonHSCT and FLT3-ITD/HSCT was 40.7 months, 53.4 months, 9.8 months and not reached, respectively (p=0.006). Compared to the wtFLT3/nonHSCT patients, the hazard ratio (95% CI) of OS for wtFLT3/HSCT, FLT3-ITD/nonHSCT and FLT3-ITD/HSCT was 1.39 (0.61-3.18), 3.57 (1.58-8.10) and 0.40 (0.11-1.59), respectively, after adjustment of age, sex, WBC, LDH, karyotype, NPM, and FAB classification. This result indicated that patients with FLT3-ITD/nonHSCT had a significantly worse outcome, but allogeneic HSCT improved the prognosis for patients with FLT3-ITD.

BACKGROUND: CD4(+)interferon (IFN)-γ(+) T cell (Th1) and CD4(+)interleukin (IL)-4(+) T cell (Th2) polarizations are crucial in the pathogenesis of graft-versus-host disease (GVHD). However, this hypothesis is largely based on animal experiments of Parent-into-F1 GVHD model. The causal relationship between kinetics of Th1, Th2 and associated cytokines and the clinical activity of GVHD in a real world situation remains unknown. METHODOLOGY: Peripheral blood was collected every week prospectively from Day 0 to Day 210 (patients without GVHD) or Day 300 (patients with chronic GVHD) after allogeneic peripheral blood stem cell transplantation in consecutive 27 patients. The frequencies of Th1 and Th2 within CD4(+) T cells were determined by flow cytometry and pplasma IFN-γ, IL-12, IL-4, and IL-10 were determined by ELISA. PRINCIPAL FINDINGS: Kinetics of Th1, Th2 frequency, and the plasma IL-10 and IFN-γ more commonly coincided with, rather than predicted, the activity of GVHD. These markers are significantly higher when acute or chronic GVHD developed. The kinetics of IL-10 is especially correlated well with the activity of GVHD during clinical course of immunosuppressive treatment. For patients with hepatic GVHD, there is a positive correlation between plasma IL-10 levels and the severity of hepatic injury. The frequency of Th2 is also significant higher in acute GVHD and tends to be higher in chronic GVHD. Interestingly, there is a very good positive correlation between the frequency of Th1 and Th2 (r = 0.951, p

The Toll-like receptors (TLRs) play a pivotal role in innate immunity for the detection of highly conserved, pathogen-expressed molecules. Previously, we demonstrated that lipopolysaccharide (LPS, TLR4 ligand)-increased macrophage motility required the participation of Src and FAK, which was inducible nitric oxide synthase (iNOS)-dependent. To investigate whether this iNOS/Src/FAK pathway is a general mechanism for macrophages to mobilize in response to engagement of TLRs other than TLR4, peptidoglycan (PGN, TLR2 ligand), polyinosinic–polycytidylic acid (polyI:C, TLR3 ligand) and CpG-oligodeoxynucleotides (CpG, TLR9 ligand) were used to treat macrophages in this study. Like LPS stimulation, simultaneous increase of cell motility and Src (but not Fgr, Hck, and Lyn) was detected in RAW264.7, peritoneal macrophages, and bone marrow-derived macrophages exposed to PGN, polyI:C and CpG. Attenuation of Src suppressed PGN-, polyI:C-, and CpG-elicited movement and the level of FAK Pi-Tyr861, which could be reversed by the reintroduction of siRNA-resistant Src. Besides, knockdown of FAK reduced the mobility of macrophages stimulated with anyone of these TLR ligands. Remarkably, PGN-, polyI:C-, and CpG-induced Src expression, FAK Pi-Tyr861, and cell mobility were inhibited in macrophages devoid of iNOS, indicating the importance of iNOS. These findings corroborate that iNOS/Src/FAK axis occupies a central role in macrophage locomotion in response to engagement of TLRs.

A patient with pathologically proven acrometastasis of his left thumb presented 3 months after esophagectomy for esophageal squamous cell carcinoma. Interestingly, there was indeed a faint uptake in his left thumb that was initially considered an artifact in the whole body bone scan taken before esophagectomy. Physicians must be aware of the possibility of acrometastasis, even if there is no other concomitant metastatic area.