Second surgery for relapsed glioblastoma: an observational study on criteria for patient selection in real life.

Aim: There is little consensus on salvage management of glioblastoma after recurrence, for lack of evidence. Materials & methods: A retrospective study of treatments in patients with recurrent glioblastoma. Results: Surgery at recurrence was related to better overall survival (OS) and progression-free survival (PFS). Surgery at recurrence, Karnofsky index, MGMT methylation status, younger age at diagnosis and number of chemotherapy cycles were positive factors for OS and PFS. The benefit of OS was relevant for a second surgery performed at least 9 months after the first one. Systemic treatments after the second surgery were linked to an improved PFS. Conclusion: Younger age, Karnofsky index, MGMT methylation status and a median time between surgeries ≥9 months may be criteria for eligibility for surgery at recurrence.

[Box: see text].

Prognostic scoring system for surgical treatment of intramedullary spinal cord metastases.

Although rare, intramedullary spinal cord metastases (ISCMs) are on the rise, most likely due to prolonged survival and improved outcomes as a result of the advances in cancer treatment for cancer patients. While the management of these lesions remains controversial, surgery for ISCM has recently been advocated for selected patients. We performed a retrospective analysis on 30 patients who were surgically treated for intramedullary spinal cord metastases in order to determine a preoperative prognostic scoring system to guide patient selection for surgical interventions. The scoring system was designed to decide between surgery or other therapeutic procedures. The five parameters selected and employed in the assessment system were: 1) patient's general condition, 2) age, 3) primary site of the cancer, 4) number of other extramedullary metastases and 5) severity of neurologic symptoms. Prognosis could not be predicted from a single parameter. These five factors were added together to give a prognostic score between 1 and 10. The average survival period of patients with a prognostic score between 1 and 3 points was 3 months; 11 patients with a score of 4 and 5 points had a mean survival of 7.63 months, while patients with a prognostic score between 6 and 10 was 14.8 months. According to our prognostic scoring system for surgical treatment of ISCM, surgery should be performed in those patients who score above 6 points, while radiotherapy/chemotherapy or palliative care is recommended for those who score between 1 and 3 points. A prognostic score of 4 and 5 represents a grey area where surgeons must use their judgment on whether to intervene either medically or surgically. This scoring system could facilitate decision-making in the management of patients with intramedullary spinal cord metastases.

The Glioma-IRE project - Molecular profiling in patients with glioma: steps toward an individualized diagnostic and therapeutic approach.

BACKGROUND: This study aimed to characterize the genetic profile of patients with glioma and discuss the impact of next-generation sequencing in glioma diagnosis and treatment. METHODS: Between 2019 and 2022, we analyzed the genetic profile of 99 patients with glioma through the Oncomine Focus Assay. The assay enables the detection of mutations in 52 driver genes, including single nucleotide variants (SNVs), copy number variants (CNVs), and gene fusions. We also collected and analyzed patients' clinic characteristics and treatment outcomes. RESULTS: Over a period of 35 months, 700 patients with glioma followed by our neuro-oncology unit were screened, and 99 were enrolled in the study; most of the patients were excluded for inadequate non-morphological MRI or lack/inadequacy of the tissue samples. Based on our findings, most patients with glioma present mutations, such as SNVs, CNVs or gene fusions. Our data were similar to those reported by The Cancer Genome Atlas Program in terms of frequency of SNVs and CNVs, while we observed more cases of gene fusions. Median overall survival, progression-free survival, and time to progression were significantly lower for patients with grade VI glioblastoma than those with other gliomas. Only four patients were offered a targeted treatment based on the mutation detected; however, only one received treatment, the others could not receive the selected treatment because of worsening clinical status. CONCLUSION: Routine timely molecular profiling in patients with glioma should be implemented to offer patients an individualized diagnostic approach and provide them with advanced targeted therapy options if available.

Surgical treatment of cerebellar metastases in elderly patients: A threshold that moves forward?

The impact of surgery for cerebellar brain metastases in elderly population has been the object of limited studies in literature. Given the increasing burden of their chronic illnesses, the decision to recommend surgery remains difficult. All patients aged ≥65 years, who underwent surgical resection of a cerebellar brain metastasis from May 2000 and May 2021 at IRCCS National Cancer Institute "Regina Elena", were analyzed. The study cohort includes 48 patients with a mean age of 70.8 years. 7 patients belonged to the II Class according to the RPA classification, 41 to the III Class; the median GPA classification was 1.5. Median pre-operative and post-operative KPS was 60. Median Charlson Comorbidity Index (CCI) was 11; median 5-variable modified Frailty Index was 2. Overall, 14 patients (29%) presented perioperative neurologic and systemic complications. 34 patients (71%) were able to perform adjuvant therapies as RT and/or CHT after surgery. A higher CCI predicted complications occurrence (p = 0.044), while significant factors for a post-operative KPS ≥70, were i) hemispheric location of the metastasis, ii) higher pre-operative KPS, iii) RPA II classification. Median Overall Survival was 7 months. A post-operative KPS <70 (p = 0.004) and a short time interval between diagnosis of the primary tumor and cerebellar metastasis appearance, were predictive for a worse outcome (p = 0.012). Our study suggests that selected elderly patients with cerebellar metastases may benefit from microsurgery to continue their adjuvant therapies, although a high complications rate should be taken in account.

Breast cancer metastasis: Is it a matter of OMICS and proper ex-vivo models?

Genomics has greatly increased the understanding of the study of breast cancer (BC) and has shaped the concept of intra-tumor heterogeneity, currently recognized as a propelling force for cancer progression. In this context, knowledge and understanding of metastatic breast cancer (mBC) has somehow lagged behind that of primary breast cancer. This may be explained by the relative scarcity of matched mBC samples, however it is possible that the mutation spectrum obtained from primary BC does not capture the full complexity of the metastatic disease. Here, we provide a few examples supporting this possibility, from public databases. We evoke the need to perform an integrated multi-OMICS characterization of mBC, to obtain a broad understanding of this complex disease, whose evolution cannot be explained solely by genomics. Pertinent to this, we suggest that rather an infrequent use of Patient-Derived -Tumor-Organoids (PDTOs) may be influenced by assuming that the metastatic conditions of PDTOs growth (mPDTOs) should be similar to those of the tissue of origin. We challenge this view by suggesting that the use of "target-organ inspired" growth conditions for mPDTOs, may better fit the emerging knowledge of metastatic disease. Thus, the integrated use of multi-OMICS and of clinically relevant mPDTOs may allow a further understanding of such disease and foster therapeutically relevant advances. We believe that our points may be valid for other solid cancers.

Recurrent glioblastoma: which treatment? A real-world study from the Neuro-oncology Unit "Regina Elena" National Cancer Institute.

BACKGROUND: The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and short duration response rate. Although clinical trials represent the "gold standard" for providing evidence on efficacy of specific treatment strategies, real-world data can be considered more representative of the "real" GBM population. OBJECTIVE: To describe the management of GBM recurrence in a large real-world sample. METHODS: We analysed retrospectively the data stored in the database of the Neuro-oncology Unit, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy. We considered only data of patients with histological diagnosis of GBM and disease recurrence during their follow-up. We excluded patients who did not receive treatment after the diagnosis. RESULTS: We analysed 422 patients (64% males, 36% females) with a mean age of 59.6 (range 16-87) years. At GBM recurrence, 135 (32.0%) patients underwent palliative care, and 287 (68.0%) underwent other treatments. Patients on palliative care were older, had a worse performance status, and a shorter time between GBM diagnosis and its recurrence. Patients who received chemotherapy in combination with other treatments (surgery and/or radiation therapy) at GBM recurrence had a longer survival than those in palliative care (p < 0.001). Surgery or radiation therapy alone did not have any effect on survival as compared with palliative care (p < 0.001). CONCLUSION: This study confirms the importance of a multidisciplinary approach even at GBM recurrence, suggesting that combination treatments play a key role in management of disease.

Multidomain and long-term cognitive evaluation in malignant glioma patients.

Aim: We performed longitudinal evaluations of the neurocognitive status in glioma patients to describe possible variations over the course of illness. Materials and methods: Glioma patients underwent a complete battery of standardized neuropsychological tests pre-radiotherapy at 6, 12 and 24 months. Results: We enrolled 130 patients, 67.7% of whom had a deficit in at least one cognitive domain. The most affected domains included executive function (n = 68, 52.3%), long-term memory (n = 46, 35.3%) and short-term memory (n = 39, 30%). At follow-up, cognitive status worsened in 31.5%, remained unchanged in 38.4% and improved in 30.1% of patients. Conclusion: This is one of few studies investigating longitudinal neurocognitive status in a wide sample of patients to monitor neuropsychological changes due to tumor progression and treatment administration.

Malignant gliomas are brain tumors with dismal prognosis that can affect patients' neurocognitive status. We performed longitudinal neuropsychological assessments to describe variations due to illness progression and treatment administration. Patients underwent a battery of standardized neuropsychological tests tapping into different cognitive domains (memory, attention, abstract reasoning, executive functions, learning), pre-radiotherapy and at 6, 12 and 24 month follow-up. We enrolled 130 patients, and almost 70% of them had at least one cognitive deficit. The most affected domains were executive function and long- and short-term memory. At follow-up assessments, cognitive status worsened in one-third of patients, whereas it remained unchanged or improved in two-thirds of patients. This is one of few longitudinal studies investigating cognitive function in a large sample of patients to monitor changes along the illness course.

Surgical treatment of solitary intradural extramedullary spinal cord metastases from solid cancers of non-neurogenic origin. A multicenter study.

PURPOSE: Intradural extramedullary spinal metastases (IESM) represent an extremely rare manifestation of systemic cancer. We evaluated the surgical indications, complications and outcome in a series of 43 patients with solitary intradural extramedullary metastases originating from solid cancer of non-neurogenic origin. METHODS: Patients' age, histopathological diagnoses of primary cancer, tumor size, spinal location, and extramedullary tumor dissemination were collected. Preoperative functional status, pre- and post-operative neurological status, extent of the tumor resection were also analyzed. RESULTS: The majority of IEMS occurred in the thoracic area, with the most common presenting symptoms ranging from motor (76.7%) to sensory (72%) deficits. Gross total resection was achieved in 55.8% of cases, while In 44.2% of patients a subtotal resection was performed due to strong adherence between the tumor and neural tissue. After surgery, 72.1% of patients exhibited improvement of symptoms in terms of pain relief and partial recovery of motor and/or sensory deficits, while neurologic functional status was severely affected postoperatively in 3 patients. CONCLUSION: Although there was no statistical significance between the different parameters and overall survival, KPS and the presence of other metastases were the strongest prognostic factors for overall survival and postoperative neurologic outcome.

Major Differences in Lymphocyte Subpopulations Between Cerebrospinal Fluid and Peripheral Blood in Non-Hodgkin Lymphoma Without Leptomeningeal Involvement: Flow Cytometry Evidence of a Cerebral Lymphatic System.

Cerebrospinal fluid (CSF) flow cytometry has a crucial role in the diagnosis of leptomeningeal disease in onco-hematology. This report describes the flow cytometry characterization of 138 CSF samples from patients affected by non-Hodgkin lymphoma, negative for disease infiltration. The aim was to focus on the CSF non-neoplastic population, to compare the cellular composition of the CSF with paired peripheral blood samples and to document the feasibility of flow cytometry in hypocellular samples. Despite the extremely low cell count (1 cell/µl, range 1.0-35) the study was successfully conducted in 95% of the samples. T lymphocytes were the most abundant subset in CSF (77%; range 20-100%) with a predominance of CD4-positive over CD8-positive T cells (CD4/CD8 ratio = 2) together with a minority of monocytes (15%; range 0-70%). No B cells were identified in 90% of samples. Of relevance, a normal, non-clonal B-cell population was documented in 5/7 (71%) patients with primary central nervous system lymphoma at diagnosis (p<0.0001), suggesting a possible involvement of blood-brain barrier cell permeability in the pathogenesis of cerebral B-cell lymphomas. The highly significant differences between CSF and paired peripheral blood lymphoid phenotype (p<0.0001) confirms the existence of an active mechanism of lymphoid migration through the meninges.

Eribulin in brain metastases of breast cancer: outcomes of the EBRAIM prospective observational trial.

Background: Eribulin shows some activity in controlling brain metastasis in breast cancer. Methods: This observational, multicenter study evaluated brain disease control rates, survival and safety in patients with brain metastatic breast cancer treated with eribulin in clinical practice. Results: A total of 34 patients were enrolled (mean age 49 years, 91% with visceral metastases) and 29 were evaluable for brain disease. Fourteen achieved disease control and showed a longer time without progression: 10 months (95% CI: 2.3-17.7) versus 4 months (95% CI: 3.3-4.7) in the control group (p = 0.029). Patients with clinical benefits at 6 months had longer survival. Leukopenia and neutropenia were the most frequent grade 3-4 toxicities. Conclusion: Eribulin confirms its effectiveness in patients with brain metastatic breast cancer. Further studies on larger cohorts are needed to confirm the results.

Surgical treatment of intramedullary spinal cord metastases: functional outcome and complications-a multicenter study.

Intramedullary spinal cord metastasis (ISCM) is a rare event in the course of advanced malignancy. Management of these lesions remains controversial. Recently, surgery for ISCM has been advocated for selected patients. We performed a retrospective analysis of the clinical course, complications, and outcome of 30 patients surgically treated for ISCM. Patients' age, histopathological diagnoses of primary cancer, tumor size, spinal location, and extramedullary tumor dissemination were collected. Preoperative functional status, pre- and postoperative neurological status, and extent of the tumor resection were also analyzed. Predominant tumor location was thoracic, followed by cervical and conus medullaris. Lung cancer constituted the majority of primary malignancies. In 9 cases, one of the indications for spinal surgery was to obtain a histopathological diagnosis. On admission, all patients presented with neurological symptoms suggestive of myelopathy. After surgery, 18 patients exhibited improvement of symptoms in terms of pain relief and partial recovery of motor and/or sensory deficits; 6 patients were unchanged, while 6 patients exhibited postoperative deterioration. Median survival time after surgery was 9.9 months. Age > 70 years old, presence of systemic metastases, preoperative neurological non functional status, and lung cancer as primary tumor were all factors associated with a worse survival prognosis. This study did not show a clear survival difference between gross total and subtotal ISCM tumor resection. Patients who underwent gross total resection had a worse functional outcome with respect to patients with only partial resection. Gross total resection with low morbidity must be the surgical target, but when not possible, subtotal resection and adjuvant therapy are a valid therapeutic option.

Hemorrhagic Attitude in Frameless and Frame-Based Stereotactic Biopsy for Deep-Seated Primary Central Nervous System Lymphomas in Immunocompetent Patients: A Multicentric Analysis of the Last Twenty Years.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare manifestation of aggressive extranodal non-Hodgkin lymphoma. In patients with deep-seated lesions, stereotactic brain biopsy (SBB) is an accepted diagnostic procedure to obtain histopathologic confirmation. OBJECTIVE: The aim of this study was to assess the feasibility, diagnostic yield, safety, and complications of stereotactic procedures in midline and deep-seated PCNSLs. METHODS: Patients selected had received a histopathologic diagnosis of PCNSL localized in deep-seated midline structures, obtained by SBB. The intraoperative frozen section was executed as an integral part of the procedure. Computed tomography scan was performed after surgery. RESULTS: A total of 476 SBBs were performed between January 2000 and December 2019 . Of these SBBs, 91 deep-seated lesions had a histologic diagnosis of PCNSL. A significant increase of the incidence of PCNSL compared with all other diseases was observed (P < 0.0001). Eight patients (8.7%) showed a symptomatic hemorrhage, 4 of whom required craniotomy. There were 4 deaths and 2 cases of permanent morbidity. The hemorrhage risk in the PCNSL group was statistically significant (P = 0.0003) compared with other histotypes. CONCLUSIONS: In suspected cases of PCNSL, a histopathologic diagnosis is necessary to distinguish it from glioblastoma or other, nonmalignant conditions. Deep-seated PCNSLs present a higher risk of biopsy-related morbidity and mortality. Intraoperative frozen section increases the diagnostic yield and reduces the number of sampling procedures. Postoperative computed tomography seems to be warranted in patients with suspected PCNSL.

Oblique Lateral Retroperitoneal Lumbar Pre-Psoas Approach for Vertebrectomy in Cancer Patients: Surgical Technique.

Due to the longer survival of cancer patients secondary to improved systemic treatments, there has been a recent increase in the incidence of spinal metastases. Metastatic disease involves the anterior vertebral body in 80% of cases. Progressive osseous invasion may result in pathologic vertebral fractures and neural structure compression. Surgical indications are spinal cord and cauda equina compression or spinal instability in patients with an expected survival of at least 6 months. Tumor resection and spine reconstruction in the lumbar region are technically demanding. Several approaches have recently been developed to access the lumbar spine: anterior lumbar approach (ALIF), lateral and extreme lateral transpsoas lumbar approach (LLIF, XLIF, DLIF), and oblique retroperitoneal lumbar pre-psoas approach (OLIF). Each technique has its advantages and drawbacks. OLIF is an emerging procedure that has progressively been used by spine surgeons. The retroperitoneal space allows direct access to the vertebra, thus avoiding injury to the paraspinal muscles, psoas muscle, and lumbar plexus. Between 2005 and 2017, 14 patients underwent somatectomy and spinal reconstruction using an oblique retroperitoneal lumbar pre-psoas approach at our institution. All were affected by lumbar vertebral metastases from solid and hematological tumors, and all presented a Tokuhashi score ≥ 12. L3 vertebral body was involved in 7 cases, L1 was involved in 3, L2 was involved in 2, and L4 was involved in 2. All patients underwent a lateral retroperitoneal approach to achieve vertebrectomy and spinal reconstruction with a cage. Spinal fixation was completed with pedicle screws and rods in 4 cases. No neurological worsening was noted except in one patient who presented a transitory deficit of the left ileopsoas muscle. The oblique retroperitoneal lumbar pre-psoas approach may be a valuable and feasible technique that is potentially able to significantly reduce tissue trauma in patients while still making it possible to achieve corpectomy and solid reconstruction of lumbar vertebral bodies. To our knowledge, this is the first reported series of patients with lumbar spinal metastases treated with the oblique retroperitoneal lumbar pre-psoas approach.

Schwannomas of the sciatic nerve: A rare and neglected diagnosis. A review of the literature with two illustrative cases.

OBJECTIVE: Schwannomas of the sciatic nerve, which is the largest nerve of the human body, are very rare accounting for ≤ 1% of all schwannomas. They often may raise confusion with other more common causes of sciatica, such as lumbar degenerative and inflammatory diseases or spinal tumors, which may often lead to a late correct diagnosis. PATIENTS AND METHODS: We present two cases of sciatic nerve schwannomas that were recently treated at our Institution, and we review the pertinent English literature on this topic over the last 15 years, yielding twenty three cases to analyze. RESULTS: Even if sciatic nerve schwannomas are a rare occurrence, a thorough clinical and radiological evaluation of the sciatic nerve should be considered whenever a sciatic pain is not otherwise explained. A positive Tinel sign and a palpable mass along the course of the sciatic nerve may be strong clues to achieve the diagnosis. Combined morphological and advanced functional MRI imaging may help to differentiate benign from malignant peripheral nerve sheath tumors, avoiding unnecessary preoperative biopsy. CONCLUSIONS: A standard microsurgical technique guided by ultrasound and neurophysiologic monitoring, allows in most of the cases a safe removal of the tumor and very satisfactory post-operative results for the patients.

Neurocognitive evaluation in older adult patients affected by glioma.

BACKGROUND: Glioblastoma (GBM) has an increasing incidence and dismal prognosis in older adults. This study evaluated neurocognitive status of an older adult population with GBM and its correlation with clinical and demographical variables. METHODS: Each patient underwent an extended neuropsychological evaluation by means of a battery of standardized tests describing eight cognitive domains: global function; verbal learning; short- and long-term memory (LTM); executive functions (EFs); abstract reasoning (AR); attention; and visuo-constructional abilities (CA). RESULTS: We assessed 79 patients with GBM (median age: 74 years). Out of this initial sample, a subgroup of seventeen patients with six-month median time underwent a follow-up test session. 46 out of the 79 patients (58.2%) presented multi-domain cognitive impairment, 24 patients (30.3%) showed single-domain cognitive impairment and only seven (9%) showed no cognitive impairment. Kaplan Meier estimator showed that patients with AR deficit had a poorer prognosis in terms of progression-free survival and overall survival (p < .001). At the multivariate analysis AR (deficit vs non; hazard ratio (HR) = 5.07, 95%; confidence interval (CI): 1.91-13.46; p < .001) was correlated with disease progression and overall survival, AR (deficit vs non; HR = 7.24, 95% CI: 2.58-20.32; p < .001). Eight out of seventeen patients who underwent follow-up test session showed cognitive improvement, five resulted in further deterioration, and four patients remained stable. LTM, EF, and CA were the most affected functions at follow-up, while verbal learning was the most improved one in patients with cognitive improvement. CONCLUSIONS: Cognitive functioning evaluation should be included among the standard clinical endpoints in the treatment of older adult neuro-oncology patients.

Open Kyphoplasty for Metastatic Spine Disease: A Retrospective Clinical Series.

OBJECTIVE: Symptomatic metastatic spine disease (MSD), is a challenging disease involving 3%-20% of patients with bone metastases. Different surgical options are available and must be tailored to the general and neurologic conditions of the patients. Open kyphoplasty (OKP) refers to decompressive hemilaminectomy, associated with a contralateral percutaneous kyphoplasty, and in some cases, to a posterior stabilization. The aim of the study was to critically review our experience during the last decade with OKP in patients with cancer. METHODS: Fifty-three patients with cancer underwent OKP for symptomatic MSD. The Tokuhashi score and Spinal Instability Neoplastic Score were calculated for each patient. Length of hospital stay, perioperative complications, incidence of adjacent-level fractures, and median survival after surgery were evaluated. Karnofsky Performance Status, visual analog scale, and Dennis Pain Score were calculated preoperatively, postoperatively, and at last follow-up. RESULTS: Median Tokuhashi score and Spinal Instability Neoplastic Score were 10 and 10, respectively. The mean volume of filling material inserted was 3.6 mL. Median operative time was 180 minutes. Complications included 8 leakages (15%), 2 permanent motor deficits (3.8%), and 2 asymptomatic pulmonary embolisms (3.8%). Mean length of hospital stay was 7 days. A significant improvement was observed in Karnofsky Performance Status, visual analog scale score, and Dennis Pain Score (P < 0.0001). Median follow-up was 16 months and overall survival 22 months. CONCLUSIONS: OKP was an effective treatment of symptomatic MSDs in selected oncologic patients with low Tokuhashi scores. It relieved lateral epidural compressions, expanded indications of palliative surgery in patients who were not otherwise surgical candidates, and rapidly dealt with cement leakages.

A multicenter real-world study of bevacizumab in heavily pretreated malignant gliomas: clinical benefit is a plausible end point?

Aim: This multicenter, retrospective study evaluates the clinical benefit (CB) of bevacizumab, alone or in combination, in recurrent gliomas (RG). Patients & methods: The CB was measured as a reduction of corticosteroid dosage and an improvement ≥20 points in the Karnofsky Performance Status lasting ≥3 months. Results: We collected data of 197 RG patients. A CB was observed in 120, patients without significant differences between patients treated with bevacizumab alone or in combination. The rate of patients who achieved a CB and free from progression at 1 year was 21.5 versus 1.4% in patients who did not report CB. Conclusion: The majority of RG patients treated with bevacizumab reported CB. Moreover, patients with CB showed improved survival.

Comorbidities in elderly patients with glioblastoma: a field-practice study.

AIM: This single-center study evaluated the effect of comorbidities on progression-free and overall survival in elderly patients with glioblastoma multiforme (GBM). PATIENTS & METHODS: Comorbid conditions were identified in each patient with the modified version of the cumulative illness rating scale (CIRS). RESULTS:  Total of 118 patients with GBM were enrolled. An age of >75 years at diagnosis, high CIRS, comorbidity index and performance status play a predictive role on survival. CONCLUSION: Comorbidities play an important prognostic role in elderly patients with GBM, a factor too often neglected in clinical practice. If the prognostic role of comorbidity measured by CIRS on outcome will be confirmed, it would be interesting to add it in the algorithm for treatment choice in elderly GBM patients.