RNA Transcripts Serve as a Template for Double-Strand Break Repair in Human Cells.

Double-strand breaks (DSBs) are toxic lesions that lead to genome instability. While canonical DSB repair pathways typically operate independently of RNA, emerging evidence suggests that RNA:DNA hybrids and transcripts near damaged sites can influence repair outcomes. However, a direct role for transcript RNA as a template during DSB repair in human cells is yet to be established.

Professional-patient discrepancies in assessing lung cancer radiotherapy symptoms: An international multicentre study.

Background And Purpose: We investigate discrepancies in the assessment of treatment-related symptoms in lung cancer between healthcare professionals and patients, and factors contributing to these discrepancies.

Materials And Methods: Data from 515 participants in the REQUITE study were analysed. Five symptoms (cough, dyspnoea, bronchopulmonary haemorrhage, chest wall pain, dysphagia) were evaluated both before and after radiotherapy.

Radiation Myelitis Risk After Hypofractionated Spine Stereotactic Body Radiation Therapy.

Importance: Stereotactic body radiation therapy (SBRT) for spinal metastases improves symptomatic outcomes and local control compared to conventional radiotherapy. Treatment failure most often occurs within the epidural space, where dose is constrained by the risk of radiation myelitis (RM). Current constraints designed to prevent RM after spine SBRT are derived from limited data.

Targeting S6K/NFκB/SQSTM1/Polθ signaling to suppress radiation resistance in prostate cancer.

In this study we have identified POLθ-S6K-p62 as a novel druggable regulator of radiation response in prostate cancer. Despite significant advances in delivery, radiotherapy continues to negatively affect treatment outcomes and quality of life due to resistance and late toxic effects to the surrounding normal tissues such as bladder and rectum. It is essential to develop new and effective strategies to achieve better control of tumor.

40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy.

Background And Purpose: A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed.

Methods: We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.

Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial.

Purpose: External-beam radiation therapy (RT) is standard of care (SOC) for pain relief of symptomatic bone metastases. We aimed to evaluate the efficacy of radiation to asymptomatic bone metastases in preventing skeletal-related events (SRE).

Methods: In a multicenter randomized controlled trial, adult patients with widely metastatic solid tumor malignancies were stratified by histology and planned SOC (systemic therapy or observation) and randomly assigned in a 1:1 ratio to receive RT to asymptomatic high-risk bone metastases or SOC alone.

High Specificity of HPV Cell-Free DNA Tests in Persons With HIV for the Detection of HPV-Related Cancer.

Introduction: Persons with HIV (PWH) experience high rates of human papillomavirus (HPV)-associated cancers compared with the general population. Plasma HPV cell-free DNA (cfDNA) tests are sensitive in patients with known HPV-associated cancers. It is not known whether these tests can screen for invasive cancers in populations with high burdens of nonmalignant HPV disease such as PWH.

Early Detection of Leptomeningeal Metastases Among Patients Undergoing Spinal Stereotactic Radiosurgery.

Purpose: The management of patients with advanced solid malignancies increasingly uses stereotactic body radiation therapy (SBRT). Advanced cancer patients are at risk for developing leptomeningeal metastasis (LM), a fatal complication of metastatic cancer. Cerebrospinal fluid (CSF) is routinely collected during computed tomography (CT) myelography for spinal SBRT planning, offering an opportunity for early LM detection by CSF cytology in the absence of radiographic LM or LM symptoms (subclinical LM).

The Impact of Targetable Mutations on Clinical Outcomes of Metastatic Epidural Spinal Cord Compression in Patients With Non-Small-Cell Lung Cancer Treated With Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy).

Background: In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC).

Objective: To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors.

Methods: This is a single-center, retrospective study.

Long-Term Clinical Outcomes of Patients with Colorectal Cancer with Metastatic Epidural Spinal Cord Compression Treated with Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy).

Background: Hybrid therapy, consisting of separation surgery followed by stereotactic body radiation therapy, has become the mainstay treatment for radioresistant spinal metastases. Histology-specific outcomes for hybrid therapy are scarce. In clinical practice, colorectal cancer (CRC) is particularly thought to have poor outcomes regarding spinal metastases.

The correlation between pre-treatment symptoms, acute and late toxicity and patient-reported health-related quality of life in non-small cell lung cancer patients: Results of the REQUITE study.

Background And Purpose: To investigate the association between clinician-scored toxicities and patient-reported health-related quality of life (HRQoL), in early-stage (ES-) and locally-advanced (LA-) non-small cell lung cancer (NSCLC) patients receiving loco-regional radiotherapy, included in the international real-world REQUITE study.

Materials And Methods: Clinicians scored eleven radiotherapy-related toxicities (and baseline symptoms) with the Common Terminology Criteria for Adverse Events version 4. HRQoL was assessed with the European Organization for Research and Treatment of Cancer core HRQoL questionnaire (EORTC-QLQ-C30).

Templated Insertions Are Associated Specifically with BRCA2 Deficiency and Overall Survival in Advanced Ovarian Cancer.

Unlabelled: Cancer cells defective in homologous recombination (HR) are responsive to DNA-crosslinking chemotherapies, PARP inhibitors, and inhibitors of polymerase theta (Pol θ), a key mediator of the backup pathway alternative end-joining. Such cancers include those with pathogenic biallelic alterations in core HR genes and another cohort of cases that exhibit sensitivity to the same agents and harbor genomic hallmarks of HR deficiency (HRD). These HRD signatures include a single-base substitution pattern, large rearrangements, characteristic tandem duplications, and small deletions.

Overview of health-related quality of life and toxicity of non-small cell lung cancer patients receiving curative-intent radiotherapy in a real-life setting (the REQUITE study).

Objectives: Radiotherapy-induced toxicity may negatively impact health-related quality of life (HRQoL). This report investigates the impact of curative-intent radiotherapy on HRQoL and toxicity in early stage and locally-advanced non-small cell lung cancer patients treated with radiotherapy or chemo-radiotherapy enrolled in the observational prospective REQUITE study.

Materials And Methods: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire up to 2 years post radiotherapy.

Clinical Outcomes of Dose-Escalated Hypofractionated External Beam Radiation Therapy (5 Gy × 5 Fractions) for Spine Metastasis.

Purpose: The objective of this study was to determine the toxicities and outcomes of patients with spinal metastasis treated with external beam radiation therapy (EBRT) to 25 Gy in 5 fractions.

Methods And Materials: Data were extracted from an institutional tumor registry for patients with spinal metastasis who were treated with EBRT to 25 Gy in 5 fractions to their spinal lesion(s). Cox regression and Kaplan-Meier analyses to determine local control and overall survival (OS) were employed.

Examining the prevalence of homologous recombination repair defects in ER+ breast cancers.

Purpose: Homologous recombination deficiency (HRD) is well characterized in triple-negative breast cancer (TNBC), but its prevalence in the hormone-receptor-positive breast cancer subtypes is not as clearly defined. It is estimated that around 50-60% of TNBC cases are deficient in HR. We sought to identify HRD cases in ER+/Her2- patients using various mutational HRD signatures.

Hybrid Therapy (Surgery and Radiosurgery) for the Treatment of Renal Cell Carcinoma Spinal Metastases.

Background: The management of spinal metastatic renal cell carcinoma (mRCC) is controversial regarding extent of resection and radiation dosing.

Objective: To determine outcomes in patients treated with hybrid therapy (separation surgery plus adjuvant stereotactic body radiation therapy [SBRT]) for mRCC.

Methods: A retrospective study of a prospectively collected cohort of patients undergoing hybrid therapy for mRCC between 2003 and 2017 was performed.

Failure mode and effect analysis for linear accelerator-based paraspinal stereotactic body radiotherapy.

Introduction: Paraspinal stereotactic body radiotherapy (SBRT) involves risks of severe complications. We evaluated the safety of the paraspinal SBRT program in a large academic hospital by applying failure modes and effects analysis.

Methods: The analysis was conducted by a multidisciplinary committee (two therapists, one dosimetrist, four physicists, and two radiation oncologists).

Genomic Signatures in HPV-Associated Tumors.

Papillomaviruses dysregulate the G1/S cell cycle transition in order to promote DNA synthesis in S phase, which is a requirement for viral replication. The human papillomaviruses (HPV) E6 and E7 oncoproteins mediate degradation of the cell cycle regulators p53 and Rb, which are two of the most universally disrupted tumor-suppressor genes in all of cancer. The G1/S checkpoint is activated in normal cells to allow sufficient time for DNA repair in G1 before proceeding to replicate DNA and risk propagating unrepaired errors.

Should Postoperative Radiation for Long Bone Metastases Cover Part or All of the Orthopedic Hardware? Results of a Large Retrospective Analysis.

Purpose: For patients with long bone metastases who undergo orthopedic stabilization surgery followed by radiotherapy (RT), it is unclear what extent of hardware coverage by the radiation field is needed for optimal tumor control.

Methods And Materials: Long bone metastases treated with surgical intervention followed by radiation between August 2011 to May 2019 from a single institution were reviewed. Local recurrence, defined as any in-bone recurrence, was identified by chart review.

Disabling the Fanconi Anemia Pathway in Stem Cells Leads to Radioresistance and Genomic Instability.

Fanconi anemia is an inherited genome instability syndrome characterized by interstrand cross-link hypersensitivity, congenital defects, bone marrow failure, and cancer predisposition. Although DNA repair mediated by Fanconi anemia genes has been extensively studied, how inactivation of these genes leads to specific cellular phenotypic consequences associated with Fanconi anemia is not well understood. Here we report that Fanconi anemia stem cells in the germline and in murine embryos display marked nonhomologous end joining (NHEJ)-dependent radiation resistance, leading to survival of progeny cells carrying genetic lesions.

Measuring nonhomologous end-joining, homologous recombination and alternative end-joining simultaneously at an endogenous locus in any transfectable human cell.

Double strand break (DSB) repair primarily occurs through 3 pathways: non-homologous end-joining (NHEJ), alternative end-joining (Alt-EJ), and homologous recombination (HR). Typical methods to measure pathway usage include integrated cassette reporter assays or visualization of DNA damage induced nuclear foci. It is now well understood that repair of Cas9-induced breaks also involves NHEJ, Alt-EJ, and HR pathways, providing a new format to measure pathway usage.

Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial.

Background: Patients with human papillomavirus-related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy.

Methods: In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia.

Replacing 30 Gy in 10 fractions with stereotactic body radiation therapy for bone metastases: A large multi-site single institution experience 2016-2018.

Background: Bone metastases cause significant morbidity in patients with cancer, and radiation therapy (RT) is an effective treatment approach. Indications for more complex ablative techniques are emerging. We sought to evaluate RT trends at a large multi-site tertiary cancer center.

Survival Trends After Surgery for Spinal Metastatic Tumors: 20-Year Cancer Center Experience.

Background: Over the last 2 decades, advances in systemic therapy have increased the expected overall survival for patients with cancer. It is unclear whether the same survival benefit has been conferred to patients requiring surgery for metastatic spinal disease.

Objective: To examine trends in postoperative survival over a 20-yr period for patients surgically treated for spinal metastatic disease.