A Brief Explanation on Surgical Approaches for Treatment of Different Brain Tumors.

The main goal of brain tumor surgery is to achieve gross total tumor resection without postoperative complications and permanent new deficits. However, when the lesion is located close or within eloquent brain areas, cranial nerves, and/or major brain vessels, it is imperative to balance the extent of resection with the risk of harming the patient, by following a so-called maximal safe resection philosophy. This view implies a shift from an approach-guided attitude, in which few standard surgical approaches are used to treat almost all intracranial tumors, to a pathology-guided one, with surgical approaches actually tailored to the specific tumor that has to be treated with specific dedicated pre- and intraoperative tools and techniques. In this chapter, the basic principles of the most commonly used neurosurgical approaches in brain tumors surgery are presented and discussed along with an overview on all available modern tools able to improve intraoperative visualization, extent of resection, and postoperative clinical outcome.

Full 3D position reconstruction of a radioactive source based on a novel hyperbolic geometrical algorithm.

A new method to locate, with millimetre uncertainty, in 3D, a γ -ray source emitting multiple γ -rays in a cascade, employing conventional LaBr3(Ce) scintillation detectors, has been developed. Using 16 detectors in a symmetrical configuration the detector energy and time signals, resulting from the γ -ray interactions, are fed into a new source position reconstruction algorithm. The Monte-Carlo based Geant4 framework has been used to simulate the detector array and a 60Co source located at two positions within the spectrometer central volume. For a source located at (0,0,0) the algorithm reports X, Y, Z values of -0.3 ± 2.5, -0.4 ± 2.4, and -0.6 ± 2.5 mm, respectively. For a source located at (20,20,20) mm, with respect to the array centre, the algorithm reports X, Y, Z values of 20.2 ± 1.0, 20.2 ± 0.9, and 20.1 ± 1.2 mm. The resulting precision of the reconstruction means that this technique could find application in a number of areas including nuclear medicine, national security, radioactive waste assay and proton beam therapy.

Use of ICG videoangiography and FLOW 800 analysis to identify the patient-specific venous circulation and predict the effect of venous sacrifice: a retrospective study of 172 patients.

OBJECTIVE The best management of veins encountered during the neurosurgical approach is still a matter of debate. Even if venous sacrifice were to lead to devastating consequences, under certain circumstances, it might prove to be desirable, enlarging the surgical field or increasing the extent of resection in tumor surgery. In this study, the authors present a large series of patients with vascular or oncological entities, in which they used indocyanine green videoangiography (ICG-VA) with FLOW 800 analysis to study the patient-specific venous flow characteristics and the management workflow in cases in which a venous sacrifice was necessary. METHODS Between May 2011 and December 2017, 1972 patients were admitted to the authors' division for tumor and/or neurovascular surgery. They retrospectively reviewed all cases in which ICG-VA and FLOW 800 were used intraoperatively with a specific target in the venous angiographic phase or for the management of venous sacrifice, and whose surgical videos and FLOW 800 analysis were available. RESULTS A total of 296 ICG-VA and FLOW 800 studies were performed intraoperatively. In all cases, the venous structures were clearly identifiable and were described according to the flow direction and speed. The authors therefore defined different patterns of presentation: arterialized veins, thrombosed veins, fast-draining veins with anterograde flow, slow-draining veins with anterograde flow, and slow-draining veins with retrograde flow. In 16 cases we also performed a temporary clipping test to predict the effect of the venous sacrifice by the identification of potential collateral circulation. CONCLUSIONS ICG-VA and FLOW 800 analysis can provide complete and real-time intraoperative information regarding patient-specific venous drainage pattern and can guide the decision-making process regarding venous sacrifice, with a possible impact on reduction of surgical complications.

Health literacy and pap testing in insured women.

Several studies have found a link between health literacy and participation in cancer screening. Most, however, have relied on self-report to determine screening status. Further, until now, health literacy measures have assessed print literacy only. The purpose of this study was to examine the relationship between participation in cervical cancer screening (Papanicolaou [Pap] testing) and two forms of health literacy-reading and listening. A demographically diverse sample was recruited from a pool of insured women in Georgia, Massachusetts, Hawaii, and Colorado between June 2009 and April 2010. Health literacy was assessed using the Cancer Message Literacy Test-Listening and the Cancer Message Literacy Test-Reading. Adherence to cervical cancer screening was ascertained through electronic administrative data on Pap test utilization. The relationship between health literacy and adherence to evidence-based recommendations for Pap testing was examined using multivariate logistic regression models. Data from 527 women aged 40 to 65 were analyzed and are reported here. Of these 527 women, 397 (75 %) were up to date with Pap testing. Higher health literacy scores for listening but not reading predicted being up to date. The fact that health literacy listening was associated with screening behavior even in this insured population suggests that it has independent effects beyond those of access to care. Patients who have difficulty understanding spoken recommendations about cancer screening may be at risk for underutilizing screening as a result.

Explainable Machine Learning Model to Predict Overall Survival in Patients Treated With Palliative Radiotherapy for Bone Metastases.

PURPOSE: The estimation of prognosis and life expectancy is critical in the care of patients with advanced cancer. To aid clinical decision making, we build a prognostic strategy combining a machine learning (ML) model with explainable artificial intelligence to predict 1-year survival after palliative radiotherapy (RT) for bone metastasis. MATERIALS AND METHODS: Data collected in the multicentric PRAIS trial were extracted for 574 eligible adults diagnosed with metastatic cancer. The primary end point was the overall survival (OS) at 1 year (1-year OS) after the start of RT. Candidate covariate predictors consisted of 13 clinical and tumor-related pre-RT patient characteristics, seven dosimetric and treatment-related variables, and 45 pre-RT laboratory variables. ML models were developed and internally validated using the Python package. The effectiveness of each model was evaluated in terms of discrimination. A Shapley Additive Explanations (SHAP) explainability analysis to infer the global and local feature importance and to understand the reasons for correct and misclassified predictions was performed. RESULTS: The best-performing model for the classification of 1-year OS was the extreme gradient boosting algorithm, with AUC and F1-score values equal to 0.805 and 0.802, respectively. The SHAP technique revealed that higher chance of 1-year survival is associated with low values of interleukin-8, higher values of hemoglobin and lymphocyte count, and the nonuse of steroids. CONCLUSION: An explainable ML approach can provide a reliable prediction of 1-year survival after RT in patients with advanced cancer. The implementation of SHAP analysis provides an intelligible explanation of individualized risk prediction, enabling oncologists to identify the best strategy for patient stratification and treatment selection.

Automated single-isocenter stereotactic body radiotherapy for multiple metastases from breast cancer: A case study.

Oligometastatic breast cancer patients can today could benefit from a multimodal approach, combining systemic therapy with metastasis-directed treatment using stereotactic body radiotherapy (SBRT). However, the possibility to synchronously treat multiple lesions is still challenging, needing the ability to generate complex dose distributions with steep dose gradients outside the lesions and major sparing of surrounding organs at risk and accurately track and reproduce the patient's position before and during radiation therapy. We report the case of an oligometastatic patient from left breast cancer, which occurred after a full course of whole breast radiotherapy, treated using the potential of modern technology including single-isocenter setup, plan automation, breath-hold technique and surface guided tracking and reproducibility of patient's position before and during radiation therapy. A 44-year-old female patient with a history of left breast cancer, specifically a luminal-B-like invasive ductal carcinoma with Her2 overexpression, was admitted to our department. The patient previously underwent a left mastectomy (pT2N0M0), 4 cycles of adjuvant chemotherapy, adjuvant radiotherapy on the chest wall and lymph nodes drainage, and 5 years of hormonal therapy. A chest wall ultrasound and positron emission tomography revealed the presence of new lesions in the area of the surgical scar from the previous mastectomy, internal mammary, axillary and retropectoral levels. The 3 lesions were simultaneously treated with a mono-isocentric VMAT plan using SBRT technique with a total dose of 30 Gy delivered in 5 fractions. Due to the technical challenges, this treatment was supported by the use of planning automation, breath-hold technique and surface-guided radiation therapy to improve the accuracy of the dose delivery. Two different plans were generated and compared to pursue the best dosimetric result, including a summed plan obtained from 3 individual SBRT plans for each lesion with a separate isocenter placed in each of them (MIP), and a single-isocenter SBRT plan able to treat multiple lesions synchronously (SIP). Because of the advantages in terms of dosimetry and dose delivery efficiency, the patient was successfully treated with the SIP plan. The treatment time was reduced to about 4.5 minutes, allowing the comfortably use of breath-hold technique. After treatment, the condition of the patient was normal, and no toxicities have been observed in follow-up. SBRT with mono isocentric VMAT planning represents the recommended approach to simultaneously treat multiple lesions in close proximity in the thoracic district.

Clinical Insights and Future Prospects: A Comprehensive Narrative Review on Immunomodulation Induced by Electrochemotherapy.

Electrochemotherapy (ECT) is an emerging therapeutic approach gaining growing interest for its potential immunomodulatory effects in cancer treatment. This narrative review systematically examines the current state of knowledge regarding the interplay between ECT and the immune system. Through an analysis of preclinical and clinical studies, the review highlights ECT capacity to induce immunogenic cell death, activate dendritic cells, release tumor antigens, trigger inflammatory responses, and occasionally manifest systemic effects-the abscopal phenomenon. These mechanisms collectively suggest the ECT potential to influence both local tumor control and immune responses. While implications for clinical practice appear promising, warranting the consideration of ECT as a complementary treatment to immunotherapy, the evidence remains preliminary. Consequently, further research is needed to elucidate the underlying mechanisms, optimize treatment protocols, explore potential synergies, and decipher the parameters influencing the abscopal effect. As the field advances, the integration of ECT's potential immunomodulatory aspects into clinical practice will need careful evaluation and collaboration among clinical practitioners, researchers, and policymakers.

Timely Palliative Care Could Be Another Benefit for Cancer Patients with Non-Malignant Pain.

Cancer patients, as well as individuals in the general population, suffer from non-malignant pain (NMP), although with variable prevalence in the few studies dealing with this topic [...].

Adequacy of Pain Management in Patients Referred for Radiation Therapy: A Subanalysis of the Multicenter ARISE-1 Study.

BACKGROUND: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. METHODS: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. RESULTS: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). CONCLUSIONS: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes.

Prognostic Score in Radiotherapy Practice for Palliative Treatments (PROPHET) Study for Bone Metastases: An Investigation Into the Clinical Effect on Treatment Prescription.

Purpose: Bone metastases frequently occur during malignant disease. Palliative radiation therapy (PRT) is a crucial part of palliative care because it can relieve pain and improve patients' quality of life. Often, a clinician's survival estimation is too optimistic. Prognostic scores (PSs) can help clinicians tailor PRT indications to avoid over- or undertreatment. Although the PS is supposed to aid radiation oncologists (ROs) in palliative-care scenarios, it is unclear what type of support, and to what extent, could impact daily clinical practice. Methods and Materials: A national-based investigation of the prescriptive decisions on simulated clinical cases was performed in Italy. Nine clinical cases from real-world clinical practice were selected for this study. Each case description contained complete information regarding the parameters defining the prognosis class according to the PS (in particular, the Mizumoto Prognostic Score, a validated PS available in literature and already applied in some clinical trials). Each case description contained complete information regarding the parameters defining the prognosis class according to the PS. ROs were interviewed through questionnaires, each comprising the same 3 questions per clinical case, asking (1) the prescription after detailing the clinical case features but not the PS prognostic class definition; (2) whether the RO wanted to change the prescription once the PS prognostic class definition was revealed; and (3) in case of a change of the prescription, a new prescriptive option. Three RO categories were defined: dedicated to PRT (RO-d), nondedicated to PRT (RO-nd), and resident in training (IT). Interviewed ROs were distributed among different regions of the country. Results: Conversion rates, agreements, and prescription trends were investigated. The PS determined a statistically significant 11.12% of prescription conversion among ROs. The conversion was higher for the residents and significantly higher for worse prognostic scenario subgroups, respectively. The PS improved prescriptive agreement among ROs (particularly for worse-prognostic-scenario subgroups). Moreover, PS significantly increased standard prescriptive approaches (particularly for worse-clinical-case presentations). Conclusions: To the best of our knowledge, the PROPHET study is the first to directly evaluate the potential clinical consequences of the regular application of any PS. According to the Prophet study, a prognostic score should be integrated into the clinical practice of palliative radiation therapy for bone metastasis and training programs in radiation oncology.

Adequacy of Pain Treatment in Radiotherapy Departments: Results of a Multicenter Study on 2104 Patients (Arise).

Aim: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. Methods: We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP­cancer pain, NCP­non-cancer pain, MP­mixed pain; intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7−10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values < 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Results: Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0%; MP: 18.5%). PMI was < 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy).Conclusions: Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy.

An Intensive Educational Intervention Significantly Improves the Adoption of Single Fractionation Radiotherapy in Uncomplicated Bone Metastases.

INTRODUCTION: An education strategy was employed in our department to increase the rate of patients with uncomplicated painful bone metastases undergoing single fractionation radiotherapy (SFRT). The purpose of this report is to analyze the results of this strategy over a 5 year period. MATERIALS AND METHODS: In January 2015, two meetings were organized in our department. In the first, data from an audit on the current SFRT rate were shown. In the second, evidence of SFRT efficacy in the relief of pain from uncomplicated bone metastases was presented. In addition, during the weekly discussion of clinical cases, the opportunity to use the SFRT was systematically recalled. Using our institutional database, all patients treated with radiotherapy for uncomplicated painful bone metastases in the period between 2014 (year considered as a reference) and 2019 were retrieved. Data regarding treatment date (year), radiotherapy fractionation, and tumor, patients, and radiation oncologists characteristics were collected. RESULTS: A total of 627 patients were included in the analysis. The rate of patients undergoing SFRT increased from 4.0% in 2014 to 63.5% in 2019 (p < 0.001). At multivariable analysis, the delivery of SFRT was significantly correlated with older patients age (>80 years), lung cancer as the primary tumor, treatment prescribed by a radiation oncologist dedicated to palliative treatments, and treatment date (2014 vs 2015-2019). CONCLUSIONS: This retrospective single-center analysis showed that a simple but intensive and prolonged departmental education strategy can increase the rate of patients treated with SFRT by nearly 16 times.

Diagnosis of Ventriculoperitoneal Shunt Malfunction: A Practical Algorithm.

OBJECTIVE: This study aims to present a practical method to accurately diagnose ventriculoperitoneal shunt (VPS) malfunction and to detect the exact level at which the system has failed to tailor VPS revision at that level only. METHODS: A tertiary referral single-center algorithm for diagnosis of VPS malfunction is proposed. Based on clinical symptoms and confirmed ventricular dilatation on computed tomography, the VPS reservoir is punctured; if no cerebrospinal fluid is obtained, ventricular catheter replacement is recommended. Conversely, if cerebrospinal fluid is obtained, a sample is sent for cultural examination and the macroscopic integrity of the whole system is checked via plain radiography in the angiographic suite. Then, through the injection of iodate contrast medium into the reservoir and selective exclusion of the proximal and distal catheters, the patency and correct VPS functioning are investigated. RESULTS: A total of 102 (56 males) patients (mean age, 41.5 years; range, 1-86 years) underwent a VPS function test from 2012 to 2018: 59 cases of VPS malfunction (57.8%) were diagnosed. Ventricular catheter obstruction/damage/displacement occurred in 12/59 patients (20.3%), valve damage in 11/59 patients (18.6%), distal catheter obstruction/damage/displacement in 17/59 patients (28.8%) and 2-level (valve/proximal catheter or valve/distal catheter) obstruction/damage/displacement in 16/59 patients (27.1%). Subclinical infection was diagnosed in 3 patients (5.1%). VPS revision was performed selectively at the level of failure. CONCLUSIONS: The proposed algorithm is a practical, simple and minimally invasive technique to accurately diagnose VPS malfunction, identifying the exact level of system failure and allowing surgical VPS revision to be tailored, avoiding unnecessary complete system replacement.

Analysis of risk factors and postoperative predictors for recurrent lumbar disc herniation.

BACKGROUND: This study identified risk factors and postoperative indicators for recurrent lumbar disc herniations (rLDH) following microdiscectomy. METHODS: We retrospectively reviewed the 1-year recurrence rate for LDH in 209 consecutive patients undergoing microdiscectomy (2013-2018). RESULTS: Utilizing a multivariate analysis, higher body mass index (BMI) and postsurgery Oswestry disability index (ODI) were significantly associated with an increased risk of rLDH. CONCLUSION: Elevated postsurgery ODI and higher BMI were significantly associated with increased risk of rLDH.

A New Method to Reconstruct in 3D the Emission Position of the Prompt Gamma Rays following Proton Beam Irradiation.

A new technique for range verification in proton beam therapy has been developed. It is based on the detection of the prompt γ rays that are emitted naturally during the delivery of the treatment. A spectrometer comprising 16 LaBr3(Ce) detectors in a symmetrical configuration is employed to record the prompt γ rays emitted along the proton path. An algorithm has been developed that takes as inputs the LaBr3(Ce) detector signals and reconstructs the maximum γ-ray intensity peak position, in full 3 dimensions. For a spectrometer radius of 8 cm, which could accommodate a paediatric head and neck case, the prompt γ-ray origin can be determined from the width of the detected peak with a σ of 4.17 mm for a 180 MeV proton beam impinging a water phantom. For spectrometer radii of 15 and 25 cm to accommodate larger volumes this value increases to 5.65 and 6.36 mm. For a 8 cm radius, with a 5 and 10 mm undershoot, the σ is 4.31 and 5.47 mm. These uncertainties are comparable to the range uncertainties incorporated in treatment planning. This work represents the first step towards a new accurate, real-time, 3D range verification device for spot-scanning proton beam therapy.

The impact of fluorescein-guided technique in the surgical removal of CNS tumors in a pediatric population: results from a multicentric observational study.

BACKGROUND: Surgery has a fundamental role in central nervous system (CNS) tumors in the pediatric population, as aggressive resection correlates with prognosis. Due to its accumulation in areas with damaged blood brain barrier, sodium fluorescein (SF) could be a valid tool to improve the extent of resection in tumors enhancing at preoperative MRI. This study is aimed to systematically assess the utility of SF in a pediatric population. METHODS: Patient data were collected in two centers, one in Italy and the other in Germany. At the induction of anesthesia, SF was administered intravenously (5 mg/kg). Surgery was performed using a YELLOW560 filter. Fluorescence intensity was graduated as bright, moderate or absent based on surgeon's opinion; furthermore, SF use was judged as "helpful," "not helpful" or "not essential" in tumor removal. RESULTS: Twenty-four patients for 27 surgical procedures were identified. In 21 of 27 (77.8%) procedures fluorescence was reported as bright or moderate, in two of 27 (7.4%) absent and in four of 27 (14.8%) data were unavailable. Intraoperative fluorescence was reported in 21 of 25 (84%) surgeries whose corresponding preoperative MRI had shown contrast enhancement. In 14 of 27 (51.8%) surgical procedures SF was considered "helpful"; in two of 27 (7.4%) not "helpful"; in seven of 27 (25.9%) "not essential." In four of 27 (14.8%) data were unavailable. No adverse effect to SF was registered. CONCLUSIONS: SF could be considered a valid and safe tool to improve visualization of tumors enhancing at preoperative MRI also in pediatric patients. Future prospective studies are needed to confirm these preliminary data.

Neural network-based identification of patients at high risk for intraoperative cerebrospinal fluid leaks in endoscopic pituitary surgery.

OBJECTIVE: Although rates of postoperative morbidity and mortality have become relatively low in patients undergoing transnasal transsphenoidal surgery (TSS) for pituitary adenoma, cerebrospinal fluid (CSF) fistulas remain a major driver of postoperative morbidity. Persistent CSF fistulas harbor the potential for headache and meningitis. The aim of this study was to investigate whether neural network-based models can reliably identify patients at high risk for intraoperative CSF leakage. METHODS: From a prospective registry, patients who underwent endoscopic TSS for pituitary adenoma were identified. Risk factors for intraoperative CSF leaks were identified using conventional statistical methods. Subsequently, the authors built a prediction model for intraoperative CSF leaks based on deep learning. RESULTS: Intraoperative CSF leaks occurred in 45 (29%) of 154 patients. No risk factors for CSF leaks were identified using conventional statistical methods. The deep neural network-based prediction model classified 88% of patients in the test set correctly, with an area under the curve of 0.84. Sensitivity (83%) and specificity (89%) were high. The positive predictive value was 71%, negative predictive value was 94%, and F1 score was 0.77. High suprasellar Hardy grade, prior surgery, and older age contributed most to the predictions. CONCLUSIONS: The authors trained and internally validated a robust deep neural network-based prediction model that identifies patients at high risk for intraoperative CSF. Machine learning algorithms may predict outcomes and adverse events that were previously nearly unpredictable, thus enabling safer and improved patient care and better patient counseling.