Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial.

Background: In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatment-switching adjustment analysis in all treated patients who received chemotherapy and subsequent immunotherapy.

Methods: Adults with stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing alterations, and ECOG performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy (four cycles, with optional maintenance pemetrexed for the nonsquamous population).

Neoadjuvant nivolumab plus chemotherapy in resectable non-small-cell lung cancer in Japanese patients from CheckMate 816.

In the open-label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event-free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non-small-cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB-IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment.

Correction: Role of caveolin-1 as a biomarker for radiation resistance and tumor aggression in lung cancer.

[This corrects the article DOI: 10.1371/journal.pone.

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death.

Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible.

Role of caveolin-1 as a biomarker for radiation resistance and tumor aggression in lung cancer.

Radiation therapy plays a major role in the treatment of lung cancer patients. However, cancer cells develop resistance to radiation. Tumor radioresistance is a complex multifactorial mechanism which may be dependent on DNA damage and repair, hypoxic conditions inside tumor microenvironment, and the clonal selection of radioresistant cells from the heterogeneous tumor site, and it is a major cause of treatment failure in non-small cell lung cancer (NSCLC).

Effect of hyperthermia and proton beam radiation as a novel approach in chordoma cells death and its clinical implication to treat chordoma.

Purpose: Chordoma is a locally aggressive tumor that most commonly affects the base of the skull/clivus, cervical, and sacral spine. Conventional radiotherapy (RT), cannot be safely increased further to improve disease control due to the risk of toxicity to the surrounding critical structures. Tumor-targeted hyperthermia (HT) combined with Proton Beam Radiation Therapy (PBRT) is known to act as a potent radiosensitizer in cancer control.

DUOX2, a New Biomarker for Disseminated Gastric Cancer's Response to Low Dose Radiation in Mice.

Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, Dual Oxidase 2 (DUOX2). Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or reduced levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; modified regimen of docetaxel, cisplatin and 5'-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 0.

Analysis of Career Stage, Gender, and Personality and Workplace Violence in a 20-Year Nationwide Cohort of Physicians in Norway.

Importance: Workplace violence (WPV) is a worldwide problem in health services. Several studies have pointed to organizational factors, such as working in psychiatry and work stress. However, there is a lack of long-term longitudinal cohort studies with respect to trends during the career and individual factors among physicians.

RhoA/ROCK pathway inhibitor ameliorates erectile dysfunction induced by radiation therapy in rats.

Objectives: Prostate cancer (PCa) treatment with radiation therapy (RT) has an excellent cure rate. However, Radiation-induced Erectile Dysfunction (RiED) is a common and irreversible toxicity impacting quality of life, and there is no FDA approved specific drug for RiED. We previously showed that prostate RT increased RhoA/ROCK signaling in the cavernous nerve (CN) and penile tissues, which may lead to RiED in rats.

A Combination of Radiotherapy, Hyperthermia, and Immunotherapy Inhibits Pancreatic Tumor Growth and Prolongs the Survival of Mice.

Background: Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. Unfortunately, only 10-20% of PC patients are candidates for surgery, with the vast majority of patients with locally-advanced disease undergoing chemotherapy and/or radiation therapy (RT). Current treatments are clearly inadequate and novel strategies are crucially required.

Online dose delivery verification in small animal image-guided radiotherapy.

Purpose: To accomplish novel radiation treatment techniques in preclinical radiation research, small animal image-guided radiotherapy systems have been increasingly integrated into preclinical radiation research over the last decade. Although such systems have sophisticated tools (such as cone-beam computed tomography-based image guidance, robotic couch, treatment planning system (TPS), and electronic portal imaging devices [EPIDs]). To our knowledge, no established technique can perform independent and online verification of the delivered dose during radiotherapy.

Life satisfaction in Norwegian medical doctors: a 15-year longitudinal study of work-related predictors.

Background: Despite many recent studies on burn-out and dissatisfaction among American medical doctors, less is known about doctors in the Scandinavian public health service. The aims of this study were to analyse long-term work-related predictors of life satisfaction among established doctors in Norway and to identify predictors in a subgroup of doctors who reported a decline in life satisfaction.

Methods: Two nationwide cohorts of doctors (n = 1052), who graduated medical school 6 years apart, were surveyed at graduation from medical school (T1, 1993/94 and 1999), and 4 (T2), 10 (T3), and 15 (T4) years later.

DNA methyltransferase inhibitors induce a BRCAness phenotype that sensitizes NSCLC to PARP inhibitor and ionizing radiation.

A minority of cancers have breast cancer gene (BRCA) mutations that confer sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis), but the role for PARPis in BRCA-proficient cancers is not well established. This suggests the need for novel combination therapies to expand the use of these drugs. Recent reports that low doses of DNA methyltransferase inhibitors (DNMTis) plus PARPis enhance PARPi efficacy in BRCA-proficient AML subtypes, breast, and ovarian cancer open up the possibility that this strategy may apply to other sporadic cancers.

BIO 300, a Nanosuspension of Genistein, Mitigates Radiation-Induced Erectile Dysfunction and Sensitizes Human Prostate Cancer Xenografts to Radiation Therapy.

Purpose: To assess whether BIO 300, a synthetic genistein nanosuspension, improves the therapeutic index in prostate cancer treatment by preventing radiation-induced erectile dysfunction (ED) without reducing tumor radiosensitivity.

Methods And Materials: Male Sprague-Dawley rats were exposed to 25 Gy of 220-kV prostate-confined x-rays. Animals were randomized to receive sham radiation therapy (RT), RT alone, RT with daily BIO 300 at 2 experimental dosing regimens, or RT with daily genistein.

Mild hyperthermia as a localized radiosensitizer for deep-seated tumors: investigation in an orthotopic prostate cancer model in mice.

Objective:: Non-ablative or mild hyperthermia (HT) has been shown in preclinical (and clinical) studies as a localized radiosensitizer that enhances the tumoricidal effects of radiation. Most preclinical in vivo HT studies use subcutaneous tumor models which do not adequately represent clinical conditions (e.g.

Immunotherapy, Radiotherapy, and Hyperthermia: A Combined Therapeutic Approach in Pancreatic Cancer Treatment.

Pancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis.

Liposomes: Clinical Applications and Potential for Image-Guided Drug Delivery.

Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic.

Cavernous Nerve Injury by Radiation Therapy May Potentiate Erectile Dysfunction in Rats.

Purpose/objectives: Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT lead to RiED; however, the precise role of RT-induced neurogenic injury in RiED has not been fully established.

Exploring the Concept of Radiation "Booster Shot" in Combination with an Anti-PD-L1 mAb to Enhance Anti-Tumor Immune Effects in Mouse Pancreas Tumors.

Radiotherapy (RT) has long been known to be immunogenic. Mounting preclinical data demonstrate a synergistic anti-tumor effect when RT is used in combination with immune check point inhibitors (ICI). However, it is unclear how to best integrate RT with an ICI (i.

Contextual Factors and Mental Distress as Possible Predictors of Hazardous Drinking in Norwegian Medical Doctors: A 15-Year Longitudinal, Nationwide Study.

Background: We have previously identified long-term individual predictors of hazardous drinking in doctors, but longitudinal studies on contextual factors (work and life stress) and mental distress being independently linked to hazardous drinking over the first 15 years of a medical career are lacking.

Methods: Two nationwide cohorts of Norwegian doctors (n = 1,052) from all 4 Norwegian universities were surveyed in their final year of medical school (1993/1994 and 1999) (T1), and 4 (T2), 10 (T3), and 15 (T4) years later. Hazardous drinking was measured using a validated 9-item version of the Alcohol Use Disorder Identification Test.

Caveolin-1: a novel prognostic biomarker of radioresistance in cancer.

Purpose: Caveolin-1 is a membrane protein highly expressed in many tumors and plays an important role in tumor progression and metastasis. This review describes the structure of the Caveolin-1 protein and its pre-clinical and clinical significance, demonstrating that Caveolin-1 is a novel biomarker for radioresistance which has the promising potential to improve the clinical outcome of cancer patients undergoing radiation treatment.

Summary: Targeted radiation therapy has shown immense benefits for cancer treatment.

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer.

Cancer is the leading cause of mortality among men and women worldwide. Despite the availability of numerous diagnostic techniques for various cancers, the overall survival rate remains low and the majority of patients die due to late diagnosis and advanced stage of the disease. Diagnosing and treating cancer at its early stages ideally during the precancerous phase could significantly increase survival rate with the possibility of cure and prolong survival.

Risk Factors Measured During Medical School for Later Hazardous Drinking: A 10-year, Longitudinal, Nationwide Study (NORDOC).

Aims: To investigate the prevalence and temporal patterns of hazardous drinking and risk factors during medical school for future hazardous drinking among doctors.

Methods: Two cohorts of graduating medical students (N = 1052) from all four Norwegian universities (NORDOC) were surveyed in their final year of medical school training (1993/94 and 1999) (T1) and again 4 (T2) and 10 (T3) years later. Longitudinally, 53% (562/1052) of the sample responded at all three time points.