Phyllodes tumors, borderline (BPT) and malignant (MPT), represent a rare group of fibroepithelial breast tumors. Due to their rarity, their treatment remains poorly codified. The precise incidence of these tumors remains unknown. TPMs represent half of breast sarcomas and 1 % of breast tumors. Their treatment at the localized stage is based on surgery, that can be conservative surgery or a mastectomy. The impact of oncoplastic techniques and immediate breast reconstruction is not documented. The excision margins of the BPT and MPT must be free, a wider margin can provide a benefit in local recurrence but in also overall survival in the case of TPM. The optimal width of the excision margin is not known. In the event of positive margins, a second surgery could make up the result of an insufficient first surgery. Chemotherapy does not seem to provide any benefit on recurrence-free survival, but the available data are particularly weak. The data on adjuvant radiotherapy are more important. This allows better local control in the event of breast-conserving surgery. The benefit of post-mastectomy radiotherapy is less documented but can be considered in cases of poor prognostic factors. The management of TPM at the metastatic stage is based on the use of chemotherapy (anthracyclines, Ifosfamide) and local treatment of metastases in cases of oligometastatic disease. Due to the rarity of these tumors, it is essential that their management be discussed within a network of qualified professionals (NETSARC+).

OBJECTIVE: With the promising results of immunotherapy in patients with stage III melanoma, the role of adjuvant radiotherapy after resection and complete lymph-node dissection must be reassessed. We evaluate the outcomes and safety of adjuvant radiotherapy and immunotherapy compared to immunotherapy only in patients with resected stage III melanoma.
METHODS: This retrospective and single institution study included patients treated for a stage III melanoma with complete lymph-node dissection and adjuvant immunotherapy from January 2019 to December 2022. The radiotherapy associated with immunotherapy group was defined by completion of immunotherapy and adjuvant radiotherapy in the lymph-node dissection area. The primary endpoint was disease-free survival. The secondary endpoints were locoregional progression, incidence of adverse events grade 3 or above and disease-free survival rate in patients with high risk of locoregional recurrence.
RESULTS: Thirty-three patients were included. Among them, twelve received adjuvant lymph-node field radiotherapy. The median duration of follow-up was 17months (range: 8-45months). Patients receiving radiotherapy and immunotherapy had a significantly higher disease stage and more frequent extracapsular extension. At 12months, the disease-free survival rate was 66.7% for the patients receiving immunotherapy alone (95% CI: 42.5-82.5%) and 83.3% for those receiving radiotherapy and immunotherapy (95% CI: 48.2-95.6%; P=0.131). The locoregional progression rate was 24% in patients receiving immunotherapy and 8% in patients receiving immunotherapy and radiotherapy (P=0.379). After adjuvant treatment, 6% of patients developed grade 3 or above immunotherapy-related events and none developed grade 3 or above radiation-related adverse events.
CONCLUSIONS: In patients with stage III melanoma, adjuvant lymph-node field radiotherapy combined with immunotherapy seems to be associated with longer disease-free survival, with acceptable tolerance. However, these results need to be confirmed by long-term and prospective studies.

OBJECTIVE: Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated.
METHODS: The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75Gy in 30 fractions of 2.5Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46Gy in 23 fractions with simultaneous integrated boost.
RESULTS: A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4years and 3.96years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P=0.0028 for both).
CONCLUSIONS: External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses.

OBJECTIVE: Many series have compared voice quality after radiotherapy or surgery for cT1 glottic carcinoma. Different meta-analyses identify better results for radiotherapy while others do not identify any difference, some finally find a superiority of surgery. The purpose of this study was to compare the voice quality in the long term of patients who underwent transoral surgery versus exclusive irradiation for the treatment of cT1 glottic carcinoma.
METHODS: The VOQUAL study was a pilot comparative multicenter cross-sectional study. The primary endpoint was the Voice Handicap Index comparison between two groups (radiotherapy or surgery). The voice assessment also consisted in the heteroevaluation of voice quality by the Grade, Roughness, Breathness, Asthenia, and Strain rating scale reported by Hirano.
RESULTS: The study included 41 adult patients with cT1 carcinoma of the vocal cord treated by cordectomy or exclusive radiation in two oncologic centers. The median Voice Handicap Index value was 20 [8; 32.5] in the surgery group and 10 [4; 18.5] in the radiotherapy group. There was no statistically significant difference between the median values and the various components F, P and E of the questionnaire (P=0.1585). The median value of the numeric dysphonia Grade, Roughness, Breathness, Asthenia, and Strain scale was 2 [0; 5] in the surgery group and 2 [0.25; 3.75] in the radiotherapy group. There was no statistically significant difference between these values (P=0.78).
CONCLUSIONS: Our study did not show any significant difference on the primary endpoints of Voice Handicap Index and Grade, Roughness, Breathness, Asthenia, and Strain scores.
METHODS: III.
BACKGROUND: The VOQUAL study was registered on the ClinicalTrials.gov platform under the number NCT04447456, in July 2020.

OBJECTIVE: Neurocytomas represent 0.25 to 0.5% of primary brain tumours and are mainly found in young adults. These tumours have neuronal differentiation. The cornerstone treatment is neurosurgery. The efficacy of other therapies, including radiotherapy, is still unclear. The objective of this study was to evaluate the management of central neurocytomas and the role of radiotherapy.
METHODS: All adult patients (age 18 years or older) newly diagnosed with a histologically confirmed neurocytoma between 2006 and 2015 in France were included.
RESULTS: One hundred and sixteen patients were diagnosed with a central neurocytoma during the study period. All patients underwent surgical resection, and six received adjuvant radiotherapy. Eleven patients received radiotherapy due to progression. After a median follow-up of 68.7 months, local failure occurred in 29 patients. The 5-year local control rate was 73.4%. According to univariate analysis, marker of proliferation Ki67 index greater than 2% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.40-1.57; P=0.027) and subtotal resection (HR: 8.48; CI: 8.01-8.99; P<0.001) were associated with an increase in local failure. Gross total resection was associated with a higher risk of sequelae epilepsy (HR: 3.62; CI: 3.42-3.83; P<0.01) and memory disorders (HR: 1.35; CI: 1.07-1.20; P<0.01). Ten patients (8.6%) died during the follow-up. The 10-year overall survival rate was 89.0%. No prognostic factors for overall survival were found.
CONCLUSIONS: The analysis showed that patients who underwent subtotal surgical resection, particularly when the tumour had a Ki67 index greater than 2%, had an increased risk of local recurrence. These patients could benefit from adjuvant radiotherapy.

OBJECTIVE: Radiation-induced optic neuropathy (RION) is rare but may lead to blindness. The mechanisms by which this occurs include endothelial and neuronal damage, but RION has been assessed very little in the case of extraocular tumors treated with high-energy proton therapy, the use of which is expanding worldwide. We assessed peripapillary microvascular changes by optical coherence tomography angiography (OCT-A) in patients undergoing high-energy proton therapy for para-optic intracranial or head and neck tumors.
METHODS: In this prospective institutional review board approved study, patients receiving>40Gy_RBE maximal PBT dose to their optic nerve between 2018 and 2020 underwent quantitative OCT-A analyses. ImageJ software was used to assess changes in the peripapillary superficial vascular complex (SVC) using vascular area density (VAD), vessel length density (VLD) and fractal dimension (FDsk). Uni- and multivariate analyses were performed.
RESULTS: Of 47 patients (78 eyes) with 29±6 months of follow-up (range 18-42), 29 patients (61.7%) had previously undergone surgery and 18 (32.1%) had microvascular abnormalities prior to proton therapy. Total radiotherapy dose was the most relevant factor in decreased peripapillary microvasculature. Duration of follow-up was associated with lower VAD (P=0.005) and mean retinal nerve fiber layer (RNFLm) thickness also decreased. There was no significant correlation between OCT-A changes and mean visual defect.
CONCLUSIONS: Peripapillary microvasculature changes may occur from tumor compression or surgery and proton therapy for extraocular tumors. OCT-A may provide quantitative and mechanistic insights into RION before the occurrence of clinical symptoms.

OBJECTIVE: The purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could contribute to target volume coverage and sparing of organ at risk for intensity-modulated curative radiation therapy of head and neck cancers.
METHODS: We performed a retrospective analysis on 20 patients treated for an oropharyngeal or oral cavity squamous cell carcinoma. We carried out a comparative dosimetric study of manual plans produced with Precision® software, compared with the plans proposed using the multicriteria optimization method (RayStation®). We assessed interoperator reproducibility on the first six patients, and dosimetric contribution in sparing organs at risk using the multicriteria optimization method.
RESULTS: Median age was 69 years, most lesions were oropharyngeal carcinoma (65%), and 35% lesions were stage T3. First, we obtained a high degree of similarity between the four operator measurements for each patient at the level of each organ. Intraclass correlation coefficients were greater than 0.85. Second, we observed a significant dosimetric benefit for contralateral parotid gland, homolateral and contralateral masseter muscles, homolateral and contralateral pterygoid muscles and for the larynx (P<0.05). For the contralateral parotid gland, the mean dose difference between the multicriteria optimization and manual plans was -2.0Gy (P=0.01). Regarding the larynx, the mean dose difference between the two plans was -4.6Gy (P<0.001).
CONCLUSIONS: Multicriteria optimization is a reproducible technique and faster than manual optimization. It allows dosimetric advantages on organs at risk, especially for those not usually taken into consideration in manual dosimetry. This may lead to improved quality of life.

BACKGROUND: Up to 30% patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) present with brain metastases. In the absence of oncogenic addiction, first-line immunotherapy, alone or in combination with chemotherapy, is the current standard of care. This review aims to synthesize the available data regarding the efficacy of immunotherapy in these patients, and to discuss the possibility of its being coordinated with local treatments such as radiotherapy.
BACKGROUND: NSCLC patients with brain metastases appear to have survival benefits with immunotherapy similar to those of NSCLC patients without brain metastases. However, this finding is based on mainly prospective studies having included highly selected patients with pre-treated and stable brain metastases. Several retrospective studies and two prospective single-arm studies have confirmed the intracranial efficacy of immunotherapy, either alone or in combination with chemotherapy.
CONCLUSIONS: The indications and optimal timing for cerebral radiotherapy remain subjects of debate. To date, there exists no randomized study assessing the addition of brain radiotherapy to first-line immunotherapy. That said, a recent meta-analysis showed increased intracerebral response when radiotherapy complemented immunotherapy.
CONCLUSIONS: For NSCLC patients with brain metastases, the available data suggest a clear benefit of first-line immunotherapy, whether alone or combined with chemotherapy. However, most of these data are drawn from retrospective, non-randomized studies with small sample sizes.

OBJECTIVE: Cranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory.
METHODS: From 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1year and 2years post-treatment. Neuropsychological tests were converted to Z-Score for comparability.
RESULTS: Twelve of the 19 patients included had a complete neuropsychological evaluation at 2years and were analysed. On the \"TEMPau\" test, no significant difference in autobiographical memory was found at 2years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study.
CONCLUSIONS: Radiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results.

Orbital radiotherapy for Graves\' ophthalmopathy is an example of non-oncological radiotherapy. First introduced in the 1930s, this treatment has become widely used since the 1980s with several studies showing proof of both effectiveness and safety: a decrease of soft tissue involvement in 70 to 80% of patients and an improvement of ocular mobility in 30 to 80% of patients. Nowadays, it\'s one of the second line treatment options recognized by the European Group on Graves\' orbitopathy in the management of a moderate to severe and active disease after failure of glucocorticoids. In that setting, orbital radiotherapy should be combined with glucocorticoids. To our knowledge, there are no practical recommendations on how orbital radiotherapy should be planned and conducted for Graves\' ophthalmopathy. Optimal dose is not defined however the most frequent regimen consists of 20Gy in ten fractions of 2Gy, though other options may yield better results. Lastly, the use of modern technique of radiotherapy such as intensity-modulated radiation therapy may allow a better sparing of organs at risk compared to three-dimensional radiotherapy using lateral opposing fields.