Management of oligometastatic/metastatic sarcomas and place of local treatments with focus on modern radiotherapy approaches.

Soft tissue sarcomas are a rare and heterogeneous disease. For localized disease, treatment is based on surgery and radiotherapy with or without chemotherapy depending on risk factors. Upfront metastases are present in 7 to 20% of cases, and are localized to the lungs in most of cases. Disseminated disease is generally considered incurable but in selected cases, aggressive local treatment of metastases allowed long survival. Treatment of primary tumour is often debated. Our purpose is to evaluate the literature concerning the role of radiotherapy in the management of primary metastatic soft tissue sarcomas.

[Predictive factors assessment of pathological response to neoadjuvant radiotherapy of soft tissue sarcomas]. / Évaluation de facteurs prédictifs de réponse pathologique à la radiothérapie néoadjuvante des sarcomes des tissus mous.

PURPOSE: Conserving surgery combined with radiotherapy in presence of local recurrence risk factors is standard treatment of soft tissue sarcomas, a group of rare and heterogeneous tumours. Radiotherapy is performed before or after surgery. In neoadjuvant setting, late radiation-induced toxicity is reduced and pathological response to radiotherapy could be achieved. A complete pathological response to radiotherapy has recently been shown to predict better survival. Our study aims at identifying predictive factors of pathological response to neoadjuvant radiotherapy (clinical, radiological or histological) of soft tissue sarcomas. PATIENTS AND METHODS: Clinical, imaging (MRI: perilesional oedema, necrosis, tumour heterogeneity, vasculonervous relationships) and pathological (pathological subtype, tumour grade, anticipated/obtained resection quality) data were retrospectively collected. Tumour response (imaging and pathological), patient outcome, acute and late radiation-induced toxicity, predictive factors of pathological response to neoadjuvant radiotherapy were studied. The 2-test or exact-Fisher test (qualitative variables) and by Student's t-test or Kruskal-Wallis test (quantitative variables) were used for statistical analysis. RESULTS: From April 2017 to April 2021, neoadjuvant radiotherapy (50Gy in 25 fractions) followed by surgical excision was performed to 36 consecutive patients with liposarcomas (n=17/36), or undifferentiated sarcomas (n=8/36). MRI response was complete in 1 patient, partial in 9 patients (n=9/36, 25%), stable in 21 patients (n=21/36, 58%) or in progression in 5 patients (n=5/36, 14%). Pathological response was observed in 22 patients (61%). No grade 3-4 acute radiation-induced toxicity was observed. Regarding late toxicity, 28% of patients had grade 1-2 oedema (n=10/36), 39% had a grade 1 fibrosis (n=14/36), and 30% grade 1 pain (n=11/36). No predictive factors of response to radiotherapy was statistically significant. CONCLUSIONS: Neoadjuvant radiotherapy is well-tolerated. No clinical, radiological or pathological predictive factors was identified for radiotherapy tumour response.

Pre- or postoperative radiotherapy for soft tissue sarcomas.

Sarcomas are rare tumours arising from mesenchymal tissue. A multimodal management in an expert centre combining surgery and radiotherapy is the current standard of care for localized soft-tissue sarcomas of the extremities, to enable limb-sparing strategies. The delivery of pre- radiotherapy or postoperative radiotherapy offers similar local control and survival rates but the toxicity profile is quite different: preoperative radiotherapy increases the risk of wound complications and postoperative radiotherapy affects long-term functional outcomes. While postoperative radiotherapy has long been the rule, especially in Europe, technical improvements with image-guided- and intensity-modulated radiotherapy associated with a better management of postoperative wounds has tended to change practices with more frequent preoperative radiotherapy. More recently the possibilities of a hypofractionated regimen or potentiation by nanoparticles to increase the therapeutic index plead in favour of a preoperative delivery of radiotherapy. The aim of this paper is to report pros and cons of pre- and post-operative radiotherapy for soft-tissue sarcomas.

[Radiotherapy for soft tissue sarcomas: Technical evolution and impact on clinical benefit]. / Radiothérapie des sarcomes des tissus mous des membres : évolution technique et impact sur le bénéfice clinique.

The standard treatment for extremity soft tissue sarcomas is based on the association of surgery and radiotherapy. This strategy allows local control improvement with the risk of increased toxicity. There is therefore a growing interest to identify those patients who will benefit from radiotherapy and those who will have the same local control with surgery alone. Furthermore, the development of toxicity has been correlated with the extension of the irradiated volume and the volume receiving high doses. Technological development as intensity modulated radiotherapy and image-guided radiotherapy allows limited irradiated volume improving the protection of the organs at risk leading to clinical benefit improvement. Moreover, efforts are being done to improve local control for the patients at high risk of local relapse. In this paper, we discuss all these mentioned aspects.

[Radiotherapy of bladder cancer]. / Radiothérapie des cancers de vessie.

Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

[Management of soft tissues sarcoma of the limbs by external beam radiation therapy]. / Prise en charge des sarcomes des tissus mous des membres par radiothérapie externe.

Soft tissue sarcomas are rare tumours. Conservative surgery followed by postoperative radiation therapy represents the gold standard in the majority of cases. Postoperative radiotherapy improves local control without affecting survival. Besides the quality of surgical excision, which remains the major prognostic factor, the importance of the irradiation volume and particularly margins used in external beam radiotherapy were also found to influence local control of the disease. In this study, we propose to conduct a literature review on the present state of our knowledge on this subject in the form of an articulated controversy: in favour or opposed to large margins in external radiotherapy.

Efficacy and safety of liposomal cytarabine in children with primary CNS tumours with leptomeningeal involvement.

PURPOSE: To assess the efficacy and safety of liposomal cytarabine in the treatment of de novo and relapsed leptomeningeal involvement in children with primary CNS tumours. METHODS: Data from clinical charts were entered into a database for consecutive unselected patients (n=20) from nine Spanish centres. Diagnosis of leptomeningeal involvement was confirmed by cytology, MRI and/or CT scan. The dose of liposomal cytarabine used varied from 20 to 50 mg, by age. RESULTS: There were 8 females and 12 males, mean age 7.3 years (range 8 months to 18 years). The tumours were: 10 medulloblastomas, 4 ependymomas, 3 primitive neuroectodermal tumours and 3 other tumours. Fourteen had undergone previous chemotherapy and 12 radiotherapy. Nine received concurrent chemotherapy and 2 concurrent radiotherapy. Median follow-up was 244.5 days (range 12- 869). Patients received a median of 5 doses (range 1-9) of liposomal cytarabine. A neurological response (complete or partial) was seen in 11/19 (58%) and a cytological response in 7/10 (64%). Median time to neurological progression exceeded 180 days (range 12-869). Adverse effects were reported in 11/20 patients, but none was grade IV. DISCUSSION: Liposomal cytarabine was well tolerated and efficacious in this patient group, but prospective randomised trials are needed.

Efficacy and safety of liposomal cytarabine in children with primary CNS tumours with leptomeningeal involvement

PURPOSE: To assess the efficacy and safety of liposomal cytarabine in the treatment of de novo and relapsed leptomeningeal involvement in children with primary CNS tumours. METHODS: Data from clinical charts were entered into a database for consecutive unselected patients (n=20) from nine Spanish centres. Diagnosis of leptomeningeal involvement was confirmed by cytology, MRI and/or CT scan. The dose of liposomal cytarabine used varied from 20 to 50 mg, by age. RESULTS: There were 8 females and 12 males, mean age 7.3 years (range 8 months to 18 years). The tumours were: 10 medulloblastomas, 4 ependymomas, 3 primitive neuroectodermal tumours and 3 other tumours. Fourteen had undergone previous chemotherapy and 12 radiotherapy. Nine received concurrent chemotherapy and 2 concurrent radiotherapy. Median follow-up was 244.5 days (range 12- 869). Patients received a median of 5 doses (range 1-9) of liposomal cytarabine. A neurological response (complete or partial) was seen in 11/19 (58%) and a cytological response in 7/10 (64%). Median time to neurological progression exceeded 180 days (range 12-869). Adverse effects were reported in 11/20 patients, but none was grade IV. DISCUSSION: Liposomal cytarabine was well tolerated and efficacious in this patient group, but prospective randomised trials are needed (AU)

[Which intensity modulated radiation therapy? From "step and shoot" to volumetric modulated arc therapy, point of view of the radiation oncologist]. / Quelle radiothérapie conformationnelle avec modulation d'intensité? De la technique "step and shoot" à l'arcthérapie, point de vue de l'oncologue radiothérapeute.

Intensity modulated radiation therapy (IMRT) offers optimal dosimetric and clinical results in terms of acute toxicity, allows augmenting the dose to the target volumes and therefore, appears promising for local control and disease-free survival. However, several pitfalls to this treatment are to be considered, namely a long treatment time and a high number of monitor unit (MU) required. The dosimetric results of the volumetric modulated arctherapy gives at least similar target coverage and preservation of organs at risk, while significantly reducing the number of required MUs and the overall treatment time. This has a potential impact on the treatment quality and the potential risk of secondary cancers. Volumetric modulated arctherapy allows implementation of stereotactic radiation therapy and complex treatments previously considered not feasible with IMRT. The future will involve this technology of high precision to determine the dose and to the target in real time using the image-guided radiotherapy. Tools combining these two methods are in development.

[Conformal intensity modulated radiation therapy for localized prostate cancer: Toward a new standard]. / Radiothérapie de conformation avec modulation d'intensité dans le cancer de prostate : vers un nouveau standard.

Radiation therapy is now widely accepted as an efficacious treatment of localized prostate cancer. Recent advances, namely with the development of conformal radiotherapy, allowed to increase the total dose in the target volumes with greater local control. A forward step achieved with intensity modulated radiotherapy (IMRT) in terms of therapeutic ratio between target volumes and critical organs. IMRT offers an inverse planning dosimetry and a modulation of the fields during irradiation. This article presents recent technical and clinical advances in IMRT focused on prostate cancer.

[How to combine hormonotherapy and radiation treatment in adjuvant breast cancer?]. / Cancers du sein : comment associer l'hormonothérapie et la radiothérapie en situation adjuvante ?

Combined radiation and hormone therapies have become common clinical practice in recent years for locally-advanced prostate cancers. The use of such concomitant therapy in the treatment of breast disease has been infrequently reported in the literature, but seems justified given the common hormonal dependence of breast cancer and the potential synergistic effect of these two treatment modalities. As adjuvant therapy, two strategies are used in daily clinical practice: upfront aromatase inhibitors or sequentially after a variable delay of tamoxifen. These molecules may, thus, interact with radiotherapy. Retrospectives studies recently published did not show any differences in terms of locoregional recurrences between concurrent or sequential radiohormonotherapy. Lung and skin fibroses due to concurrent treatment are still under debate. Nevertheless, late side effects appeared to be increased by such a treatment, particularly in hypersensitive patients identified at risk by the lymphocyte predictive test. Concurrent radiohormonotherapy should, thus, be delivered cautiously at least for these patients. This article details the potent advantages and risks of concurrent use of adjuvant hormonotherapy and radiotherapy in localized breast cancers.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) treated with 2-chlorodeoxyadenosine.

Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease (RDD) is a rare but well-defined histiocytic proliferative disorder of unknown etiology that usually presents with cervical lymphadenopathy, fever, leukocytosis, and hypergammaglobulinemia in an otherwise healthy child. Although many patients undergo spontaneous remission, a subset of patients with systemic disease has a more serious course. For those patients with a poor outcome, steroids and chemotherapeutic agents such as etoposide or 6-mercaptopurine plus low dose methotrexate have been used. We present a child with a massive cervical lymphadenopathy treated with 2-chlorodeoxyadenosine (2-CdA, cladribine) after other approaches failed.