Abstract
Predictive factors for response to regorafenib in recurrent glioblastoma, IDH-
wildtype,
are scarcely recognized. The objective of this study was to identify molecular predictive factors for ...response to regorafenib using a clinically available platform. We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma,
IDH-
wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a clinically available platform. Moreover, MGMT methylation and EGFRvIII expression analyses were performed. Six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months, in line with literature data. NGS analysis revealed a mutation in the EGFR pathway in 18% of cases and a mutation in the mitogen-activated protein-kinase (MAPK) pathway in 18% of cases. In the remaining cases, no mutations were detected. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5
vs
4.5 months,
p
= 0.0061; for OS, 7
vs
9 months,
p
= 0.1076). Multivariate analysis confirmed that MAPK pathway mutations independently predicted a shorter PFS after regorafenib treatment (
p
= 0.0188). The negative prognostic role of MAPK pathway alteration was reinforced when we combined EGFR-mutated with EGFRvIII-positive cases. Recurrent glioblastoma tumors with an alteration in MAPK pathway could belong to the mesenchymal subtype and respond poorly to regorafenib treatment, while EGFR-altered cases have a better response to regorafenib. We thus provide a molecular selection criterion easy to implement in the clinical practice.
Sarcopenia is a geriatric syndrome characterized by a progressive loss of systemic muscle mass and decreased muscle strength or physical function. Several conditions have a role in its pathogenesis, ...significantly impacting adverse outcomes such as falls, functional decline, frailty, disability, multiple hospitalizations, and mortality. In the oncological setting, sarcopenia is associated with an increased risk of treatment toxicity, postoperative complications, and a higher mortality rate related to other causes (e.g., pneumonia). In the hematological field, even more so, sarcopenia predicts toxicity and response to treatments. In patients with hematologic malignancy, low muscle mass is associated with adverse outcomes and is a predictor of overall survival and non-relapse mortality. Therefore, it is essential to correctly recognize sarcopenia, evaluate the risk factors and their impact on the patient’s trajectory, and effectively treat sarcopenia. Sarcopenia is a reversible condition. The most effective intervention for reversing it is physical exercise combined with nutrition. The objective of clinical assessment focused on sarcopenia is to be able to carry out a “tailor-made treatment”.
Purpose
Psychological distress in primary malignant brain tumour (PMBT) patients is associated with poorer outcomes. Radiotherapy (RT) often induces side effects that significantly influence ...patients’ quality of life (QoL), with potential impact on survival. We evaluated distress, anxiety, depression, and QoL over time to identify patients with difficulties in these areas who required more intense psychological support.
Methods
Psychological questionnaires—Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy (FACT-G and FACT-Br)—were completed at the beginning (T0), in the middle (T1), directly after RT (T2), and 3 months after RT (T3). We personalised the psychological support provided for each patient with a minimum of three sessions (‘typical’ schedule) and a maximum of eight sessions (‘intensive’ schedule), depending on the patients’ psychological profiles, clinical evaluations, and requests. Patients’ survival was evaluated in the glioblastoma multiforme (GBM) patients, with an explorative intent.
Results
Fifty-nine consecutive PMBT patients receiving post-operative RT were included. For patients who were reported as ‘not distressed’ at T0, no statistically significant changes were noted. In contrast, patients who were ‘distressed’ at T0 showed statistically significant improvements in DT, HADS, FACT-G, and FACT-Br scores over time. ‘Not distressed’ patients required less psychological sessions over the study duration than ‘distressed’ patients. Interestingly, ‘not distressed’ GBM patients survived longer than ‘distressed’ GBM patients.
Conclusions
Increased psychological support improved distress, mood, and QoL for patients identified as ‘distressed’, whereas psychological well-being was maintained with typical psychological support in patients who were identified as being ‘not distressed’. These results encourage a standardisation of psychological support for all RT patients.
Abstract
Purpose
One of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), ...which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus.
Methods and materials
Pre-treatment MR images from patients who underwent WBRT between 2010 and January 2020—and post-radiotherapy images in cases of relapse—were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences.
Results
We analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it.
Conclusion
These data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus.
Currently, the management of older cancer patients is directed by a personalized approach and, where possible, a tailor-made treatment. Based on our previous experiences and considering the ...opportunity of combining a geriatric department and a radiation-oncology department, we have developed a path that follows the patient from the beginning of the treatment, taking into account the complications/late toxicities and the survivors. This study aimed to evaluate the impact of remodeling and restructuring some oncology, radiotherapy, and geriatrics services based on the primary evidence for managing older cancer patients. In 2020, Gemelli ART underwent 60,319 radiation-oncology treatments, admitted 943 patients in the radiation-oncology and supportive care ward, and treated and followed 15,268 patients in clinics. The average length of stay of the admitted patients was reduced from 20.6 days to 13.2 days. In 2021, 1196 patients were assessed for frailty, 847 were admitted for toxicity, and 349 patients were evaluated within the geriatric oncology and supportive care outpatient clinic, and it was found that 59.2% were fit, 31.6% were vulnerable, and 9.2% were frail. This experience has shown a reduction in hospitalizations and the average hospital stay of patients in the case of side effects, a high toxicity to treatments, and the possibility of treating patients with a high level of complexity. This approach should represent the future target of geriatric oncology with the global management of older or complex patients with cancer.
Cancer diagnoses expose patients to traumatic stress, sudden changes in daily life, changes in the body and autonomy, with even long-term consequences, and in some cases, to come to terms with the ...end-of-life. Furthermore, rising survival rates underline that the need for interventions for emotional wellbeing is in growing demand by patients and survivors. Cancer patients frequently have compliance problems, difficulties during treatment, stress, or challenges in implementing healthy behaviors. This scenario was highlighted during the COVID-19 emergency. These issues often do not reach the clinical attention of dedicated professionals and could also become a source of stress or burnout for professionals. So, these consequences are evident on individual, interpersonal, and health system levels. Oncology services have increasingly sought to provide value-based health care, considering resources invested, with implications for service delivery and related financing mechanisms. Value-based health care can improve patient outcomes, often revealed by patient outcome measures while seeking balance with economical budgets. The paper aims to show the Gemelli Advanced Radiation Therapy (ART) experience of personalizing the patients' care pathway through interventions based on technologies and art, the personalized approach to cancer patients and their role as "co-stars" in treatment care. The paper describes the vision, experiences, and evidence that have guided clinical choices involving patients and professionals in a co-constructed therapeutic pathway. We will explore this approach by describing: the various initiatives already implemented and prospects, with particular attention to the economic sustainability of the paths proposed to patients; the several pathways of personalized care, both from the patient's and healthcare professional perspective, that put the person's experience at the Gemelli ART Center. The patient's satisfaction with the treatment and economic outcomes have been considered. The experiences and future perspectives described in the manuscript will focus on the value of people's experiences and patient satisfaction indicators, patients, staff, and the healthcare organization.
Abstract
Introduction
Following the results from the REGOMA study, regorafenib has become the first chemotherapeutic option for recurrent glioblastoma, IDH-wildtype, in many countries. However, ...predictive factors for response to regorafenib are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform.
METHODS
We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH-wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a rapid, cheap, and clinically validated platform. MGMT methylation was assessed using methylation-specific PCR, and EGFRvIII expression was assessed using RT-PCR.
RESULTS
In our series, six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months: these data are consistent with current literature. Among clinical variables, gross-total resection was endowed with a positive prognostic value for PFS (p=0.0296, log-rank test). NGS analysis revealed a mutation in the EGFR pathway (EGFR and/or PIK3CA) in 18% of cases; a mutation in the mitogen-activated protein-kinase (MAPK) pathway (RAS and/or RET) in 18% of cases; no mutations in the remaining cases. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p=0.0061; for OS, 7 vs 9 months, p=0.1076). By combining NGS analysis with RT-PCR for EGFRvIII, we identified 14 patients with EGFR pathway activation, who had a significantly longer PFS and OS after regorafenib treatment. Multivariate analysis confirmed that MAPK pathway mutations predicted a scarce response to regorafenib treatment.
Conclusions
Through an easy-to-use and cheap platform, we identified a mesenchymal, MAPK-altered signature in IDH-wildtype glioblastoma, predictive of scarce response to regorafenib at recurrence. We thus provide a molecular selection criterion to implement in the clinical practice.
Evidence shows that shift work may be correlated with insulin resistance (IR). Therefore its estimation in clinical and prevention practice is of great significance. A cross-sectional study was ...performed to examine the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) Index among healthcare shift workers (HCSW).
A total of 272 healthcare workers (HCWs) were invited to participate in the study within an occupational surveillance framework, 137 were HCSW while 135 were healthcare non-shift workers (HCNSW). Fasting glucose, insulin, and HOMA-IR Index were evaluated in each participant and correlated with shift workers.
Indicators of glucose metabolism were significantly higher in HCSW
< 0.001, and logistic regression analysis confirmed a significant positive association between increased values of HOMA-IR Index and shift workers (
< 0.05).
Shift work could be a risk factor in developing insulin resistance and metabolic syndrome.
Environmental exposure to fibers of respirable size has been identified as a risk for public health. Experimental evidence has revealed that a variety of fibers, including fluoro-edenite, can develop ...chronic respiratory diseases and elicit carcinogenic effects in humans. Fluoro-edenite (FE) is a silicate mineral first found in Biancavilla (Sicily, Italy) in 1997. Environmental exposure to its fibers has been correlated with a cluster of malignant pleural mesotheliomas. This neoplasm represents a public health problem due to its long latency and to its aggression not alerted by specific symptoms. Having several biomarkers providing us with data on the health state of those exposed to FE fibers or allowing an early diagnosis on malignant pleural mesothelioma, still asymptomatic patients, would be a remarkable goal. To these purposes, we reported the miRNA transcriptome in human normal mesothelial cell line (MeT-5A) and in the human malignant mesothelioma cell line (JU77) exposed and not exposed to FE fibers. The results showed a difference in the number of deregulated miRNAs between tumor and nontumor samples both exposed and not exposed to FE fibers. As a matter of fact, the effect of exposure to FE fibers is more evident in the expression of miRNA in the tumor samples than in the nontumor samples. In the present paper, several pathways involved in the pathogenesis of malignant pleural mesothelioma have been analyzed. We especially noticed the involvement of pathways that have important functions in inflammatory processes, angiogenesis, apoptosis, and necrosis. Besides this amount of data, further studies will be designed for the selection of the most significant miRNAs to test and validate their diagnostic potential, alone or in combination with other protein biomarkers, in high-risk individuals' liquid biopsy to have a noninvasive tool of diagnosis for this neoplasm.
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