Pulsed reduced-dose rate re-irradiation for patients with recurrent grade 2 gliomas.

Background: Patients with grade 2 glioma exhibit highly variable survival. Re-irradiation for recurrent disease has limited mature clinical data. We report treatment results of pulsed reduced-dose rate (PRDR) radiation for patients with recurrent grade 2 glioma.

Combining Obinutuzumab With Radiation for Refractory DLBCL: Retrospective Safety and Efficacy Analysis.

Purpose: Approximately 30% of patients with diffuse large B cell lymphoma (DLBCL) will develop relapsed or treatment-refractory disease after primary chemotherapy. Patients unable to undergo aggressive chemotherapy and stem cell transplant or chimeric antigen receptor T-cell (CAR T-cell) therapy have limited treatment options. Here, we investigated the safety and efficacy of combining obinutuzumab with cytoreductive radiation to all areas of disease in patients with relapsed DLBCL.

Review of recent advances in managing periocular skin malignancies.

Management of cutaneous malignancies can be particularly challenging when they are located in the periocular region. The standard of care for localized disease is complete surgical excision, but this may not be possible without significant disruption to visual structures and facial appearance. Definitive radiation may be an option for some patients who cannot or do not wish to undergo surgery.

Functional Outcomes After Transoral Plus Lateral Pharyngotomy Approach for Advanced Oral and Oropharyngeal Tumors.

Objective: The aim of this study was to evaluate our institutional experience with the combined transoral plus lateral pharyngotomy (TO+LP) approach in a subset of patients with advanced or recurrent oral and oropharyngeal malignancy.

Study Design: A retrospective study of procedures utilizing TO+LP for cancer resection between January 2007 and July 2019.

Setting: Tertiary academic medical center.

Interstitial Brachytherapy for Lip Cancer: Technical Aspects to Individualize Treatment Approach and Optimize Outcomes.

Primary radiation therapy using interstitial brachytherapy (IBT) provides excellent local tumor control for early-stage squamous cell carcinoma of the lip. Technical aspects of treatment are important to optimize outcomes. In this report, we discuss patient selection criteria, procedural details, and dosimetric considerations for performing IBT for cancers of the lip.

Targeting the GTV in medically inoperable endometrial cancer using brachytherapy.

Purpose: We aimed to determine the relationship between gross tumor volume (GTV) dose and tumor control in women with medically inoperable endometrial cancer, and to demonstrate the feasibility of targeting a GTV-focused volume using imaged-guided brachytherapy.

Methods And Materials: An endometrial cancer database was used to identify patients. Treatment plans were reviewed to determine doses to GTV, clinical target volume (CTV), and OARs.

Prospective Study of PET/MRI Tumor Response During Chemoradiotherapy for Patients With Low-risk and Intermediate-risk p16-positive Oropharynx Cancer.

Objective: The objective of this study was to examine tumor response with positron emission tomography (PET)/magnetic resonance imaging (MRI) during chemoradiotherapy as a predictor of outcome in patients with p16-positive oropharynx cancer.

Materials And Methods: Patients with p16-positive oropharynx cancer were treated with chemoradiotherapy. Low-risk (LR) disease was defined as T1-T3 and N0-2b and ≤10 pack-years and intermediate-risk (IR) disease as T4 or N2c-3 or >10 pack-years.

De-escalating Locoregional Therapy for Axillary Micrometastases in Breast Cancer: How Much is Too Much?

Background: The applicability of modern prospective data on adjuvant radiotherapy (RT) fields in patients with micrometastases is limited because many trials occurred prior to routine measurement of nodal metastasis size and modern sentinel lymph node evaluation techniques. We aimed to determine prognostic factors for patients with micrometastases and evaluate the impact of adjuvant RT on disease outcomes.

Patients And Methods: Patients diagnosed with pathologic T1-T3 N1mi breast cancers between 2004-2015 were identified.

Defining high-risk elective contralateral neck radiation volumes for oropharynx cancer.

Background: To define the location of the initial contralateral lymph node (LN) metastasis in patients with oropharynx cancer.

Methods: The location of the LN centroids from patients with oropharynx cancer and a single radiographically positive contralateral LN was defined. A clinical target volume (CTV) inclusive of all LN centroids was created, and its impact on dose to organs at risk was assessed.

Combined Immunotherapy and Stereotactic Radiotherapy Improves Neurologic Outcomes in Patients with Non-small-cell Lung Cancer Brain Metastases.

Background: The purpose of this study was to compare the outcomes of patients with non-small cell lung cancer (NSCLC) brain metastases treated with stereotactic radiotherapy (SRT) alone versus SRT and immune checkpoint inhibitors (ICIs).

Patients And Methods: Patients treated for their first diagnosis of intracranial metastases with SRT or SRT plus ICI were retrospectively identified. Overall survival (OS), local control (LC), distant brain failure (DBF), neurologic death, and rates of radiation necrosis were calculated.

Outcomes From Whole-Brain Reirradiation Using Pulsed Reduced Dose Rate Radiation Therapy.

Purpose: Recurrent intracranial metastases after whole-brain irradiation pose a clinical challenge owing to the escalating morbidity associated with their treatment. Although stereotactic radiosurgery is increasingly being used, there are still situations in which whole-brain reirradiation (ReRT) continues to be appropriate. Here, we report our experience using whole-brain pulsed reduced dose rate radiation therapy (PRDR), a method that delivers radiation at a slower rate of 0.

Clinical outcomes for larynx patients with cancer treated with refinement of high-dose radiation treatment volumes.

Background: To evaluate disease control, toxicities, and dose to dysphagia/aspiration risk structures (DARS) using a direct gross tumor volume (GTV ) to planning target volume expansion (dPTV ) for patients with squamous cell carcinoma of the larynx (LSCC).

Methods: A retrospective review was performed on patients with LSCC treated between 2003 and 2018. Clinical outcomes, toxicities, and dosimetric data were analyzed.

Opioid use in patients undergoing treatment for oral cavity cancer.

Objective: In the context of the opioid epidemic, there is value in examining the use of opioids in specific cancer patient cohorts. We analyzed opioid use in patients undergoing adjuvant therapy for oral cavity cancer to define the incidence of new persistent use beyond 3 months.

Study Design: Retrospective.

Pulsed Reduced Dose Rate for Reirradiation of Recurrent Breast Cancer.

Purpose: Locoregionally recurrent breast cancer within a previously irradiated field requires weighing the benefits of reirradiation against the increased rates of toxicity. Here we evaluate the outcomes of patients treated with pulsed reduced dose rate (PRDR) radiation therapy with concurrent low-dose capecitabine as a method to increase the therapeutic ratio of re-treatment.

Methods And Materials: Patients treated from November 2000 to June 1, 2018 with PRDR radiation therapy at University of Wisconsin were identified.

Reducing radiotherapy target volume expansion for patients with HPV-associated oropharyngeal cancer.

Purpose: To evaluate clinical outcomes and patterns of failure using a direct gross tumor volume to planning target volume expansion in patients with p16-positive oropharyngeal squamous cell carcinoma.

Methods And Materials: We performed a retrospective review of patients with p16-positive oropharyngeal squamous cell carcinomas treated between 2002 and 2017 with primary radiotherapy with or without concurrent systemic therapy. Patient and disease characteristics associated with disease control and clinical outcomes were analyzed by Cox proportional hazards regression and Kaplan-Meier analyses.

HPV impacts survival of stage IVC non-oropharyngeal HNSCC cancer patients.

Objectives: Human papillomavirus (HPV) status is a favorable prognostic marker for patients with oropharyngeal squamous cell carcinoma (OPSCC) and non-metastatic head and neck non-OPSCC. We evaluated the impact of HPV status on overall survival (OS) for patients with Stage IVC non-OPSCC.

Materials And Methods: Patients diagnosed with Stage IVC non-OPSCC and known HPV status between 2010-2013 were identified in the National Cancer Database.

STIM1 elevation in the heart results in aberrant Ca²⁺ handling and cardiomyopathy.

Stromal interaction molecule 1 (STIM1) is a Ca(2+) sensor that partners with Orai1 to elicit Ca(2+) entry in response to endoplasmic reticulum (ER) Ca(2+) store depletion. While store-operated Ca(2+) entry (SOCE) is important for maintaining ER Ca(2+) homeostasis in non-excitable cells, it is unclear what role it plays in the heart, although STIM1 is expressed in the heart and upregulated during disease. Here we analyzed transgenic mice with STIM1 overexpression in the heart to model the known increase of this protein in response to disease.

Na+ dysregulation coupled with Ca2+ entry through NCX1 promotes muscular dystrophy in mice.

Unregulated Ca(2+) entry is thought to underlie muscular dystrophy. Here, we generated skeletal-muscle-specific transgenic (TG) mice expressing the Na(+)-Ca(2+) exchanger 1 (NCX1) to model its identified augmentation during muscular dystrophy. The NCX1 transgene induced dystrophy-like disease in all hind-limb musculature, as well as exacerbated the muscle disease phenotypes in δ-sarcoglycan (Sgcd(-/-)), Dysf(-/-), and mdx mouse models of muscular dystrophy.

Overexpression of the Na+/K+ ATPase α2 but not α1 isoform attenuates pathological cardiac hypertrophy and remodeling.

Rationale: The Na+ / K+ ATPase (NKA) directly regulates intracellular Na+ levels, which in turn indirectly regulates Ca2+ levels by proximally controlling flux through the Na+ / Ca2+ exchanger (NCX1). Elevated Na+ levels have been reported during heart failure, which permits some degree of reverse-mode Ca2+ entry through NCX1, as well as less efficient Ca2+ clearance.

Objective: To determine whether maintaining lower intracellular Na+ levels by NKA overexpression in the heart would enhance forward-mode Ca2+ clearance and prevent reverse-mode Ca2+ entry through NCX1 to protect the heart.

Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice.

A critical event in ischemia-based cell death is the opening of the mitochondrial permeability transition pore (MPTP). However, the molecular identity of the components of the MPTP remains unknown. Here, we determined that the Bcl-2 family members Bax and Bak, which are central regulators of apoptotic cell death, are also required for mitochondrial pore-dependent necrotic cell death by facilitating outer membrane permeability of the MPTP.

A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo.

After injury or cytokine stimulation, fibroblasts transdifferentiate into myofibroblasts, contractile cells that secrete extracellular matrix for wound healing and tissue remodeling. Here, a genome-wide screen identified TRPC6, a Ca(2+) channel necessary and sufficient for myofibroblast transformation. TRPC6 overexpression fully activated myofibroblast transformation, while fibroblasts lacking Trpc6 were refractory to transforming growth factor β (TGF-β) and angiotensin II-induced transdifferentiation.