Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming α/β = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS ≥ 2). BED was <20 Gy (in 27%), 20-30 Gy (24%), 30-40 Gy (36%) and ≥ 40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4-5 toxicity was reported. Pain relief was achieved in 52% at 2 months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1-9.9) at 6 months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2-76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.

There is evidence of weak self-processing in autism spectrum disorder (ASD), including diminished self-reference effects (SREs) in memory. Because smaller SREs in older ASD children and adults are sometimes associated with worse social functioning, we examined this relation for the first time in ASD preschoolers (n = 21). Following a self-performed task, children completed tests of self/other source memory, verbal ability, imitation and mentalizing. Although the ASD children were outperformed on the socio-cognitive measures by non-autistic preschoolers (n = 20), they still showed a significant SRE. Moreover, the SRE, but not the socio-cognitive variables, was a significant predictor of children\'s social functioning as rated by parents. Larger SREs were linked with better social functioning, while children with stronger autism traits showed no memory advantage for information encoded self-referentially. These findings support previous research showing that self-processing impairments in ASD are mainly apparent for individuals with greater social difficulties.

Up to 80% of castration-resistant prostate cancer (CRPC) patients develop bone metastases during the natural history of disease and about 25% harbor mutations in DNA damage repair (DDR) genes. This retrospective observational study evaluated the prevalence of DDR alterations in CRPC patients and their effect on the clinical outcomes associated with bone metastases. The mutational status of CRPC patients was analyzed per FoundationOne® analysis in tissue biopsy or, when it was not possible, in liquid biopsy performed at the onset of metastatic CRPC (mCRPC). The impact of DDR gene mutations on bone-related efficacy endpoints was evaluated at the time of mCRPC diagnoses. In total, 121 mCRPC patients with bone metastases were included: 38 patients had mutations in at least one DDR gene, the remaining 83 ones had a non-mutated DDR status. DDR mutated status was associated with bone metastases volume (p = 0.006), but did not affect SRE (skeletal-related events) incidence and time to SRE onset. Liquid and tissue biopsies were both available for 61 patients with no statistically significant difference in terms of incidence and type of molecular DDR alterations. Mutated DDR status was associated with higher bone metastasic volume, although a not detrimental effect on the other bone-related efficacy endpoints was observed.

Reproductive health education is crucial to ensure young people understand their reproductive system and can make informed decisions about their sexual lives and fertility, including whether they want to have children or not. This study involved an investigation of the intended UK school curricula for 14-18 year-olds as they relate to reproductive health. Analysis revealed substantial differences. Most, but not all, specifications include sexually transmitted infections, hormonal aspects of reproduction, contraception, the menstrual cycle and assisted reproductive technology (ART). Important topics, such as endometriosis, fertility, preconception health, pregnancy, miscarriage, menopause and infertility (except in the context of ART) are missing from examination specifications and/or the RSE/RSHP curricula. We conclude that many young people in the UK are at risk of leaving school with inadequate understanding of concepts that have important implications for their reproductive health. There are differences between nations, with Scotland having the most comprehensive coverage of topics in its curriculum. High-quality reproductive health education should be an entitlement for all young people. It should give young people accurate and up-to-date information and enable them to discuss issues and develop their own thinking. Ideally, sex and reproductive health education would be taught comprehensively across the RSE/RSHP and science curricula.

Doxycycline is often used as a promoter of inducible gene expression in preclinical models; however, it can also have direct effects on tumor growth and survival. This is due in part to its ability to inhibit cell invasion and regulate matrix metalloproteinase (MMP) expression. Given that doxycycline is also osteotropic, a clinical study to assess its effects on modulation of tumor progression or prevention of skeletal-related events (SRE) in patients with bone metastases from breast cancer (the Achilles trial) was undertaken. Patients received 100 mg of oral doxycycline twice daily for 12 weeks, with serum obtained at baseline and 4, 8 and 12 weeks post-initiation of doxycycline treatment. Exploratory analysis of the effects of doxycycline on circulating levels of MMP or tissue inhibitor of matrix metalloproteinase 2 (TIMP2) was performed in enrolled patients. Statistically significant associations were observed between MMP2, MMP9 and TIMP2 at baseline with significant associations maintained between absolute levels and changes in levels of MMP2 and TIMP2 at weeks 4-12 post initiation of doxycycline. Treatment with doxycycline generally resulted in decreases in MMP2 and MMP9 levels with concurrent upregulation of TIMP2 at 12 weeks post-initiation of doxycycline treatment. Despite this, we observed no association with the levels of any of these factors with either SRE-free or overall survival in this patient cohort. In summary, despite observing hypothesized effects of doxycycline administration on surrogate markers of its anti-tumor activity, measures of circulating levels of these biomarkers were not prognostic in this patient population.

The impact of an initial skeletal-related event (SRE) and denosumab adjuvant treatment on the survival outcome of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with bone metastasis remains unclear. This retrospective study included 400 metastatic EGFR-mutated NSCLC patients. Among 190 bone metastasis patients, 61 had initial SREs and 73 received denosumab. We analyzed patient characteristics, SRE-free survival (SRE-FS), and overall survival (OS). In metastatic EGFR-mutated NSCLC, bone metastasis was associated with a poorer OS (21.7 vs. 33.0 months; p < 0.001). Bone metastasis patients with initial SREs at diagnosis had an even shorter OS, compared with those without initial SRE (15.4 vs. 23.6 months; p = 0.026). Denosumab reduced SRE incidence (hazard ratio (HR) 0.57 (95% confidence interval (CI) 0.34−0.94; p = 0.027) and was associated with improved OS (26.6 vs. 20.1 months; p = 0.015). A multivariate analysis demonstrated that denosumab treatment was correlated with a lower incidence of SRE (HR 0.61 (95% CI 0.37−0.98); p = 0.042) and better OS (HR 0.60 (95% CI 0.41−0.88); p = 0.008). In subgroup analyses, denosumab prolonged SRE-FS (HR 0.36 (95% CI 0.19−0.79); p = 0.009) in patients without initial SREs and was related to a better OS (25.3 vs. 12.9 months; p = 0.016) in patients with initial or pre-existing SREs. Osteonecrosis of the jaw was diagnosed in two patients (2.74%) receiving denosumab. Our study confirmed the association between initial SREs and a worse outcome and provided novel evidence of the survival benefit of denosumab for EGFR-mutated NSCLC patients with bone metastasis.

UNASSIGNED: Retinoblastoma (RB) is the most common intraocular malignancy in infancy and childhood. This study evaluated the clinical and imaging features, treatment, and prognosis of patients with recurrent RB with limb bone metastases and without central nervous system involvement.
UNASSIGNED: The clinical data of five patients with RB with limb bone metastases who were diagnosed at the Department of Pediatrics in Beijing Tongren Hospital between January 2015 and January 2021 were analyzed retrospectively.
UNASSIGNED: Three males and two females were included (seven eyes: four group E and one each of group D, C, and B). The most common symptom was pain. Three patients had bone marrow and lymph node metastases. Three patients had single and two had multiple skeletal lesions. The main bones that were involved were the femur, humerus, talus, and ulna. The simultaneous involvement of the bone marrow and cortex was also observed. Serum neuron-specific enolase (NSE) levels were significantly elevated in four cases and slightly elevated in one case; primary intravenous chemotherapy resulted in a decrease in NSE levels and the gradual resolution of the bone lesions. Two patients died at the time of follow-up and three were in complete remission. The results of the statistical analysis showed that anterior chamber invasion was correlated with prognosis, and there was significant difference in the decrease in the serum NSE levels after intravenous chemotherapy.
UNASSIGNED: Regular lifelong follow-up of patients with RB is warranted to identify bone metastases earlier. Anterior chamber invasion may be a risk factor. The simultaneous involvement of the bone marrow and cortex is characteristic manifestations in images of RB with bone metastases. Multidisciplinary treatment especially intravenous chemotherapy is useful, at least at the beginning.

BACKGROUND: Bone metastases (BM) are still the main cause of morbidity and mortality in cancer patients, not only because of their complications, defined as skeletal-related events (SREs), but also because of the negative impact bone pain has on quality of life (QoL) and survival, especially when opioid analgesics and locoregional treatments fail.
METHODS: A single-center prospective study was carried out on 12 patients with symptomatic BM treated with MRI-guided focused ultrasound (MR-HIFU). The primary endpoint was the effectiveness of MR-HIFU in reducing current and breakthrough cancer pain (BTCP) scores. The main secondary aims were the evaluation of circulating markers at different time-points and their relation to pain and procedure efficacy. Other secondary objectives included temporal evolution of pain response, evaluation of QoL, and side effects of the treatment. Descriptive statistics were used to evaluate primary and secondary endpoints. Questionnaires on pain and QoL completed at baseline and at 30 days were compared using appropriate statistical tests with exploratory intent.
RESULTS: MR-HIFU was successfully completed in all 12 patients enrolled between September 2015 and December 2018. On day 30, 6 (50.0%) patients showed a complete response of current pain and 6 a partial response, while 5 (41.7%) obtained a complete BTCP response. A partial response of BM evaluated by MD Anderson criteria was obtained in 9 (81.8%) patients. Only one patient progressed in the target lesion after MR-HIFU. No treatment-related adverse events were recorded. Bone turnover markers CTX/RANK-L (P) do not demonstrate any significant change with the pain or BM response.
CONCLUSIONS: In our patients, targeted therapy of painful BM with MRI-guided focused ultrasound ablation was safe and showed encouraging early-onset and functional results.

Polycyclic aromatic hydrocarbons (PAHs) are persistent toxic substances that have ubiquitous presence in water, air, soil, and sediment environments. The growth of PAH toxicities and related ecotoxicology risk in estuary sediment has a serious concern. Present study examined the PAHs concentration, sources, and ecological risk from selected sites in Subarnarekha River estuary (SRE) sediment deposits. The sum of toxic 16 PAHs was ranged from 36.8 to 670.8 ng/g (mean = 223.46 ± 196.35 ng/g). The total PAH concentration varied significantly among the sampling sites (range 511.3 ng/g to 233.8 ng/g) based on allochthonous contaminant loads. Among the 16 compounds, Phen had the highest concentration (40.18 ng/g), followed by Pye (31.86 ng/g), Flur (29.36 ng/g), and NA (19.33 ng/g). Most of the sampling sites contained abundant 3-ring and 4-5-ring PAHs. Based on diagnostic ratios and PCA analysis petroleum combustion, biomass, and coal-burning have been identified as the major sources. The PAHs had high mutagenic equivalent factor and toxic equivalent factor values posing great ecological threats and health risks.

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer among men worldwide in 2020. Skeletal-related events (SRE) like pathologic fracture or spinal cord compression are commonly seen in metastatic prostate cancer. Denosumab, a monoclonal antibody, acts by inhibiting osteoclast-mediated bone resorption in bone metastasis from solid tumors and reduces bone turnover and destruction. However, there is an increased risk of life-threatening denosumab-induced hypocalcemia with an incidence of 0.1 to 12.8%.
METHODS: Our patient is a 69-year-old man with widespread skeletal metastatic disease from primary prostate cancer who presented to the hospital complaining of generalized fatigue and joint pain. Due to severe debilitating low back pain secondary to osteochondral lesions, the patient was started on Denosumab 120 mg. On presentation, serum calcium was found to be severely low at 5.9 mg/dl (serum calcium level prior to Denosumab was 9.1 mg/dl).
UNASSIGNED: Denosumab was discontinued immediately, and the patient was started on IV calcium gluconate. Repeat serum calcium level continued to be low at 6.7 likely due to the long elimination half-life of Denosumab (25-30 days). He was transferred to a long-term acute care facility for long-term IV calcium replacement, where he succumbed to illness six weeks later.
CONCLUSIONS: Denosumab, an anti-resorptive treatment for skeletal metastasis from solid tumors, is shown to cause severe life-threatening hypocalcemia. The maximum serum drug level of Denosumab reaches 7-21 days after administration. Sustained hypocalcemia is rare and life-threatening. Clinicians should use this medication with caution due to its unpredictable side effect profile.