A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma.

Background: Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo-immunotherapy in the curative setting is not established.

Methods: This phase 2, single-arm, multicenter study evaluated neoadjuvant chemo-immunotherapy with carboplatin, nab-paclitaxel, and durvalumab in patients with resectable locally advanced HNSCC.

Attrition and withdrawal in multiple myeloma randomized controlled trials: A systematic review.

Objectives: Patients with multiple myeloma (MM) enrolled in randomized control trials (RCTs) discontinue treatment for various reasons; however, no prior study has analyzed reasons for discontinuation. We performed a systematic review of MM RCTs to investigate reasons for treatment discontinuation, imbalances between trial cohorts, and reporting practices.

Methods: A comprehensive search for RCTs in MM from 2015 to 2021 identified 45 studies meeting inclusion criteria.

AMC-070: Lenalidomide Is Safe and Effective in HIV-Associated Kaposi Sarcoma.

Purpose: Kaposi sarcoma (KS), an endothelial cell tumor associated with KS herpesvirus (KSHV), remains among the most common malignancies occurring with HIV infection (HIV-KS). As an oral anti-inflammatory, antiangiogenic, and immunomodulatory agent, lenalidomide is potentially an attractive alternative to standard chemotherapy for KS.

Experimental Design: The primary objectives of this phase I/II trial were to determine the maximum tolerated dose (MTD) and response rates for lenalidomide in HIV-KS.

Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma.

Background: To characterize genomic determinants of response to pembrolizumab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 study.

Methods: Associations between biomarkers (tumor mutational burden (TMB), neoantigen load (NL), 18-gene T-cell-inflamed gene expression profile (TcellGEP), and PD-L1 combined positive score (CPS)) and clinical outcomes with pembrolizumab were assessed in patients with R/M HNSCC (n=192). Tumor human papillomavirus (HPV) status was also evaluated with the use of p16 immunohistochemistry and whole exome sequencing (WES; HPV, mapping >20 HPV reads) in pretreatment tumor samples (n=106).

Real-World Treatment Patterns and Outcomes Among Patients With Metastatic NSCLC Previously Treated With Programmed Cell Death Protein-1/Programmed Death-Ligand 1 Inhibitors.

Introduction: Programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors are standard-of-care treatment for metastatic NSCLC (mNSCLC). Intolerance to treatment/disease progression warrants additional lines of therapy. Real-world treatment patterns and efficacy outcomes after PD-1/PD-L1 use are insufficiently characterized to inform treatment decisions.

Pharmacokinetic-based failure of a detergent virucidal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) nasal infections: A preclinical study and randomized controlled trial.

Background: The nose is the portal for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, suggesting the nose as a target for topical antiviral therapies. The purpose of this study was to assess both the in vivo and in vitro efficacy of a detergent-based virucidal agent, Johnson and Johnson's Baby Shampoo (J&J), in SARS-CoV-2-infected subjects.

Methods: Subjects were randomized into three treatment groups: (1) twice daily nasal irrigation with J&J in hypertonic saline, (2) hypertonic saline alone, and (3) no intervention.

A case of metastatic NUT carcinoma with prolonged response on gemcitabine and nab-paclitaxel.

Background: NUT carcinoma is an aggressive malignancy characterized by translocations in the  gene. There are currently no consensus treatment recommendations for NUT carcinomas.

Methods: Here, we describe the case of a previously healthy male diagnosed with NUT carcinoma after presenting with sinus pressure, found to have a sinonasal mass and distant metastatic disease in the lungs.

Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer.

Objectives: Veliparib is a potent poly(ADP)-ribose polymerase (PARP) 1 and 2 inhibitor that impedes repair of DNA damage induced by cytotoxic and radiation therapies. This phase 1 study evaluated veliparib in combination with chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer (NSCLC).

Materials And Methods: Patients received veliparib orally twice daily (BID) in escalating doses (60-240 mg, Day -3 to 1 day after last dose of radiation) combined with weekly carboplatin (area under the curve [AUC] 2 mg/mL/min), paclitaxel (45 mg/m), and daily radiation therapy (60 Gy in 30 fractions), followed by two cycles of veliparib (120-240 mg BID, Days -2 through 5 of each 21-day cycle), carboplatin (AUC 6 mg/mL/min, Day 1 of each cycle), and paclitaxel (200 mg/m, Day 1 of each cycle) consolidation.

Caregiver Education and Training: Learning Preferences of Informal Caregivers of Adult Care Recipients.

Oncology nurses play a key role in supporting caregivers through education and training in both inpatient and outpatient settings. This article describes the learning preferences of informal caregivers of adult care recipients. Caregiver respondents preferred multiple training methods, with most endorsing in-person instruction, online video instruction, and reading materials.

Consolidation With Pembrolizumab and Nab-Paclitaxel After Induction Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

Background: Induction with four cycles of platinum-based chemotherapy was the standard of care for metastatic non-small cell lung cancer (NSCLC) until the approval of immune checkpoint blockade (ICB) in the first-line setting. Switch maintenance therapy has shown promise in improving survival by exposing patients to novel, non-cross-resistant agents earlier in their treatment course.

Methods: We performed this open-label, three-arm, randomized phase II study (NCT02684461) to evaluate three sequences of consolidation with pembrolizumab and nab-paclitaxel in patients without progressive disease post induction chemotherapy.

Is the relative value of surgeon effort equal across surgical specialties?

Background: Although relative value units are used to measure physician productivity, research has demonstrated incongruencies between relative value units and actual surgeon work effort. We sought to determine whether this variation extends across surgical specialties.

Methods: A retrospective review of surgical cases was conducted using the 2017 American College of Surgeons National Surgical Quality Improvement Program database.

Sinus Development and Pneumatization in a Primary Ciliary Dyskinesia Cohort.

Background: Primary ciliary dyskinesia (PCD) is a genetically diverse disease which causes impaired mucociliary clearance, and results in pulmonary, otologic, and rhinologic disease in affected patients. Genetic mutations in multiple genes impair the ability of patients to clear mucous from the lungs, middle ear, and sinonasal cavity and lead to chronic pulmonary and sinonasal symptoms.

Methods: We identified 17 PCD patients who had available CT scans.

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication.

Purpose: Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.

Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma.

Purpose: AIDS-related Kaposi sarcoma is often incompletely controlled, requiring serial therapies. Kaposi sarcoma herpesvirus (KSHV) induces transformation of endothelial cells, where it resides in a predominately latent state. We hypothesized proteasome inhibition would have direct antitumor activity, induce lytic activation of KSHV, and inhibit HIV infectivity, improving control of both Kaposi sarcoma and HIV.

Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial.

Background: Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation). Preclinically, trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity.

A comparison of response in the presence or absence of a delay in induction therapy with bortezomib, lenalidomide, and dexamethasone.

Purpose: Lenalidomide, bortezomib, and dexamethasone (RVd) has emerged as a preferred induction therapy in multiple myeloma (MM) in the United States. Due to lenalidomide's teratogenic risk, patients and prescribers must comply with a risk evaluation and mitigation strategy (REMS) program. The REMS program limits dispensing to certain third-party specialty pharmacies, whose average prescription fill times are longer than in-house specialty pharmacies.

Frailty and health-related quality of life in older women with breast cancer.

Purpose: In older women, breast cancer and its treatment can have profound impact on their physical, mental, and social health, especially in frail patients. This study evaluated the association between frailty and long-term health-related quality of life (HRQOL) in older women undergoing breast cancer treatment.

Methods: Using the Carolina Senior Registry (CSR), participants with breast cancer were contacted to complete a follow-up HRQOL questionnaire (median 4 years).

Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012.

Background: Second-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the safety and the efficacy of pembrolizumab for the treatment of HNSCC after long-term follow-up.

Methods: Multi-centre, non-randomised trial included two HNSCC cohorts (initial and expansion) in which 192 patients were eligible.

Reference intervals and diagnostic ranges for serum free κ and free λ immunoglobulin light chains vary by instrument platform: Implications for classification of patient results in a multi-center study.

Background: Serum free light chain (FLC) immunoglobulins are key biomarkers that aid in the diagnosis, prognosis and assessment of treatment response in patients with plasma cell disorders (PCD). Here we investigated the transference of manufacturer's reported κFLC, λFLC and κ to λ FLC reference intervals (RI) and established de novo FLC RI and diagnostic ranges on four instruments at three academic medical centers. In addition, we also compared the classification of patient FLC results using manufacturer's versus established RIs and diagnostic ranges.

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck.

Background: The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer.

Methods: Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m , and daily lapatinib 1000mg for 6 weeks followed by surgical resection.

Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study.

Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment.

Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort.

Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks.

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial.

Background: Patients with recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options. We aimed to assess the safety, tolerability, and antitumour activity of pembrolizumab, a humanised anti-programmed death receptor 1 (PD-1) antibody, in patients with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck.

Methods: This study was an open-label, multicentre, phase 1b trial of patients with recurrent or metastatic squamous cell carcinoma of the head and neck.