Glioblastoma and Internal Carotid Artery Calcium Score: A Possible Novel Prognostic Partnership?

Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium score as a surrogate marker of the coronary calcium score in 32 patients with lung cancer. Subsequently, we assessed the impact of the ICA calcium score on overall survival in GBM patients treated with radio-chemotherapy. Results: We analysed 50 GBM patients. At the univariate analysis, methyl-guanine-methyltransferase gene (MGMT) promoter methylation (p = 0.048), gross total tumour resection (p = 0.017), and calcium score (p = 0.011) were significant prognostic predictors in patients with GBM. These three variables also maintained statistical significance in the multivariate analysis. Conclusions: the ICA calcium score could be a promising prognostic biomarker in GBM patients.

The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study.

PURPOSE: Adult Diffuse midline glioma (DMG) is a very rare disease. DMGs are currently treated with radiotherapy and chemotherapy even if only a few retrospective studies assessed the impact on overall survival (OS) of these approaches. METHODS: We carried out an Italian multicentric retrospective study of adult patients with H3K27-altered DMG to assess the effective role of systemic therapy in the treatment landscape of this rare tumor type. RESULTS: We evaluated 49 patients from 6 Institutions. The median age was 37.3 years (range 20.1-68.3). Most patients received biopsy as primary approach (n = 30, 61.2%) and radiation therapy after surgery (n = 39, 79.6%). 25 (51.0%) of patients received concurrent chemotherapy and 26 (53.1%) patients received adjuvant temozolomide. In univariate analysis, concurrent chemotherapy did not result in OS improvement while adjuvant temozolomide was associated with longer OS (21.2 vs. 9.0 months, HR 0.14, 0.05-0.41, p < 0.001). Multivariate analysis confirmed the role of adjuvant chemotherapy (HR 0.1, 95%CI: 0.03-0.34, p = 0.003). In patients who progressed after radiation and/or chemotherapy the administration of a second-line systemic treatment had a significantly favorable impact on survival (8.0 vs. 3.2 months, HR 0.2, 95%CI 0.1-0.65, p = 0.004). CONCLUSION: In our series, adjuvant treatment after radiotherapy can be useful in improving OS of patients with H3K27-altered DMG. When feasible another systemic treatment after treatment progression could be proposed.

Present and Future of Immunotherapy in Patients With Glioblastoma: Limitations and Opportunities.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Standard therapies, including surgical resection, chemoradiation, and tumor treating fields, have not resulted in major improvements in the survival outcomes of patients with GBM. The lack of effective strategies has led to an increasing interest in immunotherapic approaches, considering the success in other solid tumors. However, GBM is a highly immunosuppressive tumor, as documented by the presence of several mechanisms of immune escape, which may represent a reason why immunotherapy clinical trials failed in this kind of tumor. In this review, we examine the current landscape of immunotherapy strategies in GBM, focusing on the challenge of immunoresistance and potential mechanisms to overcome it. We discussed completed and ongoing clinical trials involving immune checkpoint inhibitors, oncolytic viruses, vaccines, and CAR T-cell therapies, to provide insights into the efficacy and outcomes of different immunotherapeutic interventions. We also explore the impact of radiotherapy on the immune system within the GBM microenvironment highlighting the complex interactions between radiation treatment and the immune response.

Spinal ependymoma in adults: from molecular advances to new treatment perspectives.

Ependymomas are rare glial tumors with clinical and biological heterogeneity, categorized into supratentorial ependymoma, posterior fossa ependymoma, and spinal cord ependymoma, according to anatomical localization. Spinal ependymoma comprises four different types: spinal ependymoma, spinal ependymoma MYCN-amplified, myxopapillary ependymoma, and subependymoma. The clinical onset largely depends on the spinal location of the tumor. Both non-specific and specific sensory and/or motor symptoms can be present. Owing to diverse features and the low incidence of spinal ependymomas, most of the current clinical management is derived from small retrospective studies, particularly in adults. Treatment involves primarily surgical resection, aiming at maximal safe resection. The use of radiotherapy remains controversial and the optimal dose has not been established; it is usually considered after subtotal resection for WHO grade 2 ependymoma and for WHO grade 3 ependymoma regardless of the extent of resection. There are limited systemic treatments available, with limited durable results and modest improvement in progression-free survival. Thus, chemotherapy is usually reserved for recurrent cases where resection and/or radiation is not feasible. Recently, a combination of temozolomide and lapatinib has shown modest results with a median progression-free survival (PFS) of 7.8 months in recurrent spinal ependymomas. Other studies have explored the use of temozolomide, platinum compounds, etoposide, and bevacizumab, but standard treatment options have not yet been defined. New treatment options with targeted treatments and immunotherapy are being investigated. Neurological and supportive care are crucial, even in the early stages. Post-surgical rehabilitation can improve the consequences of surgery and maintain a good quality of life, especially in young patients with long life expectancy. Here, we focus on the diagnosis and treatment recommendations for adults with spinal ependymoma, and discuss recent molecular advances and new treatment perspectives.

Case report: The lesson from opioid withdrawal symptoms mimicking paraganglioma recurrence during opioid deprescribing in cancer pain.

Pain is one of the predominant and troublesome symptoms that burden cancer patients during their whole disease trajectory: adequate pain management is a fundamental component of cancer care. Opioid are the cornerstone of cancer pain relief therapy and their skillful management must be owned by physicians approaching cancer pain patients. In light of the increased survival of cancer patients due to advances in therapy, deprescription should be considered as a part of the opioid prescribing regime, from therapy initiation, dose titration, and changing or adding drugs, to switching or ceasing. In clinical practice, opioid tapering after pain remission could be challenging due to withdrawal symptoms' onset. Animal models and observations in patients with opioid addiction suggested that somatic and motivational symptoms accompanying opioid withdrawal are secondary to the activation of stress-related process (mainly cortisol and catecholamines mediated). In this narrative review, we highlight how the lack of validated guidelines and tools for cancer patients can lead to a lower diagnostic awareness of opioid-related disorders, increasing the risk of developing withdrawal symptoms. We also described an experience-based approach to opioid withdrawal, starting from a case-report of a symptomatic patient with a history of metastatic pheochromocytoma-paraganglioma.

Actionable molecular alterations in newly diagnosed and recurrent IDH1/2 wild-type glioblastoma patients and therapeutic implications: a large mono-institutional experience using extensive next-generation sequencing analysis.

BACKGROUND: Next-generation sequencing (NGS) panels enable the identification of alterations in cancer-related genes. This may guide a molecularly targeted strategy for the treatment of glioblastoma (GBM). MATERIAL AND METHODS: We retrospectively analysed data obtained using FoundationOne®CDx in a large cohort of IDH1/2 wild-type GBM. We aimed to 1) identify potentially actionable molecular alterations at diagnosis and/or recurrence based on ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) defined categories of targetability, 2) understand the clinical implications of NGS in terms of access to and activity of targeted therapies. RESULTS: In 442 samples, an NGS profile was available in 98.2%. The median time from diagnosis to NGS profiling was 7.4 months (interquartile range (IQR): 3.4-13.2). Although about half of the patients had at least one actionable molecular alteration, only 3.4% of them were classified as ESCAT IB-IC and 6.7% as ESCAT IIB. Only 36 patients (10.5%) received personalised treatment in clinical trials or as off-label/compassionate use from second-line (median line 3). Most patients did not receive targeted therapy due to clinical deterioration/death (49.6%). Patients treated with dabrafenib/trametinib (9 patients) had the highest disease control rate of 77% and an objective response rate of 22%, with a median progression-free survival (PFS) of 5.2 months. No complete/partial responses were seen with the other regimens. 4/9 (44.4%) patients on anti-BRAF/anti-MEK, 2/4 patients (50%) on erdafitinib and 1/1 patient on capmatinib had a PFS ratio > 1.3. One recurrent GBM patient with ROS1-GOCP fusion maintained a complete response for 11.3 months on entrectinib. CONCLUSIONS: Our study demonstrated the feasibility of NGS in GBM samples. As the number of clinically relevant targets was limited and only a small group of GBM patients were treated with targeted therapy, NGS testing should be performed in the context of clinical trials. Our results support the activity of anti-BRAF/anti-MEK, while for the other agents prospective study results are needed to draw solid conclusions.

Association between thyroid function and regorafenib efficacy in patients with relapsed wild-type IDH glioblastoma: a large multicenter study.

PURPOSE: Regorafenib demonstrated encouraging results in recurrent glioblastoma patients. Some studies showed that changes in circulating thyroid hormones (fT3, fT4, fT3/fT4 ratio) can be considered as prognostic factors in patients with various types of tumors. We designed this study to investigate the relationship between baseline thyroid variables and outcome in IDH-wild type GBM patients who were treated with regorafenib. METHODS: This multicenter retrospective study included recurrent IDH-wild-type glioblastoma patients treated with regorafenib. Only patients with baseline thyroid function values (TSH, fT3, fT4, fT3/fT4 ratio) available were evaluated. RANO criteria were used to analyze neuroradiological response. Survival curves were estimated using the Kaplan-Meier method. The relationships between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4) and survival (PFS, OS) were investigated with Cox regression models. RESULTS: From November 2015 to April 2022, 134 recurrent IDH-wildtype GBM patients were treated with regorafenib and 128 of these had information on baseline thyroid function value. Median follow-up was 8 months (IQR 4.7-14.0). Objective Response Rate was 9% and Disease Control Rate was 40.9%. Median PFS was 2.7 months (95%CI 2.2-3.6) and median OS was 10.0 months (95%CI 7.0-13.0). Lower baseline TSH value in the blood was correlated with a higher rate of disease progression to regorafenib (p = 0.04). Multivariable analyses suggested a non-linear relationship between PFS (p = 0.01) and OS (p = 0.03) with baseline fT3/fT4 ratio. CONCLUSION: In recurrent wild-type IDH glioblastoma patients, baseline fT3/fT4 ratio showed a non-linear relationship with survival, with different impacts across the spectrum of fT3/fT4 ratio. Moreover, baseline TSH may be a predictor of regorafenib activity.

The role of radiation therapy and systemic treatments in meningioma: The present and the future.

Meningiomas are the most prevalent tumors of the central nervous system. Their standard treatment is surgery, which can be curative. Adjuvant radiotherapy treatment is reserved for newly diagnosed cases of grade II and grade III meningiomas in cases of recurrent disease or when surgery is not radical or feasible. However, around 20% of these patients cannot undergo further surgical and/or radiotherapy treatment. Systemic oncological therapy can find its place in this setting. Several tyrosine kinase inhibitors have been tested (gefitinib, erlotinib, sunitinib) with unsatisfactory or negative results. Bevacizumab has shown encouraging results in these settings of patients. Immunotherapy with immune checkpoint inhibitors has reported interesting results with modest objective response rates. Several ongoing studies are assessing different target therapies and multimodal therapies; the results are to be disclosed. Not only a better understanding of the molecular characteristics in meningiomas has allowed the gathering of more information regarding pathogenesis and prognosis, but in addition, the availability of new target therapy, immunotherapy, and biological drugs has widened the scope of potentially effective treatments in this patient population. The aim of this review was to explore the radiotherapy and systemic treatments of meningioma with an analysis of ongoing trials and future therapeutic perspectives.

Knowing when to discontinue Temozolomide therapy in responding aggressive pituitary tumors and carcinomas: a systematic review and Padua (Italy) case series.

INTRODUCTION: Pituitary adenomas can show a tendency to grow, despite multimodal treatment. Temozolomide (TMZ) has been used in the last 15 years in patients with aggressive pituitary tumors. TMZ requires a careful balance of different expertise, especially for selection criteria. AREAS COVERED: We conducted: (1) a systematic review of the published literature from 2006 to 2022, collecting only cases with a complete description of patient follow-up after TMZ discontinuation; (2) a description of all patients with aggressive pituitary adenoma or carcinoma treated in Padua (Italy). EXPERT OPINION: There is considerable heterogeneity in the literature: TMZ cycles duration ranged from 3 to 47 months; the follow-up time after TMZ discontinuation ranged from 4 to 91 months (mean 24 months, median 18 months), at least a stable disease has been reported in 75% of patients after a mean 13 months (range 3-47 months, median 10 months). The Padua (Italy) cohort reflects the literature. Future directions to explore are to understand the pathophysiological mechanism of TMZ resistance escape, to develop predicting factors to TMZ treatment (especially through the delineation of the underlying transformation processes), and to further expand the therapeutic applications of TMZ (as neoadjuvant, combined with radiotherapy).

Antigen rapid diagnostic test monitoring for SARS-CoV-2 in asymptomatic and fully vaccinated cancer patients: Is it cost-effective?

BACKGROUND: Routine testing for cancer patients not presenting COVID-19-related symptoms and fully vaccinated for SARS-CoV-2 prior to cancer treatment is controversial. METHODS: In this retrospective study we evaluated whether antigen-rapid-diagnostic-test (Ag-RDT) monitoring for SARS-CoV-2 in a large cohort of consecutive asymptomatic (absence of SARS-CoV-2-related symptoms such as fever, cough, sore throat or nasal congestion) and fully vaccinated cancer patients enrolled in a short period during cancer treatment has an impact on the therapeutic path of cancer patients. RESULTS: From December 27, 2021, to February 11, 2022, 2439 cancer patients were screened through Ag-RDT for SARS-CoV-2 before entering the hospital for systemic treatment. Fifty-three patients (2.17%) tested positive, of whom 7 (13.2%) subsequently developed COVID-related symptoms, generally mild. Cancer treatment was discontinued, as a precaution, in 49 patients (92.5%) due to the test positivity. CONCLUSION: SARS-CoV-2 screening in asymptomatic and fully vaccinated cancer patients during systemic treatment appeared to be not cost-effective: the low rate of SARS-CoV-2 positive patients and the low percentage of overt associated infection do not seem proportional to the direct costs (nursing work for swabs, costs of materials and patient monitoring) and indirect costs (dedicated rooms, extension of waiting times for patients and oncologists in delivering therapy as well as its discontinuation in the positive ones). It can, on the other hand, be detrimental when systemic cancer treatment is suspended as a precaution. Given the small number of patients testing positive and the rapid and favorable trend of the infection, it is recommended to always consider continuing systemic oncological treatment, especially when this impacts patient survival as in the adjuvant or neoadjuvant setting.

Impressive response to dabrafenib and trametinib plus silybin in a heavily pretreated IDH wild-type glioblastoma patient with BRAFV600E -mutant and SOX2 amplification.

Isocitrate dehydrogenase wild-type glioblastoma is the most frequent primary brain tumor in adult patients and its prognosis is still dismal with a median survival of about 1 year. BRAF V600E mutation, an important target for personalized therapy, has been identified in about 3% of these patients, but few data are available from prospective studies on the role of anti-BRAF drugs in adult glioblastoma patients. Moreover, SOX2 gene amplification and overexpression can represent an important mechanism of resistance to BRAF inhibitors by STAT3 gene activation. We present the case of a heavily pretreated 42-year-old man with BRAF V600E mutant and SOX2 amplification glioblastoma having a radiologic and metabolic [analyzed by a brain 18F-fluoro-ethyl-tyrosine([18F]FET) PET/MRI] complete response to the combination therapy with dabrafenib plus trametinib and silybin, a potent STAT3 inhibitor. The patient is currently undergoing treatment after a total of 24 months of continuation therapy with a good safety profile. In conclusion, we showed a promising activity of the personalized treatment of BRAF and MEK inhibitors in patient with BRAF V600E mutant glioblastoma; silybin can play an important role in decreasing drug resistance during BRAF inhibitor therapy, especially in patients with SOX2 amplification.

Efficacy and safety of chlorpromazine as an adjuvant therapy for glioblastoma in patients with unmethylated MGMT gene promoter: RACTAC, a phase II multicenter trial.

Introduction: Drug repurposing is a promising strategy to develop new treatments for glioblastoma. In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated MGMT gene promoter. Methods: This was a multicenter phase II single-arm clinical trial. The experimental procedure involved the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol in newly-diagnosed GBM patients carrying an unmethylated MGMT gene promoter. Progression-free survival was the primary endpoint. Secondary endpoints were overall survival and toxicity. Results: Forty-one patients were evaluated. Twenty patients (48.7%) completed 6 cycles of treatment with TMZ+CPZ. At 6 months, 27 patients (65.8%) were without progression, achieving the primary endpoint. Median PFS was 8.0 months (95% CI: 7.0-9.0). Median OS was 15.0 months (95% CI: 13.1-16.9). Adverse events led to reduction or interruption of CPZ dosage in 4 patients (9.7%). Discussion: The addition of CPZ to standard TMZ in the first-line treatment of GBM patients with unmethylated MGMT gene promoter was safe and led to a longer PFS than expected in this population of patients. These findings provide proof-of-concept for the potential of adding CPZ to standard TMZ treatment in GBM patients with unmethylated MGMT gene promoter. Clinical trial registration: https://clinicaltrials.gov/study/NCT04224441, identifier NCT04224441.

Advanced Adrenocortical Carcinoma: From Symptoms Control to Palliative Care.

The prognosis of patients with advanced adrenocortical carcinoma (ACC) is often poor: in the case of metastatic disease, five-year survival is reduced. Advanced disease is not a non-curable disease and, in referral centers, the multidisciplinary approach is the standard of care: if a shared decision regarding several treatments is available, including the correct timing for the performance of each one, overall survival is increased. However, many patients with advanced ACC experience severe psychological and physical symptoms secondary to the disease and the cancer treatments. These symptoms, combined with existential issues, debase the quality of the remaining life. Recent strong evidence from cancer research supports the early integration of palliative care principles and skills into the advanced cancer patient's trajectory, even when asymptomatic. A patient with ACC risks quickly suffering from symptoms/effects alongside the disease; therefore, early palliative care, in some cases concurrent with oncological treatment (simultaneous care), is suggested. The aims of this paper are to review current, advanced ACC approaches, highlight appropriate forms of ACC symptom management and suggest when and how palliative care can be incorporated into the ACC standard of care.

Simultaneous care in oncology: Assessment of benefit in relation to symptoms, sex, and age in 753 patients.

Background: Early activation of palliative care for patients with advanced cancer is central in the treatment trajectory. At the Veneto Institute of Oncology, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients are evaluated by an oncologist together with a palliative care team. Recently, we reported on consecutive patients admitted at SCOC from 2018 to 2021 in terms of appropriateness, process, and outcome indicators. Here, we report further analysis in the same group of 753 patients, evaluating other parameters and the correlation between symptom intensity, gender, age, and survival. Methods: SCOC data were retrieved from a prospectively maintained database. Results: Among the patients, 42.2% were women, and the median age was 68 years, with 46.7% of patients aged ≥70 years. The most prevalent disease type was gastrointestinal cancer (75.2%), and 90.9% of the patients had metastatic disease. The median score for the distress thermometer was 4; the vast majority of the patients (98.6%) reported physical problems, and 69.4% presented emotional issues. Younger women demonstrated a significantly greater median distress than other patients (p=0.0018). Almost all symptoms had a higher prevalence on the 0-3 Edmonton Symptom Assessment Scale (ESAS) score, except for fatigue. About 43.8% of the patients received systemic anticancer treatment (SAT) in the last 60 days of life, 15.0% of whom received SAT in the last month and 3.1% in the last 2 weeks. For some symptoms, women frequently had more ESAS >3. Pain and nausea were significantly less reported by older patients compared with younger adults. Men had a lower risk of having MUST score ≥ 2 (p=0.0311). Men and older patients showed a lower prognosis awareness (p=0.0011 and p=0.0049, respectively). Older patients received less SAT within the last 30 days of life (p=0.0006) and had death risk decreased by 20.0%. Conclusion: Our study identified two subgroups of patients with advanced cancer who require special attention and support due to important symptoms' burden detected by Patient Reported Outcome Measures tests: women and younger adults. These categories of patients require special attention and should be provided early access at SCOC. The role of an oncologist remains crucial to intercept all patients in need of early palliative care and balancing trade-offs of anticancer treatment in advanced metastatic disease.

The Overall Survival and Progression-Free Survival in Patients with Advanced Adrenocortical Cancer Is Increased after the Multidisciplinary Team Evaluation.

We aimed to evaluate the role of adrenal multidisciplinary team evaluation (MTE) in affecting the overall survival (OS) and progression-free survival (PFS) in patients with adrenocortical carcinoma (ACC). We included in a retrospective monocentric study 47 patients with ACC. We divided our cohort into group 1 (without adrenal-MTE discussion, ACC diagnosis from 2004 to 2012, n = 14) and group 2 (diagnosis and beginning of treatments after 2013, all discussed in the adrenal MTE, n = 33). OS was defined by the survival between the first and the last visit, while PFS as the time from the first visit to the progression of the disease. Kaplan−Meier curves were used to compare OS and PFS between Group 1 and Group 2. Group 1stages III−IV (n = 10) presented a shorter median OS than Group 2stages III−IV (25 patients, 4 vs. 31 months, p = 0.023). Likewise, the median PFS was lower in Group 1 as compared to Group 2 (2.9 vs. 17.2 months, p < 0.001). The gain in PFS (6 months) was also confirmed in stage III-IV patients (2.9 vs. 8.7 months, respectively, for Group 1 and Group 2, p = 0.02). Group 1 presented a median PFS of 4 months, while the median PFS of Group 2 was 14.7 months (p = 0.128). In conclusion, we found a significant gain in terms of survival in patients after the MTE discussion in 2013. Therefore, ACC patients should be referred to a tertiary center, ideally from the time of diagnosis, to promptly apply all available treatments, according to the single patient's clinical history and based on multidisciplinary management.

Definition of the Prognostic Role of MGMT Promoter Methylation Value by Pyrosequencing in Newly Diagnosed IDH Wild-Type Glioblastoma Patients Treated with Radiochemotherapy: A Large Multicenter Study.

Background. O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival. Methods. We evaluated glioblastoma patients with an assessment of MGMT methylation status by pyrosequencing from nine Italian centers. The inclusion criteria were histological diagnosis of IDH wild-type glioblastoma, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤2, and radio-chemotherapy treatment with temozolomide. The relationship between OS and MGMT was investigated with a time-dependent Receiver Operating Characteristics (ROC) curve and Cox regression models. Results. In total, 591 newly diagnosed glioblastoma patients were analyzed. The median OS was 16.2 months. The ROC analysis suggested a cut-off of 15% for MGMT methylation. The 2-year Overall Survival (OS) was 18.3% and 51.8% for MGMT methylation <15% and ≥15% (p < 0.0001). In the multivariable analysis, MGMT methylation <15% was associated with impaired survival (p < 0.00001). However, we also found a non-linear association between MGMT methylation and OS (p = 0.002): median OS was 14.8 months for MGMT in 0−4%, 18.9 months for MGMT in 4−40%, and 29.9 months for MGMT in 40−100%. Conclusions. Our findings suggested a non-linear relationship between OS and MGMT promoter methylation, which implies a varying magnitude of prognostic effect across values of MGMT promoter methylation by pyrosequencing in newly diagnosed IDH wild-type glioblastoma patients treated with chemoradiotherapy.

Innovating Strategies and Tailored Approaches in Neuro-Oncology.

Diffuse gliomas, the most frequent and aggressive primary central nervous system neoplasms, currently lack effective curative treatments, particularly for cases lacking the favorable prognostic marker IDH mutation. Nonetheless, advances in molecular biology allowed to identify several druggable alterations in a subset of IDH wild-type gliomas, such as NTRK and FGFR-TACC fusions, and BRAF hotspot mutations. Multi-tyrosine kinase inhibitors, such as regorafenib, also showed efficacy in the setting of recurrent glioblastoma. IDH inhibitors are currently in the advanced phase of clinical evaluation for patients with IDH-mutant gliomas. Several immunotherapeutic approaches, such as tumor vaccines or checkpoint inhibitors, failed to improve patients' outcomes. Even so, they may be still beneficial in a subset of them. New methods, such as using pulsed ultrasound to disrupt the blood-brain barrier, gene therapy, and oncolytic virotherapy, are well tolerated and may be included in the therapeutic armamentarium soon.

Cancer Patient-Reported Experience Measures (PREMs) Regarding the Policies Implemented to Contain the Spread of Sars-CoV-2 and Vaccination Campaign at Veneto Institute of Oncology.

PURPOSE: The SARS-CoV-2 spread has impacted Healthcare systems. COVID-19 pandemic has had consequences for patients with cancer, being associated with delays in diagnosis, in treatment And follow-up care, increase in overall infection rates and higher mortality. A survey on COVID-19 and a vaccination-questionnaire were developed at different times of the outbreak, to evaluate cancer patient-reported experience measures (PREMs) on the policies implemented to reduce the infection from SARS-CoV-2 and on the timing and methods of COVID-19 vaccination. PATIENTS AND METHODS: The survey was distributed to all patients accessing the Institute during the "first-wave" Of the pandemic, evaluating patients' concerns about the pandemic, the pandemics' consequences on their cancer care, and their perception Of the measures adopted to limit the infection spread. The vaccination-questionnaire was proposed to 10% of the first 5297 cancer patients vaccinated with two doses of the Pfizer-BioNTechCOVID-19 vaccine. This questionnaire aimed at assessing the degree Of satisfaction with the Institutional vaccination campaign and vaccination-related adverse events. RESULTS: From May 18th 2020 to June 15th 2020 the survey was completed by 3238 patients. Most of the responders expressed concern on the pandemic yet acknowledging their oncological disease as a priority. Measures implemented were appreciated by patients. Telemedicine was positively evaluated and the absence of the caregiver during the visit did not determine discomfort for two thirds of patients. From March 6th 2021 to May 8th 2021 the vaccination-questionnaire was completed by 357 patients. The 98.8% were satisfied with the vaccination campaign. No serious vaccination-correlated adverse events were reported. No patient had to delay/discontinue chemotherapy due to vaccination. CONCLUSION: PREMs during COVID-19 pandemic and related vaccination can provide important information to help reorganization of the health care systems for cancer care. Patients' feedback on the organizational changes implemented in the emergency period are essential for healthcare improvement and to help informed choices that are consistent with patients' needs.

PET/MR in recurrent glioblastoma patients treated with regorafenib: [18F]FET and DWI-ADC for response assessment and survival prediction.

OBJECTIVE: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. Diffusion-weighted imaging and O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography ([18F]FET PET) are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in diffusion-weighted imaging/apparent diffusion coefficient (ADC) and [18F]FET PET-derived parameters in patients who underwent PET/MR at both baseline and after starting regorafenib. METHODS: We retrospectively reviewed 16 consecutive GBM patients who underwent [18F]FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze four SD patients who underwent a third PET/MR after another four cycles of regorafenib. [18F]FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis. RESULTS: Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Kaplan-Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET- and ADC-derived metrics performed at least as well as RANO criteria (p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival. CONCLUSION: In recurrent glioblastoma patients treated with regorafenib, [18F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment. ADVANCES IN KNOWLEDGE: Simultaneous evaluation of [18F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival.