Autocontouring of primary lung lesions and nodal disease for radiotherapy based only on computed tomography images.

Background And Purpose: In many clinics, positron-emission tomography is unavailable and clinician time extremely limited. Here we describe a deep-learning model for autocontouring gross disease for patients undergoing palliative radiotherapy for primary lung lesions and/or hilar/mediastinal nodal disease, based only on computed tomography (CT) images.

Materials And Methods: An autocontouring model (nnU-Net) was trained to contour gross disease in 379 cases (352 training, 27 test); 11 further test cases from an external centre were also included.

Collagen deposition within brain metastases is associated with leptomeningeal failure after cavity-directed radiosurgery.

Background: Leptomeningeal failure (LMF) represents a devastating progression of disease following resection of brain metastases (BrM). We sought to identify a biomarker at time of BrM resection that predicts for LMF using mass spectrometry-based proteomic analysis of resected BrM and to translate this finding with histochemical assays.

Methods: We retrospectively reviewed 39 patients with proteomic data available from resected BrM.

Poly(-vinylpyrrolidone)--Poly(dimethylsiloxane)--Poly(-vinylpyrrolidone) Triblock Copolymer Polymersomes for Delivery of PARP1 siRNA to Breast Cancers.

Nearly 20% of HER2-positive breast cancers develop resistance to HER2-targeted therapies requiring the use of advanced therapies. Silencing RNA therapy may be a powerful modality for treating resistant HER2 cancers due to its high specificity and low toxicity. However, the systemic administration of siRNAs requires a safe and efficient delivery platform because of siRNA's low stability in physiological fluids, inefficient cellular uptake, immunoreactivity, and rapid clearance.

RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4 T-cell-dependent antitumor immunity.

Expanding the utility of immune-based cancer treatments is a clinical challenge due to tumor-intrinsic factors that suppress the immune response. Here we report the identification of tumoral ring finger protein 2 (RNF2), the core subunit of polycomb repressor complex 1, as a negative regulator of antitumor immunity in various human cancers, including breast cancer. In syngeneic murine models of triple-negative breast cancer, we found that deleting genes encoding the polycomb repressor complex 1 subunits Rnf2, BMI1 proto-oncogene, polycomb ring finger (Bmi1), or the downstream effector of Rnf2, remodeling and spacing factor 1 (Rsf1), was sufficient by itself to induce durable tumor rejection and establish immune memory by enhancing infiltration and activation of natural killer and CD4 T cells, but not CD8 T cells, into the tumor and enabled their cooperativity.

Efficacy and Survival after Palliative Radiotherapy for Malignant Pulmonary Obstruction.

The purpose of this study was to determine the efficacy of palliative radiotherapy (PRT) for patients with pulmonary obstruction from advanced malignancy and identify factors associated with lung re-expansion and survival. We reviewed all patients treated with PRT for malignant pulmonary obstruction ( = 108) at our institution between 2010 and 2018. Radiographic evidence of lung re-expansion was determined through review of follow-up CT or chest X-ray.

Stereotactic body radiotherapy for synchronous early stage non-small cell lung cancer.

Introduction: In patients with non-small cell lung cancer (NSCLC) who present with multiple pulmonary nodules, it is often difficult to distinguish metastatic disease from synchronous primary lung cancers (SPLC). We sought to evaluate clinical outcomes after stereotactic body radiotherapy (SBRT) alone to synchronous primary lesions.

Material And Methods: Patients with synchronous AJCC 8 Edition Stage IA-IIA NSCLC and treated with stereotactic body radiation therapy (SBRT) to all lesions between 2009-2018 were reviewed.

Marital Status and Survival in Patients Diagnosed with Melanoma.

Introduction: Previous research suggests the presence of a spouse may considerably affect melanoma detection rates through more frequent examinations, better access to healthcare, and improved social support. Yet, the role of marital status on melanoma survival is currently unknown. The aim of this study is to assess whether marital status is associated with survival following melanoma diagnosis.

Cardiac Myxoma with Cerebral Metastases and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report and Review.

 Cardiac myxomas, the most common primary cardiac tumors, are generally benign neoplasms. Primary cardiac lymphoma is a rare cardiac malignancy with a very poor prognosis. Here we present a case of a cardiac myxoma with cerebral metastases and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) arising within the cerebral metastases.

Impact of brain metastasis velocity on neurologic death for brain metastasis patients experiencing distant brain failure after initial stereotactic radiosurgery.

Purpose: Patients with high rates of developing new brain metastases have an increased likelihood of dying of neurologic death. It is unclear, however, whether this risk is affected by treatment choice following failure of primary stereotactic radiosurgery (SRS).

Methods: From July 2000 to March 2017, 440 patients with brain metastasis were treated with SRS and progressed to have a distant brain failure (DBF).

Multi-institutional validation of brain metastasis velocity, a recently defined predictor of outcomes following stereotactic radiosurgery.

Introduction: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting.

Nomogram to Predict the Benefit of Intensive Treatment for Locoregionally Advanced Head and Neck Cancer.

Purpose: Previous studies indicate that the benefit of therapy depends on patients' risk for cancer recurrence relative to noncancer mortality (ω ratio). We sought to test the hypothesis that patients with head and neck cancer (HNC) with a higher ω ratio selectively benefit from intensive therapy.

Experimental Design: We analyzed 2,688 patients with stage III-IVB HNC undergoing primary radiotherapy (RT) with or without systemic therapy on three phase III trials (RTOG 9003, RTOG 0129, and RTOG 0522).

The BET inhibitor JQ1 attenuates double-strand break repair and sensitizes models of pancreatic ductal adenocarcinoma to PARP inhibitors.

Background: DNA repair deficiency accumulates DNA damage and sensitizes tumor cells to PARP inhibitors (PARPi). Based on our observation that the BET inhibitor JQ1 increases levels of DNA damage, we evaluated the efficacy of JQ1 + the PARPi olaparib in preclinical models of pancreatic ductal adenocarcinoma (PDAC). We also addressed the mechanism by which JQ1 increased DNA damage.

Treatment patterns for ductal carcinoma in situ with close or positive mastectomy margins.

Background: Mastectomy remains an effective treatment for ductal carcinoma in situ (DCIS) but whether further therapy is warranted for close or positive margins is controversial. We aim to characterize the treatment practices of DCIS throughout the United States in patients who undergo mastectomy with close or positive margins to better understand the use of postmastectomy radiation therapy (PMRT).

Materials And Methods: Using the 2004-2013 National Cancer Database, we identified all female patients with a diagnosis of DCIS who underwent mastectomy.

Prognostic models for patients with brain metastases after stereotactic radiosurgery with or without whole brain radiotherapy: a validation study.

Purpose/objective(s): To compare the performance of five prognostic models [RTOG recursive partitioning analysis (RPA), Score Index for Radiosurgery in Brain Metastases (SIR), Barnholtz-Sloan-Kattan nomogram (BSKN), diagnosis-specific Graded Prognostic Assessment (dsGPA), and Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA)] against actual survival in patients with brain metastases treated with SRS +/- WBRT.

Materials/methods: 100 consecutive patients treated with SRS +/- WBRT between January 2006 and July 2012 were retrospectively analyzed. Patients were binned according to 33 percentiles of the predicted survival distribution for the BSKN and dsGPA models to compare with LungmolGPA, RPA and SIR.

The Evolving Role of Postmastectomy Radiation Therapy.

Throughout various eras of breast cancer therapy, postmastectomy radiation therapy (PMRT) has played an important role in the treatment of locally advanced breast cancer. PMRT decreases locoregional recurrence and may improve overall survival in patients with tumors over 5 cm or positive lymph nodes. As novel cancer therapies improve survival in breast cancer, the role of radiation therapy is evolving.

Postmastectomy Radiation Therapy: Are We Ready to Individualize Radiation?

Contemporary recommendations for postmastectomy radiation have undergone a shift in thinking away from simple stage based recommendations (one size fits all) to a system that considers both tumor biology and host factors. While surgical staging has traditionally dictated indications for postmastectomy radiation therapy (PMRT), our current understanding of tumor biology, host, immunoprofiles, and tumor microenvironment may direct a more personalized approach to radiation. Understanding the interaction of these variables may permit individualization of adjuvant therapy aimed at appropriate escalation and deescalation, including recommendations for PMRT.

Subcutaneous adipose tissue characteristics and the risk of biochemical recurrence in men with high-risk prostate cancer.

Purpose/objective(s): To assess subcutaneous adipose tissue characteristics by computed tomography (CT) as potential imaging biomarkers predictive of biochemical recurrence in men with high-risk prostate cancer receiving radiotherapy (RT).

Materials And Methods: This retrospective study included men with high-risk prostate cancer (PSA>20ng/ml, Gleason score ≥8, or clinical extraprostatic extension) treated between 2001 and 2012. All patients received definitive, dose-escalated external beam RT along with a course of neoadjuvant, concurrent, and adjuvant androgen deprivation therapy (ADT).

Poly(ADP-ribose) polymerase activity and inhibition in cancer.

Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining.

CT Measures of Bone Mineral Density and Muscle Mass Can Be Used to Predict Noncancer Death in Men with Prostate Cancer.

Purpose To determine if computed tomographic (CT) metrics of bone mineral density and muscle mass can improve the prediction of noncancer death in men with localized prostate cancer. Materials and Methods Institutional review board approval was obtained, with waiver of informed consent. All patients who underwent radiation therapy for localized prostate cancer between 2001 and 2012 with height, weight, and past medical history documented and who underwent CT that included the L4-5 vertebral interspace were included.

Association of human papillomavirus and p16 status with mucositis and dysphagia for head and neck cancer patients treated with radiotherapy with or without cetuximab: Assessment from a phase 3 registration trial.

Background: Mucositis and dysphagia are common adverse effects of radiotherapy (RT) treatment of locally advanced squamous cell cancer of the head and neck (LA-SCCHN). Chemotherapy added to RT increases survival rates but causes worse mucositis and dysphagia. The aim of this analysis was to assess the impact of p16 status on mucositis, dysphagia, and feeding tube use in LA-SCCHN among patients treated with RT±cetuximab in the phase 3 IMCL-9815 trial.