Anna Viola

We report an unusual case of brain radionecrosis following fractionated stereotactic radiotherapy (FSRT) delivered to a calvarial metastasis in a patient with metastatic luminal A breast cancer. A 40-year-old woman developed three subcentimetric brain lesions during follow-up, initially interpreted as new metastases and treated with FSRT. Subsequent radiological progression and advanced imaging suggested radionecrosis, which was confirmed histologically after surgical resection. Retrospective dosimetric analysis revealed that all lesions arose within the high-dose isodose region of the previously irradiated skull metastasis, despite compliance with established brain dose constraints. This case highlights a previously unreported risk of brain radionecrosis after stereotactic irradiation of skull bone metastases and underscores the need for caution in treatment planning and imaging interpretation.

Background: Radiation dermatitis (RD) is the most frequent side effect in patients undergoing adjuvant radiotherapy (RT) for breast cancer. Despite the skin-sparing benefits of new RT techniques, most patients develop RD. There is currently no standard treatment to prevent and soothe RD, which is generally managed with emollients, moisturizers, or corticosteroids. We conducted a prospective observational study to evaluate the rate and grade of RD with the application of a cleansing mousse and a non-steroidal emulsion during the adjuvant RT program in patients with breast cancer submitted to surgery. Materials and Methods: A cleansing mousse containing vegetable glycerin (12%), phytoextract of chamomile (0.5%), yarrow phytoextract (0.5%), sweet almond (0.1%), Oenothera oil (0.1%), and rice protein hydrolyzate (0.1%), and an emulsion containing micronized zinc oxide (3.7%), rapeseed phytosterols (1.7%), aloe (0.5%), 18-beta glycyrrhetinic acid (0.5%), alpha bisabolol (0.5%), and zanthalene (0.5%) were offered to breast cancer patients undergoing adjuvant RT to prevent the onset of RD and mitigate its severity. These specific ingredients were selected for their well-known anti-inflammatory, antioxidant, and moisturizing properties. Skin toxicities were recorded photographically and graded according to the RTOG scoring system. Results: From March 2023 to July 2023, a total of 24 patients with a median age of 59 years (range 42–75) were enrolled. Halfway through the RT treatment, 20 patients (83.3%) had G0 skin toxicity, three (12.5%) G1, one (4.2%) G2. None showed G3–G4 toxicity. At the end of RT, seven patients (29.2%) exhibited G0 skin toxicity, 14 (58.3%) G1, two (8.3%) G2, one (4.2%) G3. No patient developed G4 toxicity. Fifteen days after the end of RT, 13 patients (54.2%) had G0 skin toxicity, 10 (41.1%) G1, one (4.2%) G2, with none showing G3–G4 toxicity. Conclusions: Our data suggest that the tested topicals might be an effective option for preventing and alleviating RD. Further prospective randomized studies are needed to confirm our findings.

Purpose: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab. Methods: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively. Results: Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy. Conclusions: Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness.

Background and Objectives: Palliative care is an interdisciplinary medical specialty focused on improving the quality of life of critically ill patients, including those with frailty, during their illness. Materials and Methods: We conducted an extensive literature review on Pubmed focusing on palliative care in neuro-oncology patients admitted to intensive care units (ICUs). Results: We identified 967 articles and, after excluding 952 articles in accordance with the PRISMA flow chart, we included a total of 15 articles in the final selection. The potential role of palliative care in neuro-oncology appears necessary to ensure comprehensive end-of-life patient care. However, this seems underestimated and poorly applied, especially in the context of intensive care units. Medical personnel also face ethical dilemmas, considering not only the pathology but also the socio-spiritual context of the patient. In addition, caregivers’ understanding of prognosis and realistic goals is critical for optimal end-of-life management. Conclusions: The provision of palliative care to neuro-oncological patients admitted to ICU is a complex challenge supported by fragmented evidence. Additional research on palliative care and communication about end-of-life care in the neuro-oncology and neuro-ICU setting is needed.

Background: Infratemporal fossa (ITF) tumors represent various pathologies and are seldom described in the literature, reflecting their rarity. Here we review the literature on tumors invading ITF and describe patient characteristics, treatment strategies, and clinical outcomes. Methods: Relevant articles were retrieved from PubMed, Scopus, and Cochrane. A systematic review and meta-analysis were conducted on the clinical presentation, treatment protocols, and clinical outcomes. Result: A total of 27 articles containing 106 patients with ITF tumors (median tumor size: 24.3 cm³ [interquartile range, 15.2–42 cm³]) were included (median age: 46 years [interquartile range, 32–55 years]; 59.4% were males]). Of the confirmed tumor pathology data, schwannomas (n = 24; 26.1%) and meningiomas (n = 13; 14.1%) were the most common tumors. Facial hypoesthesia (n = 22; 18.5%), auricular/preauricular pain (n = 20; 16.8%), and headaches (n = 11; 9.2%) were the most common presenting symptoms. Of patients who had surgical resection (n = 97; 95.1%), 70 (73.7%) had transcranial surgery (TCS) and 25 (26.3%) had endoscopic endonasal surgery (EES). Among available details on the extent of resection (n = 84), gross-total resection (GTR) was achieved in 62 (73.8%), and 5 (6.0%) had biopsy only. Thirty-five (33.0%) patients had postoperative complications. Among cases with available data on reconstruction techniques (n = 8), four (50%) had adipofascial antero-lateral thigh flap, three (37.5%) had latissimus dorsi free flap, and one (12.5%) had antero-lateral thigh flap. Fourteen (13.2%) patients had adjuvant chemotherapy, and sixteen (15.1%) had adjuvant radiotherapy. During a median follow-up time of 28 months (IQR, 12.25–45.75 months), 15 (14.2%) patients had recurrences, and 18 (17.0%) patients died. The median overall survival (OS) time was 36 months (95% confidence interval: 29–41 months), and the 5-year progression-free survival (PFS) rate was 61%. Conclusion: Various tumor types with different biological characteristics invade the ITF. The present study describes patient demographics, clinical presentation, management, and outcomes. Depending on the tumor type and patient condition, patient-tailored management is recommended to optimize treatment outcomes.

Microvascular Doppler (MicroV) is a new-generation Doppler technique developed by Esaote (Esaote s.p.a., Genova, Italy), which is able to visualize small and low-flow vessels through a suppression of interfering signals. MicroV uses advanced filters that are able to differentiate tissue artifacts from low-speed blood flows; by exploiting the space–time coherence information, these filters can selectively suppress tissue components, preserving the signal coming from the microvascular flow. This technique is clinically applied to the study of the vascularization of parenchymatous lesions, often with better diagnostic accuracy than color/power Doppler techniques. The aim of this paper is to develop a reproducible protocol for the recording and collection of MicroV intraoperative ultrasound images by the use of a capable intraoperative ultrasound machine and post-processing aimed at evaluation of brain-tumor microvascularization through the analysis of radiomic features. The proposed protocol has been internally validated on eight patients and will be firstly applied to patients affected by WHO grade IV astrocytoma (glioblastoma—GBM) candidates for craniotomy and lesion removal. In a further stage, it will be generally applied to patients with primary or metastatic brain tumors. IOUS is performed before durotomy. Tumor microvascularization is evaluated using the MicroV Doppler technique and IOUS images are recorded, stored, and post-processed. IOUS images are remotely stored on the BraTIoUS database, which will promote international cooperation and multicentric analysis. Processed images and texture radiomic features are analyzed post-operatively using ImageJ, a free scientific image-analysis software based on the Sun-Java platform. Post-processing protocol is further described in-depth. The study of tumor microvascularization through advanced IOUS techniques such as MicroV could represent, in the future, a non-invasive and real-time method for intraoperative predictive evaluation of the tumor features. This evaluation could finally result in a deeper knowledge of brain-tumor behavior and in the on-going adaptation of the surgery with the improvement of surgical outcomes.

Several recent studies are providing increasing insights into reliable markers to improve the diagnostic and prognostic assessment of meningioma patients. The evidence of brain invasion (BI) signs and its associated variables has been focused on, and currently, scientific research is investing in the study of key aspects, different methods, and approaches to recognize and evaluate BI. This paradigm shift may have significant repercussions for the diagnostic, prognostic, and therapeutic approach to higher-grade meningioma, as long as the evidence of BI may influence patients’ prognosis and inclusion in clinical trials and indirectly impact adjuvant therapy. We intended to review the current knowledge about the impact of BI in meningioma in the most updated literature and explore the most recent implications on both clinical practice and trials and future directions. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a complete overview of characteristics, preoperative applications, and potential implications of BI in meningiomas. Nineteen articles were included in the present paper and analyzed according to specific research areas. The detection of brain invasion could represent a crucial factor in meningioma patients’ management, and research is flourishing and promising.

Purpose: To evaluate feasibility, toxicities, and clinical response in Stage IV patients treated with palliative “metabolism-guided” lattice technique. Patients and Methods: From June 2020 to December 2021, 30 consecutive clinical stage IV patients with 31 bulky lesions were included in this study. All patients received palliative irradiation consisting of a spatially fractionated high radiation dose delivered in spherical deposits (vertices, Vs) within the bulky disease. The Vs were placed at the edges of tumor areas with different metabolisms at the PET exam following a non-geometric arrangement. Precisely, the Vs overlapped the interfaces between the tumor areas of higher ¹⁸F-FDG uptake (>75% SUV max) and areas with lower ¹⁸F-FDG uptake. A median dose of 15 Gy/1 fraction (range 10–27 Gy in 1/3 fractions) was delivered to the Vs. Within 7 days after the Vs boost, all the gross tumor volume (GTV) was homogeneously treated with hypo-fractionated radiation therapy (RT). Results: The rate of symptomatic response was 100%, and it was observed immediately after lattice RT delivery in 3/30 patients, while 27/30 patients had a symptomatic response within 8 days from the end of GTV irradiation. Radiation-related acute grade ≥1 toxicities were observed in 6/30 (20%) patients. The rate of overall clinical response was 89%, including 23% of complete remission. The 1-year overall survival rate was 86.4%. Conclusions: “Metabolism-guided” lattice radiotherapy is feasible and well-tolerated, being able to yield very impressive results both in terms of symptom relief and overall clinical response rate in stage IV bulky disease patients. These preliminary results seem to indicate that this kind of therapy could emerge as the best therapeutic option for this patient setting.

Radiotherapy represents an essential part of the therapeutic algorithm for breast cancer patients after conservative surgery. The treatment of left-sided tumors has been associated with a non-negligible risk of developing late-onset cardiovascular disease. The cardiac risk perception has especially increased over the last years due to the prolongation of patients’ survival owing to the advent of new drugs and an ever earlier cancer detection through screening programs. Improvements in radiation delivery techniques could reduce the treatment-related heart toxicity. The deep-inspiration-breath-hold (DIBH) irradiation is one of the most advanced treatment approaches, which requires specific technical equipment and uses inspiration to displace the heart from the tangential radiation fields. However, not all patients benefit from its use. Moreover, DIBH irradiation needs patient compliance and accurate training. Therefore, such a technique may be unjustifiably cumbersome and time-consuming as well as unnecessarily expensive from a mere healthcare cost point of view. Hence the need to early select only the true beneficiaries while tailoring more effective heart-sparing techniques for the others and streamlining the workflow, especially in high-volume radiation oncology departments. In this literature overview, we collected some possible predictors of cardiac dose sparing in DIBH irradiation for left breast treatment in an effort to provide an easy-to-consult summary of simple instruments to insiders for identifying patients actually benefitting from this technique. We critically reviewed the reliability and weaknesses of each retrieved finding, aiming to inspire new insights and discussions on this much-debated topic.

Radiation therapy (RT) is an effective therapeutic option for small localized cutaneous squamous cell carcinoma (cSCC) among patients who are not eligible for or refuse surgery. RT also has a defined role as an adjuvant treatment in cases of adverse features that predispose to tumor recurrence after local excision. Since the development of cSCC is often a late consequence of chronic sun exposure, its occurrence is more common among elderly patients whose comorbidities may contraindicate surgical procedures. These could be impeded not only by frail medical conditions but also by technical issues. Indeed, an aggressive locoregional behavior of cSCC may culminate in unresectability due to widespread invasion of neighboring tissues. Moreover, cSCC could develop distant metastases. Both locally advanced and metastatic cSCCs carry a poor prognosis. In these scenarios, recent discoveries of tumor molecular targets are promoting the use of promising systemic therapies, especially immunotherapy, over RT. However, the results from using immunotherapy and, even more so, of chemotherapy are still not optimal. By contrast, advances in radiation delivery equipment can safely treat even large and complex-shaped cSCC targets in challenging body sites. In addition, RT could also have a role in metastatic cSCC settings by enhancing the effectiveness of concomitant immunotherapy. The aim of this review is to summarize and comment on the body of literature about the use of radiotherapy for operable and inoperable locally advanced cSCCs and for metastatic ones in an attempt to define its current and future role.