A mini-resonant photoacoustic sensor based on a sphere-cylinder coupled acoustic resonator for high-sensitivity trace gas sensing.

This paper reports a mini-resonant photoacoustic sensor for high-sensitivity trace gas sensing. The sensor primarily contains a sphere-cylinder coupled acoustic resonator, a cylindrical buffer chamber, and a fiber-optic acoustic sensor. The acoustic field distributions of this mini-resonant photoacoustic sensor and the conventional T-type resonant photoacoustic sensor have been carefully evaluated, showing that the first-order resonance frequency of the present mini-resonant photoacoustic sensor is reduced by nearly a half compared to that of the T-type resonant photoacoustic sensor. The volume of the developed photoacoustic cavity is only about 0.8 cm3. Trace methane is selected as the target analytical gas and a detection limit of 101 parts-per-billion at 100-s integration time has been achieved, corresponding to a normalized noise equivalent absorption (NNEA) coefficient of 1.04 × 10-8 W·cm-1·Hz-1/2. The developed mini-resonant photoacoustic sensor provides potential for high-sensitivity trace gas sensing in narrow spaces.

Highly sensitive trace gas detection based on a miniaturized 3D-printed Y-type resonant photoacoustic cell.

We report, what we believe to be, a novel miniaturized 3D-printed Y-type resonant photoacoustic cell (YRPAC) consisting of a frustum of cone-type buffer chamber and a cylindrical resonant chamber. The volume of the designed YRPAC is about 7.0 cm3, which is only about a half of the T-resonant photoacoustic cell (TRPAC). The finite element simulation of the sound field distribution of the TRPAC and YRPAC based on COMSOL shows that the photoacoustic signal is enhanced with the shape of the buffer chamber changing from the traditional cylinder to a frustum of cone. The photoacoustic spectroscopy (PAS) system, utilizing the YRPAC and TRPAC as the photoacoustic reaction units, a 1653.7 nm distributed feedback (DFB) laser as the excitation light source, a cantilever beam acoustic sensor as the acoustic sensing unit, and a high-speed spectrometer as the demodulation unit, has been successfully developed for high-sensitivity trace CH4 sensing. When the CH4 concentration is 1000 ppm, the 2f signal of YRPAC in the first-order resonance mode is 2.3 nm, which is 1.7 times higher than the 2f signal amplitude of TRPAC. The detection sensitivity and minimum detection limit for the PAS system are 2.29 pm/ppm and 52.8 parts per billion (ppb) at 100 s of averaging time. The reported YRPAC has higher sensitivity, smaller size, and faster response time compared to the conventional TRPAC, which can provide a new solution for PAS development.

Measurement of adherence and health-related quality of life during anticoagulation therapy in cancer-associated venous thromboembolism (VTE): a multicenter quantitative study.

PURPOSE: Therapy for cancer-associated venous thromboembolism (VTE) includes long-term anticoagulation, which may have substantial impact on the health-related quality of life (HRQL) of patients. We assessed patient-reported outcomes to characterize the HRQL associated with VTE treatment and to begin to examine those HRQL elements impacting anticoagulation adherence (AA). METHODS: Participants were adult cancer patients with confirmed symptomatic acute lower extremity deep venous thrombosis. Patients were excluded if there was an indication for anticoagulation other than VTE, ECOG performance status >3, or life expectancy < 3 months. Participants were assessed with a self-reported adherence tool. HRQL was measured with a 6-domain questionnaire using a seven-point Likert scale. Evaluations were performed at 30 days and 3 months after enrollment. For the primary objective, an overall adherence rate was calculated at each time point of evaluation. For the HRQL domains, non-parametric testing was used to compare results between subgroups. RESULTS: Seventy-four patients were enrolled. AA and HRQL at 30 days and 3 months were assessed in 50 and 36 participants, respectively. At 30 days the AA rate was 90%, and at 3 months it was 83%. In regard to HRQL, patients suffered frequent and moderate-severe distress in the domains of emotional and physical symptoms, sleep disturbance, and limitations to physical activity. An association between emotional or physical distress and AA was observed. CONCLUSION: Patients with VTE suffer a substantial impairment of their HRQL. Increased emotional distress correlated with better long-term AA. These results can be used to inform additional research aimed at developing novel strategies to improve AA.

TNM Staging and Overall Survival in Patients With Pheochromocytoma and Sympathetic Paraganglioma.

CONTEXT: Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors. Metastases develop in 15% to 20%. The American Joint Committee on Cancer (AJCC) established inaugural guidelines for PPGL tumor-node-metastasis (TNM) staging. OBJECTIVE: The objective of this analysis is to investigate the associations between TNM staging and overall survival (OS). METHODS: We retrospectively applied the TNM staging at the time of diagnosis of the primary tumor. The primary outcome was OS. Unadjusted survival rates were estimated by the Kaplan-Meier method. Cox proportional hazards regression models were used to evaluate the associations between OS and covariates of interest. RESULTS: The study included 458 patients. Median OS was 18.0 (95% CI, 15.6-not reached) years. At diagnosis, 126 (27.5%) tumors were stage I, 213 (46.5%) were stage II, 47 (10.3%) were stage III, and 72 (15.7%) were stage IV. The 10-year OS probabilities were 0.844 (95% CI, 0.768-0.928) for patients with stage I tumors, 0.792 (95% CI, 0.726-0.865) for stage II, 0.595 (95% CI, 0.435-0.813) for stage III, and 0.221 (95% CI, 0.127-0.384) for stage IV. Compared with stage I, the hazard ratios (HR) for death were 1.50 (0.87-2.57) for stage II, 2.85 (1.45-5.63) for stage III, and 8.88 (5.16-15.29) for stage IV (P < 0.001). Compared with patients with no germline mutations, those with RET 634/918 had better OS (HR: 0.28; 95% CI, 0.12-0.69). Other germline mutations, including SDHB, did not exhibit worse OS than patients with metastasis and sporadic disease. CONCLUSION: OS rates correlated with the recently developed AJCC TNM staging and were not worse in hereditary disease. Stage IV disease exhibited a significantly shorter OS compared with stages I-III. Future staging systems could be adjusted to better separate stages I and II.

Patterns of opioid use among Texas dental practitioners during the COVID-19 pandemic.

OBJECTIVE: The primary objective of this study is to assess factors that influence opioid prescribing by dentists and the role of these factors in the practice of dental pain control. DESIGN: A 25-question survey instrument was distributed to the study population for anonymous responses, covering dentist and practice demographics and opioid prescribing characteristics. SETTING: Private solo and group practice settings, including general practitioners and dental specialists. PARTICIPANTS: Potential participants included all active members of a large state dental professional association. MAIN OUTCOME MEASURES: They were practitioner and practice demographic traits, types of opioids prescribed, and statistical correlations. Outcome variables included practice type, practitioner gender, practice location, practice model, and years in practice. Categorical covariates were summarized statistically by frequencies and percentages, and continuous covariates were summarized by means, medians, ranges, and standard deviations. RESULTS: Strongest correlations with opioid prescribing included general practitioner (vs specialist) and male gender. The coronavirus disease 2019 pandemic was confirmed as having exerted a significant impact on opioid prescribing among the survey respondents. CONCLUSIONS: Further research is warranted to assess post-pandemic opioid prescribing patterns, and additional educational strategies regarding limitations of opioid prescriptions should be applied to general, rather than specialty, dental practitioners.

Ultra-High-Sensitivity, Miniaturized Fabry-Perot Interferometric Fiber-Optic Microphone for Weak Acoustic Signals Detection.

An ultra-high-sensitivity, miniaturized Fabry-Perot interferometric (FPI) fiber-optic microphone (FOM) has been developed, utilizing a silicon cantilever as an acoustic transducer. The volumes of the cavity and the FOM are determined to be 60 microliters and 102 cubic millimeters, respectively. The FOM has acoustic pressure sensitivities of 1506 nm/Pa at 2500 Hz and 26,773 nm/Pa at 3233 Hz. The minimum detectable pressure (MDP) and signal-to-noise ratio (SNR) of the designed FOM are 0.93 µPa/Hz1/2 and 70.14 dB, respectively, at an acoustic pressure of 0.003 Pa. The designed FOM has the characteristics of ultra-high sensitivity, low MDP, and small size, which makes it suitable for the detection of weak acoustic signals, especially in the field of miniaturized all-optical photoacoustic spectroscopy.

High-sensitivity miniature dual-resonance photoacoustic sensor based on silicon cantilever beam for trace gas sensing.

We report a miniature dual-resonance photoacoustic (PA) sensor, mainly consisting of a small resonant T-type PA cell and an integrated sensor probe based on a silicon cantilever beam. The resonance frequency of the miniature T-type PA cell is matched with the first-order natural frequency of the cantilever beam to achieve double resonance of the acoustic signal. The volume of the designed T-type PA cell is only about 2.26 cubic centimeters. A PA spectroscopy (PAS) system, employing the dual-resonance photoacoustic (PA) sensor as the prober and a high-speed spectrometer as the demodulator, has been implemented for high-sensitivity methane sensing. The sensitivity and the minimum detection limit can reach up to 2.0 pm/ppm and 35.6 parts-per-billion, respectively, with an averaging time of 100 s. The promising performance demonstrated a great potential of employing the reported sensor for high-sensitivity gas sensing in sub cubic centimeter-level spaces.

High-Sensitivity Multitrace Gas Simultaneous Detection Based on an All-Optical Miniaturized Photoacoustic Sensor.

We propose an all-optical miniaturized multigas simultaneous detection photoacoustic (PA) sensor, which is primarily composed of a copper tube, a silica cantilever, and four single-mode fibers. Three single-mode fibers are used as excitation fibers to transmit lasers of different wavelengths, and the remaining one is used as a probe fiber. The volumes of the PA cell (PAC) and the sensor are 36 µL and 71 cubic millimeters, respectively. A laser photoacoustic spectroscopy (PAS) system, using the all-optical miniaturized PA sensor as a detector, 1532.8, 1576.3, and 1653.7 nm distributed feedback (DFB) lasers as the excitation sources for acetylene (C2H2), hydrogen sulfide (H2S), and methane (CH4) gases, and a high-speed spectrometer as a demodulator, has been developed for multigas simultaneous measurements. The minimum detection limits of 4.8, 162, and 16.6 parts per billion (ppb) have been achieved for C2H2, H2S, and CH4, respectively, with an integration time of 100 s. The reported sensor shows a potential for high-sensitivity multigas simultaneous measurements in cubic millimeter-scale space.

KRD vs. VRD as induction before autologous hematopoietic progenitor cell transplantation for high-risk multiple myeloma.

Bortezomib, lenalidomide, and dexamethasone (VRD) induction is standard prior to autologous hematopoietic cell transplantation (auto-HCT) in newly diagnosed, high-risk multiple myeloma (ND-HRMM). Carfilzomib (K) is another proteasome inhibitor approved for MM. In this single-center, retrospective analysis, we compared outcomes in ND-HRMM with pre-transplant KRD or VRD induction. High-risk was defined by t(4:14), t(14:16), 1q21 gain/amplification, or del(17p). Primary endpoints were progression-free (PFS) and overall survival (OS). Of 121 ND-HRMM patients, 63 received KRD, and 58 received VRD. Post-induction, complete (CR), very good partial (VGPR), partial response (PR), and overall response (ORR) rates were 23.8%/49.2%/25.4%/98.4% with KRD, and 19%/46.6%/27.6%/93.1% with VRD. At day 100 post-auto-HCT, these were 38.1%/42.9%/19%/100% with KRD, versus 35.1%/49.1%/12.3%/94.8% with VRD. Pre-auto-HCT, 11 (18.3%) KRD and 7 (12.5%) VRD patients had minimal residual disease (MRD)-negative CR (p = 0.45). Post-auto-HCT, 14 (41.2%) and 13 (43.3%) patients had MRD-negative CR (p = 1.000). Median PFS was 38.2 (95%CI 28.7-NA) and 45.9 months (95%CI 43.2-NA) for KRD and VRD, respectively (p = 0.25). Respective 3-year PFS and OS were 53.5% (95%CI 41.1-69.6) and 95.2% (95%CI 90-100) for KRD and 64% (95%CI 51.6-79.5) and 84.2% (95%CI 73.5-96.3, p = 0.30) for VRD. Overall, KRD induction pre-auto-HCT does not improve outcomes. Prospective, randomized studies are needed to confirm these findings.

Clonal Hematopoiesis Is Associated with Increased Risk of Severe Neurotoxicity in Axicabtagene Ciloleucel Therapy of Large B-Cell Lymphoma.

To explore the role of clonal hematopoiesis (CH) in chimeric antigen receptor (CAR) T-cell therapy outcomes, we performed targeted deep sequencing on buffy coats collected during the 21 days before lymphodepleting chemotherapy from 114 large B-cell lymphoma patients treated with anti-CD19 CAR T cells. We detected CH in 42 (36.8%) pretreatment samples, most frequently in PPM1D (19/114) and TP53 (13/114) genes. Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) incidence was higher in CH-positive patients than CH-negative patients (45.2% vs. 25.0%, P = 0.038). Higher toxicities with CH were primarily associated with DNMT3A, TET2, and ASXL1 genes (DTA mutations). Grade ≥3 ICANS (58.9% vs. 25%, P = 0.02) and ≥3 cytokine release syndrome (17.7% vs. 4.2%, P = 0.08) incidences were higher in DTA-positive than in CH-negative patients. The estimated 24-month cumulative incidence of therapy-related myeloid neoplasms after CAR T-cell therapy was higher in CH-positive than CH-negative patients [19% (95% CI, 5.5-38.7) vs. 4.2% (95% CI, 0.3-18.4), P = 0.028]. SIGNIFICANCE: Our study reveals that CH mutations, especially those associated with inflammation (DNMT3A, TET2, and ASXL1), are associated with severe-grade neurotoxicities in lymphoma patients receiving anti-CD19 CAR T-cell therapy. Further studies to investigate the mechanisms and interventions to improve toxicities in the context of CH are warranted. See related content by Uslu and June, p. 382. This article is highlighted in the In This Issue feature, p. 369.

A randomized phase III study of pretransplant conditioning for AML/MDS with fludarabine and once daily IV busulfan ± clofarabine in allogeneic stem cell transplantation.

Pretransplant conditioning with Fludarabine (Flu)-Busulfan (Bu) is safe, but clofarabine (Clo) has improved antileukemic activity. Hypothesis: Flu+Clo-Bu (FCB) yields superior progression-free survival (PFS) after allogeneic transplantation. We randomized 250 AML/MDS patients aged 3-70, Karnofsky Score ≥80, with matched donors, to FCB (n = 120) or Flu-Bu (n = 130), stratifying complete remission (CR) vs. No CR, (NCR). HCT-CI scores varied, from 0 to 10. All evaluable patients engrafted. Median follow-up was 66 months (interquartile range: 58-80). Three-year relapse incidence (RI), 25% with FCB, vs. 39% with Flu-Bu (p = 0.018), offset by higher non-relapse mortality, 22.6% (95%CI: 16-30.2%) vs. 12.3% (95%CI: 6.5-19%). Three-year PFS was 52% (95%CI: 44-62%) (FCB), vs. 48% (95%CI: 41-58%) (Flu-Bu). FCB benefited CR patients less, NCR patients age ≤ 60 had 3-year 34% RI (95%CI: 19-49%) (FCB) vs. 56% (95%CI: 38-70%) after Flu-Bu (p = 0.037). NCR patients >60 years had 3-year RI 10.0% (FCB), vs. 56.0%, after Flu-Bu (p = 0.003). Bayesian regression analysis including treatment-covariate interactions showed FCB superiority in NCR patients with low HCT-CI (0-2). Serious adverse event profiles were similar for the regimens. Conditioning with FCB did not improve PFS overall, but improved disease control in NCR patients, mandating confirmatory trials. Remission status and HCT-CI should be considered when using FCB.

A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia.

We conducted a phase Ib/II multi-arm, parallel cohort study to simultaneously evaluate various immunotherapeutic agents and combinations in relapsed/refractory acute myeloid leukemia (AML). Overall, 50 patients were enrolled into one of 6 arms: (A) single agent PF-04518600 (OX40 agonist monoclonal antibody), (B) azacitidine + venetoclax + gemtuzumab ozogamicin (GO), (C) azacitidine + avelumab (anti-PD-L1 monoclonal antibody) + GO, (D) azacitidine + venetoclax + avelumab, (E) azacitidine + avelumab + PF-04518600, and (F) glasdegib + GO. Among all regimens evaluated, azacitidine + venetoclax + GO appeared most promising. In this arm, the CR/CRi rates among venetoclax-naïve and prior venetoclax-exposed patients were 50% and 22%, respectively, and the 1-year OS rate was 31%. This study shows the feasibility of a conducting a multi-arm trial to efficiently and simultaneously evaluate novel therapies in AML, a needed strategy in light of the plethora of emerging therapies. This trial was registered at www.clinicaltrials.gov as NCT03390296.

Impact of Induction With VCD Versus VRD on the Outcome of Patients With Multiple Myeloma After an Autologous Hematopoietic Stem Cell Transplantation.

Induction therapy with a triplet regimen, followed by high-dose therapy and autologous hematopoietic stem cell transplantation (auto-HCT), is the standard of care for newly diagnosed, transplant-eligible patients with multiple myeloma (MM). Bortezomib-dexamethasone with cyclophosphamide (VCD) or lenalidomide (VRD) are the most used induction regimens. However, previous studies comparing VCD and VRD showed disparate results. The goal of this retrospective study was to compare the "real-world" results of VCD and VRD in transplant-eligible MM patients outside of a clinical trial. We identified 322 patients who received VRD or VCD induction before auto-HCT at our institution. All patients received melphalan conditioning and single-agent lenalidomide maintenance therapy. Overall, 114 patients received VCD, and 208 received VRD. The median age at auto-HCT was 61.9 years (range 33.9-79.6), with 35.4% (114/322) of the cohort being 65 years of age or older. The overall response rate was 99.7% after auto-HCT, with a significantly lower complete remission rate as the final response in the VCD compared to the VRD group (34% versus 53%; P = .001). However, there was no significant difference between the best response rate of very good partial response (VGPR) or better in the VCD compared to the VRD group (92% versus 85%; P = .078). The median duration of ≥VGPR was 50.0 months (95% confidence interval [CI], 42.0-69.1) for both cohorts, and there was no difference between VCD and VRD (P = .769; hazard ratio, 0.95; 95% CI, 0.69-1.31). Median follow-up of survivors was 73 months. There was no difference in the relapse rate between VCD and VRD (P = .749). Median progression-free survival (PFS) was 48.7 months in the VCD and 44.6 months in the VRD group (P = .858). Median overall survival (OS) was 103.8 months with VCD and 101.7 months with VRD (P = .891). At 5 years, the PFS and OS were 38.1% and 76.9% for the VCD group, respectively, and 40.7% and 74.6% for the VRD group, respectively. On multivariate analysis for OS in the entire cohort, Revised International Staging System I and post-auto-HCT best response of stringent complete response (sCR)/CR emerged as significant predictors of superior OS. There was no impact of the type of induction regimen on the OS in the multivariate analysis. Induction therapy with VCD compared to VRD was associated with a lower CR rate, but there was no difference in PFS or OS between the 2 regimens.

Expression and Potential Prognostic Value of SOX9, MCL-1 and SPOCK1 in Gastric Adenocarcinoma.

Gastric cancer is a common malignancy and remains one of the leading causes of cancer-related deaths, though its incidence is in decline in most developed countries. One of the major challenges of treating gastric cancer is tumor heterogeneity, which portends a high degree of prognostic variance and the necessity for different treatment modalities. Tumor heterogeneity is at least in part due to divergent differentiation of tumor cells to clones harboring different molecular alterations. Here we studied the expression of emerging prognostic markers SOX9, MCL-1, and SPOCK1 (Testican-1) in a cohort of gastric cancer by immunohistochemistry and investigated how individual biomarkers and their combinations predict disease prognosis. We found frequent expression of SPOCK1 (in both nuclei and cytoplasm), MCL-1 and SOX9 in gastric cancer. In univariate analysis, nuclear SPOCK1 expression and pathologic TNM stage were negative prognostic markers in this cohort. In multivariate analysis, SOX9 expression stood out as a predictor of poor prognosis. Further subgroup analysis suggested prognostic value of SOX9 expression in poorly differentiated gastric adenocarcinoma. MCL-1 showed no prognostic role in this cohort.

PIONEER-Panc: a platform trial for phase II randomized investigations of new and emerging therapies for localized pancreatic cancer.

BACKGROUND: Personalized and effective treatments for pancreatic ductal adenocarcinoma (PDAC) continue to remain elusive. Novel clinical trial designs that enable continual and rapid evaluation of novel therapeutics are needed. Here, we describe a platform clinical trial to address this unmet need. METHODS: This is a phase II study using a Bayesian platform design to evaluate multiple experimental arms against a control arm in patients with PDAC. We first separate patients into three clinical stage groups of localized PDAC (resectable, borderline resectable, and locally advanced disease), and further divide each stage group based on treatment history (treatment naïve or previously treated). The clinical stage and treatment history therefore define 6 different cohorts, and each cohort has one control arm but may have one or more experimental arms running simultaneously. Within each cohort, adaptive randomization rules are applied and patients will be randomized to either an experimental arm or the control arm accordingly. The experimental arm(s) of each cohort are only compared to the applicable cohort specific control arm. Experimental arms may be added independently to one or more cohorts during the study. Multiple correlative studies for tissue, blood, and imaging are also incorporated. DISCUSSION: To date, PDAC has been treated as a single disease, despite knowledge that there is substantial heterogeneity in disease presentation and biology. It is recognized that the current approach of single arm phase II trials and traditional phase III randomized studies are not well-suited for more personalized treatment strategies in PDAC. The PIONEER Panc platform clinical trial is designed to overcome these challenges and help advance our treatment strategies for this deadly disease. TRIAL REGISTRATION: This study is approved by the Institutional Review Board (IRB) of MD Anderson Cancer Center, IRB-approved protocol 2020-0075. The PIONEER trial is registered at the US National Institutes of Health (ClinicalTrials.gov) NCT04481204 .

Insights into the effects of Fenton oxidation on PAH removal and indigenous bacteria in aged subsurface soil.

Combined chemical oxidation and bioremediation is a promising method of treating polycyclic aromatic hydrocarbon (PAH) contaminated soil, wherein indigenous soil bacteria play a critical role in the subsequent biodegradation of PAHs after the depletion of the oxidant. In this study, different Fenton conditions were applied by varying either the oxidation mode (conventional Fenton (CF), Fenton-like (LF), modified Fenton (MF), and graded modified Fenton (GMF)) or the H2O2 dosage (0%, 3%, 6%, and 10% (v/v)) to treat PAH contaminated soil. The results revealed that when equal dosages of H2O2 are applied, PAHs are significantly removed following oxidation treatment, and the removal percentages obeyed the following sequence: CF > GMF > MF > LF. In addition, higher dosages of H2O2 improved the PAH removal from soil treated with the same oxidation mode. The ranges of total PAHs removal efficiencies in the soil added 3%, 6%, and 10% of H2O2 (v/v) were 18.04%∼59.48%, 31.88%∼71.83%, and 47.56%∼78.16%, respectively. The PAH removal efficiency decreased with increasing ring numbers for the same oxidation treatment. However, the negative influences on soil bacterial abundance, community composition, and function were observed after Fenton treatment. After Fenton oxidation, the bacterial abundance in the soil received 3%, 6%, and 10% of H2O2 (v/v) decreased 1.96-2.69, 2.44-3.22, and 3.09-3.42 orders of magnitude compared to the untreated soil. The soil bacterial abundance tended to be impacted by the oxidation mode and H2O2 dosage simultaneously. While the main factor influencing the soil bacterial community composition was the H2O2 dosages. The results of this study showed that different oxidation mode and H2O2 dosage exhibited different effects on PAHs removal and soil bacteria (including abundance, community composition, and function), and there was a trade-off between the removal of PAHs and the adverse impact on soil bacteria.

PD-1 inhibitors for cutaneous squamous cell carcinoma: A meta-analysis.

PD-1 inhibitors are immunotherapeutic agents used in the treatment of advanced cutaneous squamous cell carcinoma (cSCC). This study aimed to determine the pooled objective response and disease control rates of patients with advanced cSCC treated with PD-1 inhibitors. Pubmed, Cochrane Library and EMBASE databases were searched up to 1 January 2021 to include eligible articles. Objective response rate (ORR) and disease control rate (DCR) were pooled and analysed. Subgroup analysis of the odds ratio (OR) for ORR for patients by PD-L1 tumour proportion score (TPS) was performed. Seven articles including a total of 453 patients were identified and included. Pooled estimate of ORR was 44% (95% CI: 39-49%, I2 = 23.7%) and of DCR was 66% (95% CI: 57-74%, I2 = 68.2%). Pooled odds ratio of ORR for patients by PD-L1 TPS was 2.81 (95% CI: 1.22-6.51, I2 = 0.0%). These results were derived from single-arm studies, some of which were retrospective. No head-to-head trials comparing PD-1 inhibitors have been reported. We present aggregate estimates of ORR and DCR for patients with advanced cSCC treated with PD-1 inhibitors, as well as subgroup analysis for ORR for patients by PD-L1 TPS.

Real-world long-term outcomes in multiple myeloma with VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance.

Standard-of-care for newly-diagnosed, autologous hematopoietic stem cell transplantation (auto-HCT)-eligible, multiple myeloma (MM) patients includes bortezomib, lenalidomide, and dexamethasone (VRD) induction followed by melphalan 200 mg/m2 (Mel200)-conditioned auto-HCT and lenalidomide maintenance. We completed a retrospective case series assessing outcomes of 187 MM patients who received this regimen at our institution. The 100-day non-relapse mortality incidence was zero. Before auto-HCT, 9.6 and 52.9% of patients achieved a complete response (CR) or ≥ very good partial response (VGPR), respectively. At day-100 post-transplant, 29.4 and 74.9% had achieved a CR/stringent-CR (sCR) or ≥ VGPR, respectively. At the last evaluation, 57.2% of patients had CR/sCR and 87.1% had ≥ VGPR. Median follow-up, progression-free survival (PFS), and overall survival (OS) were 63.2, 50, and 101.7 months, respectively. The 5-year PFS and OS were 43.1 and 79%. High-risk cytogenetics was associated with worse outcomes. This study illustrates that VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance are associated with good outcomes in MM.

Care Patterns for Stereotactic Radiosurgery in Small Cell Lung Cancer Brain Metastases.

INTRODUCTION: The historical standard of care for brain metastases (BMs) from small cell lung cancer (SCLC) has been whole-brain radiotherapy (WBRT). However, there is growing interest in upfront stereotactic radiosurgery (SRS) for select SCLC patients. MATERIALS AND METHODS: We invited United State-based Radiation Oncologists (ROs) via email to answer an anonymous survey using a branching logic system addressing their use of SRS and WBRT for SCLC BMs. Wilcoxon rank-sum test and Fisher's exact test were used to compare differences in continuous and categorical variables, respectively. Multivariable logistic regression analyses were fitted for outcome variables including covariates with P < .10 obtained on univariable analysis. RESULTS: In total, 309 ROs completed the survey and 290 (95.7%) reported that they would consider SRS for SCLC BMs under certain clinical circumstances. Across patient characteristics, the number of BMs was the most heavily weighted factor (mean 4.3/5 in importance), followed by performance status, cognitive function, and response to prior therapy. Fewer BMs were correlated with increased SRS use (55.8% offered SRS "very frequently" [>75% of cases] or "often" [51%-75% of cases] for 1 BM vs. 1.1% for >10 BM, P < .001). In situations where WBRT was preferred, concern for rapid intracranial progression (45.3%) and lack of high-level data (36.9%) were the most important factors. The majority (60.6%) were aware of a large recent international retrospective analysis (the FIRE-SCLC study) reporting similar OS between upfront SRS and WBRT; awareness of this study was the only respondent variable predictive of SRS use for limited BMs (19.2% of those aware of the study preferring SRS for limited [≤4] BMs before vs. 61% preferring SRS after the publication, P < .001). The majority of respondents (88.2%) expressed a willingness to enroll patients on a recently opened recently opened randomized trial, NRG-CC009, comparing SRS versus hippocampal-avoidance WBRT. CONCLUSIONS: In the first survey of SRS for SCLC BMs, we observed a high level of physician openness to upfront SRS in SCLC, particularly for patients with limited numbers of BMs, as well as significant interest in generating prospective randomized data to clarify the role of SRS in this population.

Refined HLA-DPB1 mismatch with molecular algorithms predicts outcomes in hematopoietic stem cell transplantation.

HLA-DPB1 mismatches between donor and recipient are commonly seen in allogeneic hematopoietic stem cell transplantation from an unrelated donor. HLA-DPB1 mismatch, conventionally determined by the similarity of the T-cell epitope (TCE), is associated with an increased risk of acute graft-versus-host disease (GVHD) and a decreased risk of disease relapse. We investigated the clinical impact of HLA-DPB1 molecular mismatch quantified by mismatched eplets (ME) and the Predicted Indirectly Recognizable HLA Epitopes Score (PS) in a cohort of 1,514 patients receiving hematopoietic stem cell transplants from unrelated donors matched at HLA-A, -B, -C, -DRB1/3/4/5, and - DQB1 loci. HLA-DPB1 alloimmunity in the graft-versus-host direction, determined by high graft-versus-host ME/PS, was associated with a reduced risk of relapse (hazard ratio [HR]=0.83, P=0.05 for ME) and increased risk of grade 2-4 acute GVHD (HR=1.44, P<0.001 for ME), whereas high host-versus-graft ME/PS was only associated with an increased risk of grade 2-4 acute GVHD (HR=1.26, P=0.004 for ME). Notably, in the permissive mismatch subgroup classified by TCE grouping, high host-versus-graft ME/PS was associated with an increased risk of relapse (HR=1.36, P=0.026 for ME) and grade 2-4 acute GVHD (HR=1.43, P=0.003 for PS-II). Decision curve analysis showed that graftversus- host ME outperformed other models and provided the best clinical net benefit for the modification of acute GVHD prophylaxis regimens in patients with a high risk of developing clinically significant acute GVHD. In conclusion, molecular assessment of HLA-DPB1 mismatch enables separate prediction of host-versus-graft or graft-versus-host alloresponse quantitatively and allows further refinement of HLA-DPB1 permissiveness as defined by conventional TCE grouping.