Limited applicability and implementation of the international oncology treatments guidelines in low- and middle-income countries, an example from the Mediterranean area borders.

The quality of cancer care in the modern era is based on a precise diagnosis and personalized therapy according to patients and their disease based on validated guidelines with a high level of evidence. During cancer patients' management, the objective is first to make an accurate diagnosis and then offer the best treatment, validated beforehand in a multidisciplinary board meeting, with the best benefit/risk ratio. In the context of many low- and middle-income countries, the limited available means do not allow an adequate offer, resulting in non-optimal patients' care. In addition, in many low- and middle-income countries, priority can be given to other types of disease than cancer, which may considerably reduce allocation of specific resources to cancer care. Thus, the limited availability of systemic therapy, radiotherapy machines, brachytherapy and technological development may come up against another difficulty, that of geographical distribution of the means in the countries or a lack of expertise due to insufficient training programs. For all these reasons, the implementation of the guidelines established in Western countries could be impossible for many low- and middle-income countries which, moreover, have to face a completely different epidemiology of cancers compared to developed countries. In this work, we will discuss through a few examples of common cancers on both borders of the Mediterranean area, the applicability of the guidelines and the limits of their implementation for optimal cancer care.

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.

[Practice changing clinical trials in radiation oncology in 2022]. / Les essais qui changent les pratiques : le point en 2022.

This section highlights selected specific new recommendations and/or updates that have been published during the very last years in the fields of stereotactic radiotherapy, pediatrics, lung cancer, gynecologic and breast cancer, as well as in the area of radiation oncology of urogenital cancer.

Radionecrosis after repeated courses of radiotherapy under stereotactic conditions for brain metastases: Analysis of clinical and dosimetric data from a retrospective cohort of 184 patients.

PURPOSE: Between 10 and 40% of patients with cancer will develop one or more brain metastases (BMs). Stereotactic radiotherapy (SRT) is part of the therapeutic arsenal for the treatment of de novo or recurrent BM. Its main interest is to delay whole brain radiation therapy (WBRT), which may cause cognitive toxicity. However, SRT is not exempt from long-term toxicity, and the most widely known SRT is radionecrosis (RN). The objective of this study was to analyze the occurrence of RN per BM and per patient. MATERIAL AND METHODS: Between 2010 and 2020, data from 184 patients treated for 915 BMs by two to six SRT sessions for local or distant brain recurrence without previous or intercurrent WBRT were retrospectively reviewed. RN was examined on trimestral follow-up MRI and potentially confirmed by surgery or nuclear medicine. For each BM and SRT session plan, summation V12Gy, V14Gy, V21Gy and V23Gy isodoses were collected. Volumes of intersections were created between the 12Gy isodose at the first SRT and the 18Gy isodose of the following SRT (V18-12Gy). RESULTS: At the end of follow-up, 23.0% of patients presented RN, and 6.3% of BM presented RN. Median follow-up of BM was 13.3 months (95%CI 18.3-20.8). The median interval between BM irradiation and RN was 8.7 months (95% CI 9.2-14.7). Six-, 12- and 24-month RN-free survival rates per BM were 75%, 54% and 29%, respectively. The median RN-free survival per patient was 15.3 months (95% CI 13.6-18.1). In multivariate analysis, the occurrence of RN per BM was statistically associated with local reirradiation (P<0.001) and the number of SRTs (P<0.001). In univariate analysis, the occurrence of RN per patient was statistically associated with the sum of all V18-12Gy (P=0.02). No statistical association was found in multivariate analysis. A sum of all V18-12Gy of less than 1.5ml was associated with a 14.6% risk of RN, compared with 35.6% when the sum of all V18-12Gy was superior to 1.5ml. The sum of all V18-12Gy larger than 1.5ml was associated with a 74% specificity and 53% sensitivity of RN (P<0.001). CONCLUSION: Based on these results, a small number of BMs show RN during repeated SRT for local or distant recurrent BMs. Local reirradiation was the most predictive factor of brain RN. A V18-12Gy larger than 7.6ml in the case of local reirradiation or larger than 1.5ml in proximity reirradiation were prognostic factors of RN. The more BM patients need radiation therapy, and the longer they survive after irradiation, the higher their individual risk of developing RN.

Radiation therapy for brain metastases.

We present the update of the recommendations of the French society for radiation oncology on radiation therapy for the management of brain metastases. It has evolved in recent years and has become more complex. As the life expectancy of patients has increased and retreatments have become more frequent, side effects must be absolutely avoided. Cognitive side effects must in particular be prevented, and the most modern radiation therapy techniques must be used systematically. New prognostic classifications specific to the primary tumour of patients, advances in imaging and radiation therapy technology and new systemic therapeutic strategies, are making treatment more relevant. Stereotactic radiation therapy has supplanted whole-brain radiation therapy both for patients with metastases in place and for those who underwent surgery. Hippocampus protection is possible with intensity-modulated radiation therapy. Its relevance in terms of cognitive functioning should be more clearly demonstrated but the requirement for its use is constantly increasing. New targeted cancer treatment therapies based on the nature of the primitive have complicated the notion of the place and timing of radiation therapy and the discussion during multidisciplinary care meeting to indicate the best sequences is becoming a challenging issue as data on the interaction between treatments remain to be documented. In the end, although aimed at patients in the palliative phase, the management of brain metastases is one of the locations for which technical reflection is the most challenging and treatment become increasingly personalized.

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.

Respiratory motion management for external radiotherapy treatment.

We present the update of the recommendations of the French society of oncological radiotherapy on respiratory motion management for external radiotherapy treatment. Since twenty years and the report 62 of ICRU, motion management during the course of radiotherapy treatment has become an increasingly significant concern, particularly with the development of hypofractionated treatments under stereotactic conditions, using reduced safety margins. This article related orders of motion amplitudes for different organs as well as the definition of the margins in radiotherapy. An updated review of the various movement management strategies is presented as well as main technological solutions enabling them to be implemented: when acquiring anatomical data, during planning and when carrying out treatment. Finally, the management of these moving targets, such as it can be carried out in radiotherapy departments, will be detailed for a few concrete examples of localizations (abdominal, thoracic and hepatic).

[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.

[Radiation Oncology - Recent Status]. / Krebsbehandlung: aktueller Stand der perkutanen Strahlentherapie.

Radiation Oncology - Recent Status Abstract. We summarize the most important developments and innovations in the field over the past years and illustrate resulting external radiation treatment schedules and related treatment tolerance, focusing on hypofractionation.

[Ultra-hypofractionated radiotherapy for the treatment of localized prostate cancer: Results, limits and prospects]. / Radiothérapie en hypofractionnement extrême appliquée au traitement du cancer localisé de la prostate : résultats, limites et perspectives.

Still an emerging approach a few years ago, stereotactic body radiation therapy (SBRT) has ranked as a valid option for the treatment of localized prostate cancer. Inherent properties of prostatic adenocarcinoma (low α/ß) make it the perfect candidate. We propose a critical review of the literature trying to put results into perspective to identify their strengths, limits and axes of development. Technically sophisticated, the stereotactic irradiation of the prostate is well tolerated. Despite the fact that median follow-up of published data is still limited, ultra-hypofractionated radiotherapy seems very efficient for the treatment of low and intermediate risk prostate cancers. Data seem satisfying for high-risk cancers as well. New developments are being studied with a main interest in treatment intensification for unfavorable intermediate risk and high-risk cancers. Advantage is taken of the sharp dose gradient of stereotactic radiotherapy to offer safe reirradiation to patients with local recurrence in a previously irradiated area.

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] / Radiothérapie du carcinome épidermoïde du larynx de stade précoce, étage glottique : intérêt de l'hypofractionnement ?

Hypofractionated radiotherapy of early-stage squamous cell carcinoma of the glottic larynx is a promising treatment option. This can be divided into radiotherapy with moderate hypofractionation (up to 2.5Gy per fraction), more intense hypofractionation (between 2.5 and 4.5Gy per fraction) and stereotactic radiotherapy (above 4.5Gy per fraction). Most studies evaluating moderate hypofractionation show a local control rate between 85 and 95%. Acute laryngeal toxicity is superior to conventional treatment, but only for grades 1 and 2, with no significant difference reported for severe toxicity. Stereotactic radiotherapy in this pathology is also an emerging entity, but some authors have reported significant toxicity. There are currently no standardized guidelines for treatment and management regimen. We conducted a systemic review of published prospective and retrospective trials to evaluate efficacy, toxicity, and discuss future directions.

[Stereotactic body radiotherapy for locally advanced pancreatic cancer: A systemic review]. / Radiothérapie stéréotaxique dans le cancer du pancréas localement avancé : revue de la littérature.

Stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) is an emerging treatment option. Most studies showed local control of approximately 75% with no evidence of improved overall survival. Gastrointestinal toxicities could be significant, ranging up to 22% for acute toxicities≥grade 3+ and 44% for late toxicities≥grade 3+. Currently, no standardized guidelines for treatment and management scheme. We conducted a systemic review of published prospective and retrospective trials to evaluate the efficacy, safety, technical data, and discuss future directions.

[Repeated irradiation of brain metastases under stereotactic conditions: A review of the literature]. / Irradiations répétées de métastases cérébrales en conditions stéréotaxiques : revue de la littérature.

Stereotactic radiotherapy has become a standard in the management of patients with brain metastases; its main interest is to differ whole brain radiotherapy, provider of neurocognitive toxicity and to increase the rate of local control. The repetition of radiotherapy sessions under stereotactic conditions is not codified, neither on the number of technically and clinically possible sessions, nor on the maximum total number or volume of metastases to be treated. The purpose of this review is to analyse the data in the literature concerning repeated irradiations under stereotactic conditions. The second reirradiation in stereotactic condition shows satisfactory results in terms of overall survival, local control, and toxicity. However, we lack data for patients receiving more than two sessions of SRS as well as to define dose constraints to reirradiated healthy tissues. Prospective trials are still needed to validate the management of recurrent brain metastases after initial SRS.

[Choice optimisation of radiation therapy technique for central neurocytomas from literature data]. / Optimisation du choix de la technique d'irradiation des neurocytomes centraux à partir des données de la littérature.

Neurocytomas represent 0,25 to 0,5 of brain tumours. These tumours have neuronal differentiation. It's a young adult disease. The main treatment is neurosurgery. The place of other therapies is still unclear, noticeably with regards to radiotherapy. This review aim is to determine the place and the modalities of radiotherapy in the management of neurocytomas. A literature search using PubMed allowed to select the most relevant studies. Finally, 22 studies were selected according to pre-established criteria to answer the problem. All studies were retrospective studies except one. The analysis conclusion defined radiotherapy as a treatment of choice in selected patients, when surgical resection was incomplete or when tumour was atypical.

[Prognosis factors after lung stereotactic body radiotherapy for non-small cell lung carcinoma]. / Facteurs de récidive après radiothérapie stéréotaxique des cancers bronchiques non à petites cellules.

Lung cancer is the fourth most common cancer in France with a prevalence of 30,000 new cases per year. Lobectomy surgery with dissection is the gold standard treatment for T1-T2 localized non-small cell lung carcinoma. A segmentectomy may be proposed to operable patients but fragile from a respiratory point of view. For inoperable patients or patients with unsatisfactory pulmonary function tests, local treatment with stereotactic radiotherapy may be proposed to achieve local control rates ranging from 85 to 95% at 3-5 years. Several studies have examined prognostic factors after stereotaxic pulmonary radiotherapy. We conducted a general review of the literature to identify factors affecting local control.

[Radiotherapy for ovarian carcinoma management: Literature review]. / Place de la radiothérapie dans le traitement des cancers ovariens : revue de la littérature.

Ovarian cancer is the fifth most common cancer in women in France with 4714 new cases in 2017. More than 70% of patients whose disease is initially locally advanced will present locoregional or distant recurrence. Therapeutic options in this situation are not consensual. They are based on chemotherapy possibly associated with an iterative cytoreductive surgery when it is bearable by the patient. The place of radiotherapy in the management of the disease is hidden in the vast majority of national or international standards. We conducted a general review of the literature to clarify the role of irradiation in the global management of ovarian cancers, particularly in recurrence.

[Functional stereotactic radiosurgery: Indications and perspectives]. / Radiochirurgie fonctionnelle : indications et perspectives.

Stereotactic radiosurgery (SRS) is a non-invasive technique that enables to create brain focal lesions with a high precision and localization. Thus, functional brain disorders can be treated by SRS in case of pharmacoresistance or inoperability. To date, treatment of trigeminal neuralgia is the most described and known indication. Other indications will be developed in the future like movement disorders, refractory epilepsy, obsessive compulsive disorder and severe depression. We present here a review of actual and future indications of functional brain SRS with their level of evidence. All these SRS treatments have to be strictly conducted by trained teams with an excellent collaboration between radiation physicists, medical physicists, neurosurgeons, neurologists, psychiatrists and probably neuroradiologists.

[Stereotactic body radiotherapy: Passing fad or revolution?] / Radiothérapie stéréotaxique : changement de monde ou effet de mode ?

Stereotactic body radiotherapy (SBRT) is a young technology that can deliver a high dose of radiation to the target, utilizing either a single dose or a small number of fractions with a high degree of precision within the body. Various technical solutions co-exist nowadays, with particular features, possibilities and limitations. Health care authorities have currently validated SBRT in a very limited number of locations, but many indications are still under investigation. It is therefore challenging to accurately appreciate the SBRT therapeutic index, its place and its role within the anticancer therapeutic arsenal. The aim of the present review is to provide SBRT definitions, current indications, and summarize the future ways of research. There are three validated indications for SBRT: un-resecable T1-T2 non small cell lung cancer, <3 slow-growing pulmonary metastases secondary to a stabilized primary, and the tumours located close to the medulla. In other situations, the benefit of SBRT is still to be demonstrated. One of the most promising way of research is the ablative treatment of oligo metastatic cancers, with recent studies suggesting a survival benefit. Furthermore, the most recent data suggest that SBRT is safe. Finally, the SBRT combined with immune therapies is promising, since it could theoretically trigger the adaptative anticancer response.

Hypofractionated stereotactic radiotherapy for challenging brain metastases using 36 Gy in six fractions.

PURPOSE: Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm3) or brain metastases located next to critical structures. MATERIAL AND METHODS: Patients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated. RESULTS: Sixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity. CONCLUSION: The 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.

[Inter- and intrafraction imaging during stereotactic body radiation therapy: Which solutions for which tumours?] / Imagerie inter- et intrafractions en radiothérapie stéréotaxique extracrânienne : quelles solutions pour quelles tumeurs ?

Due to high dose gradients, stereotactic body radiation therapy requires high precision in the location of the tumour. Uncertainties in the positioning can introduce serious damage on organs at risk and consequently can reduce tumour local control. A better tumour location can be achieved by controlling its position with an efficient inter and intrafraction imaging procedure. The various imaging techniques available on treatment systems are presented and performances are discussed. Finally, propositions are given in terms of imaging system according to the location treated by stereotactic body radiation therapy.