Clinical performance of implanted devices used in surgical treatment of patients with spinal tumors: a systematic review.

PURPOSE: Implanted devices used in metastatic spine tumor surgery (MSTS) include pedicle screws, fixation plates, fixation rods, and interbody devices. A material to be used to fabricate any of these devices should possess an array of properties, which include biocompatibility, no toxicity, bioactivity, low wear rate, low to moderate incidence of artifacts during imaging, tensile strength and modulus that are comparable to those of cortical bone, high fatigue strength/long fatigue life, minimal or no negative impact on radiotherapy (RT) planning and delivery, and high capability for fusion to the contiguous bone. The shortcomings of Ti6Al4V alloy for these applications with respect to these desirable properties are well recognized, opening the field for an investigation about novel biomaterials that could replace the current gold standard. Previously published reviews on this topic have exhibited significant shortcomings in the studies they included, such as a small, heterogenous sample size and the lack of a cost-benefit analysis, extremely useful to understand the practical possibility of applying a novel material on a large scale. Therefore, this review aims to collect information about the clinical performance of these biomaterials from the most recent literature, with the objective of deliberating which could potentially be better than titanium in the future, with particular attention to safety, artifact production and radiotherapy planning interference. The significant promise showed by analyzing the clinical performance of these devices warrants further research through prospective studies with a larger sample size also taking into account each aspect of the production and use of such materials. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to improve the reporting of the review. The search was performed from March 2022 to September 2023. RESULTS: At the end of the screening process, 20 articles were considered eligible for this study. Polyetheretherketone (PEEK), Carbon-fibre reinforced polyetheretherketone (CFR-PEEK), long carbon fiber reinforced polymer (LCFRP), Polymethylmethacrylate (PMMA), and carbon screw and rods were used in the included studies. CONCLUSION: CFR-PEEK displays a noninferior safety and efficacy profile to titanium implanted devices. However, it also has other advantages. By decreasing artifact production, it is able to increase detection of local tumor recurrence and decrease radiotherapy dose perturbation, ultimately bettering prognosis for patients necessitating adjuvant treatment. Nonetheless, its drawbacks have not been explored fully and still require further investigation in future studies. This does not exclude the fact that CFR-PEEK could be a valid alternative to titanium in the near future.

Induction chemotherapy backbone in frail patients with advanced NSCLC treated with chemotherapy plus pembrolizumab: a single institution retrospective audit of dose intensities from modified regimens.

Guidelines historically recommended mono-chemotherapy for the 1st line treatment of elderly patients with non-small cell lung cancer (NSCLC) and poor performance status (PS). Nowadays, there is no clear indication whether chemo-immunotherapy (chemo-IO) combinations can be effectively delivered in this population. We collected induction chemotherapy data in consecutive patients with advanced NSCLC treated with carboplatin-based chemotherapy regimens plus pembrolizumab, to compute the received dose intensity (RDI) from standard regimens or patient-tailored regimens modified due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous and squamous NSCLC, treated with carboplatin-pemetrexed or carboplatin-paclitaxel doublets plus pembrolizumab, respectively. The majority of patients were aged ≥ 70 years (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an Eastern Cooperative Oncology Group (ECOG) - PS of 0, 1 and 2, respectively. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori modified regimens due to poor PS, age, or comorbidities. Among patients with non-squamous NSCLC, median received doses of carboplatin and pemetrexed were 1.37 AUC/week and 138.8 mg/m2/week, with RDIs of 86% and 75% (p < 0.01) for patients treated with standard or modified regimens, respectively. Of note, the RDI was 57.9% among patients with ECOG-PS 2. However, patients treated with modified regimens experienced similar toxicities as those treated with standard regimens, despite being older (p < 0.01), with higher PS (p < 0.01) and more comorbid (p = 0.03). Patients treated with modified regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among patients with squamous NSCLC, 90% received modified regimens upfront, with median received doses of carboplatin and paclitaxel of 1.19 AUC/week and 40 mg/m2/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemotherapy plus pembrolizumab in frail patients, the RDI seems to be subtherapeutic, especially in those with squamous histology. Dedicated trials are needed to implement combination strategies in this population.

Artificial Intelligence in Detection, Management, and Prognosis of Bone Metastasis: A Systematic Review.

BACKGROUND: Metastasis commonly occur in the bone tissue. Artificial intelligence (AI) has become increasingly prevalent in the medical sector as support in decision-making, diagnosis, and treatment processes. The objective of this systematic review was to assess the reliability of AI systems in clinical, radiological, and pathological aspects of bone metastases. METHODS: We included studies that evaluated the use of AI applications in patients affected by bone metastases. Two reviewers performed a digital search on 31 December 2023 on PubMed, Scopus, and Cochrane library and extracted authors, AI method, interest area, main modalities used, and main objectives from the included studies. RESULTS: We included 59 studies that analyzed the contribution of computational intelligence in diagnosing or forecasting outcomes in patients with bone metastasis. Six studies were specific for spine metastasis. The study involved nuclear medicine (44.1%), clinical research (28.8%), radiology (20.4%), or molecular biology (6.8%). When a primary tumor was reported, prostate cancer was the most common, followed by lung, breast, and kidney. CONCLUSIONS: Appropriately trained AI models may be very useful in merging information to achieve an overall improved diagnostic accuracy and treatment for metastasis in the bone. Nevertheless, there are still concerns with the use of AI systems in medical settings. Ethical considerations and legal issues must be addressed to facilitate the safe and regulated adoption of AI technologies. The limitations of the study comprise a stronger emphasis on early detection rather than tumor management and prognosis as well as a high heterogeneity for type of tumor, AI technology and radiological techniques, pathology, or laboratory samples involved.

Concurrent Use of Abemaciclib and Radiotherapy in Metastatic Breast Cancer Patients: A Single-Center Experience.

INTRODUCTION: There is little evidence regarding the safety and efficacy of the combination of abemaciclib plus radiotherapy (RT). The majority of studies investigated the combination of RT with palbociclib or ribociclib reporting that hematological toxicity is common. Given the unique toxicity profile of abemaciclib with greater gastrointestinal toxicity compared to hematological toxicity, we wanted to evaluate the toxicity of the combination with RT in metastatic breast cancer (BC) patients. METHODS: Patients with histologically proven metastatic or locally advanced BC treated with RT and concurrent abemaciclib were selected. Toxicity was assessed according to the NCI-CTCAE V4.0. RESULTS: Thirty-two metastatic sites were treated in 19 patients and analyzed. All patients received abemaciclib during the RT course. A total of 68% of patients received a full dose of abemaciclib during RT. Also, 71.9% of patients received a palliative intent (median dose = 30 Gy, range = 8-30 Gy), and 26.3% were treated for 9 oligo-metastatic or oligo-progressive sites of disease with stereotactic body RT (median dose = 30 Gy, range 21-30 Gy, given in 3-5 fractions). Overall, the rate of G3 toxicity was 15.7%. The rate of G3 hematological toxicity was 10.6% (2/19 patients, one G3 neutropenia and one G3 anemia). No patient presented diarrhea, including those treated for RT sites close to the bowel. One patient developed G3 skin toxicity. Pain significantly improved after RT (mean value NRS pre-RT = 3.9, SD = 3.07; mean value NRS after RT = 0.9, SD = 0.46; p < 0.0001). CONCLUSION: Abemaciclib and concomitant RT seem well tolerated showing acceptable toxicity.

Circulating receptor activator of nuclear factor kappa-B ligand (RANKL) levels predict response to immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC).

BACKGROUND: Receptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor microenvironment and immune cell responses. This study aimed to assess the prognostic significance of soluble RANKL in patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD1)/programmed death-ligand 1 (PDL1) checkpoint inhibitor therapy. METHODS: Plasma RANKL levels were measured in 100 patients with advanced NSCLC without bone metastases undergoing monotherapy with PD1/PDL1 checkpoint inhibitors. To establish the optimal cut-off value, we used the Cutoff Finder package in R. Survival curves for four distinct patient groups, according to their RANKL and PDL1 levels (high or low), were generated using the Kaplan-Meier method and compared with the log-rank test. The Cox regression model calculated HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS). RESULTS: The optimal RANKL cut-off was established at 280.4 pg/mL, categorizing patients into groups with high or low RANKL levels. A significant association was observed between increased RANKL concentrations and decreased survival rates at 24 months, only within the subgroup expressing high levels of PDL1 (p=0.002). Additionally, low RANKL levels in conjunction with elevated PDL1 expression correlated with improved PFS (median 22 months, 95% CI 6.70 to 50 vs median 4 months, 95% CI 3.0 to 7.30, p=0.009) and OS (median 26 months, 95% CI 20 to not reached vs median 7 months, 95% CI 6 to 13, p=0.003), indicating RANKL's potential as an indicator of adverse prognosis in these patients. Multivariate analysis identified RANKL as an independent negative prognostic factor for both PFS and OS, regardless of other clinicopathological features. CONCLUSION: These results highlight the prognostic and predictive value of RANKL specifically in patients with high PDL1 expression.

Sacituzumab Govitecan for the treatment of advanced triple negative breast cancer patients: a multi-center real-world analysis.

Objective: The objective of this multicenter, observational, retrospective analysis was to evaluate the safety and efficacy of sacituzumab govitecan in metastatic triple-negative breast cancer (mTNBC) patients managed according to common clinical practice in Italy. Methods: Data were retrieved by 7 sites. Triple-negative BC was defined by the lack of expression of estrogen receptor (ER <1%), progesterone receptor (PgR <1%) and human-epidermal growth factor receptor-2 (HER2 0, 1+, 2+ ISH-not amplified) according to standard ASCO-CAP criteria. Demographic and clinical characteristics were collected. Premedication, dose modifications and treatment schedule were based on the approved label of the product. Adverse events (AEs) were assessed according to NCI-CTCAE v5.0. Results: Fifty-seven eligible patients who received sacituzumab govitecan for mTNBC were included. Median age was 53 years (range 25-75). Approximately 70% of patients had an initial diagnosis of TNBC. Median time from the diagnosis of metastatic BC to start of sacituzumab govitecan was 17 months (range 0-97) and median number of previous therapies was 3 (range 1-7). The most common sites of metastasis were lymph nodes (63.1% of patients), lung (57.9%), bone (50.8%) and liver (38.6%). Eight (14.0%) patients had a disease-free interval ≤12 months. A total of 32 (56.1%) deaths were observed and the median overall survival (OS) was 12.43 months (95% CI, 7.97 months-not reached). At a median follow-up of 10.6 months, 45 patients (78.9%) had progression and the median progression-free survival (PFS) was 4.9 months (95% CI, 3.7-7.1 months). Partial tumour response was observed in 19 patients (33.3%), stable disease in 16 (28.1%) and disease progression in 22 patients (38.6%). The most common treatment-related AEs were anemia (66.6% of patients), alopecia (66.6%), neutropenia (59.6%), nausea (42.1%) and diarrhea (38.6%). Neutropenia was the most common serious treatment-related AE: 21.0% and 8.7% of patients experienced grade 3 or 4 neutropenia, respectively. Twenty-two patients (38.6%) reduced the dose and 5.3% permanently discontinued treatment. Conclusion: The results of this real-world analysis showed that both safety and efficacy of sacituzumab govitecan in mTNBC patients are consistent with that previously reported in regulatory trials. The use of premedication and supportive measures was associated with a satisfactory toxicity profile.