Helical tomotherapy craniospinal irradiation in primary brain tumours: Toxicities and outcomes in a peadiatric and adult population.

Objective: As craniospinal irradiation (CSI) is delivered more frequently by helical tomotherapy (HT) with few reports about late effects, we analysed all patients treated in our centre over an 11-year period. Methods and materials: Our study included all patients that underwent CSI by HT, between September 2009 and January 2020, in the Department of Radiation Oncology of the Toulouse Cancer Institute. Acute radiotherapy toxicities were reported and medium- to long-term outcomes analysed. Results: Among the 79 patients included, 70.9 % were younger than 18 years at diagnosis, the median age was 13 (range: 1-52) at the time of radiation therapy, 67.1 % of patients had medulloblastoma. Half of them (49.4 %) had a metastatic disease at diagnosis. The median dose of CSI was 36 Gy (range, 18-36). Seventy-seven patients received a radiation boost to the original location of the primary tumour (97.5 %), 32 patients also received a boost to their metastatic sites (40.5 %). Median follow-up was 55.5 months (95 %CI = [41.2; 71.8]). The 3-year event-free survival rate was 66.3 % (95 %CI = [54.2; 75.9]). Most patients presented with acute haematological toxicities during CSI (85.9 %), predominantly severe thrombocytopenia (39.7 %). Among the 64 patients assessed for medium- and long-term outcomes, 52 survived and 47 were alive and disease-free at the latest follow-up visit on record. There were 3.8 % secondary tumours: two meningiomas and one diffuse intrinsic pontine glioma. Adult and paediatric patients respectively presented with secondary cataract (4.3 % vs 22.0 %), persistent hearing disorders (26.1 % vs 29.3 %), pulmonary or cardiac late effects (4.3 % vs 2.4 %), hormonal pituitary gland deficiencies (30.0 % vs 56.8 %) and psycho-cognitive disorders (56.5 % vs 53.7 %). Conclusion: CSI dispensed by HT, did not result in any additional acute or late toxicities when compared to 3D-CSI. There was no increase in the secondary tumour rate compared to that reported in the literature.

Intraepithelial tumor-infiltrating lymphocytes shape loco-regional PET/CT spread of locally advanced cervical cancer.

BACKGROUND: Data suggest an association between positron emission tomography/CT (PET/CT) metabolic metrics and tumor microenvironment in several malignancies, and a potential role of PET/CT to monitor response to immunotherapy. OBJECTIVE: To evaluate the correlation between tumor loco-regional extension and tumor-infiltrating lymphocyte infiltration in locally advanced cervical cancer prior to concurrent chemo-radiotherapy.The secondary objective was to assess the association between tumor-infiltrating lymphocytes and PET/CT metabolic metrics. METHODS: Patients with locally advanced cervical cancer and negative para-aortic extensions on PET/CT were included. Two senior nuclear medicine physicians specializing in gynecologic oncology reviewed all PET/CT exams, and extracted tumor maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis, as well as pelvic lymph node involvement. One senior gynecologic oncology pathologist assessed intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. Intraepithelial tumor-infiltrating lymphocytes were categorized following previous studies as <1% and >1%. The cut-off for stromal tumor-infiltrating lymphocytes was chosen empirically: intermediate <60% and high >60%. RESULTS: 86 patients were included. Intraepithelial tumor-infiltrating lymphocytes were not significantly associated with tumor metabolic metrics. Intraepithelial tumor-infiltrating lymphocytes were not significantly associated with maximum standard uptake value (p=0.16), or metabolic tumor volume (p=0.19). Tumors with <1% intraepithelial tumor-infiltrating lymphocytes score were associated with a higher MRI tumor size (≥ median) (63.3% vs 39.3%, p=0.04). Patients with pelvic lymph node uptake were significantly more frequent in patients with high stromal tumor-infiltrating lymphocytes score (≥60%) (61.5% vs 31.7%, p=0.009). CONCLUSIONS: Poor or absent intraepithelial tumor-infiltrating lymphocytes were associated with more advanced disease at diagnosis and larger tumor size. Tumor-infiltrating lymphocytes were not associated with tumor metabolic activity. Intraepithelial and stroma tumor-infiltrating lymphocytes are not redundant and should be assessed separately. Further work is needed to evaluate the association between tumor metabolic profile and immune populations, including different T-cell subtypes for patient selection for immunotherapy strategies.

Brainstem toxicity after proton or photon therapy in children and young adults with localized intracranial ependymoma: A French retrospective study.

BACKGROUND AND PURPOSE: Ependymoma is the third most frequent childhood braintumor. Standard treatment is surgery followed by radiation therapy including proton therapy (PBT). Retrospective studies have reported higher rates of brainstem injury after PBT than after photon therapy (XRT). We report a national multicenter study of the incidence of brainstem injury after XRT versus PBT, and their correlations with dosimetric data. MATERIAL AND METHODS: We included all patients aged < 25 years who were treated with PBT or XRT for intracranial ependymoma at five French pediatric oncology reference centers between 2007 and 2020. We reviewed pre-irradiation MRI, follow-up MRIs over the 12 months post-treatment and clinical data. RESULTS: Of the 83 patients, 42 were treated with PBT, 37 with XRT, and 4 with both (median dose: 59.4 Gy, range: 53­60). No new or progressive symptomatic brainstem injury was found. Four patients presented asymptomatic radiographic changes (punctiform brainstem enhancement and FLAIR hypersignal), with median onset at 3.5 months (range: 3.0­9.4) after radiation therapy, and median offset at 7.6 months (range: 3.7­7.9). Two had been treated with PBT, one with XRT, and one with mixed XRT-PBT. Prescribed doses were 59.4, 55.8, 59.4 and 54 Gy. CONCLUSION: Asymptomatic radiographic changes occurred in 4.8% of patients with ependymoma in a large national series. There was no correlation with dose or technique. No symptomatic brainstem injury was identified.

The long-term impact of irradiation on functional connectivity in brain circuits involved in memory processes after pediatric posterior fossa tumor.

PURPOSE: Memory is one of the main specific cognitive domains impaired with attention and processing speed after a pediatric brain tumor. This work explored the long-term impact of radiotherapy in children with posterior fossa tumor (PFT) on brain connectivity in neural circuits involved in memory using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: A total of 20 irradiated and 15 non-irradiated PFT survivors, and 21 healthy controls, prospectively included in the IMPALA study (NCT04324450), performed memory tests assessing episodic, procedural, and working memories and were subjected to an rs-fMRI. We manually contoured main structures involved in memory to explore connectivity at rest in a seed-to-voxel analysis. The groups were compared and differences in connectivity were correlated with behavioral scores and irradiation doses. RESULTS: The performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients. Irradiated survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. CONCLUSION: The results of this study highlight that irradiation has a long-term impact on brain connectivity in brain circuits involved in memory after pediatric PFT with a specific radiation-dose effect in supratentorial structures.

Management of tumor volume changes during preoperative radiotherapy for extremity soft tissue sarcoma: a new strategy of adaptive radiotherapy.

BACKGROUND: Using adaptive radiotherapy (ART), to determine objective clinical criteria that identify extremity soft tissue sarcoma (ESTS) patients requiring adaptation of their preoperative radiotherapy (RT) plan. PATIENTS AND METHODS: We included 17 patients with a lower extremity ESTS treated between 2019 and 2021 with preoperative RT, using helicoidal intensity-modulated RT (IMRT) tomotherapy, before surgical resection. We collected clinical, tumor parameters and treatment data. Repositioning was ascertained by daily Megavoltage computed tomography (MVCT) imaging. Using the PreciseART technology we retrospectively manually delineated at least one MVCT for each patient per week and recorded volume and dosimetric parameters. A greater than 5% change between target volume and planned target volume (PTV) dosimetric coverage from the initial planning CT scan to at least one MVCT was defined as clinically significant. RESULTS: All 17 patients experienced significant tumor volume changes during treatment; 7 tumors grew (41%) and 10 shrank (59%). Three patients (18%), all undifferentiated pleomorphic sarcomas (UPS) with increased volume changes, experienced significant reductions in tumor dose coverage. Seven patients required a plan adaptation, as determined by practical criteria applied in our departmental practice. Among these patients, only one ultimately experienced a significant change in PTV coverage. Three patients had a PTV decrease of coverage. Among them, 2 did not receive plan adaptation according our criteria. None of the patients with decreased tumor volumes had reduced target volume coverage. Monitoring volume variations by estimating gross tumor volume (GTV) on MVCT, in addition to axial and sagittal linear tumor dimensions, appeared to be most effective for detecting reductions in PTV coverage throughout treatment. CONCLUSIONS: Variations in ESTS volume are evident during preoperative RT, but significant dosimetric variations are rare. Specific attention should be paid to grade 2-3 UPSs during the first 2 weeks of treatment. In the absence of dedicated software in routine clinical practice, monitoring of tumor volume changes by estimating GTV may represent a useful strategy for identifying patients whose treatment needs to be replanned.

A CT-based radiomics classification model for the prediction of histological type and tumour grade in retroperitoneal sarcoma (RADSARC-R): a retrospective multicohort analysis.

BACKGROUND: Retroperitoneal sarcomas are tumours with a poor prognosis. Upfront characterisation of the tumour is difficult, and under-grading is common. Radiomics has the potential to non-invasively characterise the so-called radiological phenotype of tumours. We aimed to develop and independently validate a CT-based radiomics classification model for the prediction of histological type and grade in retroperitoneal leiomyosarcoma and liposarcoma. METHODS: A retrospective discovery cohort was collated at our centre (Royal Marsden Hospital, London, UK) and an independent validation cohort comprising patients recruited in the phase 3 STRASS study of neoadjuvant radiotherapy in retroperitoneal sarcoma. Patients aged older than 18 years with confirmed primary leiomyosarcoma or liposarcoma proceeding to surgical resection with available contrast-enhanced CT scans were included. Using the discovery dataset, a CT-based radiomics workflow was developed, including manual delineation, sub-segmentation, feature extraction, and predictive model building. Separate probabilistic classifiers for the prediction of histological type and low versus intermediate or high grade tumour types were built and tested. Independent validation was then performed. The primary objective of the study was to develop radiomic classification models for the prediction of retroperitoneal leiomyosarcoma and liposarcoma type and histological grade. FINDINGS: 170 patients recruited between Oct 30, 2016, and Dec 23, 2020, were eligible in the discovery cohort and 89 patients recruited between Jan 18, 2012, and April 10, 2017, were eligible in the validation cohort. In the discovery cohort, the median age was 63 years (range 27-89), with 83 (49%) female and 87 (51%) male patients. In the validation cohort, median age was 59 years (range 33-77), with 46 (52%) female and 43 (48%) male patients. The highest performing model for the prediction of histological type had an area under the receiver operator curve (AUROC) of 0·928 on validation, based on a feature set of radiomics and approximate radiomic volume fraction. The highest performing model for the prediction of histological grade had an AUROC of 0·882 on validation, based on a radiomics feature set. INTERPRETATION: Our validated radiomics model can predict the histological type and grade of retroperitoneal sarcomas with excellent performance. This could have important implications for improving diagnosis and risk stratification in retroperitoneal sarcomas. FUNDING: Wellcome Trust, European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group, the National Institutes for Health, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022­2023 : Prise en charge du cancer du col de l'utérus avancé.

French recommendations for clinical practice, Nice/Saint-Paul-de-Vence 2022-2023: Management of advanced cervical cancer The prognosis of cervical cancer remained pejorative until recently, first-line treatment consisting of platinum-based chemotherapy, associated with bevacizumab whenever possible, without any other therapeutic innovation for several years. However in 2022, immunotherapy appeared in the therapeutic landscape. Pembrolizumab can now be prescribed, thanks to the early access status granted by the HAS in September 2022, in patients with PD-L1 positive tumors. In parallel, bevacizumab generic is now reimbursed, allowing its association with chemotherapy on top of pembrolizumab, if indicated. For patient relapsing after platinium salts, and who never received immunotherapy, cemiplimab could be delivered and reimboursed since spring 2023, whatever could be PD-L1 status. Pretherapeutic work-up includes imaging combining MRI and PET/CT or CT of the chest, abdomen and pelvis, as well as evaluation of PD-L1 status on tumor and immune cells to define the CPS score that will determine eligibility to pembrolizumab treatment (CPS > 1). Possibilities of locoregional treatment depend on individual situations and are discussed on a case-by-case basis in multidisciplinary meetings. Early supportive care is always recommended and inclusion in clinical trials must be systematically considered.

High dose (54 Gy) pre-operative helical tomotherapy for retroperitoneal liposarcoma: Results of a phase II multicenter study.

PURPOSE: To evaluate efficacy and feasibility of high-dose intensity-modulated radiotherapy (RT) with pre-operative helical tomotherapy, delivering 54 Gy/30 fractions in patients with retroperitoneal liposarcomas (RPLS). MATERIALS AND METHODS: Patients with operable, biopsy-proven, RPLS were included in this phase II multicenter study (ClinicalTrials.gov: NCT01841047). The primary objectives were to analyze loco-regional relapse free survival (LRFS), overall survival (OS) and toxicities, graded according to CTCAE V3.0. RESULTS: From April 2009 to September 2013, 48 patients were included. Histological types were: 20 well differentiated and 28 dedifferentiated liposarcomas. Median clinical target volume (CTV) was 2570 cc (range, 230-8734 cc). The radio-surgical schedule was completed as planned in all patients apart from one. A monobloc wide excision was achieved for all patients. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1, 2%).With a median follow-up of 5.5 years, 3-year LRFS rate was 74.2% (95%CI: [59.1%; 84.5%]). At 5 years, cumulative incidence of loco-regional relapse for well differentiated and dedifferentiated RPLS was 10% and 18%, respectively. The 5-year OS was 73.9% [95%CI: 58.7-84.3%]. During RT, the most common grade 3-4 adverse events were hematological (N = 20; 41.6%). After surgery and during follow-up, 17 patients (35.4%) presented a grade 3-4 toxicity. Two patients (4.1%) died due to a duodenal toxicity. Nine second cancers were observed. CONCLUSION: From this phase II trial of preoperative RT in RPLS patients, the dose level proposed cannot be considered safe, leading to non-negligible toxicity and second cancers rates. Our results, combined with STRASS-1 study, suggest that the ideal indication of RT for patients with RPLS still remains to be determined.

Respective Roles of Surgery, Chemotherapy, and Radiation Therapy for Recurrent Pediatric and Adolescent Ependymoma: A National Multicentric Study.

PURPOSE: Half of the children and adolescents treated for intracranial ependymoma experience recurrences that are not managed in a standardized manner. This study aimed to retrospectively evaluate recurrence treatments. METHODS AND MATERIALS: We assessed overall survival (OS) and progression-free survival (PFS) after a first relapse in a population of patients from the Pediatric Ependymoma Photons Protons and Imaging study (PEPPI study) who were treated with surgery and radiation therapy in French Society of Childhood Cancer reference centers between 2000 and 2013. Data were analyzed using the Cox model as well as a landmark analysis at 4 months that accounted for the guarantee-time bias. RESULTS: The median follow-up of the whole population of 202 patients was 105.1 months, with a 10-year OS of 68.2% and PFS of 45.5%. Among the 100 relapse cases, 68.0% were local relapses, 20.0% were metastatic, and 12.0% were combined (local and metastatic). Relapses were treated by surgery (n = 79) and/or reirradiation (n = 52) and/or chemotherapy (n = 22). The median follow-up after relapse was 77.8 months. The OS and PFS at 5 years were 43.1% and 16.2%, respectively. After surgery or radiation therapy of the first relapse, OS and PFS were more favorable, whereas treatments that included chemotherapy with or without focal treatment were associated with worse OS and PFS. In the multivariate analysis, stereotactic hypofractionated reirradiation after surgery was associated with a significantly better outcome (OS, P = .030; PFS, P = .008) and chemotherapy with a worse outcome (OS, P = .028; PFS, P = .033). CONCLUSIONS: This analysis of relapse treatments within the PEPPI study determined that irrespective of whether the relapse was localized or metastatic, treatments that included surgery and/or reirradiation had better outcomes.

PARa-aOrtic LymphAdenectomy in locally advanced cervical cancer (PAROLA trial): a GINECO, ENGOT, and GCIG study.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control. PRIMARY OBJECTIVES: To demonstrate if chemoradiation with tailored external beam radiation field based on surgical staging and pathologic examination of the para-aortic lymph node is associated with improved 3-year disease-free survival compared with patients staged with PET/CT staging only. STUDY HYPOTHESIS: Surgical staging followed by tailored chemoradiation will improve disease-free survival while avoiding unnecessary prophylactic extended-field chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 cervical cancer. TRIAL DESIGN: This is an international multicenter, randomized, phase III study. Eligible patients will be randomized 1:1 between PET/CT staging followed by chemoradiation (control arm), or surgical staging followed by tailored chemo-radiation (experimental arm). Randomization will be stratified by tumor stage according to TNM classification, center, and adjuvant treatment. MAJOR INCLUSION/EXCLUSION CRITERIA: Main inclusion criteria are histologically proven PET/CT FIGO stage IIIC1 cervical cancer. Main exclusion criteria include unequivocal positive common iliac or para-aortic lymph node at pre-therapeutic imaging PET/CT. PRIMARY ENDPOINTS: The primary endpoint is disease-free survival defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause. SAMPLE SIZE: 510 eligible patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The estimated date for completing accrual will be Q2 2027. The estimated date for presenting results will be Q4 2030. TRIAL REGISTRATION NUMBER: NCT05581121.

Clinical reliability of pedicled perforator flaps in the management of adult limb and trunk soft tissue sarcomas: Experience of two French expert centres.

INTRODUCTION: Limb-sparing surgery combined with radiation has become the standard treatment for soft tissue sarcomas. Despite the many advantages of reconstruction procedures, such as muscle-sparing flap and local reconstruction, the use of pedicled perforator flaps remains non-consensual due to doubts about their reliability when associated with radiotherapy. This study evaluated their surgical reliability in reconstructive surgery for limb and trunk soft tissue sarcomas, in terms of healing time, wound disorders, and postoperative complications, regardless of radiation timing. PATIENTS AND METHODS: We realized a retrospective, observational, bi-center study (Cancer University Institute of Toulouse Oncopole, France and Bergonié Institute Bordeaux, France) and describes pedicled perforator flaps performed between January 2015 and January 2021. RESULTS: A total of 74 flaps were included. The median age of the population was 70-year-old. The group consisted of 68.8% (n = 51/74) propeller flaps. We found a partial necrosis rate of 28.4% (n = 21/74), scar disunion of 48.6% (n = 36/74), local infection of 10.8% (n = 8/74), and venous congestion of 13.5% (n = 10/74). Only 16.2% (n = 12/74) required secondary surgical repair to a local complication. The average length of stay was 7.3 days  [1.0-25.0]. The mean operating time of our flaps was 133.4 min [38.0-280.0]. CONCLUSIONS: Pedicled perforator flaps are a surgical technique that can be used in reconstructive surgery for limb and trunk soft tissue sarcomas in adults, regardless of radiation timing. However, these flaps carry a high rate of postoperative complications so they should be reserved for expert surgeons in referral centers.

Metabolic activity determines survival depending on the level of lymph node involvement in cervical cancer.

BACKGROUND: To assess the impact of PET/CT functional parameters on survival, locoregional, and distant failure according to the most distant level of lymph node [18F]FDG uptake in patients with locally advanced cervical cancer (LACC). METHODS: Retrospective study including 148 patients with LACC treated with concurrent chemoradiotherapy after PET/CT and para-aortic lymph node (PALN) surgical staging. Two senior nuclear medicine physicians reviewed all PET/CT exams and retrieved tumor and lymph node metabolic parameters: SUVmax, MTV, TLG. Oncological outcomes according to metabolic parameters and level of lymph node spread on PET/CT were assessed. RESULTS: In patients without lymph node uptake on PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 5.14 95%CI = [2.15-12.31]), OS (HR = 6.10 95%CI = [1.89-19.70]), and time to distant (HR = 4.73 95%CI = [1.55-14.44]) and locoregional recurrence (HR = 5.18 95%CI = [1.72-15.60]). In patients with pelvic lymph node (PLN) uptake but without PALN uptake on [18F]FDG-PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 3.17 95%CI = [1.02-9.83]) and OS (HR = 3.46 95%CI = [0.96-12.50]), and the number of PLN fixations was associated with DFS (HR = 1.30 95%CI = [1.10-1.53]), OS (HR = 1.35 95%CI = [1.11-1.64]), and time to distant (HR = 1.35 95%CI = [1.08-1.67]) and locoregional recurrence (HR = 1.31 95%CI = [1.08-1.59]). There was no significant association between cervical tumor metabolic or lymph node metrics and survival outcome in patients with PALN uptake. CONCLUSIONS: Cervical MTV is more accurate than SUVmax to predict survival outcome in patients with locoregional disease confined to the pelvis and should be implemented in routine clinical practice. Prognostic value of metabolic metrics disappears with PALN uptake, which is associated with distant failure in nearly half of patients.

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma.

PURPOSE: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. METHODS AND MATERIALS: Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. RESULTS: During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. CONCLUSIONS: NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.

Treatment related factors associated with the risk of breast radio-induced-sarcoma.

BACKGROUND AND PURPOSE: The Radiation Induced Sarcoma (RIS) is a rare but serious adverse event following radiotherapy (RT). Current RT techniques are more precise, but irradiate a larger volume at a low dose. This study aimed to describe radiation characteristics in a large series of patients suffering from RIS. MATERIALS AND METHODS: Patient-representative voxel-based anthropomorphic phantoms were used to reconstruct patient-specific RT fields for 125 patients diagnosed with RIS after primary breast cancer. For each patient, the location of the RIS onset site was determined and transferred onto the phantom as a contour. Using a treatment planning system (TPS), the dose distribution on the RIS in the phantom was calculated. RESULTS: The mean dose (Dmean) received in the area where RIS subsequently developed was 47.8 ± 11.6 Gy. The median dose in the zones where RIS later developed ranged from 11 Gy to 58.8 Gy. The median time from RT to RIS development was 8 years (range 2-32 years). Analysis for predictors of time to radiation-induced sarcoma development highlighted a significant impact of age of patient during the RT whereas in multivariable analysis chemotherapy and hormonotherapy for primary breast cancer were not associated with a significant difference in time to diagnosis of RIS. CONCLUSIONS: This study highlights that the dose received by the tissue in which the RIS developed was almost 47 Gy. These results are encouraging for the use of new RT techniques increasing volumes receiving low doses, without fear of an excess of RIS over the next 10 years.

A prospective behavioral and imaging study exploring the impact on long-term memory of radiotherapy delivered for a brain tumor in childhood and adolescence.

BACKGROUND: Posterior fossa tumors represent two thirds of brain tumors in children. Although progress in treatment has improved survival rates over the past few years, long-term memory impairments in survivors are frequent and have an impact on academic achievement. The hippocampi, cerebellum and cerebellar-cortical networks play a role in several memory systems. They are affected not only by the location of the tumor itself and its surgical removal, but also by the supratentorial effects of complementary treatments, particularly radiotherapy. The IMPALA study will investigate the impact of irradiation doses on brain structures involved in memory, especially the hippocampi and cerebellum. METHODS/DESIGN: In this single-center prospective behavioral and neuro-imaging study, 90 participants will be enrolled in three groups. The first two groups will include patients who underwent surgery for a posterior fossa brain tumor in childhood, who are considered to be cured, and who completed treatment at least 5 years earlier, either with radiotherapy (aggressive brain tumor; Group 1) or without (low-grade brain tumor; Group 2). Group 3 will include control participants matched with Group 1 for age, sex, and handedness. All participants will perform an extensive battery of neuropsychological tests, including an assessment of the main memory systems, and undergo multimodal 3 T MRI. The irradiation dose to the different brain structures involved in memory will be collected from the initial radiotherapy dosimetry. DISCUSSION: This study will provide long-term neuropsychological data about four different memory systems (working memory, episodic memory, semantic memory, and procedural memory) and the cognitive functions (attention, language, executive functions) that can interfere with them, in order to better characterize memory deficits among the survivors of brain tumors. We will investigate the correlations between neuropsychological and neuroimaging data on the structural (3DT1), microstructural (DTI), functional (rs-fMRI), vascular (ASL) and metabolic (spectroscopy) impact of the tumor and irradiation dose. This study will thus inform the setting of dose constraints to spare regions linked to the development of cognitive and memory functions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04324450, registered March 27, 2020, updated January 25th, 2021. Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04324450.

Brachytherapy for uterine cervix-limited acute myeloid leukemia relapse.

Acute myeloid leukemia (AML) may extend to extra-medullary sites at diagnosis or at relapse, either isolated or associated with bone marrow disease. Granulocytic sarcoma of uterine cervix is rare, and there is no established treatment for this disease. Two cases of uterine cervix-limited AML relapse showed that brachytherapy may be an effective therapeutic option in this setting along with chemotherapy, with good tolerance.

Hypofractionated stereotactic body radiation therapy (SBRT) in pediatric patients: preliminary toxicity results of a national prospective multicenter study.

OBJECTIVES: While hypofractionated stereotactic body radiotherapy (SBRT) has been largely adopted in the adult setting, its use remains limited in pediatric patients. This is due, among other factors, to fear of potential toxicities of hypofractionated regimens at a young age. In this context, we report the preliminary acute (<3 months from SBRT) and middle-term (3-24 months) toxicity results of a national prospective study investigating SBRT in pediatric patients. METHODS: Between 2013 and 2019, 61 patients were included. The first 40 patients (median age: 12 y, range: 3-20) who completed a 2-year-follow-up were included in the present analysis. SBRT was used for treating lung, brain or (para)spinal lesions, either as first irradiation (35%) or in the reirradiation setting (65%). RESULTS: Acute and middle-term grade ≥2 toxicities occurred in 12.5 and 7.5% of the patients, respectively. No grade ≥4 toxicities occurred. Almost all toxicities occurred in the reirradiation setting. CONCLUSION: SBRT showed a favorable safety profile in young patients treated for lung, brain, and (para)spinal lesions. ADVANCES IN KNOWLEDGE: SBRT appeared to be safe in pediatric patients treated for multiple oncology indications. These results support further evaluation of SBRT, which may have a role to play in this patient population in the future.

Performance of Multiparametric Functional Imaging to Assess Peritoneal Tumor Burden in Ovarian Cancer.

PURPOSE: The aim of the study was to evaluate the clinical utility of pretreatment 18F-FDG PET/CT with quantitative evaluation of peritoneal metabolic cartography in relation to staging laparoscopy for ovarian carcinomatosis. PATIENTS AND METHODS: A retrospective review of prospectively collected data from 84 patients with FIGO (International Federation of Gynecology and Obstetrics) stage IIIC to IV ovarian cancer was carried out. All patients had a double-blinded 18F-FDG PET/CT review. Discriminant capacity of metabolic parameters to identify peritoneal carcinomatosis in the 13 abdominal regions according to the peritoneal cancer index was estimated with area under the receiver operating characteristic curve (AUC). RESULTS: The metabolic parameter showing the best trade-off between sensitivity and specificity to predict peritoneal extension compared with peritoneal cancer index score was the metabolic tumor volume (MTV), with a Spearman ρ equal to 0.380 (P < 0.001). The AUC of MTV to diagnose peritoneal involvement in the upper abdomen (regions 1, 2, and 3) ranged from 0.740 to 0.765. MTV AUC values were lower in the small bowel regions (9-12), ranging from 0.591 to 0.681, and decreased to 0.487 in the pelvic region 6. 18F-FDG PET/CT also improved the detection of extra-abdominal disease, upstaging 35 patients (41.6%) from stage IIIC to IV compared with CT alone and leading to treatment modification in more than one third of patients. CONCLUSIONS: 18F-FDG PET/CT metrics are highly accurate to reflect peritoneal tumor burden, with variable diagnostic value depending on the anatomic region. MTV is the most representative metabolic parameter to assess peritoneal tumor extension.

Assessment of an onco-sexology support and follow-up program in cervical or vaginal cancer patients undergoing brachytherapy.

PURPOSE: Women's sexual health and wellbeing with cervical or vaginal cancer may be largely affected by complications from external beam radiotherapy (EBRT) and utero-vaginal brachytherapy (BT), of which vaginal stenosis is the main complication. The objective of this study was to assess the impact of support by a nurse sexologist on sexuality, vaginal side-effects, and the quality of clinical follow-up in patients treated with brachytherapy for cervical or vaginal cancer. METHODS: We performed a retrospective study of the sexuality of women treated for cervical or vaginal cancer. Data from patients with cervical or vaginal cancer who underwent brachytherapy between 2013 and 2017 were collected at Institut Universitaire de Cancer de Toulouse-Oncopôle (IUCT-Oncopôle). Patients were divided into two groups: group A (intervention group) received support from a nurse sexologist and group B (control group) did not. The chi-square test and a logistic multivariate model were used for data analysis. RESULTS: A total of 156 patients were included in this study, including 57.7% who were followed by a nurse sexologist. We observed low compliance in using vaginal dilators after brachytherapy and/or radiotherapy over time regardless of the group, and patients' sexual activity was inadequately addressed. Information regarding the resumption of sexuality 2 months after treatment was missing in 1.1% of patients in group A and in 36.4% of patients in group B. Multivariate analysis showed that patients in group A had a lower risk of developing vaginal stenosis with OR crude = 0.5 (95% CI = 0.25-0.92) and OR adj. = 0.5 (95% CI = 0.26-1.09) compared with those in group B. CONCLUSION: This retrospective study highlights the lack of information collected by physicians during follow-up concerning the sexuality of patients with cervical or vaginal cancer treated by EBRT and BT. The support offered by nurse sexologists in improving patients' sexual activity and reducing their physical side-effects such as vaginal stenosis is likely to be beneficial. A prospective study is currently being conducted to validate the present findings.

Phase II study of concomitant radiotherapy with atezolizumab in oligometastatic soft tissue sarcomas: STEREOSARC trial protocol.

INTRODUCTION: Up to 50% of soft tissue sarcoma (STS) patients develop metastases in the course of their disease. Cytotoxic therapy is a standard treatment in this setting but yields average tumour response rates of 25% at first line and ≤10% at later lines. In oligometastatic stage, stereotactic body radiation therapy (SBRT) allows reaching high control rates at treated sites (≥80%) and is potentially equally effective to surgery in term of overall survival. In order to shift the balance towards antitumour immunity by multisite irradiation, radiation could be combined with inhibitors of the immunosuppressive pathways. METHODS AND ANALYSIS: STEREOSARC is a prospective, multicentric, randomised phase II, designed to evaluate the efficacy of SBRT associated with immunotherapy versus SBRT only. Randomisation is performed with a 2:1 ratio within two arms. The primary objective is to evaluate the efficacy, in term of progression-free survival (PFS) rate at 6 months, of immunomodulated stereotactic multisite irradiation in oligometastatic sarcoma patients. The secondary objectives include PFS by immune response criteria, overall survival, quality-of-life evaluation and developing mathematical models of tumour growth and dissemination predictive of oligometastatic versus polymetastatic evolution. Patients will be randomised in two groups: SBRT with atezolizumab and SBRT alone. The total number of included patients should be 103. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov (ID: NCT03548428). ETHICS AND DISSEMINATION: This study has been approved by Comité de Protection des Personnes du sud-ouest et outre-mer 4 on 18 October 2019 (Reference CPP2019-09-076-PP) and from National Agency for Medical and Health products Safety (Reference: MEDAECNAT-2019-08-00004_2017-004239-35) on 18 September 2019.The results will be disseminated to patients upon individual request or through media release from scientific meetings. The results will be communicated through scientific meetings and publications.