Stereotactic body radiation therapy for liver metastases in oligometastatic disease.

Oligometastatic cancers designate cancers in which the number of metastases is less than five, corresponding to a particular biological entity whose prognosis is situated between a localized and metastatic disease. The liver is one of the main sites of metastases. When patients are not suitable for surgery, stereotactic body radiotherapy provides high local control rate, although these data come mainly from retrospective studies, with no phase III study results. The need for a high therapeutic dose (biologically effective dose greater than 100Gy) while respecting the constraints on the organs at risk, and the management of respiratory movements require expertise and sufficient technical prerequisites. The emergence of new techniques such as MRI-guided radiotherapy could further increase the effectiveness of stereotactic radiotherapy of liver metastases, and thus improve the prognosis of these oligometastatic cancers.

Indication and perspectives of radiation therapy in the setting of de-novo metastatic prostate cancer.

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer.

Radiation therapy of the primary tumour and/or metastases of digestive metastatic cancers.

Metastatic gastrointestinal cancer is not an uncommon situation, especially for pancreatic, gastric, and colorectal cancers. In this setting, few data are available on the impact of the treatment of the primary tumour. Oligometastatic disease is associated with longer survival in comparison with more advanced disease. Metastasis-directed therapy, such as stereotactic body radiotherapy, seems related to better outcomes, but the level of evidence is low. In most tumour locations, prospective data are very scarce and inclusion in ongoing trials is strongly recommended.

[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.

[Stereotactic Body Radiation Therapy for less than 3cm (stage I) and 5cm (stage II) inoperable lung tumors: 10 years experience of Montpellier Cancer Institute]. / Radiothérapie stéréotaxique (RTST) pulmonaire des tumeurs de moins de 3cm (stade I) et 5cm (stade II) non opérées : 10 ans d'expérience de l'Institut du Cancer de Montpellier (ICM).

PURPOSE: Search for predictive factors on survival and local control for less than 3 centimeters (cm) (stage I) and 5cm (stage II) inoperable lung tumors treated by Stereotactic Body Radiation Therapy (SBRT) in a retrospective monocentric study from Montpellier Cancer Institute (ICM) PATIENTS AND METHOD: Every patients treated at ICM for a stage I or II inoperable lung tumors from 2009 to 2019 were analyzed. RESULTS: One hundred and seventy nine lesions were treated in 176 patients, with a major part (82,7%) in operated due to chronic obstructive pulmonary disease. Median overall survival for all patients was 71,7 months with a 35 months follow-up and the 2 years loco-regional free survival was 94,0 months. Better associated outcomes were stage I (median overall survival 71,7 versus 29,0 months P=0,004 ; HR=2,37 P=0,005), BED≥150Gy (median time-to-progression not reached versus 76,7 months P=0,025), small size of Planning Target Volume (PTV) (HR=0,42 P=0,032 when PTV<15,6 cc). 7,3% of all patients developed radiation pneumonitis. CONCLUSION: SBRT is associated with an excellent overall survival and a high rate of local control for less than 3cm (stage I) and 5cm (stage II) lung tumors but a low rate of toxicities. For these patients with many comorbidities, BED over 150Gy seems to be associated with a better loco-regional free survival, while cause of death is often other than lung cancer.

Acceptance, commissioning and quality assurance of the MRIdian®: Site experience and three years follow-up.

PURPOSE: This study presents the methodology and results of the acceptance and periodical quality controls on the MRIdian®. MATERIALS AND METHODS: The impact of the magnetic field on other machines was investigated by controlling nearby linacs dose profiles. The image quality of the 0.345T MR scanner was evaluated, also assessing the integrated linear accelerator influence. The photon beams lateral and depth dose profiles were measured in motorized water tanks, along dose rate and output factors, and compared to Monte Carlo (MC) calculations. The isocenter position, gantry angles and multi-leaf collimator (MLC) position were controlled using film dosimetry. Gating latency and dosimetric accuracy were controlled with a dynamic phantom. RESULTS: The magnetic field had no significant impact on other nearby linacs. Image quality was within tolerances and did not vary over time. Dose profiles measured showed good agreement with MC data, with maximum differences of 1.3% in-field. Output factors were within 0.8% of calculated values. Imaging and radiative isocenter matched within 0.9±0.4mm over all monthly controls. Gantry rotation was precise within -0.1±0.2°, with an isocenter variation of 1.4±0.3mm diameter. The average MLC position was within 0.4±0.1mm of theoretical value. Finally, the gating latency was 0.14±0.07sec and the gated dose within 0.3% of base value. CONCLUSION: All results are within the tolerances fixed by ViewRay® and show low variations over 2 years, comforting the use of small margins and gating for high-dose adaptive treatments.

[Stereotactic body radiotherapy of primary liver tumours: Indications and new techniques]. / Radiothérapie stéréotaxique des tumeurs primitives hépatiques : indications et nouvelles techniques.

The incidence of primary hepatic tumours is increasing and the reference treatments by liver transplantation or surgical resection do not allow to compensate for this increase because of the lack of grafts, or the low proportion of initially resectable tumours. The challenges for radiotherapy of primary liver tumors are multiple: physical, biological, medical and technological. Liver stereotactic body radiotherapy is sometimes the only local treatment option and is progressively finding its place for these tumors, even if the recognition of the indications would deserve a better standardization of international recommendations. The heterogeneity of practices and techniques is a major obstacle to the development of randomized studies, despite the excellent oncological results published. The latest ASTRO 2022 guidelines, the recent publication of the guidelines from the French society for radiation oncology on external radiotherapy and brachytherapy procedures ("RecoRad™ 2.0"), and the inclusion in prospective clinical trials will help to homogenize protocols and improve recognition of the technique. The first data from the new techniques of adaptive radiotherapy and MR-guided radiotherapy, whose objectives are to improve targeting and reduce liver or gastrointestinal toxicity, confirm the excellent results of liver SBRT and allow the potential indications to be extended to locations that were previously difficult to treat.

News in magnetic resonance imaging use for radiation oncology.

The purpose of this article is to give a summary of the progress of magnetic resonance imaging (MRI) in radiotherapy. MRI is an important imaging modality for treatment planning in radiotherapy. However, the registration step with the simulation scanner can be a source of errors, motivating the implementation of all-MRI simulation methods and new accelerators coupled with on-board MRI. First, practical MRI imaging for radiotherapy is detailed, but also the importance of a coherent imaging workflow incorporating all imaging modalities. Second, future evolutions and research domains such as quantitative imaging biomarkers, MRI-only pseudo computed tomography and radiomics are discussed. Finally, the application of MRI during radiotherapy treatment is reviewed: the use of MR-linear accelerators. MRI is increasingly integrated into radiotherapy. Advances in diagnostic imaging can thus benefit radiotherapy, but specific radiotherapy constraints lead to additional challenges and require close collaboration between radiologists, radiation oncologists, technologists and physicists. The integration of quantitative imaging biomarkers in the radiotherapy process will result in mutual benefit for diagnostic imaging and radiotherapy. MRI-guided radiotherapy has already been used for several years in clinical routine. Abdominopelvic neoplasias (pancreas, liver, prostate) are the preferred locations for treatment because of their favourable contrast in MRI, their movement during irradiation and their proximity to organs at risk of radiation exposure, making the tracking and daily adaptation of the plan essential. MRI has emerged as an increasingly necessary imaging modality for radiotherapy planning. Inclusion of patients in clinical trials evaluating new MRI-guided radiotherapy techniques and associated quantitative imaging biomarkers will be necessary to assess the benefits.

Role of radiotherapy in the management of bladder cancer: Recommendations of the French society for radiation oncology.

We present the recommendations of the French society of oncological radiotherapy on the indications and techniques for external beam radiotherapy for bladder cancer.

Tumour and normal tissue radiosensitivity.

The place of personalized treatments is highly increasing in medical and radiation oncology. During the last decades, a huge number of assays have been developed to predict responses of normal tissues and tumours. These tests have not yet been included into daily clinical practice but the recent developments of radiation oncology are paving the way of personalized strategies including the risk of tumour recurrence and normal tissue reactions. Concerning tumor radiosensitivity prediction, no test are currently used, even if the radiosensitivity index and the genome-based model for adjusting radiotherapy dose assays seem the most promising with level II of evidence. Commercial developments are under progress. Concerning normal tissue radiosensitivity prediction, single nucleotide polymorphims of prostate cancer patients and radiation-induced CD8 T-lymphocyte apoptosis breast and prostate assays are of level I of evidence. They can be proposed before the beginning of radiotherapy in order to propose personalized treatments according to both risks of tumour and normal tissue radiosensitivity. Commercial developments are also under way.

[Treatment of oligometastatic or oligoprogression cancer]. / Traitement des oligometastases et oligoprogression.

We propose in this short review to report the impact of stereotactic body radiation therapy (SBRT) in oligometastatic or oligoprogressive cancer patients in terms of metastatic progression-free and global survival, and to identify the place of SBRT in patient's pathway.

[Predictive assays for responses of tumors and normal tissues in radiation oncology]. / Outils pour la prédiction de la réponse tumorale et des tissus sains en oncologie radiothérapie.

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the target volume. Tumor sensitivity to radiotherapy may be particularly inconstant depending on location, histology, somatic genetic parameters and the capacity of the immune system to infiltrate the tumor. In addition, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In a same population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists, namely in terms of late side effects that are in principle non-reversible. This review details the different radiobiological approaches that have been developed to better predict the tumor response but also the radiation-induced late effects.

[Liver stereotactic body radiotherapy: Clinical features and technical consequences, results. Which treatment machine in which situation?] / Radiothérapie stéréotaxique hépatique : particularités cliniques et implications techniques, résultats. Quelle machine pour quelle situation ?

Liver stereotactic body radiotherapy is a developing technique for the treatment of primary tumours and metastases. Its implementation is complex because of the particularities of the treated organ and the comorbidities of the patients. However, this technique is a treatment opportunity for patients otherwise in therapeutic impasse. The scientific evidence of liver stereotactic body radiotherapy has been considered by the French health authority as insufficient for its widespread use outside specialized and experienced centers, despite a growing and important number of retrospective and prospective studies, but few comparative data. This article focuses on the specific features of stereotactic body radiotherapy for liver treatments and the results of published studies of liver stereotactic body radiotherapy performed with classic linear accelerators and dedicated radiosurgery units.

Prospective medical analysis of radiation therapist image repositioning during image-guided radiotherapy.

PURPOSE: Radiation oncologists are responsible for deciding which day-to-day variations are acceptable or not in the treatment setup. However, properly qualified and trained radiation therapists might be capable to perform image registration. We evaluated in our centre the capability and accuracy of radiation therapists to validate positioning images in a prospective study. METHODS AND PATIENTS: A total of 84 patients treated for prostate, head and neck, lung or breast cancer was prospectively and randomly included from July 2011 to July 2013 in radiotherapy unit of our institution. For each patient, three positioning images were randomly analysed. Two radiation oncologists analysed all positioning images and shifts decided by the radiation therapists in an independent and blinded way. The radiation oncologists had to decide whether to validate or not this shift and give a corresponding additional shift, if any. A theoretical disagreement rate less than 5% between radiation therapists and radiation oncologists was planned. RESULTS: A total of 240 images were analysed (head and neck: 15.0%; prostate: 14.2%; breast: 55.0%; lung: 15.8%). The global disagreement between radiation oncologists and radiation therapists for all the images analysed was 2.5% 95% confidence interval (95% CI) [1.0-5.0], corresponding to six images out of 240. A 100% agreement was reached for prostate and lung images, a 97.2% agreement for head and neck images and a 96.2% agreement for breast images. CONCLUSIONS: The radiation therapist validation for repositioning images seemed accurate for image-guided radiotherapy in our institution. Periodic evaluation and in-house training are warranted when routine delegation of image registration to radiation therapists is considered.

[Stereotactic body radiotherapy for liver tumors: State of the art]. / Radiothérapie en conditions stéréotaxiques des tumeurs hépatiques : état de l'art.

Thanks to the improvement in radiotherapy physics, biology, computing and imaging, patients presenting with liver tumors can be efficiently treated by radiation. Radiotherapy has been included in liver tumors treatment guidelines at all disease stages. Liver stereotactic radiotherapy has to be preferred to standard fractionated radiotherapy whenever possible, as potentially more efficient because of higher biological equivalent dose. Liver stereotactic radiotherapy planning and delivery require extensive experience and optimal treatment quality at every step, thus limiting its availability to specialized centres. Multicentre studies are difficult to develop due to a large technical heterogeneity. Respiratory management, image guidance and immobilization are considerations as important as machine type. The use of multimodal planning imaging is compulsory to achieve expected contouring quality. Treatment efficacy is difficult to assess following liver stereotactic radiotherapy, but local control is high and toxicity unusual. As a consequence, liver stereotactic radiotherapy is part of multimodal and multidisciplinary management of liver tumors.

Advanced penile cancer with iliac lymph node involvement treated with radiation and concurrent gemcitabine.

Penile cancer is a rare entity with only 2000 new cases a year in the United States. Even though early stage penile cancer has an excellent prognosis, patients with positive pelvic lymph nodes have an overall 5-year survival rate under 10%. There is no consensus for the management of pelvic node-positive patients, although most guidelines are in favour of pelvic lymph node dissection for patients with two or more positive nodes, followed by adjuvant chemotherapy. We describe here the case of a patient with numerous metastatic lymph nodes at diagnosis, treated with chemoradiation (66Gy with concurrent gemcitabine) after failure of first-line chemotherapy and still alive and disease-free 7 years after diagnosis.

[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.

[Does nodal irradiation (clavicular and internal mammary chains) increase the toxicity of adjuvant breast radiotherapy?]. / L'irradiation des aires ganglionnaires (sus-claviculaire et mammaire interne) augmente-t-elle la toxicité de la radiothérapie adjuvante mammaire?

Treatment volume is a major risk factor of radiation-induced toxicity. As nodal irradiation increases treatment volume, radiation toxicity should be greater. Nevertheless, scientific randomised data do not support this fact. However, a radiation-induced toxicity is possible outside tangential fields in the nodal volumes not related to breast-only treatment. Treatment should not be adapted only to the disease but personalized to the individual risk of toxicity for each patient.

[Impact of intensity-modulated radiotherapy on node irradiation for breast cancer]. / Impact de la modulation d'intensité dans l'irradiation des aires ganglionnaires du cancer du sein.

Irradiation of node areas is still a complex challenge in external radiotherapy for breast cancer. Acceptable target coverage is always balanced by protection of organs at risk and patient morphology. Intensity-modulated radiotherapy increases the quality of dose distribution on the planning target volume, but modifies dramatically the irradiation coverage of critical structures in a different way compared to 3D treatment. In this paper we analyze this new technique in breast treatment with node regions, its expected gain and potential risks.

[Radiosensitivity settings in breast cancer]. / Paramètres de radiosensibilité des cancers du sein.

Breast cancers are highly radiosensitive since the risk of recurrences and of mortality after adjuvant radiotherapy following breast-conserving surgery is decreased by 15.7% and 3.8%, respectively at 10 years. The total dose if irradiation also significantly increases local control: a boost of 16 Gy to the tumour bed after breast-conserving surgery reduces the absolute risk of recurrence by 4% at 10 years. Breast cancers are sensitive to the dose per fraction, as shown by the results from four randomized trials which compared standard irradiation (50 Gy/25 fractions) with a hypofractionated scheme: no statistical difference was observed in locoregional recurrence and overall survival at 10 years. The α/ß ratio, which reflects the dose per fraction and is theoretically over 10 Gy for tumour tissues, has been estimated between 2.2 and 4.4 Gy for breast cancers. Molecular abnormalities, such as overexpression of HER1 (especially in triple negative breast cancer) and HER2, induce a higher radioresistance. In vitro studies showed that targeted therapies, which block these receptors, increase breast cancer radiosensitivity. Tumour stem cells have been identified in breast cancers and are characterized by a higher radioresistance. This radioresistance could be related to a better repair of radiation-induced DNA damages and a decrease of reactive oxygen species (ROS), which are involved in their occurrence. In the future, a better understanding of genetics tumour abnormalities will allow to identify new radiosensitivity settings in breast cancers.