Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial.

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ).

A Real-World Data Retrospective Cohort Study of Low Estrogen Receptor-Positive Early Breast Cancer: Natural History and Treatment Outcomes.

Purpose: Estrogen receptor-positive (ER) breast cancer (BC) is a heterogeneous disease, and there is an ongoing debate regarding the optimal cut point for clinically relevant ER expression. We used a real-world database to assess the prognostic and predictive values of lower ER expression levels on treatment outcomes with endocrine therapy.

Methods: We used a nationwide electronic health record database.

Fatal Allograft Rejection and Cardiac Allograft Vasculopathy After Treatment With Pembrolizumab for Metastatic Melanoma in a Heart Transplant Recipient: A Case Report.

Checkpoint inhibitors decrease the progression of many cancers. However, the experience in immunosuppressed patients is limited, with reports of possible serious adverse events. We present a heart transplant recipient treated with pembrolizumab for metastatic melanoma who developed fatal rejection.

Nivolumab and Stereotactic Radiosurgery for Patients With Breast Cancer Brain Metastases: A Nonrandomized, Open-Label Phase 1b Study.

Purpose: We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone.

Methods And Materials: The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases.

Real-world benefit of combination palbociclib and endocrine therapy for metastatic breast cancer and correlation with neutropenia.

Background: Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression-free survival (PFS) in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real-world benefit of first-line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors.

Methods: This study included HR-positive, HER2-negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018.

Thrombotic Microangiopathy: A Rare Breast Cancer-associated Complication Treated Successfully With Doxorubicin and Cyclophosphamide.

Background: Thrombotic microangiopathy (TMA) is a clinical syndrome consisting of hemolytic anemia, thrombocytopenia, and presence of schistocytes on peripheral blood smear secondary to disorders of systemic microvascular thrombosis. Malignancy-associated TMA is a rare entity and shares clinical features with that of HUS and TTP usually seen in patients with metastatic cancer, tumor cell infiltration of the bone marrow and/or response to cancer-directed therapy.

Case Report: We present a rare case of TMA secondary to breast cancer without evidence of bone marrow infiltration responsive to doxorubicin and cyclophosphamide treatment, after failed plasmapheresis with prednisone and later, eculizumab.

A Phase I Trial of Talimogene Laherparepvec in Combination with Neoadjuvant Chemotherapy for the Treatment of Nonmetastatic Triple-Negative Breast Cancer.

Purpose: Talimogene laherparepvec (TVEC) is an oncolytic herpes simplex 1 virus approved for treatment of melanoma. We hypothesized intratumoral TVEC may enhance response to neoadjuvant chemotherapy (NAC). This article reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC).

Recurrence risk of early-stage melanoma of the external ear: an investigation of surgical approach and sentinel lymph node status.

Surgical management of external ear melanoma presents unique technical challenges based on the unique anatomy and reconstruction concerns. Surgical technique, including preservation of cartilage, is variable and impact on recurrence is unclear. Our goal was to investigate surgical approach, including extent of surgical resection and sentinel lymph node biopsy (SLNB), and the impact on recurrence.

A Phase II Trial of Selinexor (KPT-330) for Metastatic Triple-Negative Breast Cancer.

Lessons Learned: Single-agent selinexor has limited activity in heavily pretreated patients with metastatic triple-negative breast cancer.Selinexor 60 mg by mouth twice weekly was generally well tolerated with a side-effect profile consistent with previous clinical trials.Future studies of selinexor in this population should focus on combination approaches and a biomarker-driven strategy to identify patients most likely to benefit.

The Immune Checkpoint Kick Start: Optimization of Neoadjuvant Combination Therapy Using Game Theory.

Purpose: In an upcoming clinical trial at the Moffitt Cancer Center for women with stage 2/3 estrogen receptor-positive breast cancer, treatment with an aromatase inhibitor and a PD-L1 checkpoint inhibitor combination will be investigated to lower a preoperative endocrine prognostic index (PEPI) that correlates with relapse-free survival. PEPI is fundamentally a static index, measured at the end of neoadjuvant therapy before surgery. We have developed a mathematical model of the essential components of the PEPI score to identify successful combination therapy regimens that minimize tumor burden and metastatic potential, on the basis of time-dependent trade-offs in the system.

Rigor prophylaxis in stage IV melanoma and renal cell carcinoma patients treated with high dose IL-2.

Background: Rigors are a significant adverse event during interleukin-2 (IL2) therapy for metastatic melanoma and renal cell carcinoma. Meperidine has been a mainstay for rigor prophylaxis but there is a paucity of data regarding possible alternatives.

Methods: Ninety one patients receiving IL2 therapy for metastatic renal cell carcinoma and melanoma at Huntsman Cancer institute (HCI), Utah from May 2009 to October 2016 were retrospectively evaluated for rigor prophylaxis.

Neutrophil-to-lymphocyte Ratio (NLR) as a predictor for recurrence in patients with stage III melanoma.

Neutrophil-to-lymphocyte ratio is a strong predictor for overall survival and disease free survival in many cancers. Our study is the first investigation aiming to determine the predictive value of neutrophil-to-lymphocyte ratio on prognosis of patients with stage III melanoma. This retrospective study utilized a cohort of 107 patients with stage III melanoma treated at Huntsman Cancer Institute, University of Utah, from May 2002 to March 2016.

A phase I trial of azacitidine and nanoparticle albumin bound paclitaxel in patients with advanced or metastatic solid tumors.

Background: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel.

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis.

Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs.

A Phase I Study of Neoadjuvant Chemotherapy With Nab-Paclitaxel, Doxorubicin, and Cyclophosphamide in Patients With Stage II to III Breast Cancer.

Background: The aims of this study were to assess the safety and tolerability of nanoparticle albumin bound paclitaxel (nab-paclitaxel), doxorubicin, and cyclophosphamide as combination therapy for breast cancer patients in the neoadjuvant setting and to assess the overall clinical response and pathologic complete response (pCR).

Patients And Methods: Twenty-six women with newly diagnosed stage II to III histologically or cytologically proven adenocarcinoma of the breast with negative HER2 status were enrolled. Patients were treated with nab-paclitaxel 100 mg/m, doxorubicin 50 mg/m, and cyclophosphamide 500 mg/m on day 1 and nab-paclitaxel 100 mg/m on day 8 in a 21-day cycle for 6 cycles total.

Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis.

An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines.

Narcoleptic-like Episodes in a Patient Receiving Pegylated Interferon-alpha 2b: A Case Report and Review of Literature.

A 26-year-old male developed narcoleptic-like episodes while on pegylated interferon-alpha 2b (peg-IFN-α2b) therapy for stage IIIB melanoma. Once peg-IFN-α2b was discontinued, the narcoleptic-like episodes eradicated. A case report and review of the literature are presented in this article.

Complete response to azacitidine priming and nab-paclitaxel in non-Hodgkin lymphoma resistant to biochemotherapy.

The standard of care for first-line therapy in diffuse large B-cell lymphoma (DLBCL) is the rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) regimen. For patients who fail to respond, have an incomplete response or relapse, numerous effective options exists besides salvage cisplatin-based regimen and autologous stem cell therapy. Even with this approach, the outcome remains very poor for this group of patients.

A Case Report of Pneumocystis Jiroveci Pneumonia in a Patient with Metastatic Breast Cancer.

We describe a 69-year-old woman with metastatic breast cancer who developed dyspnea on exertion, persistent cough, fever and fatigue while on everolimus and exemestane combination. The initial differentials included opportunistic infection such as pneumocystis jiroveci pneumonia (PJP) vs. pneumonitis.

miR-125b regulates differentiation and metabolic reprogramming of T cell acute lymphoblastic leukemia by directly targeting A20.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy. Although it has been reported that overexpression of miR-125b leads to T-ALL development, the underlying mechanisms of miR-125b action are still unclear. The goal of this study is to delineate the role of miR-125b in T-ALL development.

A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma.

Purpose: Intratumoral interleukin-2 (IL-2) is effective but does not generate systemic immunity. Intravenous ipilimumab produces durable clinical response in a minority of patients, with potentially severe toxicities. Circulating anti-tumor T cells activated by ipilimumab may differ greatly from tumor-infiltrating lymphocytes activated by intratumoral ipilimumab in phenotypes and functionality.

miR-125b functions as a key mediator for snail-induced stem cell propagation and chemoresistance.

Chemoresistance is a major obstacle in cancer treatment. Our previous studies have shown that miR-125b plays an important role in chemoresistance. Here we report a novel mechanism that up-regulation of miR-125b through Wnt signaling by Snail enriches cancer stem cells.