Search

IntroductionWhile radiotherapy has long been recognized for its ability to directly ablate cancer cells through necrosis or apoptosis, radiotherapy-induced abscopal effect suggests that its impact extends beyond local tumor destruction thanks to immune response. Cellular proliferation and necrosis have been extensively studied using mathematical models that simulate tumor growth, such as Gompertz law, and the radiation effects, such as the linear-quadratic model. However, the effectiveness of radiotherapy-induced immune responses may vary among patients due to individual differences in radiation sensitivity and other factors.MethodsWe present a novel macroscopic approach designed to quantitatively analyze the intricate dynamics governing the interactions among the immune system, radiotherapy, and tumor progression. Building upon previous research demonstrating the synergistic effects of radiotherapy and immunotherapy in cancer treatment, we provide a comprehensive mathematical framework for understanding the underlying mechanisms driving these interactions.ResultsOur method leverages macroscopic observations and mathematical modeling to capture the overarching dynamics of this interplay, offering valuable insights for optimizing cancer treatment strategies. One shows that Gompertz law can describe therapy effects with two effective parameters. This result permits quantitative data analyses, which give useful indications for the disease progression and clinical decisions.DiscussionThrough validation against diverse data sets from the literature, we demonstrate the reliability and versatility of our approach in predicting the time evolution of the disease and assessing the potential efficacy of radiotherapy-immunotherapy combinations. This further supports the promising potential of the abscopal effect, suggesting that in select cases, depending on tumor size, it may confer full efficacy to radiotherapy.

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.

The field of precision radiation therapy has seen remarkable advancements in both experimental and computational methods. Recent literature has introduced various approaches such as Spatially Fractionated Radiation Therapy (SFRT). This unconventional treatment, demanding high-precision radiotherapy, has shown promising clinical outcomes. A comprehensive computational scheme for SFRT, extrapolated from a case report, is proposed. This framework exhibits exceptional flexibility, accommodating diverse initial conditions (shape, inhomogeneity, etc.) and enabling specific choices for sub-volume selection with administrated higher radiation doses. The approach integrates the standard linear quadratic model and, significantly, considers the activation of the immune system due to radiotherapy. This activation enhances the immune response in comparison to the untreated case. We delve into the distinct roles of the native immune system, immune activation by radiation, and post-radiotherapy immunotherapy, discussing their implications for either complete recovery or disease regrowth.

Key Clinical Message Ependymomas are primary brain tumors that predominantly affect individuals between 0 and 4 years of age. Although ependymomas have a propensity for recurrence and the potential to spread within the central nervous system through cerebrospinal fluid (resulting in drop metastases), reports of extra‐neural metastatic localizations are exceedingly rare in the existing literature. This case report presents a unique and rare instance of recurrent intracranial anaplastic ependymoma with a late‐onset giant scalp metastasis. Abstract A 55‐year‐old male patient with a medical history of partial resection of an atypical supratentorial left temporal ependymoma presented with a recurrent anaplastic ependymoma, which had been managed with surgery and radiotherapy. After a 4‐year follow‐up, the patient developed a subcutaneous mass in the left parietal region of the scalp. A multidisciplinary team of neurosurgeons and plastic surgeons performed a surgical procedure, which included en bloc removal of the scalp lesion, resection of 1 cm of unaffected skin, and craniotomy to address an osteolytic area in the parietal skull bone. Skin autografts were used for reconstruction. Histological examination confirmed metastasis of anaplastic ependymoma in the scalp. After a delay in starting chemotherapy due to concerns related to the COVID‐19 pandemic, the patient eventually initiated chemotherapy, leading to disease stability at a short‐term follow‐up. Scalp metastases from ependymoma are rarely reported in the literature. Management of such cases necessitates aggressive surgical resection, followed by adjuvant chemotherapy and radiotherapy. A multidisciplinary approach is recommended to ensure effective and targeted therapy, with a focus on preserving aesthetics, particularly in pediatric cases.

Background: Craniovertebral junction (CVJ) schwannomas are rare, with surgery and stereotactic radiosurgery (SRS) being effective yet challenging options. We systematically reviewed the literature on CVJ schwannomas. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA statement to include studies reporting CVJ schwannomas. Clinical features, management, and outcomes were analyzed. Results: We collected 353 patients from 101 included articles. Presenting symptoms were mostly neck pain (30.3%) and headache (26.3%), with most cranial neuropathies involving the XII (31.2%) and X (24.4%) nerves. Most tumors originated from C2 (30.9%) and XII (29.4%) nerves, being extracranial (45.1%) and intradural-extradural (44.2%). Erosion of C1–C2 vertebrae (37.1%), the hypoglossal canal (28.3%), and/or jugular foramen (20.1%) were noted. All tumors were operated, preferably with the retrosigmoid approach (36.5%), with the far-lateral approach (29.7%) or with the posterior approach and cervical laminectomy (26.9%), far-lateral approaches (14.2%), or suboccipital craniotomy with concurrent cervical laminectomy (14.2%). Complete tumor resection was obtained most frequently (61.5%). Adjuvant post-surgery stereotactic radiosurgery was delivered in 5.9% patients. Median follow-up was 27 months (range, 12–252). Symptom improvement was noted in 88.1% of cases, and cranial neuropathies showed improvement in 10.2%. Post-surgical complications occurred in 83 patients (23.5%), mostly dysphagia (7.4%), new cranial neuropathies (6.2%), and cerebrospinal fluid leak (5.9%). A total of 16 patients (4.5%) had tumor recurrence and 7 died (2%), with median overall survival of 2.7 months (range, 0.1–252). Conclusions: Microsurgical resection is safe and effective for CVJ schwannomas. Data on SRS efficacy and indications are still lacking, and its role deserves further evaluation.

BackgroundThe rarity of hand acrometastases hampers the consensus-building for their optimal management among the involved oncology professionals. In the current literature, demolitive surgery overcomes the use of palliative radiotherapy, which proved to be ineffective in more than 30% of cases treated with classic palliative dose schemes, carrying also a not negligible radiation-related adverse event rate. Against this background, stereotactic body radiation therapy (SBRT) could emerge as a well-balanced therapeutic option.Case summaryHere we describe the methods and outcomes of a SBRT treatment of a painful and function-limiting hand acrometastasis in a patient with a history of stage IIIB lung adenocarcinoma. We delivered a total dose of 30 Gy in five daily fractions to a soft-tissue metastasis abutting the fifth metacarpal bone through the SBRT protocol generally used for intracranial treatments. A few weeks later, the patient reported a clinical complete response with acrometastasis and pain disappearance, function recovery, and no significant toxicity. The acrometastasis was the first sign of an atypical cancer progression.ConclusionsSBRT for hand acrometastases is feasible and might have the best therapeutic profile among the currently available treatment options for this rare clinical scenario. Larger investigations are needed to confirm the present single-case experience.

IntroductionMalignant peripheral nerve sheath tumors (MPNSTs) are a group of rare soft tissue sarcomas of mesenchymal origin. These tumors generally require extensive local excision owing to their aggressive potential. Though the role of radiotherapy is controversial, in this report, we present the case of an MPNST in the forearm that was treated with microsurgery followed by image-guided radiation therapy to achieve complete tumor disappearance at the 18-month follow-up.Case reportA 69-year-old woman with underlying paranoid schizophrenia was referred to our department with pain, severe swelling, and ecchymosis of her right forearm. Physical examination showed hypoesthesia in the segments innervated by the median nerve and reduced motor strength of her right hand. A gadolinium-enhanced MRI showed a large malignant peripheral nerve sheath tumor (13 x 8 x 7 cm) of the median nerve in the forearm. She underwent microsurgical en-bloc tumor resection with sparing of the median nerve. Thirty-five days postoperatively, she underwent image-guided radiotherapy (IGRT) using volumetric modulated arc therapy (VMAT). Serial MRI scans of the forearm with Gadolinium and whole-body CT scan with contrast enhancement at 30 days, 6 months, 1 year, and 18 months postoperatively documented no tumor recurrence, remnants, or metastases.ConclusionsIn this report, we demonstrate the successful use of advanced radiotherapy techniques such as IGRT while avoiding demolitive surgery for MPNST. Though a longer follow-up is necessary, at the 18-month follow-up, the patient demonstrated good outcomes from surgical resection followed by adjuvant RT for MPNST in the forearm.

(1) Background: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has been used as an immunotherapeutic agent in bladder cancer and has shown non-specific beneficial effects. This report presents a unique case of GBM regression following BCG therapy for bladder cancer, suggesting the potential systemic immunomodulatory effects of BCG on GBM. (2) Case Presentation: A 67-year-old male with a history of bladder cancer treated with BCG presented with neurological symptoms. Imaging revealed two GBM lesions, and surgery was performed to remove one. Subsequently, the patient experienced complete tumor regression after initial stability. (3) Conclusions: This case highlights the potential of BCG or other immunotherapies in GBM treatment and underscores the need for further research. Understanding the immunomodulatory effects of BCG on GBM could lead to innovative therapies for this devastating disease; although, overcoming the immune evasion mechanisms in the brain is a significant challenge. Further investigation is warranted to explore this promising avenue of research.

Aims: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). Methods: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). Discussion: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. Trial registration: NCT number: NCT04891471.

Background: Paraneoplastic gastroparesis is a gastrointestinal syndrome that rarely precedes a tumor diagnosis. To increase awareness of this rare clinical entity, we present a case of severe gastroparesis, which was later proven to be associated with a thymoma. Case report: A 55-year old man had the sudden onset of severe abdominal cramps and abdominal distension, early satiety with postprandial nausea, acid regurgitation, belching, and flatulence. He lost about 20 pounds. The physical and imaging examination revealed stomach distension, gastroparesis, and the presence of a solid mass in the anterior mediastinum. Radical surgery was performed to remove the thymoma and, given the high value of Mib-1, the patient was submitted to postoperative chest radiation therapy. After thymectomy, a diagnosis of paraneoplastic myasthenia gravis with subacute autonomic failure was made. Conclusion: Autoimmune gastroparesis should be considered as a potential paraneoplastic syndrome in patients with thymoma, myasthenia gravis, and delayed gastric emptying in the absence of mechanical obstruction.

Background and Objectives: Juvenile nasopharyngeal angiofibroma (JNA) is an angiomatous hamartoma of the nasal cavity. It is a benign but locally aggressive vascular tumor of the nasopharynx affecting adolescent males. Many surgical procedures are in practice, but the extended endonasal endoscopic (EEE) approach for JNAs is a suitable and effective technique. Materials and Methods: Fifteen adolescent patients having JNA who underwent extended endonasal endoscopic (EEE) surgery from January 2010 to January 2022 were studied retrospectively. Patients having residual and recurrent JNAs and those who underwent surgery other than EEE were excluded. Results: The average age of the patients was 18.3 years of age. A total of six patients (40%) each had stage V and IV while three patients (20%) had stage III JNAs. Gross total removal was achieved in eight (53.3%) patients and seven (43.7%) had partial removal. There was no per or postoperative mortality. All the patients had at least 3 years of postoperative follow-up and during follow-ups, seven patients were found to have residual tumors, and two had recurrences. Discussion: During the last decades, the endoscopic approach for the resection of JNAs has gained increasing popularity due to its obvious advantages over transfacial approaches. The magnified and angled field of view “behind the corner” helping in a more complete inspection for the resection and shorter hospitalization time makes it a better choice than the other approaches. Conclusions: Endoscopy is an excellent approach for primary JNA. It allows well visualization and precise removal of the angiofibroma. An endoscopic multiangle, multicorridor skull base approach including Denker’s anteromedial maxillotomy is suitable and preferable for the resection of extensive JNAs.

Background: The favorable role of SBRT for lymph-nodal oligometastases from prostate cancer has been reported by several retrospective and prospective experiences, suggesting a more indolent natural history of disease when compared to patients with bone oligometastases. This retrospective multicenter study evaluates the outcomes of a cohort of patients treated with stereotactic body radiotherapy for lymph-nodal oligometastases. Methods: Inclusion criteria were up to five lymph-nodal oligometastases detected either with Choline-PET or PSMA-PET in patients naïve for ADT or already ongoing with systemic therapy and at least 6 Gy per fraction for SBRT. Only patients with exclusive lymph-nodal disease were included. The primary endpoint of the study was LC; a toxicity assessment was retrospectively performed following CTCAE v4.0. Results: A total of 100 lymph-nodal oligometastases in 69 patients have been treated with SBRT between April 2015 and November 2022. The median age was 73 years (range, 60–85). Oligometastatic disease was mainly detected with Choline-PET in 47 cases, while the remaining were diagnosed using PSMA-PET, with most of the patients treated to a single lymph-nodal metastasis (48/69 cases), two in 14 cases, and three in the remaining cases. The median PSA prior to SBRT was 1.35 ng/mL (range, 0.3–23.7 ng/mL). Patients received SBRT with a median total dose of 35 Gy (range, 30–40 Gy) in a median number of 5 (range, 3–6) fractions. With a median follow-up of 16 months (range, 7–59 months), our LC rates were 95.8% and 86.3% at 1 and 2 years. DPFS rates were 90.4% and 53.4%, respectively, at 1 and 2 years, with nine patients developing a sequential oligometastatic disease treated with a second course of SBRT. Polymetastatic disease-free survival (PMFS) at 1 and 2 years was 98% and 96%. Six patients needed ADT after SBRT for a median time of ADT-free survival of 15 months (range, 6–22 months). The median OS was 16 months (range, 7–59) with 1- and 2-year rates of both 98%. In multivariate analysis, higher LC rates and the use of PSMA-PET were related to improved DPFS rates, and OS was significantly related to a lower incidence of distant progression. No G3 or higher adverse events were reported. Conclusions: In our experience, lymph-nodal SBRT for oligometastatic prostate cancer is a safe and effective option for ADT delay with no severe toxicity.

Aim: To evaluate if hyaluronic acid reduces proctitis episodes with respect to corticosteroids in prostate cancer patients submitted to radical or adjuvant radiotherapy. Methods: A consecutive series of eligible patients received hyaluronic acid enemas as supportive care (experimental group, from January 2013 to June 2015). A historical group (control group), treated from October 2011 to December 2012, received beclomethasone dipropionate suppositories. We registered each patient’s data regarding acute and chronic proctitis. All patients were treated with static-intensity-modulated radiotherapy coupled to a daily set-up verification with orthogonal anterior–posterior/lateral X-ray pairs. Results: A total of 269 patients, 175 in the experimental group and 94 in the control group, was evaluated; 2 Gy/day (up to a total median dose of 80 Gy) and 2.7 Gy/day (up to a total median dose of 67.5 Gy) fractionation schemes were used for 216 and 53 patients, respectively. All patients had a good tolerance to radiotherapy, reporting no G3 or greater proctitis. No significant difference was reported concerning the total rate of proctitis between the two groups but only with respect to its grade: a higher G2 rate within the control group. There was no correlation between daily dose fractionation and toxicity grade. Conclusions: Hyaluronic acid enemas might be effective in reducing the severity of radiation proctitis.

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.

The standard treatment of locally advanced rectal cancer is neoadjuvant chemoradiotherapy before surgery. For those patients experiencing a complete clinical response after the treatment, a watch-and-wait strategy with close monitoring may be practicable. In this respect, the identification of biomarkers of the response to therapy is extremely important. Many mathematical models have been developed or used to describe tumor growth, such as Gompertz’s Law and the Logistic Law. Here we show that the parameters of those macroscopic growth laws, obtained by fitting the tumor evolution during and immediately after therapy, are a useful tool for evaluating the best time for surgery in this type of cancer. A limited number of experimental observations of the tumor volume regression, during and after the neoadjuvant doses, permits a reliable evaluation of a specific patient response (partial or complete recovery) for a later time, and one can evaluate a modification of the scheduled treatment, following a watch-and-wait approach or an early or late surgery. Neoadjuvant chemoradiotherapy effects can be quantitatively described by applying Gompertz’s Law and the Logistic Law to estimate tumor growth by monitoring patients at regular intervals. We show a quantitative difference in macroscopic parameters between partial and complete response patients, reliable for estimating the treatment effects and best time for surgery.

Old or very old oncological patients represent a heterogeneous and frail population due to concomitant comorbidities. Whether radiotherapy alone or in combination with novel cancer drugs may provide a clear benefit in this setting of patients is still a matter of debate.The aim of our review is to analyze the evaluation process and the different therapeutic possibilities in older cancer patients, focusing on the different and most disparate applications of radiotherapy. We reviewed the most recent literature on radiotherapy in older patients providing clinical evidence of treatment related toxicity, tolerance and outcomes using standard fractionated and/or hypofractionated irradiation alone or in combination with chemotherapy, targeted and immunotherapy.In older cancer patients unfit for systemic therapy or surgery, radiotherapy represents a valid therapeutic approach, both with curative and palliative intents, ensuring excellent patient compliance in terms of local toxicity and adherence to therapy.

Radiotherapy represents a first-line treatment for many inoperable lung tumors. New technologies offer novel opportunities for the treatment of lung cancer with the administration of higher doses of radiation in smaller volumes. Because both therapeutic and toxic treatment effects are dose-dependent, it is important to identify a minimal dose protocol for each individual patient that maintains efficacy while decreasing toxicity. Cancer stem cells sustain tumor growth, promote metastatic dissemination, and may give rise to secondary resistance. The identification of effective protocols targeting these cells may improve disease-free survival of treated patients. In this work, we evaluated the existence of individual profiles of sensitivity to radiotherapy in patient-derived cancer stem cells (CSCs) using both in vitro and in vivo models. Both CSCs in vitro and mice implanted with CSCs were treated with radiotherapy at different dose intensities and rates. CSC response to different radiation doses greatly varied among patients. In vitro radiation sensitivity of CSCs corresponded to the therapeutic outcome in the corresponding mouse tumor model. On the other side, the dose administration rate did not affect the response. These findings suggest that in vitro evaluation of CSCs may potentially predict patients’ response, thus guiding clinical decision.

BackgroundPrimary intracranial ependymomas (IE) are rare brain tumors rarely metastasizing outside the central nervous system. We systematically reviewed the literature on extra-neural metastases from primary IEs.MethodsPubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of extra-neural metastases from primary IEs. Clinical features, management strategies, and survival were analyzed.ResultsWe collected 48 patients from 43 studies. Median age was 13 years (range, 2-65). Primary IEs were frequently located in the parietal (22.9%) and frontal (16.7%) lobes, and mostly treated with resection (95.8%) and/or radiotherapy (62.5%). Most IEs were of grade-III (79.1%), and few of grade-I (6.3%) or grade-II (14.6%). 45 patients experienced intracranial recurrences, mostly treated with resection (86.7%), radiotherapy (60%), and/or chemotherapy (24.4%). Median time-interval from primary IEs was 28 months (range, 0-140). Most extra-neural metastases were diagnosed at imaging (37.5%) or autopsy (35.4%). Extra-neural metastases were multifocal in 38 patients (79.1%), mostly involving cervical or hilar lymph-nodes (66.7%), lung/pleura (47.9%), and/or scalp (29.1%). Surgical resection (31.3%), chemotherapy (31.3%) and locoregional radiotherapy (18.8%) were the most common treatments for extra-neural metastases, but 28 (58.3%) patients were not treated. At last follow-up, 37 patients died with median overall-survivals from primary IEs of 36 months (range, 1-239), and from extra-neural metastases of 3 months (range, 0.1-36). Overall-survival was significantly longer in patients with grade-I and II IEs (P=0.040).ConclusionExtra-neural metastases from primary IEs are rare, but mostly occur at later disease stages. Multidisciplinary management strategies should be intended mostly for palliation.

Objective: The aim of this work is to define a methodological strategy for the minimally invasive tubular retractor (MITR) parafascicular transulcal approach (PTA) for the management of brain tumors sited in eloquent areas. Methods: An observational prospective study was designed to evaluate the benefits of PTA associated with MITRs, tractography and intraoperative cortical stimulation. They study was conducted from June 2018 to June 2021. Information regarding white matter tracts was processed, preventing a potential damage during the approach and/or resection. All patients older than 18 years who had a single brain tumor lesion were included in the study. Patients with a preoperative Karnofsky Performance Scale (KPS) score greater than 70% and a Glasgow Coma Scale (GCS) score > 14 points were included. Results: 72 patients were included in the study, the mean age was 49.6, the most affected gender was male, 12.5% presented aphasia, 11.1% presented paraphasia, 41.6% had motor deficit, 9.7% had an affection in the optic pathway, the most frequently affected region was the frontal lobe (26.3%), the most frequent lesions were high-grade gliomas (34.7%) and the measurement of the incisions was on average 5.58 cm. Of the patients, 94.4% underwent a total macroscopic resection and 90.2% did not present new postoperative neurological deficits. In all cases, a PTA was used. Conclusion: Tubular minimally invasive approaches (MIAs) allow one to perform maximal safe resection of brain tumors in eloquent areas, through small surgical corridors. Future comparative studies between traditional and minimally invasive techniques are required to further investigate the potential of these surgical nuances.

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: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, marks a step forward the future diagnostic approach to these neoplasms. Alongside this, radiomics has experienced rapid evolution over the last several years, allowing us to correlate tumor imaging heterogeneity with a wide range of tumor molecular and subcellular features. Radiomics is a translational field focused on decoding conventional imaging data to extrapolate the molecular and prognostic features of tumors such as gliomas. We herein analyze the state-of-the-art of radiomics applied to glioblastoma, with the goal to estimate its current clinical impact and potential perspectives in relation to well-rounded patient management, including the end-of-life stage. Methods: A literature review was performed on the PubMed, MEDLINE and Scopus databases using the following search items: “radiomics and glioma”, “radiomics and glioblastoma”, “radiomics and glioma and IDH”, “radiomics and glioma and TERT promoter”, “radiomics and glioma and EGFR”, “radiomics and glioma and chromosome”. Results: A total of 719 articles were screened. Further quantitative and qualitative analysis allowed us to finally include 11 papers. This analysis shows that radiomics is rapidly evolving towards a reliable tool. Conclusions: Further studies are necessary to adjust radiomics’ potential to the newest molecular requirements pointed out by the 2021 WHO classification of CNS tumors. At a glance, its application in the clinical routine could be beneficial to achieve a timely diagnosis, especially for those patients not eligible for surgery and/or adjuvant therapies but still deserving palliative and supportive care.

Intraoperative ultrasound (IOUS) is becoming progressively more common during brain tumor surgery. We present data from our case series of brain tumor surgery performed with the aid of IOUS in order to identify IOUS advantages and crucial aspects that may improve the management of neurosurgical procedures for brain tumors. From January 2021 to September 2021, 17 patients with different brain tumors underwent brain tumor surgery aided by the use of IOUS. During surgery, the procedure was supported by the use of multiples ultrasonographic modalities in addition to standard B-mode: Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS). In selected cases, the use of IOUS during surgical procedure was combined with neuronavigation and the use of intraoperative fluorescence by the use of 5-aminolevulinic acid (5-ALA). In one patient, a preoperative ultrasound evaluation was performed through a former iatrogenic skull defect. This study confirms the role of IOUS in maximizing the EOR, which is strictly associated with postoperative outcome, overall survival (OS), and patient’s quality of life (QoL). The combination of ultrasound advanced techniques such as Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS) is crucial to improve surgical effectiveness and patient’s safety while expanding surgeon’s view.

IntroductionMetastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit–risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models.MethodsWe treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed.ResultsWe observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system.ConclusionsPET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system’s role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it.

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.

I read the paper by Ivanov et al. [...]

Background: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses. Results: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm3 (range, 2.9–57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7–60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1–10) post-NaSRT. Median follow-up was 19.2-months (range, 1–41.3). Actuarial post-treatment rates were 4% (95%CI: 2–6%) for symptomatic radiation necrosis, 15% (95%CI: 12–18%) and 47% (95%CI: 42–52%) for local and distant recurrences, 6% (95%CI: 3–8%) for leptomeningeal metastases, 81% (95%CI: 75–87%) and 59% (95%CI: 54–63%) for 1-year local tumor control and overall survival. Conclusion: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.

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.

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.

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.

The role of immunotherapy is gaining ever-increasing interest in the neuro-oncological field, and this is also expanding to the management of intracranial meningioma. Meningiomas are still the most common primary adult tumor of the CNS, and even though surgery and/or radiotherapy still represent cornerstones of their treatment, recent findings strongly support the potential role of specific immune infiltrate cells, their features and genomics, for the application of personalized treatments and prognostic implications. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a descriptive and complete overview about the characteristics, role and potential implications of immunology in meningioma tumors. Seventy articles were included and analyzed in the present paper. The meningioma microenvironment reveals complex immune tumor-immune cells interactions that may definitely influence tumor progression, as well as offering unexpected opportunities for treatment.

Targeting cell cycle has become the gold standard for metastatic breast cancer (MBC), being cyclin-dependent kinase inhibitors (CDKIs) cornerstones of its treatment, alongside radiotherapy (RT). To date, no definite evidence regarding safety and efficacy of the combination of CDKIs plus radiotherapy (RT) is currently available. Purpose of this review is to collect data in favor or against the feasibility of the association of CDKIs + RT, describing its potential adverse events. Our review shows how CDKI + RT allows an overall satisfying disease control, proving to be effective and causing a grade of toxicity mainly influenced by the site of irradiation, leaning to favourable outcomes for sites as liver, spine or brain and to poorer outcomes for thoracic lesions or sites close to viscera; controversial evidence is instead for bone treatment. Toxicity also varies from patient to patient. To sum up, our contribution enriches and enlightens a still indefinite field regarding the feasibility of CDKIs + RT, giving cues for innovative clinical management of hormone-responsive MBC.

Background: The development of [68Ga]Ga-DOTA-SSTR PET tracers has garnered interest in neuro-oncology, to increase accuracy in diagnostic, radiation planning, and neurotheranostics protocols. We systematically reviewed the literature on the current uses of [68Ga]Ga-DOTA-SSTR PET in brain tumors. Methods: PubMed, Scopus, Web of Science, and Cochrane were searched in accordance with the PRISMA guidelines to include published studies and ongoing trials utilizing [68Ga]Ga-DOTA-SSTR PET in patients with brain tumors. Results: We included 63 published studies comprising 1030 patients with 1277 lesions, and 4 ongoing trials. [68Ga]Ga-DOTA-SSTR PET was mostly used for diagnostic purposes (62.5%), followed by treatment planning (32.7%), and neurotheranostics (4.8%). Most lesions were meningiomas (93.6%), followed by pituitary adenomas (2.8%), and the DOTATOC tracer (53.2%) was used more frequently than DOTATATE (39.1%) and DOTANOC (5.7%), except for diagnostic purposes (DOTATATE 51.1%). [68Ga]Ga-DOTA-SSTR PET studies were mostly required to confirm the diagnosis of meningiomas (owing to their high SSTR2 expression and tracer uptake) or evaluate their extent of bone invasion, and improve volume contouring for better radiotherapy planning. Some studies reported the uncommon occurrence of SSTR2-positive brain pathology challenging the diagnostic accuracy of [68Ga]Ga-DOTA-SSTR PET for meningiomas. Pre-treatment assessment of tracer uptake rates has been used to confirm patient eligibility (high somatostatin receptor-2 expression) for peptide receptor radionuclide therapy (PRRT) (i.e., neurotheranostics) for recurrent meningiomas and pituitary carcinomas. Conclusion: [68Ga]Ga-DOTA-SSTR PET studies may revolutionize the routine neuro-oncology practice, especially in meningiomas, by improving diagnostic accuracy, delineation of radiotherapy targets, and patient eligibility for radionuclide therapies.

(1) Introduction: Adult-onset pilocytic astrocytoma (APA) accounts for only 1.5% of all brain tumors, and studies regarding APA are limited. This review is focused on the history, clinical course, cytogenetics, neuroimaging features, management, and outcome of APAs. (2) Methods: Using a systematic search protocol in Google Scholar, PubMed, and Science Direct databases, the authors extracted cases of APA predilecting the temporal lobe from inception to December 2020. Articles lacking necessary data were excluded from this study. Data were analyzed using IBM SPSS 23 statistical package software. (3) Results: A total of 32 patients, 14 (43.8%) males and 18 (56.2%) females, with a male/female ratio of 0.77/1, were grouped. The mean age of the patients was 34.22 ± 15.17 years, ranging from 19 to 75. The tumors were predominantly located in the left side. We have also discussed the clinical presentation, and headache was the most common complaint, followed by visual disturbance. Preoperative neuroimaging features demonstrated cystic lesions in 16 patients, with mural nodule in 5 patients; intracerebral hemorrhage was present in 1 patient, and solid enhancing mass was observed in 3 patients. Only our reported case presented as a solid calcified mass. Most of the patients (78.1%) underwent a gross total resection (GTR), only 5 (21.9%) underwent subtotal resection (STR). The outcome and prognosis history were excellent, and no recurrence was observed. (4) Conclusion: Most of the APAs of the temporal lobe follow benign clinical courses, but some patients exhibit aggressive clinical behavior. There was no history of recurrence after treatment at up to 27 years of follow-up.

Background: Gliomas infiltrating the corpus callosum (G-I-CC) majorly impact patient quality-of-life, but maximally safe tumor resection is challenging. We systematically reviewed the literature on G-I-CC. Methods: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with G-I-CC. Clinicopathological features, treatments, and outcomes were analyzed. Results: We included 52 studies comprising 683 patients. Most patients experienced headache (33%), cognitive decline (18.7%), and seizures (17.7%). Tumors mostly infiltrated the corpus callosum genu (44.2%) with bilateral extension (85.4%) into frontal (68.3%) or parietal (8.9%) lobes. Most G-I-CC were glioblastomas (84.5%) with IDH-wildtype (84.9%) and unmethylated MGMT promoter (53.5%). Resection (76.7%) was preferred over biopsy (23.3%), mostly gross-total (33.8%) and subtotal (32.5%). The tumor-infiltrated corpus callosum was resected in 57.8% of cases. Radiation was delivered in 65.8% of patients and temozolomide in 68.3%. Median follow-up was 12 months (range, 0.1–116). In total, 142 patients (31.8%) experienced post-surgical complications, including transient supplementary motor area syndrome (5.1%) and persistent motor deficits (4.3%) or abulia (2.5%). Post-treatment symptom improvement was reported in 42.9% of patients. No differences in rates of complications (p = 0.231) and symptom improvement (p = 0.375) were found in cases with resected versus preserved corpus callosum. Recurrences occurred in 40.9% of cases, with median progression-free survival of 9 months (0.1–72). Median overall survival was 10.7 months (range, 0.1–116), significantly longer in low-grade tumors (p = 0.013) and after resection (p < 0.001), especially gross-total (p = 0.041) in patients with high-grade tumors. Conclusions: G-I-CC show clinicopathological patterns comparable to other more frequent gliomas. Maximally safe resection significantly improves survival with low rates of persistent complications.

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.

(1) Background: Treatment of cancer-related pain is still challenging, and it can be managed by both medical and interventional therapies. Spinal Cord Stimulation (SCS) is a minimally invasive technique, and its use is rapidly increasing in the treatment of chronic pain. (2) Materials and Methods: Our study aims to perform a review of the pertinent literature about current evidences in cancer pain treatment by Spinal Cord Stimulation. Moreover, we created a database based on case reports or case series (18 studies) in the literature. We analyzed a clinical group of oncological patients affected by intractable pain undergoing SCS implantation, focusing on outcome. (3) Results: The analysis of the 18 included studies in our series has shown a reduction in painful symptoms in 48 out of 56 treated patients (87.51%); also 53 out of 56 patients (96.64%) have shown an improvement in their Quality of Life (QoL). (4) Conclusions: Spinal Cord Stimulation can be considered an efficient method in the treatment of cancer-related pain. However, literature regarding SCS for the treatment of cancer-related pain is largely represented by case reports and small case series, with no effective population studies or Randomized Controlled Trials demonstrating the efficacy and the level of evidence. Further prospective studies are needed.

(1) Introduction: Primary intraosseous osteolytic meningiomas (PIOM) are non-dural-based tumors predominantly presenting an osteolytic component with or without hyperostotic reactions. They are a subset of primary extradural meningiomas (PEM). In this study, we present a peculiar case with a systematic literature review and propose a new classification considering the limitations of previous classification systems. (2) Materials and Methods: Using a systematic search protocol in Google Scholar, PubMed, and Scopus databases, we extracted all case studies on PIOM published from inception to December 2020. A 46-year-old female patient form Dhaka, Bangladesh, was also described. The search protocol was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. (3) Results: Here, we present a 46-year-old female patient with PIOM who successfully underwent bifrontal craniotomy and gross total removal (GTR) of the tumor. At 6-month follow-up, no tumor recurrence was shown. Including our new case, 55 total cases from 47 articles were included in the analysis. PIOMs were in closer frequency among males (56.4%) and females (43.6%). The most common tumor location was the frontal and parietal calvarium, most commonly in the frontal bone (29.1%). Surgical resection was the predominant modality of treatment (87.3%); only 1.8% of patients were treated with radiotherapy, and 5.4% received a combination of surgery and radiotherapy. Gross total resection (GTR) was achieved in 80% of cases. Extracranial extension was reported in 41.8% of cases, dural invasion in 47.3%, and recurrence in 7.3%. Whole-body 68 Ga-DOTATOC PET/CT has also been reported as a useful tool both for differential diagnosis, radiotherapy contouring, and follow-up. Current treatments such as hydroxyurea and bevacizumab have variable success rates. We have also suggested a new classification which would provide a simple common ground for further research in this field. (4) Conclusions: Surgical resection, especially GTR, is the treatment of choice for PIOM, with a high GTR rate and low risk of complications and mortality. More research is needed on the differential diagnosis and specific treatment of PIOM.

Background: In recent decades, the application of machine learning technologies to medical imaging has opened up new perspectives in neuro-oncology, in the so-called radiomics field. Radiomics offer new insight into glioma, aiding in clinical decision-making and patients’ prognosis evaluation. Although meningiomas represent the most common primary CNS tumor and the majority of them are benign and slow-growing tumors, a minor part of them show a more aggressive behavior with an increased proliferation rate and a tendency to recur. Therefore, their treatment may represent a challenge. Methods: According to PRISMA guidelines, a systematic literature review was performed. We included selected articles (meta-analysis, review, retrospective study, and case–control study) concerning the application of radiomics method in the preoperative diagnostic and prognostic algorithm, and planning for intracranial meningiomas. We also analyzed the contribution of radiomics in differentiating meningiomas from other CNS tumors with similar radiological features. Results: In the first research stage, 273 papers were identified. After a careful screening according to inclusion/exclusion criteria, 39 articles were included in this systematic review. Conclusions: Several preoperative features have been identified to increase preoperative intracranial meningioma assessment for guiding decision-making processes. The development of valid and reliable non-invasive diagnostic and prognostic modalities could have a significant clinical impact on meningioma treatment.

Spine represents the most common site for metastatic disease involvement. Due to the close relationship between the spinal cord and critical structures, therapeutic management of spinal metastases remains challenging. Spinal localization can lead to neurological sequelae, which can significantly affect the quality of life in patients with a limited life expectancy. The authors conducted a systematic literature review according to PRISMA guidelines in order to determine the impact of the most updated palliative care on spinal metastases. The initial literature search retrieved 2526 articles, manually screened based on detailed exclusion criteria. Finally, 65 studies met the inclusion criteria and were finally included in the systematic review. In the wide scenario of palliative care, nowadays, recent medical or surgical treatments represent valuable options for ameliorating pain and improving patients QoL in such this condition.

Gliomas, particularly high-grade gliomas, represent the most common and aggressive tumors of the CNS and are still burdened by high mortality and a very poor prognosis, regardless of the type of therapy. Their diagnosis and monitoring rely on imaging techniques and direct biopsy of the pathological tissue; however, both procedures have inherent limitations. To address these limitations, liquid biopsies have been proposed in this field. They could represent an innovative tool that could help clinicians in the early diagnosis, monitoring, and prognosis of these tumors. Furthermore, the rapid development of next-generation sequencing (NGS) technologies has led to a significant reduction in sequencing cost, with improved accuracy, providing a molecular profile of cancer and leading to better survival results and less disease burden. This paper focuses on the current clinical application of liquid biopsy in the early diagnosis and prognosis of cancer, introduces NGS-related methods, reviews recent progress, and summarizes challenges and future perspectives.

(1) Background: Meningiomas are usually benign encapsulated intracranial tumors with well-defined borders that offer a high chance of cure with complete removal. The aim of this study was to evaluate the association between preoperative MRI features and surgical plane of cleavage. (2) Materials and Methods: This was a cross-sectional observational study conducted in the Department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University. Data were recorded from 48 study participants with confirmed intracranial meningioma and analyzed by IBM SPSS (version 23). (3) Results: The highest incidence of intracranial meningioma was observed in the third decade of life of our study participants. The female to male ratio was 1.82:1. The most common location of meningiomas was convexity (29.16%), sphenoid wing (22.91%), parasagittal (20.83%), and falcine (14.58%). Most of the patients (68.8%) had medium-sized tumors, and 75.0% exhibited hyperintense signal change in the tumor parenchyma on T2-weighted imaging. One-third (33.3%) of patients were characterized as no edema, focal edema, and lobar/hemispheric edema. There was no statistically significant association between tumor size and types of surgical cleavage plane. Different signal intensities of tumor parenchyma, as well as types of peritumoral edema, showed no statistically significant association with surgical cleavage plane (p > 0.05). (4) Conclusion: There was no association among the size of the tumor, extent of peritumoral edema, the intensity of the tumor on T2-weighted images, and the types of surgical cleavage plane. Future studies with larger sample sizes are required to find out more precise findings.

(1) Background: The aim of the present study was to evaluate our institutional outcome in tuberculum sellae meningioma (TSM) patients treated microsurgically using multiple skull base approaches, including a transcranial approach and an extended endonasal transsphenoidal approach. (2) Materials and Methods: This is a retrospective study that includes 34 patients with TSM. The study aimed to observe the efficacy of the different common approaches used by a single neurosurgeon. All the patients were evaluated preoperatively and during follow-up with campimetry, head CT scan, and post-contrast MRI. (3) Results: After a transcranial approach, visual acuity improved in 86.20%, was stable in 10.34%, and deteriorated in 3.45%. Through transsphenoidal surgery, vision improved in 80%, was static in 20%, and deteriorated in 0%. Transcranial approaches included pterional, mini-bifrontal basal, and supraciliary keyhole microscopic craniotomies. Gross total removal was performed in 58.82%, near total in 10.34%, and partial removal in 3.45%. The transcranial/supraciliary keyhole endoscopic-assisted approach showed a gross total removal rate of 80%, and near total in 20%. The transsphenoidal approach showed a gross total removal rate of 60%, near total in 20%, and partial removal in 20%. (4) Conclusion: Endoscopic-assisted keyhole supraciliary mini craniotomy for resection of tuberculum sellae meningioma offers low morbidity and good visual outcome. The endonasal route is preferred for the removal of TSM when they are small and midline placed. The major limitation of this approach is a narrow surgical corridor and the restriction on midline-placed lesions. Gross total removal was better achieved with mini-bifrontal basal and pterional craniotomies.

Tumor volume regression during and after chemo and radio therapy is a useful information for clinical decisions. Indeed, a quantitative, patient oriented, description of the response to treatment can guide towards the modification of the scheduled doses or the evaluation of the best time for surgery. We propose a macroscopic algorithm which permits to follow quantitatively the time evolution of the tumor volume during and after radiochemotherapy. The method, initially validated with different cell-lines implanted in mice, is then successfully applied to the available data for partially responding and complete recovery patients.

In spinal surgery, 3D prothesis represents a useful instrument for spinal reconstruction after the removal of spinal tumors that require an “en bloc” resection. This represents a complex and demanding procedure, aiming to restore spinal length, alignment and weight-bearing capacity and to provide immediate stability. Thus, in this systematic review the authors searched the literature to investigate and discuss the advantages and limitations of using 3D-printed custom-made vertebral bodies in the treatment of spinal tumors. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, with no limits in terms of date of publication. The collected studies were exported to Mendeley. The articles were selected according to the following inclusion criteria: availability of full articles, full articles in English, studies regarding the implant of 3D custom-made prothesis after total or partial vertebral resection, studies regarding patients with a histologically confirmed diagnosis of primary spinal tumor or solitary bone metastasis; studies evaluating the implant of 3d custom-made prothesis in the cervical, thoracic, and lumbar spine. Nineteen published studies were included in this literature review, and include a total of 87 patients, 49 males (56.3%) and 38 females (43.7%). The main tumoral location and primary tumor diagnosis were evaluated. The 3D custom-made prothesis represents a feasible tool after tumor en-bloc resection in spinal reconstruction. This procedure is still evolving, and long-term follow-ups are mandatory to assess its safeness and usefulness.

Background: Surgical resection remains the preferred treatment in spine giant cell tumors (SGCTs), but it is not always feasible. Conservative strategies have been studied for inoperable cases. We systematically reviewed the literature on inoperable SGCTs treated with denosumab, radiotherapy or selective arterial embolization (SAE). Methods: PubMed, Scopus, Web-of-Science, Ovid-EMBASE, and Cochrane were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to include studies of inoperable SGCTs treated with denosumab, radiotherapy or SAE. Treatment outcomes were analyzed and compared with a random-effect model meta-analysis. Results: Among the 17 studies included, 128 patients received denosumab, 59 radiotherapy, and 43 SAE. No significant differences in baseline patient characteristics were found between the three groups. All strategies were equally effective in providing symptom improvement (p = 0.187, I2 = 0%) and reduction in tumor volume (p = 0.738, I2 = 56.8%). Rates of treatment-related complications were low (denosumab: 12.5%; radiotherapy: 8.5%; SAE: 18.6%) and comparable (p = 0.311, I2 = 0%). Patients receiving denosumab had significantly lower rates of local tumor recurrence (10.9%) and distant metastases (0%) compared to patients receiving radiotherapy (30.5%; 8.5%) or SAE (35.6%; 7%) (p = 0.003, I2 = 32%; p = 0.002, I2 = 47%). Denosumab was also correlated with significantly higher overall survival rates at 18 months (99.2%) and 24 months (99.2%) compared to radiotherapy (91.5%; 89.6%) and SAE (92.5%; 89.4%) (p = 0.019, I2 = 8%; p = 0.004, I2 = 23%). Mortality was higher in patients receiving SAE (20.9%) or radiotherapy (13.6%) compared to denosumab (0.8%) (p < 0.001), but deaths mostly occurred for unrelated diseases. Conclusions: Denosumab, radiotherapy, and SAE are safe and effective for inoperable SGCTs. Clinical and radiological outcomes are mostly comparable, but denosumab may provide superior tumor control.

(1) Objective—Intraoperative Magnetic Resonance Imaging (IOMRI) guided surgery has revolutionized neurosurgery and has especially impacted the field of Neuro-Oncology, with randomized controlled trails demonstrating improved resection, fewer postoperative deficits and enhanced survival rates. Bibliometric analysis allows for analysing chronological trends and measuring the impact and directions of research in a particular field. To the authors’ knowledge, this is the first Bibliometric analysis conducted on IOMRI. (2) Methods—a title specific search of the Web of Science database was executed using the keywords ‘intraoperative MRI’, ‘intraoperative magnetic resonance imaging’, and “IOMRI’ on 23rd April 2021. Results—663 articles met the inclusion criteria and were included in the final analysis. In addition, the 100 most cited were analysed as well. Among these 100 articles, 76 were original research papers, while 14 others were review articles. Amongst all the authors, Ganslandt contributed the maximum number of articles, with USA being the largest single source of these articles, followed by Germany. Interestingly, a shift of trends from “Image guided surgery’ and ‘accuracy’ in the early 2000s to ‘extent of resection’, ‘impact’, and ‘survival’ in the later years was noted. (3) Conclusions—IOMRI has now become an integral part of neurosurgery, especially in neuro-oncology. Focus has now shifted from implementation to refinement of technique in the form of functional and oncological outcomes. Therefore, future research in this direction is imperative and will be of more impact that in any other sub-field related to IOMRI.