Resilience and spiritual well-being as resources for coping with radiotherapy and surviving in patients with glioblastoma.

OBJECTIVES: The primary aims of this multicenter, prospective observational study were to investigate spiritual well-being, resilience, and psychosocial distress in an Italian sample of glioblastoma patients undergoing radiochemotherapy. The secondary aim was to explore the influence of demographic, clinical, and psychological characteristics on survival. METHODS: The assessment was conducted only once, within the first week of radiochemotherapy treatment. Spiritual well-being was evaluated by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-Sp-12), and religious/spiritual beliefs and practices were evaluated by the System of Belief Inventory. Resilience was evaluated by the Connor-Davidson Resilience Scale (CD-RISC). Psychosocial distress was evaluated the by Distress Thermometer and Hospital Anxiety Depression Scale. We conducted an univariable analysis of overall survival (OS) using data from the most recent follow-up available, considering demographic and clinical variables that could influence survival. Follow-up was defined as either the time of death or the latest follow-up visit recorded. RESULTS: We recruited 104 patients, and the median follow-up time was 18.3 months. "Distressed" patients had lower scores than "not distressed" patients on the FACIT-Sp-12 and CD-RISC. While OS was not significant according to the FACIT-Sp-12 threshold, the Kaplan-Meier log-rank test was 0.05 according to the CD-RISC threshold. Among demographic variables, age showed significant associations with OS (p = 0.011). Resilience showed significant associations with OS (p = 0.025). SIGNIFICANCE OF RESULTS: Data showed that high spiritual well-being was associated with high resilience and an absence of psychosocial distress in our sample of glioblastoma patients undergoing radiochemotherapy. Patients with greater resilience survived longer than those with lesser resilience. Profiling spiritual well-being and resilience in glioblastoma patients undergoing radiochemotherapy can be seen as a resource to identify novel characteristics to improve clinical take-in-charge of glioblastoma patients.

The Italian version of the Pediatric Quality of Life Inventory™ (PEDSQL™) 3.0 healthcare satisfaction hematology/oncology module: reliability and validity in radiation oncology.

BACKGROUND: Health-related quality of life (HRQOL) measurement has become an important health care outcome even in oncological pediatric scenario. During radiation therapy care path, pediatric patients and their relatives may suffer from emotional and psychosocial distress not only related to cancer diagnosis, but also due to the procedure and the required daily routine. Despite the high prevalence of psychosocial consequences in this setting, instruments that inquire pediatric HRQOL and healthcare satisfaction have rarely been studied in Italy. Purpose of this study was to investigate reliability and linguistic validation of the PedsQL™ healthcare satisfaction Hematology/Oncology module from its original English version to Italian language. METHODS: Three phases standard procedure of cross-culture adaptation were used to create Italian version of PedsQL™ healthcare satisfaction Hematology/Oncology module. Forward translations and backward translations were performed. Finally, a pilot-testing for understandability of the 'pre-final' version was conducted with parents of children attending our Radiotherapy Center using two methodologies of Cognitive Interviewing ("Think-aloud Interviews" and "Respondent Debriefing"), in order to obtain the final Italian version of the PedsQL™ healthcare satisfaction Hematology/Oncology module. RESULTS: Twenty-five parents (2 father, 23 mothers) were recruited during their children's radiotherapy treatment and the grammatically and conceptually acceptable pre-final version of the PedsQL™ Healthcare Satisfaction Hematology/Oncology Module was administered. The questionnaire was well understood reflecting its linguistic adaptation. Compliance with questionnaire administration was optimal. All subjects stated that the questions were interesting to express their opinion, most of them reported that all the questions of each section were clearly comprehensible and easy to understand, suggesting minimal changes that were double-checked with back translation. Furthermore, six of them spontaneously asked to complete the questionnaire in order to review the assistance received during radiotherapy. CONCLUSION: Our Italian version of the PedsQL™ 3.0 Healthcare Satisfaction Hematology/Oncology Module seems to be a valid and functional instrument to indagate Healthcare Satisfaction.

The role of stereotactic radiotherapy in addition to immunotherapy in the management of melanoma brain metastases: results of a systematic review.

Aim of this study was to systematically review the literature to assess efficacy and safety of stereotactic radiotherapy (SRT) in combination with immunotherapy for the treatment of melanoma brain metastases (MBM). The literature was searched using PubMed, Scopus, and Embase. Studies comparing SRT plus immunotherapy versus SRT or immunotherapy alone were deemed eligible for inclusion. Two studies showed improved overall survival after SRT plus immunotherapy in melanoma cancer patients with brain metastases. Three studies reported data on LC and DFS showing as SRT plus immunotherapy did not improve local control and DFS rates. G3-G4 toxicity was reported in only one study (20% in the SRT plus immunotherapy group versus 23% in the immunotherapy group). Despite SRT plus concurrent immunotherapy seems associated with possible survival advantage and low ≥ G3 late toxicity rates, the quality of evidence is very low. Therefore, in patients with brain metastases from melanoma, SRT plus immunotherapy should be evaluated on an individual basis after discussion by a multidisciplinary team.

Personalised support of brain tumour patients during radiotherapy based on psychological profile and quality of life.

PURPOSE: Psychological distress in primary malignant brain tumour (PMBT) patients is associated with poorer outcomes. Radiotherapy (RT) often induces side effects that significantly influence patients' quality of life (QoL), with potential impact on survival. We evaluated distress, anxiety, depression, and QoL over time to identify patients with difficulties in these areas who required more intense psychological support. METHODS: Psychological questionnaires-Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy (FACT-G and FACT-Br)-were completed at the beginning (T0), in the middle (T1), directly after RT (T2), and 3 months after RT (T3). We personalised the psychological support provided for each patient with a minimum of three sessions ('typical' schedule) and a maximum of eight sessions ('intensive' schedule), depending on the patients' psychological profiles, clinical evaluations, and requests. Patients' survival was evaluated in the glioblastoma multiforme (GBM) patients, with an explorative intent. RESULTS: Fifty-nine consecutive PMBT patients receiving post-operative RT were included. For patients who were reported as 'not distressed' at T0, no statistically significant changes were noted. In contrast, patients who were 'distressed' at T0 showed statistically significant improvements in DT, HADS, FACT-G, and FACT-Br scores over time. 'Not distressed' patients required less psychological sessions over the study duration than 'distressed' patients. Interestingly, 'not distressed' GBM patients survived longer than 'distressed' GBM patients. CONCLUSIONS: Increased psychological support improved distress, mood, and QoL for patients identified as 'distressed', whereas psychological well-being was maintained with typical psychological support in patients who were identified as being 'not distressed'. These results encourage a standardisation of psychological support for all RT patients.

Combining Magnetic Resonance Imaging with Systemic Monocyte Evaluation for the Implementation of GBM Management.

Magnetic resonance imaging (MRI) is the gold standard for glioblastoma (GBM) patient evaluation. Additional non-invasive diagnostic modalities are needed. GBM is heavily infiltrated with tumor-associated macrophages (TAMs) that can be found in peripheral blood. FKBP51s supports alternative-macrophage polarization. Herein, we assessed FKBP51s expression in circulating monocytes from 14 GBM patients. The M2 monocyte phenotype was investigated by qPCR and flow cytometry using antibodies against PD-L1, CD163, FKBP51s, and CD14. MRI assessed morphologic features of the tumors that were aligned to flow cytometry data. PD-L1 expression on circulating monocytes correlated with MRI tumor necrosis score. A wider expansion in circulating CD163/monocytes was measured. These monocytes resulted in a dramatic decrease in patients with an MRI diagnosis of complete but not partial surgical removal of the tumor. Importantly, in patients with residual tumor, most of the peripheral monocytes that in the preoperative stage were CD163/FKBP51s- had turned into CD163/FKBP51s+. After Stupp therapy, CD163/FKBP51s+ monocytes were almost absent in a case of pseudoprogression, while two patients with stable or true disease progression showed sustained levels in such circulating monocytes. Our work provides preliminary but meaningful and novel results that deserve to be confirmed in a larger patient cohort, in support of potential usefulness in GBM monitoring of CD163/FKBP51s/CD14 immunophenotype in adjunct to MRI.

Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study of a response-adapted strategy.

This study aimed to define the maximum tolerated dose (MTD) of temozolomide (TMZ) concurrent with radiotherapy (RT) after high-dose methotrexate (HD-MTX) for newly diagnosed primary central nervous system lymphoma (PCNSL). Adult patients with PCNSL were treated according to a response-adapted strategy. HD-MTX (3.5 g/m2) was followed by concomitant RT and escalating TMZ (50-60-75 mg/m2/day, 5 days/week). The total radiation dose was modulated according to the patient's response to HD-MTX. All patients received 30 Gy to the whole brain plus leptomeninges to C2, including the third posterior of the orbital cavity (clinical target volume 2; CTV2), plus 6, 10, or 16 Gy to the primary site, including the residual mass (CTV1), if a complete response (CR), partial response (PR)/stable disease (SD), or progressive disease (PD) was observed, respectively. Acute toxicities were graded according to the RTOG-EORTC criteria. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity or grade 3-4 hepatic toxicity, although 75 mg/m2/day was the maximum dose regardless of DLT. Neurocognitive function was evaluated using the Mini-Mental State Examination. Three patients were enrolled at each TMZ dose level (total = 9 patients). Twelve lesions were treated. Six patients received 2 cycles of HD-MTX, while 3 received only 1 cycle because of hepatic or renal toxicity. All patients completed chemoradiotherapy without interruptions. No DLT events were recorded. TMZ appears to be tolerable at a dose of 75 mg/m2/day when administered concomitantly with radiotherapy and after HD-MTX.

A new frontier of image guidance: Organs at risk avoidance with MRI-guided respiratory-gated intensity modulated radiotherapy: Technical note and report of a case.

The case of a 50-year-old man affected by a rhabdomiosarcoma metastatic lesion in the left flank Is reported. The patient was addressed to 50.4 Gy radiotherapy with concomitant chemotherapy in order to locally control the lesion. A Tri-60-Co magnetic resonance hybrid radiotherapy unit was used for treatment delivery and a respiratory gating protocol was applied for the different breathing phases (Free Breathing, Deep Inspiration Breath Hold and Final Expiration Breath Hold). Three intensity modulated radiation therapy (IMRT) plans were calculated and Final Expiration Breath Hold plan was finally selected due to the absence of PTV coverage differences and better organs at risk sparing (i.e. kidneys). This case report suggests that organs at risk avoidance with MRI-guided respiratory-gated Radiotherapy is feasible and particularly advantageous whenever sparing the organs at risk is of utmost dosimetric or clinical importance.

Correction to: Multimodal treatment of pediatric patients with Askin's tumors: our experience.

[This corrects the article DOI: 10.1186/S12957-018-1434-2.].

Multimodal treatment of pediatric patients with Askin's tumors: our experience.

BACKGROUND: We report our experience and outcomes about the management of Askin's tumors [AT], which are rare primitive neuroectodermal tumors (PNETs) that develop within the soft tissue of the thoracopulmonary region, typically in children and adolescents. METHODS: We retrospectively analyzed the charts of 9 patients affected by AT (aged 6-15 years), treated at the Paediatric Oncology Unit of Gemelli University Hospital in Rome between January 2001 and December 2016. RESULTS: All nine patients underwent to biopsy followed by neoadjuvant chemotherapy. At the end of the neoadjuvant chemotherapy, they underwent to surgical removal of the residual tumor. Five patients with positive tumor margins and/or necrosis< 90% received local radiotherapy. Two patients with metastasis received an intensified treatment, with the addition of high dose adjuvant chemotherapy followed by peripheral blood stem cells rescue. No statistically significant correlation was found between outcome and gender; the presence of any metastasis and the radiotherapy. The overall survival was 65.14 months (95% confidence interval [95%CI], 45.81-84.48), and the 5 years survival was 60%, at a median follow-up of 53.1 months. CONCLUSION: Our study confirms that a multimodal treatment with surgery, chemotherapy, and radiotherapy may increase the survival in AT pediatric patients.

Low-dose radiotherapy and concurrent FOLFIRI-bevacizumab: a Phase II study.

AIMS: Low-dose radiation therapy (LDRT) can increase biological efficacy of chemotherapy. This Phase II trial evaluates LDRT plus FOLFIRI-bevacizumab (FOLFIRI-B) in metastatic colorectal cancer. PRIMARY OBJECTIVE: raising the clinical complete response rate from 5 to 25%. SECONDARY OBJECTIVES: toxicity, progression-free survival. Patients underwent 12 FOLFIRI-B cycles plus two daily LDRT fractions (20 cGy/6 h interval) on each cycle. Statistical analysis was planned on 18 patients. RESULTS: Results on 18 patients are reported. Specifically considering irradiated sites: 15/18 patients had a partial (11/18) or complete (4/18) response. Among 11 partial responders, three became a pathological CR after surgery. Grade 3-4 toxicity was recorded in two patients (11.1%). At median follow-up of 30 months (range: 8-50), 7/18 patients progressed in irradiated sites. CONCLUSION: Seven out of 18 patients (38.9%) had clinical or pathological CR in lesions treated with LDRT. Further studies on this newer treatment modality seem justified.

Can automation in radiotherapy reduce costs?

BACKGROUND: Computerized automation is likely to play an increasingly important role in radiotherapy. The objective of this study was to report the results of the first part of a program to implement a model for economical evaluation based on micro-costing method. To test the efficacy of the model, the financial impact of the introduction of an automation tool was estimated. A single- and multi-center validation of the model by a prospective collection of data is planned as the second step of the program. MATERIAL AND METHODS: The model was implemented by using an interactive spreadsheet (Microsoft Excel, 2010). The variables to be included were identified across three components: productivity, staff, and equipment. To calculate staff requirements, the workflow of Gemelli ART center was mapped out and relevant workload measures were defined. Profit and loss, productivity and staffing were identified as significant outcomes. Results were presented in terms of earnings before interest and taxes (EBIT). Three different scenarios were hypothesized: baseline situation at Gemelli ART (scenario 1); reduction by 2 minutes of the average duration of treatment fractions (scenario 2); and increased incidence of advanced treatment modalities (scenario 3). By using the model, predicted EBIT values for each scenario were calculated across a period of eight years (from 2015 to 2022). RESULTS: For both scenarios 2 and 3 costs are expected to slightly increase as compared to baseline situation that is particularly due to a little increase in clinical personnel costs. However, in both cases EBIT values are more favorable than baseline situation (EBIT values: scenario 1, 27%, scenario 2, 30%, scenario 3, 28% of revenues). CONCLUSION: A model based on a micro-costing method was able to estimate the financial consequences of the introduction of an automation tool in our radiotherapy department. A prospective collection of data at Gemelli ART and in a consortium of centers is currently under way to prospectively validate the model.

Occurrence and predictors of the fatigue in high-grade glioma patients.

A better knowledge of the fatigue could be of the greatest importance for the high-grade glioma (HGG) patients, who are a unique and vulnerable population. The aim of this study was to evaluate the occurrence and the predictors of the fatigue in HGG patients, using a specific fatigue scale. The study was designed as a cross-sectional study. The study population included sixty-seven consecutive outpatients with HGG. We used these measures: Brief Fatigue Inventory, Karnofsky Performance Scale, Functional Independence Measure, Brief Psychiatric Rating Scale and Psychological Distress Inventory and SF-36, EORTC QLQ-30 and EORTC QLQ-BN20 for quality of life (QoL). Sixteen out of sixty-seven (23.9 %) patients were affected by Anaplastic Astrocytoma and 51/67 (76.1 %) by Glioblastoma Multiforme. About one-third (36.2 %) of patients had a clinically relevant fatigue (Brief Fatigue Inventory ≥3). In regression analysis, physical and mental aspects of QoL were statistically significant related with fatigue (p < 0.01 and p < 0.02, respectively). Our data underlined the relevant occurrence of fatigue in HGG patients and support the development of further studies exploring a tailored rehabilitation program.

Adaptive optimization by 6 DOF robotic couch in prostate volumetric IMRT treatment: rototranslational shift and dosimetric consequences.

The purpose of this study was to investigate the magnitude and dosimetric relevance of translational and rotational shifts on IGRT prostate volumetric-modulated arc therapy (VMAT) using Protura six degrees of freedom (DOF) Robotic Patient Positioning System. Patients with cT3aN0M0 prostate cancer, treated with VMAT simultaneous integrated boost (VMAT-SIB), were enrolled. PTV2 was obtained adding 0.7 cm margin to seminal vesicles base (CTV2), while PTV1 adding to prostate (CTV1) 0.7 cm margin in all directions, except 1.2 cm, as caudal margin. A daily CBCT was acquired before dose delivery. The translational and rotational displacements were corrected through Protura Robotic Couch, collected and applied to the simulation CT to obtain a translated CT (tCT) and a rototranslated CT (rtCT) on which we recalculated the initial treatment plan (TP). We analyzed the correlation between dosimetric coverage, organs at risk (OAR) sparing, and translational or rotational displacements. The dosimetric impact of a rototranslational correction was calculated. From October 2012 to September 2013, a total of 263 CBCT scans from 12 patients were collected. Translational shifts were < 5 mm in 81% of patients and the rotational shifts were < 2° in 93% of patient scans. The dosimetric analysis was performed on 172 CBCT scans and calculating 344 VMAT-TP. Two significant linear correlations were observed between yaw and the V20 femoral heads and between pitch rotation and V50 rectum (p < 0.001); rototranslational correction seems to impact more on PTV2 than on PTV1, especially when margins are reduced. Rotational errors are of dosimetric significance in sparing OAR and in target coverage. This is relevant for femoral heads and rectum because of major distance from isocenter, and for seminal vesicles because of irregular shape. No correlation was observed between translational and rotational errors. A study considering the intrafractional error and the deformable registration is ongoing.

Long-term analysis of gemcitabine-based chemoradiation after surgical resection for pancreatic adenocarcinoma.

PURPOSE: To evaluate the efficacy in terms of local control (LC) of 24 h infusion of gemcitabine plus radiotherapy after surgery for pancreatic cancer. METHODS: Weekly gemcitabine (100 mg/m(2)) was provided as a 24-hour infusion during the course of radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). Patients subsequently received five cycles of gemcitabine monochemotherapy (1,000 mg/m(2) 1, 8, q21). The primary end point of the study was to achieve a 2-year LC rate of ≥80 % with type I and II errors of 5 and 20 %. The study was designed to accrue a maximum sample size of 35 patients. Secondary end points were toxicity evaluation, metastasis-free survival (MFS), and overall survival (OS). RESULTS: Data of 35 patients were available. Most of the patients (n = 27; 77.1 %) had duodeno-cephalo-pancreatectomy, 5 (14.3 %) distal pancreatectomy, and 3 (8.6 %) total pancreatectomy. The pathological stages were T1-T2 (n = 7; 20.0 %), T3-T4 (n = 28; 80.0 %), N0 (n = 17; 48.6 %), and N1 (n = 18; 51.4 %). Thirty patients (85.7 %) completed chemoradiation. Twenty-three patients (65.7 %) received further sequential chemotherapy. Acute toxicity was acceptable. No late toxicity occurred. The median follow-up period was 64 (range 24-118) months, and 2-year crude rate of LC was 83 (median not reached). Median MFS and OS were 26.5 and 22.5 months, respectively. CONCLUSIONS: The rate of LC met the main goal of the study. The regimen resulted in a high LC rate but failed to show a benefit in terms of OS or MFS, thus suggesting the need for a more intensified multimodal approach.

Automatic delineation for replanning in nasopharynx radiotherapy: what is the agreement among experts to be considered as benchmark?

BACKGROUND AND PURPOSE: Anatomic changes during head and neck radiotherapy require replanning. The primary aim of this study is the definition of the agreement among experts in the head and neck automatic delineation frame to use as benchmark. The secondary goal is to assess the reliability of automatic delineation for nasopharynx radiotherapy and time saving. MATERIAL AND METHODS: A computed tomography (CT) scan was acquired in 10 nasopharynx patients along intensity-modulated radiotherapy (IMRT) treatment for replanning. Deformable registration with replanning autocontouring of the structures was performed using VelocityAI 2.3© software defining Structure Set A. The optimization of these contours was obtained through revision by a skilled operator, drawing Structure Set B. An ex novo Structure Set C was segmented on the replanning CT-scan by an expert delineation team. The mean Dice's Similarity Index (mDSI) was calculated between Structure Set A and B, A and C, and between B and C for each volume. All segmentation times for organs at risk (OARs) and clinical target volume (CTV) were recorded and compared. RESULTS: We validated the replanning autocontoured Structure Sets for 10 patients. For volumetric analysis we observed mDSI values of 0.87 for the OARs, 0.70 for nodes, 0.90 for CTV in the Structure Set A-B comparison and respectively of 0.74, 0.63 and 0.78 for the Structure Set A-C one, and 0.78, 0.78 and 0.85 for Structure Set B-C, which represents the existing expert based benchmark. We calculated a mean saved time in Structure Set B of 30 minutes. CONCLUSIONS: Autocontouring procedures offer considerable segmentation time saving with acceptable reliability of the contours, even if an independent check procedure for their optimization is still required to increase their adherence to referential benchmark gold standard among experts, which stands at a 0.80 DSI value.

Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1).

BACKGROUND: We performed a dose-escalation trial to determine the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) with standard concurrent and sequential-dose temozolomide (TMZ) in patients with glioblastoma multiforme. METHODS: Histologically proven glioblastoma patients underwent IMRT dose escalation. IMRT was delivered over 5 weeks with the simultaneous integrated boost (SIB) technique to the two planning target volumes (PTVs) defined by adding 5-mm margin to the respective clinical target volumes (CTVs). CTV1 was the tumor bed plus the enhancing lesion with 10-mm margin; CTV2 was the area of perifocal edema with 20-mm margin. Only the PTV1 dose was escalated (planned dose escalation: 60, 62.5, 65, 67.5, 70 Gy) while the PTV2 dose remained the same (45 Gy). RESULTS: Forty consecutive glioblastoma patients were treated. While no dose-limiting toxicity (DLT) was recorded during the dose escalation up to 67.5/2.7 Gy, two out of the first six consecutively enrolled patients on the highest dose level (70/2.8 Gy) experienced a DLT, and therefore a cohort expansion was required. 3/14 patients experienced a DLT on the highest planned dose level, and therefore the MTD was not exceeded. After a median follow-up time of 25 months no grade >2 late neurological toxicity was recorded. CONCLUSIONS: By using a SIB IMRT technique, a radiation dose of 70 Gy in 25 fractions (biological effective dose--BED--of 92.8 Gy) can be delivered with concurrent and sequential standard dose TMZ, without unacceptable acute toxicity in patients with glioblastoma.

KIT 1 (Keep in Touch) Project-Televisits for Cancer Patients during Italian Lockdown for COVID-19 Pandemic: The Real-World Experience of Establishing a Telemedicine System.

To evaluate the adoption of an integrated eHealth platform for televisit/monitoring/consultation during the COVID-19 pandemic. METHODS: During the lockdown imposed by the Italian government during the COVID19 pandemic spread, a dedicated multi-professional working group was set up in the Radiation Oncology Department with the primary aim of reducing patients' exposure to COVID-19 by adopting de-centralized/remote consultation methodologies. Each patient's clinical history was screened before the visit to assess if a traditional clinical visit would be recommended or if a remote evaluation was to be preferred. Real world data (RWD) in the form of patient-reported outcomes (PROMs) and patient reported experiences (PREMs) were collected from patients who underwent televisit/teleconsultation through the eHealth platform. RESULTS: During the lockdown period (from 8 March to 4 May 2020) a total of 1956 visits were managed. A total of 983 (50.26%) of these visits were performed via email (to apply for and to upload of documents) and phone call management; 31 visits (1.58%) were performed using the eHealth system. Substantially, all patients found the eHealth platform useful and user-friendly, consistently indicating that this type of service would also be useful after the pandemic. CONCLUSIONS: The rapid implementation of an eHealth system was feasible and well-accepted by the patients during the pandemic. However, we believe that further evidence is to be generated to further support large-scale adoption.

Dabrafenib-Trametinib and Radiotherapy for Oligoprogressive BRAF Mutant Advanced Melanoma.

The clinical management of metastatic melanoma has been changed by BRAF (BRAFi) and MEK inhibitors (MEKi), which represent a standard treatment for BRAF-mutant melanoma. In oligoprogressive melanoma patients with BRAF mutations, target therapy can be combined with loco-regional radiotherapy (RT). However, the association of BRAF/MEK inhibitors and RT needs to be carefully monitored for potential increased toxicity. Despite the availability of some reports regarding the tolerability of RT + target therapy, data on simultaneous RT and BRAFi/MEKi are limited and mostly focused on the BRAFi vemurafenib. Here, we report a series of metastatic melanoma patients who received fractioned RT regimens for oligoprogressive disease in combination with the BRAFi dabrafenib and the MEKi trametinib, which have continued beyond progression. None of the cases developed relevant adverse events while receiving RT or interrupted dabrafenib and trametinib administration. These cases suggest that a long period of dabrafenib/trametinib interruption during radiotherapy for oligoprogressive disease can be avoided. Prospective trials are warranted to assess the efficacy and safety of the contemporary administration of BRAF/MEK inhibitors and radiotherapy for oligoprogressive disease.

May we routinely spare hippocampal region in primary central nervous system lymphoma during whole brain radiotherapy?

PURPOSE: One of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus. METHODS AND MATERIALS: Pre-treatment MR images from patients who underwent WBRT between 2010 and January 2020-and post-radiotherapy images in cases of relapse-were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences. RESULTS: We analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it. CONCLUSION: These data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus.

Intracranial melanocytic meningeal tumours and melanosis oculi: case report and literature review.

BACKGROUND: Melanocytic meningeal tumours are rare extra-axial neoplasms of the nervous system, with only three reported cases in the cavernous sinus. Herein we describe for the first time the association of ocular melanosis and multiple intracranial melanocytic meningeal tumours, with the presenting lesion being in the cavernous sinus. The importance of this association is discussed together with the diagnostic and therapeutic challenges of the case. CASE PRESENTATION: A 20-year-old man presented with a left sixth cranial nerve deficit; general examination documented only congenital melanosis of the homolateral eye. MRI examination showed a space occupying lesion in the left cavernous sinus, which was followed conservatively for 2 years, until a new space occupying lesion was evident at the level of the right frontal convexity: both lesions presented with neuroradiological characteristics suggestive of melanin content.The frontal convexity lesion was removed: intraoperatively the dura was markedly and diffusely melanotic. Histological examination documented a melanocytic meningeal tumour, with a proliferative index of 3 %. The patient underwent 3D-Conformal Radiation Therapy on the lesion of the cavernous sinus (total dose 5040 cGy), with initial tumour reduction. Three years later, due to a symptomatic growth, he underwent partial removal of the lesion in the cavernous sinus. Histological examination was unchanged. He then received adjuvant Temozolomide with Low Dose Fractionated Radiation Therapy (LD-FRT). Due to further disease progression cisplatin plus fotemustine were administered, concomitant with LD-FRT: after two cycles MRI documented significant disease regression. After a period of apparent disease control, the patient presented with persistent cough and evidence of multiple thoracic metastases, which lead to his death, seven years after presentation. CONCLUSIONS: Intracranial melanocytic meningeal tumours are challenging lesions, both from a diagnostic and therapeutic point of view; though rare, the possible association with ocular melanosis should be recognized and might facilitate an early diagnosis. Surgery remains the best possible option when feasible. In the event of partial resection, this "benign" disease might be clinically aggressive.