[Treatment of localized rectal cancer in 2024]. / Prise en charge du cancer du rectum localisé en 2024.

The management of localized rectal cancer has evolved significantly over the last two years. On one hand, intensification of treatments (radio-chemotherapy, chemotherapy, then surgery) for the most advanced tumors has shown an improvement in clinical results compared to less intense regiments. On the other hand, the possibility, as for prostate cancers, of opting for active surveillance without surgery in patients presenting a complete clinical response after a treatment phase, is now accepted. More recently, the Swiss recommendations for the surveillance of rectal cancer have been modified and now differ from those of colon cancers, by incorporating pelvic MRI and rectoscopy in addition, as well as special guidelines for tumors under active surveillance.

La prise en charge du cancer du rectum localisé a beaucoup évolué ces deux dernières années. D'un côté, l'intensification des traitements (radio-chimiothérapie, chimiothérapie, puis chirurgie) pour les tumeurs les plus avancées a montré une amélioration des résultats cliniques par rapport aux traitements moins intenses. De l'autre côté, la possibilité, comme pour les cancers de la prostate, d'opter pour une surveillance active sans chirurgie chez les patients présentant une réponse clinique complète après une phase de traitement est aujourd'hui acceptée. Plus récemment, les recommandations suisses pour la surveillance du cancer du rectum ont été modifiées et se différencient maintenant de celles des cancers du côlon, en incorporant IRM pelvienne et rectoscopie en sus, de même qu'un suivi spécial pour les tumeurs en surveillance active.

Endobronchial coil spring fiducial markers for CyberKnife® stereotactic body radiation therapy.

BACKGROUND AND OBJECTIVE: SBRT is an alternative treatment for early-stage inoperable lung cancer. Metallic FM allow to increase tumour tracking precision by CyberKnife®. Currently used techniques for FM placement have many limitations; transthoracic insertion has a high risk for pneumothorax, endovascular insertion requires expertise and dedicated angiography infrastructure and endobronchial linear-gold FM dislocate frequently. This is the first study to assess the safety and efficacy of cs-FM endobronchial insertion under fluoroscopy with or without R-EBUS assessment. METHODS: We retrospectively evaluated all consecutive patients undergoing endobronchial cs-FM placement for at least one PPL <25 mm between 10.2015 and 12.2019. TBB of the PPL were performed in case of a typical R-EBUS signal. PPL tracking accuracy by CyberKnife, complications, cs-FM migration rate and procedure duration were analysed. RESULTS: A total of 52 patients were treated during 55 procedures and 207 cs-FM were placed in 70 PPL. Tracking was successful for 65 of 70 (93%) PPL. R-EBUS was performed for 33 (47%) PPL and TBB for 9 (13%) PPL. Bronchospasm occurred once and any other complications were observed. Migration of cs-FM occurred in 16 of 207 (8%) cs-FM. Migration was more frequent when the target was in a previously irradiated area (P = 0.022). The median bronchoscopy duration was 31.5 min (n = 48 procedures). CONCLUSION: Bronchoscopic cs-FM placement is a rapid and safe procedure. It is associated with a low migration rate and allows precise SBRT delivery. Previous irradiation of the PPL was associated with a higher migration rate.

Percussion assisted radiation therapy in Hodgkin lymphoma allows a marked reduction in heart dose.

BACKGROUND AND PURPOSE: Early-stage Hodgkin lymphoma (HL) is a highly curable disease but the treatment can induce late complications many years later. Irradiation of the healthy heart is inevitable during radiation treatment of mediastinal sites. We developed a novel method to induce a prolonged apnea-like state that can help decrease the dose to organs at risk during radiation therapy. We present the results of the first 8 HL patients treated routinely with percussion assisted radiation therapy (PART) in our clinic. MATERIAL AND METHODS: We used a newly developed high-frequency non-invasive ventilation system to suppress respiratory motion for prolonged periods and push the heart away from the treated volume. RESULTS: All 8 patients were able to rapidly learn the technique and had an advantage to be treated by PART. We lowered the mean heart dose by an average of 3 Gy with similar target coverage compared to a classical free breathing treatment plan. They were all treated for 15 radiotherapy sessions by PART without any notable side effects. CONCLUSIONS: Percussion assisted radiation therapy can be used routinely to reduce the dose to the heart in Hodgkin lymphoma.

Oncological outcome, functional results and costs after unplanned excision of musculoskeletal soft tissue sarcoma.

BACKGROUND: Treatment of soft tissue sarcomas (STS) should only be initiated once the diagnosis is fully established. Resection of tumors of unknown nature should be avoided. Nevertheless, specialized centers continue to face numbers of unplanned excisions (UPE) in STS. AIM: To compare oncologic and functional outcomes, number of surgeries, length of hospital stay and treatment costs of UPE versus planned excision (PE) in STS. METHOD: A retrospective single tertiary center study was performed on 201 patients. Survival, local and distant recurrence rates were compared between PE (n = 137) and UPE (n = 64). In a subgroup analysis of 60 patients, functional outcome (MSTS and TESS scores), and socio-economic impact (number of surgeries, length of hospital stay and treatment costs) in "functional planned excision" (fPE) group (n = 30) and "functional unplanned excision" (fUPE) group (n = 29) were compared. RESULTS: There was no significant difference in oncological outcome between PE and UPE. In the subgroup analysis, we found a non-significant difference in functional outcome. Patients in the fUPE had significantly more surgeries (3.5 vs. 1.4; p < 0.00001) and costs of their management was 64% higher than fPE (p = 0.048). Hospital stay was longer after fUPE but not statistically significant (18.3 days vs. 11.8 days; p = 0.13). CONCLUSION: Even though oncological and functional outcomes are comparable after PE and UPE of STS, the number of surgeries, length of hospital stay and treatment costs were higher in patients with UPE. Our data underscore the importance of specialized STS treatment centers including multidisciplinary management.

Factors Associated with Condom Use among a Sample of Men Who Have Sex with Men (MSM) Residing in Rural Oklahoma.

Public health literature often neglects populations from rural communities, particularly with men who have sex with men (MSM). Although HIV/STI infections are decreasing slightly, there is an increase within rural MSM, thus opening the door for further research on condom use behavior in a rural context. In-depth interviews were conducted with 40 MSM in rural Oklahoma regarding their condom use and sexual behaviors. A qualitative analysis revealed five themes with respect to condom usage: physical discomfort of condoms, relationship trust, usage based on the type of sexual act, substance use, and knowledge of a partner's HIV/STI status. A sixth theme within the context of rural Oklahoma revealed participants' fear of physical/verbal abuse, hesitations seeking medical help due to confidentially issues, and general acknowledgment of the lack of education and resources available. Implications include increasing mobile testing locations and a push for marketing greater confidentially within health service providers.

Current landscape of palliative radiotherapy for non-small-cell lung cancer.

Radiotherapy (RT) is a cornerstone in the management of advanced stage III and stage IV non-small-cell lung cancer (NSCLC) patients. Despite international guidelines, clinical practice remains heterogeneous. Additionally, the advent of stereotactic ablative RT (SABR) and new systemic treatments such as immunotherapy have shaken up dogmas in the approach of these patients. This review will focus on palliative thoracic RT for NSCLC but will also discuss the role of stereotactic radiotherapy, endobronchial brachytherapy (EBB), the interest of concomitant treatments (chemotherapy and immunotherapy), and the role of RT in lung cancer emergencies with palliative intent.

Novel inverse planning optimization algorithm for robotic radiosurgery: First clinical implementation and dosimetric evaluation.

PURPOSE: A novel optimization algorithm (VOLO™) for robotic radiosurgery in the Precision™ treatment planning system was evaluated for different SRS/SBRT treatments and compared with the previous Sequential Optimization (SO) algorithm. MATERIALS AND METHODS: Fifty cases of brain, spine, prostate and lung tumors previously optimized with SO, were re-planned with VOLO™ algorithm keeping the same prescription, collimator type and size, optimization shells, and blocking structures. The dosimetric comparison involved target coverage, conformity (CI), gradient (GI) and homogeneity indexes, specific indicators of dose to OARs and number of nodes, beams, MU and delivery time. For brain only, plans were IRIS- and MLC-based (10 each). The remaining 30 plans were all IRIS-based. RESULTS: VOLO™ optimization was significantly superior for target coverage for prostate and spine, CI for brain, and for brain and urethra dose sparing. SO gave significantly better results for GI for prostate. VOLO™ showed a significantly steeper dose fall-off for brain MLC-based, while for prostate and spine SO was superior. For IRIS-based plans, VOLO™ significantly reduced the nodes (36%), beams (14%), and MU (31%). This led to an average reduction of delivery time of 20% (from 8% for brain to 30% for prostate). For MLC-based plans, VOLO™ significantly increased the nodes and beams (42%) keeping the same number of MU. The averaged delivery time increased by 18%. CONCLUSIONS: With respect to SO, VOLO™ optimization algorithm provided better results in terms of delivery time for IRIS-based and of quality of dose distribution for MLC-based plans, respectively.

Barriers to Access and Adoption of Pre-Exposure Prophylaxis for the Prevention of HIV Among Men Who Have Sex With Men (MSM) in a Relatively Rural State.

Biomedical intervention approaches, including antiretroviral pre-exposure prophylaxis (PrEP), have been demonstrated to reduce HIV incidence among several at-risk populations and to be cost effective. However, there is limited understanding of PrEP access and uptake among men who have sex with men (MSM) residing in relatively rural states. Twenty semistructured interviews were conducted (August-November 2016) to assess opinions of and perceived barriers to accessing and adopting PrEP among MSM residing in Oklahoma. Participants perceived substantial barriers to accessing PrEP including a stigmatizing environment and less access to quality, LGBT-sensitive medical care. Overall, geographic isolation limits access to health providers and resources that support sexual health for Oklahoma MSM. Addressing stigma situated across ecological levels in an effort to increase adoption of PrEP by MSM residing in rural states remains necessary. Without this, social determinants may continue to negatively influence PrEP adoption and sexual health outcomes.

How could breast cancer molecular features contribute to locoregional treatment decision making?

Systemic treatments are tailored to breast cancer (BC) heterogeneity, which is not yet taken into account for radiotherapy (RT) personalization. The primary objective of this review is to summarize existing data suggesting BC subtypes and genetic assays are prognostic and predictive biomarkers useful for RT decision-making and to provide implications for their incorporation into future translational and clinical research. The evidence suggesting that BC subtypes also exhibit distinct "locoregional recurrence (LRR)" patterns is retrospective but consistent and validated in over fifteen studies. The HER-2 positive and triple negative subtypes are the most susceptible to locoregional failure. The high risk of the HER-2 positive subtype can be reversed with trastuzumab administration. Very little is known on the subtypes' intrinsic radiosensitivity properties. Genetic assays have assessed retrospectively signatures' prognostic and predictive value in patients' cohorts (several coming from prospective studies) for LRR risk and radiotherapy (RT) benefit. Further confirmation is needed before their introduction into clinical routine. Evidence on the use of molecular biomarkers for adjuvant RT tailoring is emerging but needs validation and introduction into prospective studies. The plethora of modern RT options (partial breast irradiation, hypofractionation), as well as recent evidence pointing towards more extensive radiotherapy, demand introduction of biological features into clinical trials to improve therapeutic decisions. Open questions, such as tailoring of irradiation after neo-adjuvant chemotherapy in complete responders and the understanding of the interplay between local control, systemic recurrence and survival given modern systemic treatments, need to be addressed under the prism of biology within this heterogeneous disease. Intrinsic radiobiological properties within this heterogeneity need to be highlighted in order to further improve outcomes.

Apnea-like suppression of respiratory motion: First evaluation in radiotherapy.

BACKGROUND AND PURPOSE: Compensation for respiratory motion is needed while administering radiotherapy (RT) to tumors that are moving with respiration to reduce the amount of irradiated normal tissues and potentially decrease radiation-induced collateral damages. The purpose of this study was to test a new ventilation system designed to induce apnea-like suppression of respiratory motion and allow long enough breath hold durations to deliver complex RT. MATERIAL AND METHODS: The High Frequency Percussive Ventilation system was initially tested in a series of 10 volunteers and found to be well tolerated, allowing a median breath hold duration of 11.6 min (range 3.9-16.5 min). An evaluation of this system was subsequently performed in 4 patients eligible for adjuvant breast 3D conformal RT, for lung stereotactic body RT (SBRT), lung volumetric modulated arc therapy (VMAT), and VMAT for palliative pleural metastases. RESULTS: When compared to free breathing (FB) and maximal inspiration (MI) gating, this Percussion Assisted RT (PART) offered favorable dose distribution profiles in 3 out of the 4 patients tested. PART was applied in these 3 patients with good tolerance, without breaks during the "beam on time period" throughout the overall courses of RT. The mean duration of the apnea-like breath hold that was necessary for delivering all the RT fractions was 7.61 min (SD=2.3). CONCLUSIONS: This first clinical implementation of PART was found to be feasible, tolerable and offers new opportunities in the field of RT for suppressing respiratory motion.

[Sarcoma centres : a necessary tool in the management of patients and for research.] / Centre des sarcomes : un nouvel outil pour améliorer la prise en charge du patient et soutenir la recherche.

Sarcomas are rare diseases, the treatment of which requires an appropriate technical plateform and a broad spectrum of multidisciplinary specialists. Many are initially treated by unplanned excision, and then referred to specialized centres. Secondary treatments may lead to higher complication rates and local recurrence, with lower functional outcome, life quality and possibly overall survival. In order to improve the accessibility for referral to a specialist centre, the coordination of clinical and research activities, and the quality of the management of sarcomas in general, Lausanne University Hospital (CHUV) has opened a Sarcoma centre on October 1st 2016. The objective of the present paper is to illustrate the concept and provide useful clinical recommendations.

Les sarcomes sont des maladies rares, dont la prise en charge multidisciplinaire nécessite un plateau technique important. Ils font souvent l'objet d'une excision initiale accidentelle, nécessitant une reprise en milieu spécialisé, avec un risque majoré de complications et de récidive locale, un impact sur la fonction, voire la survie. La prise en charge des sarcomes est réservée aux centres de référence, où il est souvent difficile pour le praticien de trouver un interlocuteur à qui adresser un patient ou demander un avis. Pour les cliniciens et les chercheurs, il est souvent compliqué de coordonner les activités. Pour en améliorer la prise en charge globale, le CHUV a donc créé un centre des sarcomes, inauguré le 1er octobre 2016. Le présent article a pour but d'illustrer cette problématique et de rappeler quelques données cliniques utiles.

Why did Swiss citizens refuse a comprehensive second-hand smoke ban?

The ill effects of second-hand smoke are now well documented. To protect the population from exposure to tobacco smoke, comprehensive smoking bans are necessary as expressed in the WHO Framework Convention on Tobacco Control and its guidelines. Switzerland has only a partial smoking ban full of exceptions which has been in effect since 2010, which reproduces the so-called Spanish model. In September 2012, the Swiss citizens refused a proposal for a more comprehensive ban. This case study examines the reasons behind this rejection and draws some lessons that can be learnt from it.

Loss of cutaneous TSLP-dependent immune responses skews the balance of inflammation from tumor protective to tumor promoting.

Inflammation can promote or inhibit cancer progression. In this study we have addressed the role of the proinflammatory cytokine thymic stromal lymphopoietin (TSLP) during skin carcinogenesis. Using conditional loss- and gain-of-function mouse models for Notch and Wnt signaling, respectively, we demonstrate that TSLP-mediated inflammation protects against cutaneous carcinogenesis by acting directly on CD4 and CD8 T cells. Genetic ablation of TSLP receptor (TSLPR) perturbs T-cell-mediated protection and results in the accumulation of CD11b(+)Gr1(+) myeloid cells. These promote tumor growth by secreting Wnt ligands and augmenting ß-catenin signaling in the neighboring epithelium. Epithelial specific ablation of ß-catenin prevents both carcinogenesis and the accumulation of CD11b(+)Gr1(+) myeloid cells, suggesting tumor cells initiate a feed-forward loop that induces protumorigenic inflammation.

Improved health of hospitality workers after a Swiss cantonal smoking ban.

QUESTIONS UNDER STUDY: Hospitality workers are a population particularly at risk from the noxious effects of environmental tobacco smoke (ETS). The Canton of Vaud, Switzerland banned smoking in public places in September 2009. This prospective study addresses the impact of the ban on the health of hospitality workers. METHODS: ETS exposure was evaluated using a passive sampling device that measures airborne nicotine; lung function was assessed by spirometry; health-related quality of life, ETS exposure symptoms and satisfaction were measured by questionnaire. RESULTS: 105 participants (smokers and non-smokers) were recruited initially and 66 were followed up after one year. ETS exposure was significantly lower after the ban. Hospitality workers had lower pre-ban forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) values than expected. FEV1 remained stable after the ban, with a near-significant increase in the subgroup of asthmatics only. FVC increased at one year follow-up from 90.42% to 93.05% (p = 0.02) in the entire cohort; women, non-smokers and older participants gained the greatest benefit. The health survey showed an increase in physical wellbeing after the ban, the greatest benefit being observed in non-smokers. ETS exposure symptoms were less frequent after the ban, especially red and irritated eyes and sneezing. The new law was judged useful and satisfactory by the vast majority of employees, including smokers. CONCLUSION: The recent cantonal ban on smoking in public places brought about an improvement in lung function, physical well-being and ETS symptoms of hospitality workers, including smokers.

Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin.

BACKGROUND: The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth. METHODOLOGY AND PRINCIPAL FINDINGS: To study the function of Notch signaling in the skin of adult mice, we made use of a series of conditional gene targeted mice that allow inactivation of several components of the Notch signaling pathway specifically in the skin. We demonstrate that skin-specific inactivation of Notch1 and Notch2 simultaneously, or RBP-J, induces the development of a severe form of atopic dermatitis (AD), characterized by acanthosis, spongiosis and hyperkeratosis, as well as a massive dermal infiltration of eosinophils and mast cells. Likewise, patients suffering from AD, but not psoriasis or lichen planus, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes induces the production of thymic stromal lymphopoietin (TSLP), a cytokine deeply implicated in the pathogenesis of AD. The AD-like associated inflammation is accompanied by a myeloproliferative disorder (MPD) characterized by an increase in immature myeloid populations in the bone marrow and spleen. Transplantation studies revealed that the MPD is cell non-autonomous and caused by dramatic microenvironmental alterations. Genetic studies demontrated that G-CSF mediates the MPD as well as changes in the bone marrow microenvironment leading to osteopenia. SIGNIFICANCE: Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system.

Multiple roles of Notch signaling in the regulation of epidermal development.

Recent studies have shown that Notch signaling plays an important role in epidermal development, but the underlying molecular mechanisms remain unclear. Here, by integrating loss- and gain-of-function studies of Notch receptors and Hes1, we describe molecular information about the role of Notch signaling in epidermal development. We show that Notch signaling determines spinous cell fate and induces terminal differentiation by a mechanism independent of Hes1, but Hes1 is required for maintenance of the immature state of spinous cells. Notch signaling induces Ascl2 expression to promote terminal differentiation, while simultaneously repressing Ascl2 through Hes1 to inhibit premature terminal differentiation. Despite the critical role of Hes1 in epidermal development, Hes1 null epidermis transplanted to adult mice showed no obvious defects, suggesting that this role of Hes1 may be restricted to developmental stages. Overall, we conclude that Notch signaling orchestrates the balance between differentiation and immature programs in suprabasal cells during epidermal development.

Corneal epithelial cell fate is maintained during repair by Notch1 signaling via the regulation of vitamin A metabolism.

Integrity and preservation of a transparent cornea are essential for good vision. The corneal epithelium is stratified and nonkeratinized and is maintained and repaired by corneal stem cells. Here we demonstrate that Notch1 signaling is essential for cell fate maintenance of corneal epithelium during repair. Inducible ablation of Notch1 in the cornea combined with mechanical wounding show that Notch1-deficient corneal progenitor cells differentiate into a hyperplastic, keratinized, skin-like epithelium. This cell fate switch leads to corneal blindness and involves cell nonautonomous processes, characterized by secretion of fibroblast growth factor-2 (FGF-2) through Notch1(-/-) epithelium followed by vascularization and remodeling of the underlying stroma. Vitamin A deficiency is known to induce a similar corneal defect in humans (severe xerophthalmia). Accordingly, we found that Notch1 signaling is linked to vitamin A metabolism by regulating the expression of cellular retinol binding protein 1 (CRBP1), required to generate a pool of intracellular retinol.