Target volume delineation for radiotherapy of meningiomas: an ANOCEF consensus guideline.

PURPOSE: Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF). MATERIALS AND METHODS: A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus. RESULTS: Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes. CONCLUSION: New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.

Comparison of compressed sensing and controlled aliasing in parallel imaging acceleration for 3D magnetic resonance imaging for radiotherapy preparation.

Magnetic resonance imaging (MRI) for radiotherapy is often based on 3D acquisitions, but suffers from low signal-to-noise ratio due to immobilization device and flexible coil use. The aim of this study was to investigate if Compressed Sensing (CS) improves image quality for 3D Turbo Spin Echo acquisitions compared with Controlled Aliasing k-space-based parallel imaging in equivalent acquisition time for intracranial T1, T2-Fluid-Attenuated Inversion Recovery (FLAIR) and pelvic T2 imaging. Qualitative ratings suffered from large inter-rater variability. CS-T1 brain MRI was superior numerically and qualitatively. CS-T2-FLAIR brain MRI was numerically superior, but rater equivalent. CS-T2 pelvic MRI was equivalent without gain.

Technical note: Unexpected external markers artifact in 3D k-space based parallel imaging turbo spin-echo magnetic resonance imaging.

PURPOSE: MRI for radiotherapy planning requires spatial referencing using immobilization devices and markers. Clinical images of a difficult-to-interpret artifact are presented, resembling a metastasis, which occurs when combining CAIPIRINHA k-space-based parallel imaging (PI), 3D distortion correction, and external markers. METHODS: A 3D variable flip angle Turbo Spin Echo sequence was used on a 1.5 T and 3 T MRI using flexible and head and neck coils. Two types of markers were tested: Liquimark LM1 and Spee-D-Mark. A silicone oil phantom was used that represents low signal intensity, such as gray matter. 3D Fourier transforms were also used to show the issue's origin. RESULTS: The markers can appear in an unexpected region of a patient, not in the same original or reconstructed slice nor in a rectilinear direction in a slice, especially when using CAIPIRINHA acceleration with 3D distortion correction. The probability of occurrence was respectively 13% and 80% for distances of <=2 mm and >2 mm between marker and patient, for example when using thermoplastic masks. Clinical cases are shown where this semi-randomly occurring artifact appears post contrast only, and thus can be interpreted as metastases. The artifact did not appear when using compressed sensing acceleration. CONCLUSION: Markers used for radiotherapy MRI application can introduce additional artifacts that can be interpreted as metastases. However, other high signal intensity structures on the surface of a patient, such as the ear, can lead to an equivalent error.

Stereotactic body radiotherapy for intramedullary metastases: a retrospective series at the Oscar Lambret center and a systematic review.

BACKGROUND: Intramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature. METHODS: We included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined. RESULTS: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed. CONCLUSION: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients.

Stereotactic irradiation of non-small cell lung cancer brain metastases: evaluation of local and cerebral control in a large series.

Stereotactic radiotherapy (SRT) of brain metastases (BM) results are often reported in the heterogeneous primitive population. Here, we report our experience in consecutively treated patients who underwent SRT alone for BM from non-small cell lung cancer (NSCLC). This retrospective analysis included consecutive patients with no history of cerebral treatment who underwent Cyberknife™ SRT for BM from NSCLC in our institution from 2007 to 2016. One hundred patients were included in the study, with a median follow-up of 33 months (20-64). Mean age was 63 years (SD ± 10); 88% had Karnofsky Performance Status (KPS) > 70; 67% had unique BM; 18 patients received single-fraction SRT (20-25 Gy), and 82 received hypo-fractionated SRT (HSRT) (24-36 Gy in 3-5 fractions). We reported a complication rate of 17% (2% of G3-4). Median survival was 10.1 months [95% confidence interval (CI) 7.8-13.9]. At 1 year, local and cerebral control rates were respectively 78.7% (95% CI 70-86.5%) and 43% (95% CI 33.5-53%). Thirty patients underwent salvage treatment (whole brain radiation therapy, n = 13; SRT, n = 14; surgery, n = 3). Cyberknife™-based SRT is an effective treatment associated with high local control rate with low morbidity for patients with NSCLC's BM. Close follow-up is necessary to perform salvage treatment.

Treatment and outcomes in patients with central nervous system metastases from breast cancer in the real-life ESME MBC cohort.

AIM: The aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort. METHODS: Neurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Significant contributors to NPFS were determined using a multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2-8.4) and 5.5 months (95% CI: 5.2-5.8), respectively. In multivariate analysis, age >70 years (vs <50 years; HR = 1.40; 95% CI: 1.24-1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71-2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02-1.27), ≥3 metastatic sites (vs < 3; HR = 1.32; 95% CI: 1.21-1.43) and ≥3 previous treatment lines (vs < 3; HR = 1.75; 95% CI: 1.56-1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs <9 months; HR = 0.88; 95% CI: 0.78-0.98) was associated with longer NPFS. CONCLUSIONS: This study describes current treatment patterns of MBC patients in a "real life" setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies.

Efficacy and Tolerance of Post-operative Hypo-Fractionated Stereotactic Radiotherapy in a Large Series of Patients With Brain Metastases.

Purpose: The aim of this study was to assess, in a large series, the efficacy and tolerance of post-operative adjuvant hypofractionated stereotactic radiation therapy (HFSRT) for brain metastases (BMs). Materials and Methods: Between July 2012 and January 2017, 160 patients from 2 centers were operated for BM and treated by HFSRT. Patients had between 1 and 3 BMs, no brainstem lesions or carcinomatous meningitis. The primary endpoint was local control. Secondary endpoints were distant brain control, overall survival (OS) and tolerance to HFSRT. Results: 73 patients (46%) presented with non-small cell lung cancer (NSCLC), 23 (14%) had melanoma and 21 (13%) breast cancer. Median age was 58 years (range, 22-83 years). BMs were synchronous in 50% of the cases. The most frequent prescription regimens were 24 Gy in 3 fractions (n = 52, 33%) and 30 Gy in 5 fractions (n = 37, 23%). Local control rates at 1 and 2 years were 88% [95%CI, 81-93%] and 81% [95%CI, 70-88%], respectively. Distant control rate at 1 year was 48% [95%CI, 81-93%]. In multivariate analysis, primary NSCLC was associated with a significant reduction in the risk of death compared to other primary sites (HR = 0.57, p = 0.007), the number of extra-cerebral metastatic sites (HR = 1.26, p = 0.003) and planning target volumes (HR = 1.15, p = 0.012) were associated with a lower OS. There was no prognostic factor of time to local progression. Median OS was 15.2 months [95%CI, 12.0-17.9 months] and the OS rate at 1 year was 58% [95% CI, 50-65%]. Salvage radiotherapy was administered to 72 patients (45%), of which 49 received new HFSRT. Ten (7%) patients presented late grade 2 and 4 (3%) patients late grade 3 toxicities. Thirteen (8.9%) patients developed radiation necrosis. Conclusions: This large multicenter retrospective study shows that HFSRT allows for good local control of metastasectomy tumor beds and that this technique is well-tolerated by patients.

What is the normal tissues morbidity following Helical Intensity Modulated Radiation Treatment for cervical cancer?

BACKGROUND AND PURPOSE: To report on normal tissues morbidity following IMRT for cervix cancer. MATERIAL AND METHODS: The first 61 patients of a prospective series were included. 50 Gy to the PTV 1(pelvis) and 60 Gy to the PTV 2 (centro-pelvic disease and GTV nodes) were delivered concomitantly in 28 fractions, followed by a brachytherapy boost. For the small bowel, 50 Gy was the maximal dose, while V45 and V40 had to be <50 cc and 200 cc, respectively. For the bladder, rectum and sigmoid structures, 60 Gy was the maximal dose, and V45 and V40 had to be <20% and <50%. Acute and late toxicity data were prospectively collected. RESULTS: The median follow-up period was 40 months (range: 23-60). 30% and 90% of acute and moderate late side effects were reported respectively. Considering the AUC data of the organs at risk (OAR) DVH, late morbidity and doses were significantly linked (p⩽0.03), predominantly between 10 Gy and 40 Gy, considering the small bowel and sigmoid colon. The high dose regions exhibited no significant impact. CONCLUSION: The moderate dose volumes represent the predominant cause of morbidity after IMRT. Prospective trials are thus required to investigate new ways of dose distribution within the OAR.

Evidence based and new developments in re-irradiation for recurrent or second primary head and neck cancers.

PURPOSE OF REVIEW: The standard treatment for recurrent or second primary head and neck cancers is surgery which can only be performed in 25% of the patients. For inoperable patients, three options can be discussed: supportive care only, chemotherapy or radiotherapy with or without chemotherapy. The goal of this article is to review the indications and new developments in re-irradiation for recurrent or second primary head and neck cancers. RECENT FINDINGS: The le Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC)-le Groupe d'Oncologie et de Radiothérapie Tête et Cou (GORTEC) (99-01) trial showed that radio-chemotherapy improved disease-free survival for a highly selected population. All conventional and conformational radiotherapy series showed improved local control and disease-free survival rates, but at the expense of acute and late toxicities demanding a drastic patients selection. New radiotherapy techniques such as intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) have improved oncological results with reduced toxicities, offering treatments which are spread over six to seven weeks for IMRT and two weeks for SBRT. SUMMARY: Re-irradiation is an attractive alternative treatment for selected inoperable patients and its effectiveness can be potentiated by systemic treatments such as chemotherapy or targeted therapy. The development of new radiotherapy techniques such as IMRT and SBRT has improved healthy tissues tolerance and future studies should help define the specific IMRT and SBRT indications.

[Reirradiation for recurrent or second primary head and neck cancers]. / La radiothérapie en territoire irradié des tumeurs de la tête et du cou.

Recurrences or second primary head and neck cancers meant, for a long time, therapeutic dead ends. Surgery was the standard treatment, but could only be achieved in 25% of the patients. The GETTEC-GORTEC (99-01) randomized trial showed that radiochemotherapy improved disease-free survival for a highly selected population. For inoperable patients, three options can be discussed: supportive care only, chemotherapy or radiotherapy with or without chemotherapy. The EXTREME protocol showed that combining platinum, 5FU and cetuximab improved overall survival for recurrent or metastatic forms. This is certainly the best option for advanced forms, which are not accessible to radiotherapy. Concerning radiotherapy, only one randomized trial compared chemoradiotherapy to chemotherapy alone using methotrexate. The overall survival, the main objective in this study, was not improved, however, the enrollment was incomplete and included many advanced stage tumors. Other articles are based on Vokes' initial work of radiochemotherapy delivered in split-course over a period of 11 weeks. All conventional and conformational radiotherapy series showed improved local control and disease-free survival rates, but at the expense of acute and late toxicities demanding a drastic patients selection. New radiotherapy techniques such as intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) have reduced toxicities with a likely oncological results improvement, offering treatments which are spread over six to seven weeks for IMRT and two weeks for SBRT. The better treatment tolerance allows an increasing number of eligible patients. The main future objective will be to define the specific IMRT and SBRT indications.