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.

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.

Management of head and neck carcinomas with synchronous or metachronous oligometastatic disease: Role of locoregional radiotherapy and metastasis-directed radiotherapy.

Head and neck carcinomas are initially metastatic in about 15% of cases. Radiotherapy is a cornerstone in the multimodal strategy at the locoregional phase. In patients with head and neck cancer, often heavily pretreated and with comorbidities, who relapse locoregionally or at distant sites, radiotherapy has also become increasingly important at the metastatic phase. Data on the optimal sequence of systemic treatments and metastasis-directed treatments including stereotactic irradiation are still lacking. Several randomized head and neck trials have been initiated that should provide important answers, including one recent GORTEC trial.

Stereotactic body radiation therapy for bone oligometastases.

Stereotactic body radiation therapy is effective for the local management of oligometastases (at most five metastases) with a benefit in survival and local control. Most studies on the management of oligometastases focus on all oligometastatic sites in primary cancer and very few focus on a single oligometastatic site. In particular, there are few data on bone oligometastases, which represent one of the preferred sites for secondary cancer locations. This article focuses on the benefit of stereotactic radiotherapy for bone oligometastases of all cancers by histological types, and reviews the results of major studies in this field.

[Ethical stakes of information in radiation oncology: Thinking the risk and building the therapeutic alliance]. / Enjeux éthiques de l'information en oncologie radiothérapie : penser le risque et construire l'alliance thérapeutique.

Informing patients before receiving radiation therapy is a fundamental ethical imperative. As a condition of the possibility of autonomy, information allows people to make health decisions concerning themselves, which is required by French law. This information includes in particular the potential risks due to radiation therapy. It is therefore necessary to think about what risk is, and how to define and assess it, in order to finally communicate it. The practice of informing people involves many ethical issues relating to the very content of the information, the form in which it is transmitted or even the intention that leads the health professional to say (or not to say) the risk. The transmission of information also questions the way to build a relationship of trust with the patients and how to integrate their own representations about these treatments. Between the risks of paternalism or even defensive medicine, this practice is at the heart of our professional practice.

[Stereotactic radiotherapy for operable stage I non-small cell lung cancer]. / Place de la radiothérapie stéréotaxique pour les cancers bronchiques non à petites cellules de stade I opérables.

Standard treatment stage of non-small cell lung cancer is currently surgery. For inoperable patients, stereotactic body radiotherapy is the reference treatment. This non-invasive technique has developed considerably and its excellent results in terms of carcinological control and tolerance raise the question of its indication for operable patients, especially for old patients and/or with comorbidities. This article reviews the available data in the literature of the place of stereotactic body radiotherapy for medically operable patients with stage I non-small cell lung cancer.

[The morbidity and mortality review meetings in radiotherapy departments: Procedure, implementation and prospects of the "Proust" French national project]. / Revue de morbidité et mortalité en radiothérapie : procédure, implémentation et perspectives du projet national français « Proust ¼.

Radiation-induced acute and late toxicity depends on several parameters. The type, severity and duration of morbidity are mainly related to irradiated volume, total dose and its fractionation and the intrinsic radiosensitivity of the patients. The follow-up of these toxicities is essential. However, unlike many specialties, morbidity and mortality reviews procedures are not developed as part of quality governance programs in radiation therapy departments for the monitoring of toxicity which sometimes hinder the patients' quality of life. One French survey published within the framework of the project entitled Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (Proust), conclude that there was a lack of knowledge of morbidity and mortality reviews and considerable confusion between these reviews and other quality processes without perspective for the local morbidity and mortality reviews development in a large number of the participated centers. In this article, we will discuss the procedure of the "ideal morbidity and mortality reviews" and its implementation through a monocentric experience started in 2015. Thus, the Proust project is a unique opportunity to implement and standardize a national morbidity and mortality reviews implementation in radiation therapy departments by involving the French regions.

Stereotactic radiotherapy for ultracentral lung tumours.

Ultracentral (UC) lung lesions are generally defined by the presence of the tumour or the Planning Target Volume (PTV) abutting proximal bronchial tree (PBT) or the esophagus. Initial reports rose awareness regarding the potential toxicity of stereotactic body radiotherapy (SBRT) when delivered to UC lesions. Major concerns include necrosis, stenosis, and bleeding of the PBT. Technological improvements now enable the delivery of more accurate treatments, possibly redefining the historical "no-fly zone". In this review, studies focusing on the treatment of UC lesions with SBRT are presented. The narrow therapeutic window requires a multidisciplinary approach.

Could conventionally fractionated radiation therapy coupled with stereotactic body radiation therapy improve local control in bone oligometastases?

PURPOSE: To describe clinical outcomes of stereotactic body radiation therapy (SBRT) applied alone or as a boost after a conventionally fractionated radiation therapy (CFRT) for the treatment of bone oligometastases. MATERIAL AND METHODS: This retrospective cohort study included patients treated with SBRT from January 2007 to December 2015 in the Institut de cancérologie de Lorraine in France. The inclusion criteria involved adults treated with SBRT for one to three bone metastases from a histological proven solid tumor and a primary tumor treated, an Eastern Cooperative Oncology Group (ECOG) score inferior or equal to 2. Local control (LC), overall survival (OS), progression free survival (PFS), bone progression incidence (BPI), skeletal related events free survival (SRE-FS), toxicity and pain response were evaluated. RESULTS: Forty-six patients and 52 bone metastases were treated. Twenty-three metastases (44.2%) received SBRT alone mainly for non-spine metastases and 29 (55.8%) a combination of CFRT and SBRT mainly for spine metastases. The median follow-up time was 22months (range: 4-89months). Five local failures (9.6%) were observed and the cumulative incidences of local recurrence at 1 and 2years respectively were 4.4% and 8% with a median time of local recurrence of 17months (range: 4-36months). The one- and two-years OS were 90.8% and 87.4%. Visceral metastasis (HR: 3.40, 95% confidence interval [1.10-10.50]) and a time from primary diagnosis (TPD)>30months (HR: 0.22 [0.06-0.82]) were independent prognostic factors of OS. The 1 and 2years PFS were 66.8% and 30.9% with a median PFS time of 18months [13-24]. The one- and two-years BPI were 27.7% and 55.3%. In multivariate analysis, unfavorable histology was associated with worse BPI (HR: 3.19 [1.32-7.76]). The SRE-FS was 93.3% and 78.5% % at 1 and 2years. The overall response rate for pain was 75% in the evaluable patients (9/12). No grade≥3 toxicity nor especially no radiation induced myelopathy (RIM), two patients developed asymptomatic vertebral compression fractures. CONCLUSION: The sole use of SBRT or its association with CFRT is an efficient and well-tolerated treatment that allows high LC for bone oligometastases.

Impact of EGFRA289T/V mutation on relapse pattern in glioblastoma.

BACKGROUND: Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFRA289mut) is associated with a more infiltrative phenotype. The primary objective of this study was to explore the impact of the EGFRA289 mutation on the pattern of relapse after chemoradiotherapy-based treatment of patients suffering from newly diagnosed glioblastoma. PATIENTS AND METHODS: An ancillary study from a prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFRA289 status (mutated versus wild-type). The primary endpoint was the overlap score (varying from 0 to 1) between the initial irradiated tumor volume (Vinit) and the relapse volume (Vr). Secondary endpoints explored the impact of EGFRA289mut on survival. RESULTS: One hundred twenty-eight patients were included and analyzed: 11% had EGFRA289mut glioblastoma (n = 14/128). EGFRA289mut glioblastomas had a relapse pattern that was more marginal than EGFRA289wt glioblastomas: a median overlap score Vinit/Vr of 0.96 was observed in the EGFRA289mut group versus 1 in the EGFRA289wt group (P = 0.05). Half of the population with EGFRA289mut tumor (n = 7/14) had a marginal relapse (i.e. overlap scoreVr/Vinit ≤ 0.95) compared to 23.7% (n = 27/114) in the EGFRA289wt group, P = 0.035. EGFRA289mut did not influence survival. CONCLUSION: We highlighted a link between the EGFRA289 mutation and the relapse pattern in glioblastoma. The independent role of EGFRA289mut and its clinical implication should now be explored in further studies.

[What dose escalation in the treatment of locally advanced non-small cell lung cancer?] / Quelle augmentation de doses dans le traitement des cancers bronchiques non à petites cellules localement avancés ?

Despite significant therapeutic advances in the treatment of locally advanced inoperable non-small cell lung cancer (NSCLC), notably through adjuvant immunotherapy, the rate of therapeutic failure remains high. The use of positron emission tomography with fluorodeoxyglucose (FDG-PET), respiratory motion and intensity modulated radiotherapy (IMRT) have led to therapeutic improvements with reduced toxicity and better local control. The optimal dose to be delivered remains unknown due to discordant results of studies for almost 20 years and the way to define the area to benefit from a dose increase (whole volume, subvolume defined by pre- or per-radiotherapy PET).

[Crisis situations: Ethical reflection on prioritization of care access in radiation oncology]. / Situations de crise : réflexion éthique sur la priorisation de l'accès aux soins en oncologie radiothérapie.

Understood as a disruption of the conditions of care practice according to established protocols or procedures, crisis situations in radiation oncology departments can have multiple causes. Their seriousness can sometimes impose changes in the decision-making, organizational or technical paradigms. A possible consequence may be the need to make prioritization decisions in access to care, when there is a mismatch between the care needs of a population and the available health resources (whether technical or human). The specificities of care pathways and the wide variety of clinical situations in radiation oncology make these ethical decisions particularly difficult. Anticipation, collegial and multi-professional decision-making procedures or the integration of patient representatives in these prioritization processes are essential tools. Particular attention must be paid to the information to be provided to patients in a concern of transparency and respect. Prioritization situations are real tests for our departments. They go beyond the purely technical aspect of radiation oncology. They can lead to real ethical suffering for health professionals when their values come up against the limits imposed by crisis situations.

Radiotherapy of bone metastases.

We present the update of the recommendations of the French society of oncological radiotherapy on bone metastases. This is a common treatment in the management of patients with cancer. It is a relatively simple treatment with proven efficacy in reducing pain or managing spinal cord compression. More complex treatments by stereotaxis can be proposed for oligometastatic patients or in case of reirradiation. In this context, increased vigilance should be given to the risks to the spinal cord.

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.

Histosurgical mapping of endoscopic endonasal surgery of sinonasal tumours to improve radiotherapy guidance.

PURPOSE: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). MATERIAL AND METHODS: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. RESULTS: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. CONCLUSIONS: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

[Stereotactic body radiation therapy for non-spine bone oligometastatic disease]. / Radiothérapie stéréotaxique des métastases osseuses du squelette périphérique.

PURPOSE: Stereotaxic radiotherapy is performed regularly for the irradiation of non-spine bone metastases, but its place is not well understood. MATERIALS AND METHODS: This article in stereotaxic radiotherapy of non-spine bones oligometastases presents the current scientific data relating to the indications, to virtual simulation, to the delineation of target volumes, to the total dose and fractionation, to the efficacy and tolerance. RESULTS: Oligometastatic patients are classified into 4 categories: oligorecurrences, oligometastasis, oligopersistence, oligoprogression. The prognosis will be evaluated according to the following characteristics: primary tumor, quantitative characteristics, kinetics, qualitative characteristics. The delineation of GTV includes extensions to the soft tissue and bone marrow with the aid of MRI and PET. The CTV corresponds to a margin of 2 to 5mm and the PTV to a margin of 2mm. The most widely used irradiation schemes are: 1 single fraction of 18 to 24Gy/1 fr; 24Gy/2 fr; 27 to 30Gy/3 fr; 30 to 35Gy/5 fr. Stereotaxis provides 90% local control at 1 year and good pain control. The side effects are not very marked. CONCLUSION: Stereotaxic radiotherapy is feasible, non-invasive, minimally toxic and effective with good local control and good pain relief. The main issue remains selecting the patients most likely to benefit from it.

[Stereotactic body radiation therapy for spine bone oligometastatic disease]. / Radiothérapie stéréotaxiques des métastases osseuses des lésions vertébrales.

Stereotactic radiotherapy is an ever more common technique, regardless of the location treated. However, spinal stereotactic radiotherapy requires a particular technicality in order to ensure its proper realization. There is now a large literature defining the type of imaging to be used, the dose to be delivered and the delineation of target volumes. This technique can achieve a significant local control and an interesting analgesic efficiency. However, its place in relation to conventional radiotherapy remains limited because it requires MRI imaging and a significantly longer patient management during the treatment fraction. In this context, it is currently mainly restricted to oligometastatic patients or for re-irradiations.

[Ethical stakes in palliative care in radiation oncology]. / Enjeux éthiques de la pratique des soins à visée palliative en oncologie radiothérapique.

In 2021, the Ethics Commission of the SFRO has chosen the issue of the practice of palliative care in radiotherapy oncology. Radiation oncology plays a central role in the care of patients with cancer in palliative phase. But behind the broad name of palliative radiotherapy, we actually find a large variety of situations involving diverse ethical issues. Radiation oncologists have the delicate task to take into account multiple factors throughout a complex decision-making process. While the question of the therapeutic indication and the technical choice allowing it to be implemented remains central, reflection cannot be limited to these decision-making and technical aspects alone. It is also a question of being able to create the conditions for a singularity focused care and to build an authentic care relationship, beyond technicity. It is through this daily ethical work, in close collaboration with patients, and under essential conditions of multidisciplinarity and multiprofessionalism, that our fundamental role as caregiver can be deployed.

Prognostic value of low skeletal muscle mass in patient treated by exclusive curative radiochemotherapy for a NSCLC.

Low skeletal muscle mass is a well-known prognostic factor for patients treated for a non-small-cell lung cancer by surgery or chemotherapy. However, its impact in patients treated by exclusive radiochemotherapy has never been explored. Our study tries to evaluate the prognostic value of low skeletal muscle mass and other antropometric parameters on this population. Clinical, nutritional and anthropometric date were collected for 93 patients treated by radiochemotherapy for a NSCLC. Anthropometric parameters were measured on the PET/CT by two methods. The first method was a manual segmentation at level L3, used to define Muscle Body Area (MBAL3), Visceral Fat Area (VFAL3) and Subcutaneous Fat Area (SCFAL3). The second method was an software (Anthropometer3D), allowing an automatic multislice measurement of Lean Body Mass (LBMAnthro3D), Fat Body Mass (FBMAnthro3D), Muscle Body Mass (MBMAnthro3D), Visceral Fat Mass (VFMAnthro3D), and Sub-Cutaneous Fat Mass (SCFMAnthro3D) on the PET/CT. All anthropometrics parameters were normalised by the patient's height. The primary end point was overall survival time. Univariate and then stepwise multivariate cox analysis were performed for significant parameters. Finally, Spearman's correlation between MBAL3 and MBMAnthro3D was assessed. Forty-one (44%) patients had low skeletal muscle mass. The median overall survival was 18 months for low skeletal muscle mass patients versus 36 months for non-low skeletal muscle mass patients (p = 0.019). Low skeletal muscle mass (HR = 1.806, IC95% [1.09-2.98]), serums albumin level < 35 g/l (HR = 2.203 [1.19-4.09]), Buzby Index < 97.5 (HR = 2.31 [1.23-4.33]), WHO score = 0 (HR = 0.59 [0.31-0.86] and MBMAnthro3D < 8.56 kg/m2 (HR = 2.36 [1.41-3.90]) were the only significant features in univariates analysis. In the stepwise multivariate Cox analysis, only MBMAnthro3D < 8.56 kg/m2 (HR = 2.16, p = 0.003) and WHO score = 0 (HR = 0.59, p = 0.04) were significant. Finally, muscle quantified by MBAL3 and MBMAnthro3D were found to be highly correlated (Spearman = 0.9). Low skeletal muscle mass, assessed on the pre-treatment PET/CT is a powerful prognostic factor in patient treated by radiochemotherapy for a NSCLC. The automatic software Anthropometer3D can easily identify patients a risk that could benefit an adapted therapy.

[Postoperative radiotherapy after immediate breast reconstruction]. / Irradiation en situation postopératoire après reconstruction mammaire.

Immediate breast reconstruction versus delayed breast reconstruction improves quality of life of breast cancer patients undergoing total mastectomy without impacting oncologic outcomes. Two types of immediate reconstruction are possible, implant-based reconstruction or autologous reconstruction. These reconstructions interpose a tissue in the operating bed, which modifies target volume definition compared to a wall without reconstruction Post mastectomy radiotherapy increases the rate of postoperative complications for both surgical procedures. Recent guidelines were published about target volume definition in the post mastectomy setting after implant-based reconstruction. Guidelines about target volume definition after autologous reconstruction are still awaited. The aim of our work is to present the different surgical procedures for immediate breast reconstruction, their complications, and the definition of the postmastectomy target volume.