Effects of Radiation Therapy and Chemotherapy on the Musculoskeletal System.

The effects of radiation and chemotherapy on the musculoskeletal (MSK) system are diverse, and interpretation may be challenging. The different lines of treatment have effects on diseased and normal marrow, and they may lead to complications that must be differentiated from recurrence or progression. This review analyzes the changes induced by radiotherapy and chemotherapy in the MSK system in the adult and pediatric population, and the expected associated imaging findings. Treatments are often combined, so the effects may blend. Awareness of the spectrum of changes, complications, and their imaging appearances is paramount for the correct diagnosis. The assessment of body composition during and after treatment allows potential interventions to implement long-term outcomes and personalize treatments. Imaging techniques such as computed tomography or magnetic resonance imaging provide information on body composition that can be incorporated into clinical pathways. We also address future perspectives in posttreatment assessment.

Imaging of Bone Marrow: From Science to Practice.

The study of the bone marrow may pose important challenges, due to its changing features over the life span, metabolic stress, and in cases of disease or treatment. Bone marrow adipocytes serve as storage tissue, but they also have endocrine and paracrine functions, contributing to local and systemic metabolism.Among different techniques, magnetic resonance (MR) has the benefit of imaging bone marrow directly. The use of advanced MR techniques for bone marrow study has rapidly found clinical applications. Beyond the clinical uses, it has opened up pathways to assess and quantify bone marrow components, establishing the groundwork for further study of its implications in physiologic and pathologic conditions.We summarize the features of the bone marrow as an organ, address the different modalities available for its study, with a special focus on MR advanced techniques and their addition to analysis in recent years, and review some of the challenges in interpreting the appearance of bone marrow.

Imaging of Metabolic Bone Diseases: The Spine View, Part I.

Metabolic bone diseases comprise a wide spectrum. Of them, osteoporosis is the most frequent and the most commonly found in the spine, with a high impact on health care systems and on morbidity due to vertebral fractures (VFs).This article discusses state-of-the-art techniques on the imaging of metabolic bone diseases in the spine, from the well-established methods to the latest improvements, recent developments, and future perspectives.We review the classical features of involvement of metabolic conditions involving the spine. Then we analyze the different imaging techniques for the diagnosis, characterization, and monitoring of metabolic bone disease: dual-energy X-ray absorptiometry (DXA) and DXA-based fracture risk assessment applications or indexes, such as the geometric parameters, Bone Strain Index, and Trabecular Bone Score; quantitative computed tomography; and magnetic resonance and ultrasonography-based techniques, such as radiofrequency echographic multi spectrometry. We also describe the current possibilities of imaging to guide the treatment of VFs secondary to metabolic bone disease.

Imaging of Metabolic Bone Diseases: The Spine View, Part II.

Metabolic bone diseases comprise a wide spectrum. Osteoporosis, the most frequent, characteristically involves the spine, with a high impact on health care systems and on the morbidity of patients due to the occurrence of vertebral fractures (VFs).Part II of this review completes an overview of state-of-the-art techniques on the imaging of metabolic bone diseases of the spine, focusing on specific populations and future perspectives. We address the relevance of diagnosis and current status on VF assessment and quantification. We also analyze the diagnostic techniques in the pediatric population and then review the assessment of body composition around the spine and its potential application. We conclude with a discussion of the future of osteoporosis screening, through opportunistic diagnosis and the application of artificial intelligence.

Osimertinib in advanced EGFR-T790M mutation-positive non-small cell lung cancer patients treated within the Special Use Medication Program in Spain: OSIREX-Spanish Lung Cancer Group.

BACKGROUND: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. METHODS: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites. PRIMARY OBJECTIVE: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. RESULTS: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. CONCLUSION: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. TRIAL REGISTRATION: Clinical trial registration number: NCT03790397 .

Sports and Metabolic Bone Disease.

Physical activity (PA) increases bone mass and bone strength through different mechanisms and also reduces the risk of falls in the elderly, through proprioception and balance training. The benefits seen in adolescence continue into adulthood. Exercise delays and attenuates the effects of osteoporosis, and particular sports activities may be recommended to improve bone mineral density (BMD) of the spine or regional BMD, improve balance, and prevent falls. Stress injuries related to exercise are more common in osteopenic and osteoporotic individuals.Sports activity may in some cases be detrimental for bone health, with nutrition restriction a frequent cause for negative effects of the practice of PA on bone. The examples are the so-called female athlete triad of menstrual dysfunction resulting in reduced estrogen levels, low energy due to malnutrition, and decreased BMD. A similar triad is described in male athletes. This review analyzes the effects of sport on bone metabolism and in particular its relationship with metabolic bone disease.

Clinical management and outcome of patients with advanced NSCLC carrying EGFR mutations in Spain.

BACKGROUND: Although the benefit of first-line epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) over chemotherapy has been demonstrated in several clinical trials, data from clinical practice is lacking and the optimal EGFR TKI to be used remains unclear. This study aims to assess the real-life diagnostic and clinical management and outcome of patients with advanced non-small-cell lung cancer (NSCLC) carrying EGFR mutations in Spain. METHODS: All consecutive patients recently diagnosed with advanced or metastatic NSCLC from April 2010 to December 2011 in 18 Spanish hospitals and carrying EGFR mutations were retrospectively evaluated. RESULTS: Between March and November 2013, a total of 187 patients were enrolled (98.3% Caucasian, 61.9% female, 54.9% never-smokers, 89.0% adenocarcinoma). Mutation testing was mainly performed on biopsy tumour tissue specimens (69.0%) using a qPCR-based test (90%) (47.0% Therascreen EGFR PCR Kit). Common sensitising mutations were detected in 79.8% of patients: 57.1% had exon 19 deletions and 22.6% exon 21 L858R point mutations. The vast majority of patients received first-line therapy (n = 168; 92.8%). EGFR TKIs were the most commonly used first-line treatment (81.5%), while chemotherapy was more frequently administered as a second- and third-line option (51.9% and 56.0%, respectively). Of 141 patients who experienced disease progression, 79 (56.0%) received second-line treatment. After disease progression on first-line TKIs (n = 112), 33.9% received chemotherapy, 8.9% chemotherapy and a TKI, and 9.8% continued TKI therapy. Most patients received first-line gefitinib (83.0%), while erlotinib was more frequently used in the second-line setting (83.0%). Progression-free survival (PFS) and overall survival (OS) in patients harbouring common mutations were 11.1 months and 20.1 months respectively (exon 19 deletions: 12.4 and 21.4 months; L858R: 8.3 and 14.5 months), and 3.9 months and 11.1 months respectively for those with rare mutations. CONCLUSION: EGFR TKIs (gefitinib and erlotinib) are used as the preferred first-line treatment while chemotherapy is more frequently administered as a second- and third-line option in routine clinical practice in Spain. In addition, efficacy data obtained in the real-life setting seem to concur with data from EGFR TKI phase III pivotal studies in NSCLC.

Geriatric assessment in clinical practice for patients with stage IV non-small-cell lung cancer: The Grup de Investigació I Divulgació Oncològica experience.

Therapeutic decision-making for older patients with stage IV non-small-cell lung cancer (NSCLC) with no identifiable activating mutation is complex. In this prospective study, we evaluated the usefulness of geriatric assessment (GA) in identifying frail patients. Stage IV NSCLC patients ≥70 years of age were evaluated with GA and classified according to this evaluation into three different groups: fit, vulnerable and frail. Classifications based on GA, treatment decision, toxicity and overall survival were analysed. In total, 93 patients were included. Median age was 76 (70-92) years and 90% were men. Most patients had performance status (PS) 0 or 1 (82%), unrelated to their GA (p = 0.006). GA groups were associated with overall survival (p = 0.000), treatment decision (p = 0.0001), and toxicity (p = 0.0001). Chemotherapy was delivered to 100% of fit patients, to 48% of vulnerable patients, and to only 8% of frail patients (p = 0.000). Toxicity was higher in vulnerable patients than in fit individuals (p = 0.000). Multivariable analysis showed PS (p = 0.001), active treatment (p < 0.001) and GA group (p = 0.001) to be prognostic factors related to survival. Our results suggest that GA identified patients with poor natural prognosis.

Vertebroplasty and Kyphoplasty in Vertebral Osteoporotic Fractures.

Vertebroplasty and kyphoplasty are minimally invasive treatments and indispensable tools in the treatment of osteoporotic compression fractures. This method of treatment is performed using fluoroscopy or a scanner control an access via the pedicle or the posterolateral angle of the vertebral body. Vertebroplasty requires a smaller caliber needle than kyphoplasty, so it is technically easier. Vertebroplasty uses high-pressure injection, whereas in kyphoplasty the injection is held at low pressure, which together with the effect of compression on the bone that the balloon produces reduces the risk and rate of cement leakage. Vertebroplasty is effective in managing osteoporotic compression vertebral fractures, with improvement in pain and quality of life in the immediate postoperative period and over the medium term.Both techniques have a very low complication rate. There is no consensus on whether the emergence of new fractures in the cases treated by vertebroplasty and kyphoplasty are related to mechanical variations that were introduced or is a complication related to the age and evolution of the patient's osteoporosis. Even with this risk of new fractures, the improvement in quality of life obtained after vertebroplasty and kyphoplasty treatment is worthwhile. The benefits outweigh the risks.

[Sentinel lymph node in pulmonary carcinoma. Molecular study after radioisotope detection]. / El ganglio centinela en el carcinoma pulmonar. Estudio molecular tras detección con radioisótopo.

INTRODUCTION: Metastatic lymph node affectation is the main prognostic factor in localized lung cancer. Pathological study of the obtained samples even after an adequate lymphadenectomy, present tumoral relapses of 40% of stage I patients after oncological curative surgery. In this paper we have studied micrometastasis in the sentinel lymph node by molecular methods in patients with stage I lung cancer. MATERIAL AND METHODS: The sentinel node was marked by injecting peritumorally performed just after performing the thoracotomy with 2 mCi of nanocoloid of albumin (Nanocol®) marked with 99mTc in 0.3 ml. Guided with a Navigator® gammagraphic sensor, we proceeded to its resection. RNA of the tissue was extracted and the presence of genes CEACAM5, PLUNC and CK7 in mRNA was studied. RESULTS: Twenty nine 29 patients were included. Of the tested genes, CEACAM5 and PLUNC were the ones that showed a high expression in lung tissue. Of the 29 analyzed sentinel lymph nodes, 7 (24%) were positive in the molecular study. A positive sentinel lymph node was found in 4/7 adenocarcinomas and 3/12 squamous-cell tumors. Affected lymph nodes were: station 5 (1/3), station 7 (0/6), station 9 (0/1); station 10 (5/11); station 11 (1/1). CONCLUSIONS: Detection of sentinel node in patients with stage I lung cancer by marking with radioisotope is a feasible technique. The application of molecular techniques shows the tumoral affectation in cases staged as stage I.

Describing differences among populations of thoracic tumors patients under and over 80 years: Data analysis from the SLCG thoracic tumor registry.

OBJECTIVES: Cancer is a disease of old age; however, most studies usually included minority of patients fit elderly. The purpose is to investigate the clinical characteristics and genetic information of patients with thoracic tumors who are 80 years old or older compared to those under 80 years old. STUDY DESIGN AND METHODS: The Thoracic Tumor Registry (TTR) is a Spanish observational, prospective cohort study that included patients diagnosed with thoracic tumors. Data were collected from medical records related to sociodemographic, epidemiological, clinical, molecular/genetic, and treatment outcome variables. RESULTS: The total number of patients, recruited from August 2016 to April 2023, was 26.193 (93,1 % were younger than 80 years and 6,9 % were 80 years or older). In the group of older patients: the male ratio increased (72,9 % vs. 80 %); the number of elderly people who had never smoked or were ex-smokers increased (9,9 % vs. 21,1 % and 44,8 % vs. 61,3 %, respectively) and the number of current smokers decreased (43,3 % vs. 17,5 %); had higher ECOG performance status at diagnosis (for ECOG ≥ 2, 15 % vs. 32,9 %), and there were more patients with previous cancer (17,3 % vs. 28 %). The proportion of men is higher than that of women (73 % vs. 27 % in <80 years and 80 % vs. 20 % in ≥80 years). For all biomarkers, the proportion of patients who had a molecular determination was lower in older patients. There were no differences in terms of alterations in the biomarkers tested; except for EGFR, for which the positivity rate was higher in patients aged 80 years and older (25 % vs. 15,3 %). CONCLUSION: The proportion of older patients with targeted mutations is higher. So, at least at diagnosis, it should be proceeded in a standard way. Then, when it comes to treatment, comorbidities and patient's baseline situation should be considered. CLINICAL TRIAL REGISTRATION: NCT02941458.

The value of multislice computed tomography in the diagnosis of elbow fractures.

Within the sports pathology it is vital the functional recovery of the lesions. To achieve this goal it is necessary very precise anatomical information. The elbow region is made up of three bones that together they have a complex relationship. Range of motion is wide and is thanks to the form of their components. To obtain precise information we need complex imaging techniques that allow us to avoid overlaps that show conventional radiology. Thanks to the development of CT multislices we have a high precision tool. Following the classification of the AO Foundation describes all types of fracture and provides images with 3D reconstruciton which allows you to schedule surgery the surgeon with a degree of prior information that approximates the excellence.

Particularities on Anatomy and Normal Postsurgical Appearances of the Hip.

Detailed knowledge of anatomy helps to understand pathologic processes. This article focuses on the anatomy and functionality of the hip, with emphasis on recently studied concepts and anatomic features that have an association with the development of symptoms. The most common anatomic variants posing a challenge for diagnosis and other common findings in asymptomatic patients are reviewed. Good understanding of the different surgical procedures helps in providing as much information as possible to guarantee a favorable outcome, improving prognosis. We review what are the commonly expected postsurgical appearances and the most common postsurgical complications.

Particularities on Anatomy and Normal Postsurgical Appearances of the Ankle and Foot.

The anatomy of the ankle and foot is complex, allowing for a wide range of functionality. The movements of the joints represent a complex dynamic interaction. A solid understanding of the characteristics and actions of the anatomic elements helps explain the mechanisms and patterns of injury. This article reviews the anatomy, with special focus on concepts that are the object of recent study and the features that favor the development of symptoms. Good understanding of the surgical procedures helps in providing information to guarantee a favorable outcome. We review the commonly expected postsurgical appearances and the most common postsurgical complications.

Determination of hexanal and heptanal in saliva samples by an adapted magnetic headspace adsorptive microextraction for diagnosis of lung cancer.

In this work, an analytical method for the determination of two endogenous aldehydes (hexanal and heptanal) as lung cancer biomarkers in saliva samples is presented for the first time. The method is based on a modification of magnetic headspace adsorptive microextraction (M-HS-AME) followed by gas chromatography coupled to mass spectrometry (GC-MS). For this purpose, an external magnetic field generated by a neodymium magnet is used to hold the magnetic sorbent (i.e., CoFe2O4 magnetic nanoparticles embedded into a reversed-phase polymer) in the headspace of a microtube to extract the volatilized aldehydes. Subsequently, the analytes are desorbed in the appropriate solvent and the extract is injected into the GC-MS system for separation and determination. Under the optimized conditions, the method was validated and showed good analytical features in terms of linearity (at least up to 50 ng mL-1), limits of detection (0.22 and 0.26 ng mL-1 for hexanal and heptanal, respectively), and repeatability (RSD ≤12%). This new approach was successfully applied to saliva samples from healthy volunteers and those with lung cancer, obtaining notably differences between both groups. These results reveal the prospect of the method as potential diagnostic tool for lung cancer by saliva analysis. This work contributes to the Analytical Chemistry field presenting a double novelty: on the one hand, the use of M-HS-AME in bioanalysis is unprecedentedly proposed, thus expanding the analytical potential of this technique, and, on the other hand, the determination of hexanal and heptanal is carried out in saliva samples for the first time.

Sex Differences in the Efficacy of Immune Checkpoint Inhibitors in Neoadjuvant Therapy of Non-Small Cell Lung Cancer: A Meta-Analysis.

Non-small cell lung cancer (NSCLC) is one of the world's leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies in early disease stage treatments, as neoadjuvant immunotherapy has shown promising results. Among many of the factors that may influence responses, the role played by sex is attracting increased interest and needs to be addressed. Here, we aim to first review the state of the art regarding neoadjuvant ICIs, whether they are administered in monotherapy or in combination with chemotherapy at stages IB-IIIA, particularly at stage IIIA, before analyzing whether sex may influence responses. To this end, a meta-analysis of publicly available data comparing male and female major pathological responses (MPR) and pathological complete responses (pCR) was performed. In our meta-analysis, MPR was found to be significantly higher in females than in males, with an odds ratio (OR) of 1.82 (95% CI 1.13-2.93; p = 0.01), while pCR showed a trend to be more favorable in females than in males, but the OR of 1.62 was not statistically significant (95% CI 0.97-2.75; p = 0.08). Overall, our results showed that sex should be systematically considered in future clinical trials settings in order to establish the optimal treatment sequence.

Brief report: High incidence of peridiagnosis thromboembolic events in patients with BRAF-mutant lung cancer.

INTRODUCTION: We aimed to determine if advanced BRAF-mutant NSCLC has a higher thromboembolic events (TEE) rate than the expected. METHODS: Between 2008 and 2021, 182 patients with BRAF-mutant advanced NSCLC (BRAF V600E, n = 70; BRAF non-V600E, n = 112) were retrospectively identified from 18 centers in Spain. Patients received chemotherapy (n = 147), immunotherapy (n = 69), targeted therapy (n = 42), and immunotherapy + chemotherapy (n = 26). RESULTS: Incidence rate of TEE was 26.4 % (95%CI: 19.9 %-32.9 %). A total of 72 TEE were documented among 48 patients, as 18 patients (37.5 %) developed more than one event. Median time to TEE onset was 2 months, 69 % of TEE occurred in the peridiagnostic period (+/- 90 days from cancer diagnosis), and in 16 pts. (33 %) TEE was the form of lung cancer presentation. Although most TEE were only venous (82 %; PE, n = 33; DVT, n = 16), arterial events were reported in 31 % and occurred earlier, or TEE presented in atypical locations (13.9 %). TEE were related to high hospitalization rate (59 %), recurrence (23 %), and mortality (10.4 %) despite appropriate anticoagulant/antiaggregant treatment. Median OS in patients without-TEE was 19.4 months (95%CI: 4.6-34.1), and significantly shorter in patients with arterial-TEE vs venous-TEE vs both of them: 9.9 months (95%CI: 0-23.5) vs 41.7 months (95%CI: 11.3-72.2 m) vs 2.7 months (95%CI: 2.1-3.3), p = 0.001. Neither clinical or molecular features (BRAF V600E/non-V600E), nor cancer treatment was associated to TEE occurrence. Khorana score underperformed to predict thrombosis at cancer diagnosis, as only 19.2 % of patients were classified as high-risk. CONCLUSIONS: Thrombotic events represent a new clinical feature of BRAF-mutant lung cancer. Patients with almost a 30 % incidence of TEE should be offered systematic anticoagulation.