Ultraviolet radiation thin film dosimetry: A review of properties and applications.

Spectroradiometry, radiometry, and dosimetry are employed for the measurement of ultraviolet radiation (UVR) irradiance and non-ionizing exposure. Different types of UVR dosimeter have been developed for measuring personal and environmental UVR exposures since film dosimetry was pioneered in the 1970s. An important type of dosimeter is the thin film variant, which contains materials that undergo changes in optical absorbance when exposed to UVR.

Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations.

Importance: Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing.

Objective: To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA-like genomic profile and patients without a tumor BRCA-like profile.

The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer.

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer, who were germline BRCA1 and BRCA2 wild type. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery.

AGO-OVAR 28/ENGOT-ov57. Niraparib alone versus niraparib in combination with bevacizumab in patients with carboplatin-taxane-based chemotherapy in advanced ovarian cancer: a multicenter randomized phase III trial.

Background: Phase III trial data have shown a significant benefit by the addition of a maintenance treatment with niraparib, irrespective of BRCA or HRD status, in patients with advanced high-grade ovarian cancers; and, a significant benefit of the combination of olaparib and bevacizumab compared with bevacizumab monotherapy in HRD positive patients. However, it is unclear whether a PARP inhibitor monotherapy is sufficient, or if the addition of bevacizumab is needed.

Primary Objectives: This trial will investigate if the treatment strategy of carboplatin/paclitaxel/bevacizumab/niraparib is superior to the treatment of carboplatin/paclitaxel/niraparib in an all-comer population.

Homologous Recombination Deficiency and Cyclin E1 Amplification Are Correlated with Immune Cell Infiltration and Survival in High-Grade Serous Ovarian Cancer.

Background: How molecular profiles are associated with tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC) is incompletely understood. Therefore, we analyzed the TME and molecular profiles of HGSOC and assessed their associations with overall survival (OS).

Methods: Patients with advanced-stage HGSOC treated in three Dutch hospitals between 2008-2015 were included.

Effect of HIPEC according to HRD/BRCAwt genomic profile in stage III ovarian cancer: Results from the phase III OVHIPEC trial.

The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin to interval cytoreductive surgery improves recurrence-free (RFS) and overall survival (OS) in patients with stage III ovarian cancer. Homologous recombination deficient (HRD) ovarian tumors are usually more platinum sensitive. Since hyperthermia impairs BRCA1/2 protein function, we hypothesized that HRD tumors respond best to treatment with HIPEC.

Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients.

Background: The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.

Ovarian Cancer-Specific -like Copy-Number Aberration Classifiers Detect Mutations Associated with Homologous Recombination Deficiency in the AGO-TR1 Trial.

Purpose: Previously, we developed breast cancer like and -like copy-number profile shrunken centroid classifiers predictive for mutation status and response to therapy, targeting homologous recombination deficiency (HRD). Therefore, we investigated and like classification in ovarian cancer, aiming to acquire classifiers with similar properties as those in breast cancer. We analyzed DNA copy-number profiles of germline - and -mutant ovarian cancers and control tumors and observed that existing breast cancer classifiers did not sufficiently predict mutation status.

A Phase I dose-escalation study of two cycles carboplatin-olaparib followed by olaparib monotherapy in patients with advanced cancer.

Preclinical studies have shown synergistic effects when combining PARP1/2 inhibitors and platinum drugs in BRCA1/2 mutated cancer cell models. After a formulation change of olaparib from capsules to tablets, we initiated a dose finding study of olaparib tablets bidaily (BID) continuously with carboplatin to prepare comparative studies in this patient group. Patients were included in a 3 + 3 dose-escalation schedule: olaparib 25 mg BID and carboplatin area under the curve (AUC) 3 mg*min/mL d1/d22, olaparib 25 mg BID and carboplatin AUC 4 mg*min/mL d1/d22, followed by increasing dose-levels of olaparib from 50 mg BID, 75 mg BID, to 100 mg BID with carboplatin at AUC 4 mg*min/mL d1/d22.

Biologically effective solar ultraviolet exposures and the potential skin cancer risk for individual gold medalists of the 2020 Tokyo Summer Olympic Games.

Personal solar ultraviolet radiation exposure models were developed for 144 Olympic events scheduled outdoors from across the 33 sport disciplines that will compete in Tokyo between 24 July and 9 August 2020. Ambient exposure models were developed from existing atmospheric parameters measured over Tokyo (35.7°N 139.

Response of metastatic mouse invasive lobular carcinoma to mTOR inhibition is partly mediated by the adaptive immune system.

Effective treatment of invasive lobular carcinoma (ILC) of the breast is hampered by late detection, invasive growth, distant metastasis, and poor response to chemotherapy. Phosphoinositide 3-kinase (PI3K) signaling, one of the major druggable oncogenic signaling networks, is frequently activated in ILC. We investigated treatment response and resistance to AZD8055, an inhibitor of mammalian target of rapamycin (mTOR), in the (KEP) mouse model of metastatic ILC.

The Simulated Ocular and Whole-Body Distribution of Natural Sunlight to Kiteboarders: A High-Risk Case of UVR Exposure for Athletes Utilizing Water Surfaces in Sport.

Kiteboarding is an aquatic sporting discipline that has not yet been considered in the literature to date in terms of solar ultraviolet radiation (UVR) measurement. Kiteboarders need to look upward and are placed obliquely relative to the horizon when towed behind an overhead kite over a reflective water surface. This research defines the typical body surface orientation of a kiteboarder in motion through video vector analysis and demonstrates the potential risk to ocular and skin surface damage through practical measurement of solar UVR using a manikin model.

Publisher Correction: Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial.

In the version of this article originally published, there was an error in Fig. 3j. A label on the heatmap read "TGF-α signaling via NF-κB".

Assessment of Biologically Effective Solar Ultraviolet Exposures for Court Staff and Competitors During a Major Australian Tennis Tournament.

Sport is an integral and enduring part of many societies, such as Australia. Participation in outdoor sports, such as tennis, comes with a very real risk of dangerous solar ultraviolet exposure which can result in erythema (sunburn), serious conditions such as skin cancer, including melanoma, and eye conditions such as cataracts and pterygium. This study remotely assesses the effective ultraviolet exposures in response to the increased sun safety awareness at a major summertime tennis tournament in Australia.

Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial.

The efficacy of programmed cell death protein 1 (PD-1) blockade in metastatic triple-negative breast cancer (TNBC) is low, highlighting a need for strategies that render the tumor microenvironment more sensitive to PD-1 blockade. Preclinical research has suggested immunomodulatory properties for chemotherapy and irradiation. In the first stage of this adaptive, non-comparative phase 2 trial, 67 patients with metastatic TNBC were randomized to nivolumab (1) without induction or with 2-week low-dose induction, or with (2) irradiation (3 × 8 Gy), (3) cyclophosphamide, (4) cisplatin or (5) doxorubicin, all followed by nivolumab.

EZH2 Is Overexpressed in -like Breast Tumors and Predictive for Sensitivity to High-Dose Platinum-Based Chemotherapy.

Purpose: BRCA1-deficient breast cancers carry a specific DNA copy-number signature ("") and are hypersensitive to DNA double-strand break (DSB) inducing compounds. Here, we explored whether (i) EZH2 is overexpressed in human -deficient breast tumors and might predict sensitivity to DSB-inducing drugs; (ii) EZH2 inhibition potentiates cisplatin efficacy in -deficient murine mammary tumors.

Experimental Design: EZH2 expression was analyzed in 497 breast cancers using IHC or RNA sequencing.

Frequent Homologous Recombination Deficiency in High-grade Endometrial Carcinomas.

Purpose: The elevated levels of somatic copy-number alterations (SCNAs) in a subset of high-risk endometrial cancers are suggestive of defects in pathways governing genome integrity. We sought to assess the prevalence of homologous recombination deficiency (HRD) in endometrial cancers and its association with histopathologic and molecular characteristics.

Experimental Design: Fresh tumor tissue was prospectively collected from 36 endometrial cancers, and functional HRD was examined by the ability of replicating tumor cells to accumulate RAD51 protein at DNA double-strand breaks (RAD51 foci) induced by ionizing radiation.

The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting.

Background: Patients with BRCA1-like tumors correlate with improved response to DNA double-strand break-inducing therapy. A gene expression-based classifier was developed to distinguish between BRCA1-like and non-BRCA1-like tumors. We hypothesized that these tumors may also be more sensitive to PARP inhibitors than standard treatments.

BRCA1-like profile is not significantly associated with survival benefit of non-myeloablative intensified chemotherapy in the GAIN randomized controlled trial.

Purpose: The BRCA1-like profile identifies tumors with a defect in homologous recombination due to inactivation of BRCA1. This profile has been shown to predict which stage III breast cancer patients benefit from myeloablative, DNA double-strand-break-inducing chemotherapy. We tested the predictive potential of the BRCA1-like profile for adjuvant non-myeloablative, intensified dose-dense chemotherapy in the GAIN trial.

A phase I followed by a randomized phase II trial of two cycles carboplatin-olaparib followed by olaparib monotherapy versus capecitabine in BRCA1- or BRCA2-mutated HER2-negative advanced breast cancer as first line treatment (REVIVAL): study protocol for a randomized controlled trial.

Background: Preclinical studies in breast cancer models showed that BRCA1 or BRCA2 deficient cell lines, when compared to BRCA proficient cell lines, are extremely sensitive to PARP1 inhibition. When combining the PARP1 inhibitor olaparib with cisplatin in a BRCA1-mutated breast cancer mouse model, the combination induced a larger response than either of the two compounds alone. Several clinical studies have investigated single agent therapy or combinations of both drugs, but no randomized clinical evidence exists for the superiority of carboplatin-olaparib versus standard of care therapy in patients with BRCA1- or BRCA2--mutated metastatic breast cancer.