Radiation-activated nanoparticles: Which combination to optimize radiosensitization?

Radiotherapy plays a crucial role in the treatment of various cancers. With the ongoing technological advancements in radiotherapy equipment, allowing for increasingly precise targeting of tumours, there are numerous strategies being explored to enhance its effectiveness by combining it with other therapies. Among these, metal nanoparticles seem to have a promising future driven by their ability to locally amplify the dose deposited by ionizing radiation, and to radiosensitize cells by modifying their oxidative status. Recent advancements in understanding the mechanisms of action of these nanoparticles have provided valuable insights for the development of new therapeutic combinations. Among these, the combination with immunotherapies would make it possible to benefit both from the amplified local effect of radiotherapy by nanoparticles and to induce a better antitumour immune response. In this article, we review shortly the existing literature on ongoing combinations and suggest potential novel therapies associated with the combination of radiotherapy and nanoparticles.

[Comprehensive therapeutic strategy for localized esophageal cancer. Second part : interest of multimodal approaches with or without surgery]. / Comment je traite... les cancers localisés de l'œsophage. Etat actuel des données et stratégie thérapeutique. 2ème partie : l'intérêt des approches multimodales avec ou sans chirurgie.

In recent years, the treatment of esophagus cancer has been completely changed, thus competing the dogma of surgery as the cornerstone treatment. Multimodality treatments as radio-chemotherapy directly followed by surgery, or delayed surgery, significantly improve patient survival compared to surgery alone. Neoadjuvant radiochemotherapy is associated with a higher complete pathologic response rate and improved survival compared to chemotherapy alone. Immediate surgery after radio-chemotherapy is challenged for patients who present a complete clinical response, especially in case of squamous cell carcinoma. Indeed, systematic resection is associated with a significant postoperative mortality rate and has not proven any survival advantage in complete clinical responders as opposed to delayed resection in case of locally persistent or recurrent disease. In squamous cell carcinoma, this could lead to organ preservation, thus avoiding the mortality and durable functional impairment of esophagectomy. This review will discuss the positioning of the multimodality treatment strategy with neoadjuvant radiochemotherapy and chemotherapy and also the strategy of organ preservation.

Depuis quelques années, le traitement du cancer de l'œsophage est en pleine mutation, bousculant ainsi le grand dogme de la chirurgie comme pierre angulaire du traitement. Par rapport à la chirurgie seule, les traitements multimodaux de radiochimiothérapie suivis, directement ou de façon différée, par la chirurgie améliorent significativement les chances de survie prolongée des patients. Comparée à la chimiothérapie néodjuvante, la radiochimiothérapie néoadjuvante démontre un taux de réponse pathologique complet plus élevé qui résulte en une survie prolongée. Chez les très bons répondeurs cliniques, la question de la place de la résection chirurgicale d'emblée est remise en question, surtout pour les carcinomes épidermoïdes. Chez ces patients, la résection systématique par rapport à un acte différé n'offre pas d'avantage en survie, expose le patient à un risque de mortalité significatif alors qu'un certain nombre de patients n'auront jamais à être opérés. Le seul bénéfice actuellement démontré de la résection est une amélioration du contrôle local; or, le devenir du patient est principalement lié à la récidive métastatique. Dans cette revue, nous positionnons et discutons la place des différents traitements multimodaux, chimiothérapie et radiochimiothérapie néoadjuvantes, ainsi que la place de la préservation d'organe par rapport à une chirurgie d'emblée après une radiochimiothérapie.

[Comprehensive therapeutic strategy for localized esophageal cancer]. / Comment je traite... les cancers localisés de l'œsophage. Etat actuel des données et stratégie thérapeutique. 1ère partie : le point sur les approches chirurgicales et non chirurgicales.

Esophageal cancers represent a highly heterogeneous entity mixing two different tumour types : AdenoCarcinoma (ADC) and Squamous Cell Carcinoma (SSC). Developing in the same organ, they are very often considered as a unique pathology and, consequently, the same therapeutic strategy is indiscriminately applied. Esophageal cancer treatments are particularly complex and require a multidisciplinary approach. Despite impressive advances in the tumour statidifaction, surgery, radiotherapy and chemotherapy, the overall prognosis remains grim even at an early stage of the disease. In order to improve the treatment of esophageal cancers and the patient’s survival, we need to consider that ADC and SCC represent two different pathologies requiring specific therapeutic strategies. This review in two parts will present recent data from clinical trials under the scope of tumour histology to set up dedicated therapeutic strategies. In this first part, we explain the restricted role of surgical resection, the prognostic factors and the results of exclusive combined chemotherapy and radiation in localized esophageal cancer.

Les cancers de l'œsophage concernent deux entités d'histologie et de pathogenèse différentes : les carcinomes épidermoïdes (CE) et les adénocarcinomes (ADC). Ils se développent dans un même organe et sont souvent considérés comme une seule et unique maladie avec, comme conséquence, une stratégie thérapeutique identique. Leur traitement est complexe et requiert une prise en charge multidisciplinaire. Bien que les techniques de mise au point de la pathologie, de traitement par chirurgie, de radiothérapie et de chimiothérapie se soient améliorées, le pronostic de la maladie reste péjoratif, même à un stade précoce. L'amélioration de la prise en charge et de la survie des patients nécessite de considérer les CE et les ADC comme deux pathologies distinctes, impliquant des approches thérapeutiques qui leur soient spécifiquement dédiées. Cette revue en deux parties analyse les différents aspects thérapeutiques des cancers de l'œsophage sous l'angle de l'histologie et permet de dégager des stratégies spécifiques. Cette première partie est consacrée aux limites de la résection chirurgicale, aux facteurs pronostiques et aux résultats des traitements par radio-chimiothérapie exclusive des cancers localisés.

[Evolution in the therapeutic strategy of localized resectable pancreatic ductal adenocarcinoma]. / Evolution dans la prise en charge de l'adénocarcinome du pancréas localisé estimé résécable.

Pancreatic ductal adenocarcinoma is characterized by a high rate of early metastatic relapse. Surgical resection is still recognized as the cornerstone upfront therapy. However, reported 5 years survival rates are inferior to 20-25% even when surgery is followed by chemotherapy. Margins involvement on the surgical specimen (50 to 85%) and lymph node involvement (around 70%) both strongly impact survival. Median survivals are close to those of locally advanced diseases treated by chemotherapy or chemoradiotherapy, 15 to 16 months. This review focuses on adverse prognostic factors, post-operative outcomes and their impact on multimodality therapy completion rates and survivals in patients undergoing upfront surgery. Current data and emerging results from neoadjuvant series could lead to a change in the therapeutic strategy.

[CRITICAL VIEWPOINT ON THE CURRENT APPROACH OF LOCALIZED PANCREATIC DUCTAL ADENOCARCINOMA]. / COMMENT JE TRAITE ... Point de vue critique sur l'approche actuelle du cancer du pancréas localize.

Surgical resection followed by chemotherapy is the actual standard of care for localized, deemed resectable, pancreatic ductal adenocarcinoma. Despite a better selection of surgical candidates and the actual performance of expert teams, the proportion of patients with a prolonged survival has not been ameliorated during the last three decades. The morphological determinants of resectability are the subject of limitations. In the future, only a better understanding of the biological process, an earlier diagnosis of purely localized disease and more efficient systemic therapies may lead to a better prognosis. Meanwhile, taking into account the prognostic factors associated with a lower chance of cure is currently a matter of debate. The optimal therapeutic sequence, being a surgery-first or a neoadjuvant approach is controversial. The theoretical advantages of preoperative chemotherapy eventually associated with chemo-radiation are demonstrated in other tumours and applicable to pancreatic cancer without any excess of operative mortality, early progression rates and, on the contrary with positive survival data. The completion rates of multi-modal therapy are in favour of the preoperative approach, which also gives the opportunity to select the best candidates for surgical resection.

[Radiobiology for beginners]. / La radiobiologie pour les néophytes.

Modern radiotherapy issues from tremendous evolution over the last years in the fields of computers, imaging and robotics. The optimization of the dose distribution among the tumor target, while simultaneously keeping the dose across healthy tissues as low as possible, results in the renewal of basic radiobiological concepts. The typical example is the rediscovery of hypo-fractionated radiotherapy.

[Functional imaging and radiotherapy]. / Utilisation de l'imagerie fonctionnelle en radiothérapie.

Medical imaging plays a crucial role in the diagnosis, staging and therapeutic strategy of oncologic patients. The development of medical imaging over the last decade has allowed significant progresses in radiotherapy. Indeed, medical imaging is now considered the corner stone of radiotherapy. The main challenge for the radiation oncologist consists in the tumour identification with a view to irradiate the tumour at a curative dose while avoiding healthy tissues. To achieve these goals, the radiotherapist daily uses anatomical imaging such as computed tomography (CT) or magnetic resonance imaging (MRI). Since several years now, the development of functional imaging such as positron emission tomography (PET) combined with CT or functional MRI has opened new perspectives in the management of oncologic diseases. Indeed, these imaging techniques offer new information on tumour metabolism that may be taken into account to plan the radiotherapy treatment. This article illustrates the different imaging techniques used in radiotherapy and the role of functional imaging for establishing new therapeutic strategies in radiation oncology.

[Radiotherapy in rectal cancer: when, why and how?]. / La radiothérapie dans le cancer du rectum: quand, comment et pourquoi?

Since several decades, radiotherapy plays a crucial role in the management and local control of the rectal adenocarcinoma. The local recurrences pattern of the rectal tumor has completely changed with the systematic use of the Total Mesorectal Excision surgery (TME). In this context, the rate of radiotherapy needs to be reviewed. In this article we propose an overview of the main studies using radiotherapy in a pre- or post-operative setting in the context ofTME surgery. This will help to better define the indications of radiotherapy in rectal cancer.

[Radiotherapy for elderly patient with rectal cancer: which benefit?]. / La radiothérapie dans le cancer du rectum chez la personne âgée: quel bénéfice pour quel traitement?

Age acts as a major risk factor of cancer. In the near future, with the aging of the population, we will treat more and more elderly patients with oncologic disease. Unfortunately, these patients are often excluded from randomized trials. How can we, therefore, define guidelines for this particular population of patients? Moreover, older patients often present multiple morbidities synchronously with the oncologic disease. This constellation of diseases makes the therapeutic strategy even more difficult. The highest incidence of rectal cancer is observed at 80 years old or above. This is significantly older than the mean age of the population included in clinical trials. Although, the prognosis of young patients with rectal cancer has improved over the past few decades, this is not the case for patients over 75 years old. A geriatric evaluation, as a part of a multidisciplinary approach, may allow to better select patient able to benefit from a combined treatment. Radiotherapy plays a crucial role in the treatment of rectal cancer. There are no solid data currently available on the real impact of radiotherapy on survival in an elderly population with rectal cancer. Do these patients really benefit from this treatment and what is the impact of radiotherapy on their quality of life? This review will try to give some answers to these important questions.