Radiotherapy in the management of lung oligometastases.

In recent years, the development of both medical imaging and new systemic agents (targeted therapy and immunotherapy) have revolutionized the field of oncology, leading to a new entity: oligometastatic disease. Adding local treatment of oligometastases to systemic treatment could lead to prolonged survival with no significant impact on quality of life. Given the high prevalence of lung oligometastases and the new systemic agents coming with increased pulmonary toxicity, this article provides a comprehensive review of the current state-of-art for radiotherapy of lung oligometastases. After reviewing pretreatment workup, the authors define several radiotherapy regimen based on the localization and size of the oligometastases. A comment on the synergistic combination of medical treatment and radiotherapy is also made, projecting on future steps in this specific clinical setting.

Transforaminal lumbar interbody fusion with placement of steerable banana cage: A single-center retrospective analysis of radiographic parameters of success.

INTRODUCTION: The transforaminal lumbar interbody fusion (TLIF) is among the most utilized methods for the surgical treatment of lumbar degenerative disc disease. The TLIF has advanced significantly with several iterative changes since its inception in the early 1980s, with the advent of several generations of interbody types, shapes, and materials. Steerable curvilinear interbodies are among the most recent innovations in this space and may offer biomechanical advantages, namely in preservation of lumbar and segmental lordosis. While radiographic parameters have been investigated for other cage shapes and lumbar interbody fusion techniques, no study has investigated postoperative radiographic outcomes specific to TLIFs done with curvilinear interbodies. METHODS: This study is a retrospective review of TLIFs performed with curvilinear interbodies between 2019 and 2022 at a single institution. Upright radiographs were obtained preoperatively and at several timepoints postoperatively. Radiographic variables including interspace height and segmental lordosis were collected. RESULTS: 26 surgeries with 32 curvilinear interbodies were performed across 3 years. There was significant increase in segmental lordosis at the L4-L5 (p = 0.0183) and L5-S1 levels (p = 0.004) as well as interspace height postoperatively at levels L3-L4 (p = 0.011) and L4-L5 (p = 0.002). Pain as measured with the numeric rating scale significantly improved in the overall cohort postoperatively (p<0.001). CONCLUSIONS: TLIF with curvilinear interbody placement increases segmental lordosis and interspace height at the L4-L5 and L5-S1 levels, and increased interspace height at the L3-L4 and L4-L5 levels. Further investigation into additional radiographic parameters is warranted and expanded cohort size would benefit deeper analysis of other spinal levels. IMPLICATIONS FOR PRACTICE: As an increasing number of cage designs and materials are brought to market, studies such as this allow for better understanding of cage specific outcomes allowing for better informed device selection.

Radiotherapy in the management of synchronous metastatic lung cancer.

Metastatic lung cancer classically portends a poor prognosis. The management of metastatic lung cancer has dramatically changed with the emergence of immune checkpoint inhibitors, targeted therapy and due to a better understanding of the oligometastatic process. In metastatic lung cancers, radiation therapy which was only used with palliative intent for decades, represents today a promising way to treat primary and oligometastatic sites with a curative intent. Herein we present through a literature review the role of radiotherapy in the management of synchronous metastatic lung cancers.

Intraoperative motive for incomplete resection in primary retroperitoneal sarcoma.

INTRODUCTION: Surgical resection is the current standard of care for retroperitoneal sarcoma (RPS). Recent data suggests that up to 5% of patient have incomplete (R2) resection. The exact reason why patients scheduled for surgery with a curative intent to treat ended up with an R2 resection is largely unknown. AIM OF THE STUDY: To identify intraoperative findings responsible for incomplete (R2) resection in primary RPS. METHODS: All records of consecutive patients scheduled for a non-metastatic primary RPS surgery between 1995 and 2020 in a tertiary care sarcoma centre were retrospective analyzed. RESULTS: Among the 347 patients scheduled for surgery, 13 (3.7%) had an incomplete (R2) resection. The reasons for incomplete surgery were intraoperative finding of vascular involvement of great vessels in 5 patients, previously undetected peritoneal metastases in 5 patients, invasion of contralateral kidney/ureter in 2 patients and the need to preserve both kidneys in 1 patient because of his past medical history. Among these patients, 3 had a laparotomy without resection and 10 had a partial resection (i.e. debulking surgery). Severe postoperative complications occurred in 5 patients. The median length of stay in hospital was 19days. After a median follow-up of 12months, the median survival of patients after incomplete resection was 18months. The 1-y, 5-y and 8-y overall survival (OS) for these patients were 46%, 14%, and 7%, respectively. CONCLUSION: Incomplete (R2) resection for a primary RPS surgery is rare in specialized sarcoma center. The next steps should be to identify the preoperative criteria that lead to this accurate selection and to define the best practice in front of a peroperative discovery of an unresectable RPS. LEVEL OF EVIDENCE: III.

Microfluidic Design of Streamlined Alginate Hydrogel Micromotors with Run and Tumble Motion Patterns.

Autonomous micromotors demonstrate remarkable advancements in biomedical applications. A noteworthy example is streamlined motors, which display enhanced movement efficiency with low fluid-resistance. However, existing streamlined motors, primarily constructed from inorganic materials, present challenges due to their complex fabrication procedures and lack of a soft interface for interaction with biological systems. Herein, a novel design of biodegradable streamlined alginate hydrogel micromotors with a teardrop shape by microfluidics is introduced. The platform enables the high-throughput fabrication of monodisperse micromotors with varied dimensions. By incorporating Pt-coated Fe3 O4 nanoparticles, micromotors are equipped with dual capabilities of catalytic propulsion and accurate magnetic guidance. Through precisely tuning the localization regions of catalysts within the micromotors, the streamlined hydrogel micromotors not only exhibit enhanced propelling efficiency, but also accomplish distinct motion patterns of run and tumble. The design provides insights for developing advanced micromotors capable of executing intricate tasks across diverse application scenarios.

Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants.

Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, direct evidence of subsequent transmission and continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate not only that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome but also that patients with persistent infections can transmit these viral variants. Thus, there is, an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.

Issues around food in mixed families of adolescent girls with bulimia nervosa: A qualitative study with photo-elicitation.

OBJECTIVES: Bulimia nervosa (BN) is a common psychiatric disorder among adolescent girls with potentially significant complications. Family relationships play a major role in the development and progression of this disorder. Studies in migrant populations suffering from eating disorders show contrasting results depending on the generation of migrants: first generation migrants have fewer eating disorders than the native population, while the prevalence of this disorder is more important than the latter among second and third generation migrants. In our clinical experience, we have frequently encountered so-called "mixed" families, which are families composed of one migrant parent and one non-migrant parent. Research focusing on this kind of family is scarce which is why we chose to explore their dynamic. METHODS: This study explored the issues around food and family relationships of adolescent girls suffering from BN, a topic that, to date, has not yet been studied. Ten interviews were conducted with five adolescent girls with BN between the ages of 16 and 20 and their parents, using photo-elicitation to enrich the collected data. RESULTS: The results were organized around two axes: (1) identity issues around food, that is the assimilation process described by both parents and adolescents concerning family meals and food habits, and how the adolescents struggle to manage this interbreeding; and (2) transmission issues with the consequences the migrant parent has to deal with to transmit his/her cultural identity with food while being far away from the homeland, and the difficulties between this parent and his/her child to share this heritage. Both issues, identity and transmission, appear to be central among these families. CONCLUSIONS: Our results suggest a difficulty in mentalizing identity issues in adolescent girls; the function of appeasement around non-mentalized tensions was highlighted. In our opinion, in this particular context, BN acts as a means of expressing the difficulty of their mixed culture. This enables it to draw some clinical implications, especially using mentalization-based therapy which has already shown efficacy in adolescents with borderline personality disorder and ED.

Movement Velocity as an Indicator of Mechanical Fatigue and Resistance Exercise Intensity in Cross Modalities.

Purpose: This study analyzed the acute mechanical response to three workouts of the day (WOD) protocols in as many repetitions as possible (AMRAP), every minute on the minute (EMOM), and for time (FT) models by quantifying the degree of mechanical fatigue induced by popular resistance exercises in the Cross modalities, front squat (FS), and shoulder press (SP). We also analyzed whether the exercises' fastest velocity (Vfastest) could be an objective indicator of relative intensity (%1RM). Methods: Nine trained men performed three FS and SP exercises protocols. The degree of fatigue was quantified by the velocity loss (VL) achieved in both exercises and the velocity loss achieved in the WOD (VLWOD). Results: The VLWOD in the AMRAP, EMOM, and FT protocols was 73.2 ± 10.9%, 61.6 ± 15.1%, and 76.1 ± 8.8%, respectively. In the AMRAP and FT protocol, the Vfastest showed very strong relationships with the %1RM for FS and SP (r = -0.83, -0.75, respectively, p < .01); while in the EMOM protocol, there was a strong relationship between these variables, only for the SP (r = -0.61, p < .05). In the FT protocol, we observed an extremely strong relationship for FS (r = -0.91, p < .001) and very strong (r = -0.71, p < .05) for SP between these variables. Conclusion: Therefore, the AMRAP and FT training models induce the highest degrees of mechanical fatigue in the FS and SP exercises, and the Vfastest is a reliable tool for estimating relative intensity in resistance exercises of Cross modalities.

[Practice changing clinical trials in radiation oncology in 2022]. / Les essais qui changent les pratiques : le point en 2022.

This section highlights selected specific new recommendations and/or updates that have been published during the very last years in the fields of stereotactic radiotherapy, pediatrics, lung cancer, gynecologic and breast cancer, as well as in the area of radiation oncology of urogenital cancer.

Impact of radiotherapy schedule on survival of patients treated with immune-checkpoint inhibitors for advanced melanoma and non-small cell lung cancer.

PURPOSE: Preclinical and clinical data suggest a potential benefit in the addition of radiotherapy (RT) to immune-checkpoint inhibitors (ICI) during the treatment of advanced cancers. Nevertheless, the ideal patients for this approach and the optimal RT regimen is still debated. MATERIAL AND METHODS: The aim of this study was to determine the effect RT schedule has on survival for advanced non-small cell lung cancer and melanoma patients (pts) treated with ICI (anti-PD1 or anti-CTLA4) and concomitant RT. RESULTS: A total of 58 pts were identified, of which 26 received RT concomitantly with ICI while the remaining 32 pts were treated with RT at the time of progression under ICI. The RT parameters associated with outcome include dose per fraction, biological effective dose, RT to all targets and lung irradiation. Independent predictors of improved progression-free survival were lung irradiation, melanoma histology, oligometastatic status (<6 metastasis), presence of liver metastasis, PNN<7000/mm3 and normal LDH. Independent predictors of improved overall survival were melanoma histology and normal LDH. Among pts who were irradiated at progression, 68.7% had an overall clinical benefit and had a median extension of ICI use by 2.3 months (range: 0-29.1), among which 2 presented with an abscopal effect. CONCLUSIONS: The irradiation of lung metastases may increase survival in patients under ICI. RT at progression could prolong the use of ICI, and neutrophilia and LDH should be considered during patient selection of this combined RT/ICI approach.

Postgraduate oncology educational shifts during the COVID-19 pandemic: results of faculty and medical student surveys.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted clinical practice, research and teaching. During peaks, virtual courses were implemented but these changes are poorly described, especially for oncology postgraduate students and faculty teachers. PATIENTS AND METHODS: We administered two surveys from June 2021 to October 2021 to students and faculty teachers (250 and 80 responses, respectively) who registered at Gustave Roussy School of Cancer Sciences (Université Paris-Saclay) during 3 consecutive university years (October 2018 to October 2021), where a major shift to e-learning was associated with COVID-19 pandemic. RESULTS: Most students were female (53%), attending physicians (50%), aged 30-39 years (54%) and 2020-2021 (66.4%) was the main year of training. Most faculty teachers were male (58%), aged 40-50 years (44%) and had participated in training for at least 3 years (83%). More than half of the students received 100% virtual training [55% versus 45% face-to-face/mixed teaching modalities; online (84%) versus remote teaching (16%)]. Only 34% of students declared >80% 'active listening' and only 16% of teachers considered e-learning to be more suitable (compared with face-to-face) for postgraduate education. Virtual teaching decreased student-teacher interactions as compared with mixed/face-to-face (lessons were sufficiently interactive for 54% students if virtual only teaching versus for 71% if other teaching modalities; P = 0.009). Teachers stated that virtual learning did not lead to any improvements in terms of attendance (68%), interaction (74%) and quality of teaching (68%). However, most faculty (76%) acknowledged that partial e-learning training should be maintained outside the pandemic, if it represents ≤50% of the whole teaching (teachers: 79% versus student: 66%; P = 0.04). CONCLUSIONS: COVID-19 accelerated the transition toward novel practices. Students and faculty teachers agreed on the need for future mixed (≤50% e-learning) teaching modalities. Adequate formation and the use of codified best newer virtual practices are required.

Early phase trials in soft-tissue sarcomas: clinical benefit of inclusion in early lines of treatment, molecular screening, and histology-driven trials.

BACKGROUND: The prognosis of patients with advanced soft-tissue sarcomas (STS) remains dismal, and systemic therapeutic options are limited. Early phase trials are becoming increasingly safe and effective. This study aimed to identify the prognostic factors for progression-free survival (PFS). PATIENTS AND METHODS: This retrospective analysis included all STS patients participating in early phase trials at Gustave Roussy and Léon Bérard between 1 January 2012 and 31 December 2020. RESULTS: Overall, 199 patients accounted for 214 inclusions in advanced STS. The most frequent histotypes were well-differentiated/dedifferentiated liposarcomas (n = 55), leiomyosarcomas (n = 53), synovial sarcomas (n = 22), undifferentiated pleomorphic sarcomas (n = 15), angiosarcomas (n = 12), and myxoid liposarcomas (n = 10). The median PFS was 2.8 months (95% confidence interval 2.7-4.1 months). The median PFS in the first, second, and later lines was 8.3, 5.4, and 2.6 months, respectively (P = 0.00015). The median PFS was 2.8 months in case of molecular screening, 4.1 months in case of histology-driven screening, and 1.6 months (P = 0.00014) in the absence of either screening modalities. In univariate analysis, histotype (P = 0.026), complex genomics (P = 0.008), number of prior lines (P < 0.001), prior anthracyclines (P < 0.001), number of metastatic sites (P = 0.003), liver metastasis (P < 0.001), lung metastasis (P < 0.001), absence of molecular or histology-driven screening (P < 0.001), first-in-human trials (P < 0.001), dose-escalation cohorts (P = 0.011), and Royal Marsden Hospital (RMH) score >1 (P < 0.001) were significantly associated with shorter PFS. In multivariate analysis, independent prognostic factors for shorter PFS were myxoid liposarcoma (P = 0.031), ≥2 prior lines of treatment (P = 0.033), liver metastasis (P = 0.007), and RMH score >2 (P = 0.006). Factors associated with improved PFS were leiomyosarcomas (P = 0.010), molecular screening (P = 0.025), and histology-driven screening (P = 0.010). The median overall survival rates were 36.3, 12.6, and 9.2 months in the first, second, and later lines, respectively (P = 0.0067). The grade 3-4 toxicity rate was 36%. CONCLUSIONS: Early phase trials provide an active therapeutic option for STS, even in first-line settings. Molecular screening and histology-driven trials further improve the clinical benefit.

Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron.

The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in November 2021 in South Africa and Botswana, as well as in a sample from a traveller from South Africa in Hong Kong1,2. Since then, Omicron has been detected globally. This variant appears to be at least as infectious as Delta (B.1.617.2), has already caused superspreader events3, and has outcompeted Delta within weeks in several countries and metropolitan areas. Omicron hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness2,4-6. Here we investigated the virus-neutralizing and spike protein-binding activity of sera from convalescent, double mRNA-vaccinated, mRNA-boosted, convalescent double-vaccinated and convalescent boosted individuals against wild-type, Beta (B.1.351) and Omicron SARS-CoV-2 isolates and spike proteins. Neutralizing activity of sera from convalescent and double-vaccinated participants was undetectable or very low against Omicron compared with the wild-type virus, whereas neutralizing activity of sera from individuals who had been exposed to spike three or four times through infection and vaccination was maintained, although at significantly reduced levels. Binding to the receptor-binding and N-terminal domains of the Omicron spike protein was reduced compared with binding to the wild type in convalescent unvaccinated individuals, but was mostly retained in vaccinated individuals.

Development and validation of a patient-reported outcome in systemic sclerosis: the Hand scleroDerma lived Experience (HAnDE) scale.

BACKGROUND: Hand involvement in systemic sclerosis (SSc) is at the core of the disease, with a substantial impact on both functional aspects and quality of life. There is no patient-reported outcome (PRO) scale globally assessing hand involvement in SSc. OBJECTIVES: To develop and validate a PRO scale, the Hand scleroDerma lived Experience (HAnDE) scale, to assess the lived experience of hand involvement in patients with SSc. METHODS: This was an exploratory sequential mixed-methods study with two phases: (i) PRO development through an inductive process to analyse the structure of lived experience, involving 21 patients with SSc; and (ii) PRO validation by assessing the psychometric properties of the scale among 105 patients with SSc. RESULTS: Phase 1 enabled us to generate the 18-item provisional scale. From Phase 2, the mean (SD) total score of the scale was 29·16 (16·15). The item reduction process retained 16 items with five levels of answers (range 0-64). Internal consistency of the 16-item version was excellent (Cronbach's alpha = 0·946). Construct validity was very good, principal component analysis pointing towards a unidimensional instrument, with one factor explaining 56% of the variance, and concurrent validity being confirmed: Cochin Hand Function Scale r = 0·66; Health Assessment Questionnaire - Disability index r = 0·58; Hospital Anxiety and Depression Scale, anxiety r = 0·51, depression r = 0·4; Mouth Handicap in Systemic Sclerosis scale r = 0·61; 36-Item Short Form Health Survey, physical component r = -0·48, mental component r = -0·46; and Kapandji score r = -0·46. The correlations were statistically significant (P < 0·05). CONCLUSIONS: We propose, for future trials and clinical practice in SSc, a new PRO, the HAnDE scale, that assesses all the dimensions - functional, aesthetic, relational, existential and emotional - of the lived experience of hand involvement in SSc.

First use of the Adolescent Depression Rating Scale (ADRS) in the management of young people with severe acne treated with isotretinoin: a pilot study of an active monitoring of depressive disorders by dermatologists.

BACKGROUND: During isotretinoin treatment, special attention is required to detect any symptom or change in the mental health of patients. The monitoring is complex for adolescents because of confounding factors such as mood changes associated with adolescence and puberty and the higher psychosocial impairment due to the acne itself. AIM: To determine the utility of the Adolescent Depression Rating Scale (ADRS) for monitoring symptoms in adolescents before and during isotretinoin treatment in dermatology real-life practice. METHODS: This was a national, multicentre prospective study that enrolled a random sample of dermatologists treating adolescents. An algorithm including ADRS score and its changes between consecutive visits was used. At each visit, dermatologists rated their satisfaction with ADRS and its ease of use, while patients rated the acceptability of the ADRS. RESULTS: In total, 70 dermatologists used the algorithm for 1227 visits of 283 adolescents receiving isotretinoin. Of these 70 dermatologists, 80.8% were satisfied/very satisfied with the ADRS, 82.7% considered the use of the ADRS in clinical practice to be easy/very easy and 75% considered that the ADRS enabled them to discuss more easily the risk of depression with their patients. For the patients, acceptability of the ADRS was considered good by 93.8%. CONCLUSIONS: The implementation of the ADRS could be valuable in dermatology practice, optimizing the monitoring of patients and the good use of isotretinoin.

Lung metastases radiation therapy.

We present an update of the French society of oncological radiotherapy recommendation regarding indication, doses, and technique of radiotherapy for intrathoracic metastases. The recommendations for delineation of the target volumes and critical organs are detailed.

Sulfonated melanin derivatives: theoretical evaluation of local reactivities and chemical structures.

Melanins are natural macromolecules present in several organisms responsible for photoprotection, photosensitivity, ion chelation, and thermoregulation. Such materials have attracted attention due to their interesting electronic properties, which suggest their possible application in biocompatible devices. However, the low typical solubility of traditional melanins does not allow the production of good quality thin films. In this sense, soluble compounds obtained via alternative synthetic routes, for instance, via levodopa (L-DOPA) oxidation in sulfonated solvents (S-melanins), can be considered interesting technological materials. Despite this, the structural and electronic features of these compounds are not fully understood. In this context, here we present a theoretical study on the local reactivities of S-melanin building blocks to better understand possible mechanisms involved in its synthesis and propose extended structures of this material. For this purpose, condensed-to-atoms Fukui indices were evaluated in the framework of the density functional theory (DFT). The obtained results show that the different side groups present in S-melanins do not significantly influence the reactivity of the compound in relation to non-functionalized melanins, indicating that both materials can present similar macroscopic structures.