Multi-institutional, randomized, controlled trial to assess the efficacy and tolerability of a reusable, self-contained cryotherapy delivery device.

Purpose: Cryotherapy is an effective mucositis intervention for selected chemotherapy regimens, but reliance on ice chips has limited its applicability. Our objective was to assess the efficacy and tolerability of a reusable, self-contained, device as an alternative delivery mode.

Methods: A total of 164 patients randomized 2:1 received the device (Chemo Mouthpiece; CMP]) + best supportive care (BSC) (arm A) or BSC only (control, arm B), across 16 study sites.

Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate.

Multimodal temporal therapy orchestrated to leverage immunotherapy, tumor-targeted chemotherapy, and natural killer (NK) cell therapy may provide an opportunity to induce immunogenic cell death for tumor response and increased survival in patients with recurrent cancer. The interleukin-15 (IL-15) superagonist N-803, an enhancer of NK cells, CD4 + T cells, cytotoxic CD8 + T cells, and memory T-cell activity, combined with off-the-shelf PD-L1-targeted high-affinity NK (PD-L1 t-haNK) cells represent novel immunotherapies designed to overcome an immunosuppressive tumor microenvironment (TME). The epidermal growth factor receptor-targeted antibody-nanocell conjugate E-EDV-D682 provides tumor-targeted chemotherapy in the form of its anthracycline metabolite PNU159682 (nemorubicin) cargo and is currently being studied in combination with immunomodulatory EDVs delivering the adjuvant α-galactosyl ceramide (GC).

Datopotamab-deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer.

Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes.

ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer.

Importance: There are insufficient data comparing 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence.

Objective: To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence.

Design, Setting, And Participants: This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023.

A Phase I/II Trial of Sapanisertib in Advanced Anaplastic and Radioiodine Refractory Differentiated Thyroid Carcinoma.

Background: There are limited therapeutic options for patients with recurrent/metastatic anaplastic thyroid carcinoma (ATC) and radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC) refractory to multikinase inhibitors. This multicenter trial evaluated sapanisertib, a next-generation oral kinase inhibitor of mTOR complexes 1/2, in ATC and RAIR DTC.

Methods: A safety run-in phase I was followed by nonrandomized phase II trial in ATC, with an exploratory cohort in RAIR DTC.

Two-Year Tumor Outcomes of a Phase 2B, Randomized, Double-Blind Trial of Avasopasem Manganese (GC4419) Versus Placebo to Reduce Severe Oral Mucositis Owing to Concurrent Radiation Therapy and Cisplatin for Head and Neck Cancer.

Purpose: Avasopasem manganese (GC4419), an investigational selective dismutase mimetic radioprotector, reduced duration, incidence, and severity of severe oral mucositis (World Health Organization grade 3-4) in a phase 2b, randomized, double-blind trial of patients receiving concurrent cisplatin (cis) and radiation therapy (RT) for head and neck cancer. We report the secondary endpoints of final 1- and 2-year tumor outcomes and exploratory data on trismus and xerostomia.

Methods And Materials: Patients with locally advanced oral cavity or oropharynx cancer to be treated with definitive or postop cis and RT were randomized to 1 of 3 arms: 30 mg avasopasem, 90 mg avasopasem, or placebo.

Complete response to avelumab and IL-15 superagonist N-803 with Abraxane in Merkel cell carcinoma: a case study.

Merkel cell carcinoma (MCC) is a rare aggressive form of skin cancer originating in neuroendocrine cells. The antiprogrammed death ligand 1 (PD-L1) monoclonal antibody (mAb) avelumab has been approved for treatment of MCC, but options are limited, should it be ineffective as a monotherapy. Combined therapy with low/moderate dose nab-paclitaxel and an interleukin 15 (IL-15)-based therapeutic such as the IL-15 'superagonist' N-803 may increase response by activation of the immune system.

Randomized, Phase II Study Prospectively Evaluating Treatment of Metastatic Esophageal, Gastric, or Gastroesophageal Cancer by Gene Expression of : SWOG S1201.

Purpose: Platinum-based therapy is the standard of care in patients who have HER2-negative, advanced esophagogastric cancer (AEGC). Retrospective data suggest that intratumoral levels may determine platinum sensitivity. A randomized, phase II study was performed in patients with AEGC to explore whether the efficacy of a platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) versus a non-platinum-containing regimen of irinotecan and docetaxel (IT) differed according to levels.

Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer.

Purpose: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM).

Patients And Methods: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction.

The Pan-Cancer Landscape of Coamplification of the Tyrosine Kinases KIT, KDR, and PDGFRA.

Purpose: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable.

Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial.

Importance: Locoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC.

Objective: To assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC.

Single-cell transcriptomes reveal the mechanism for a breast cancer prognostic gene panel.

The clinical benefits of the MammaPrint signature for breast cancer is well documented; however, how these genes are related to cell cycle perturbation have not been well determined. Our single-cell transcriptome mapping (algorithm) provides details into the fine perturbation of all individual genes during a cell cycle, providing a view of the cell-cycle-phase specific landscape of any given human genes. Specifically, we identified that 38 out of the 70 (54%) MammaPrint signature genes are perturbated to a specific phase of the cell cycle.

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.

Background: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit.

Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial.

Background: Stomatitis is a class effect associated with the inhibition of mTOR and is associated with everolimus therapy for breast cancer. Topical steroids might reduce stomatitis incidence and severity, and the need for dose reductions and interruptions of everolimus. Anecdotal use of topical steroid oral prophylaxis has been reported in patients with breast cancer.

Comprehensive Genomic Profiling of Clinically Advanced Medullary Thyroid Carcinoma.

Objective: The aim of this study was to determine the genomic alterations of cancer-related genes in advanced medullary thyroid carcinoma during the course of clinical care.

Methods: Hybrid-capture-based comprehensive genomic profiling was performed on 34 consecutive medullary thyroid carcinoma cases to identify all four classes of genomic alterations, and outcome for an index patient was collected.

Results: RET was mutated in 88% (30/34) of cases, with RET M918T being responsible for 70% (21/30) of the RET alterations.

Pancytopenia in a patient with cystinosis secondary to myelosuppression from cystine crystal deposition: a case report.

Introduction: Cystinosis is a rare metabolic genetic disorder caused by a mutation in the cystinosin lysosomal cystine transporter gene. Clinically, it is characterized by systemic accumulation of cystine crystals in tissues causing end-organ dysfunction in the kidney, eyes, muscles, and other organs in the body. In very rare cases, it can also involve the bone marrow and the resulting cystine crystal deposition can cause myelosuppression leading to pancytopenia.

Composite liver tumors: a radiologic-pathologic correlation.

Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC.