Brain Mass and Encephalization Quotients in the Domestic Industrial Pig (Sus scrofa)

open6siIn the present study we examined the brain of fetal, newborn, and adult pigs raised for meat production. The fresh and formalin-fixed weights of the brain have been recorded and used, together with body weight, to calculate the Encephalization Quotient (EQ). The weight of the cerebellum has been used to calculate the Cerebellar Quotient (CQ). The results have been discussed together with analogue data obtained in other terrestrial Cetartiodactyla (including the domestic bovine, sheep, goat, and camel), domesticated Carnivora, Proboscidata, and Primates. Our study, based on a relatively large experimental series, corrects former observations present in the literature based on smaller samples, and emphasizes that the domestic pig has a small brain relative to its body size (EQ = 0.38 for adults), possibly due to factors linked to the necessity of meat production and improved body weight. Comparison with other terrestrial Cetartiodactyla indicates a similar trend for all domesticated species.openMinervini, Serena; Accogli, Gianluca; Pirone, Andrea; Graïc, Jean-Marie; Cozzi, Bruno; Desantis, SalvatoreMinervini, Serena; Accogli, Gianluca; Pirone, Andrea; Graic, JEAN-MARIE; Cozzi, Bruno; Desantis, Salvator

Biological Bases of Immune-Related Adverse Events and Potential Crosslinks With Immunogenic Effects of Radiation

Immune checkpoint inhibitors have gained an established role in the treatment of different tumors. Indeed, their use has dramatically changed the landscape of cancer care, especially for tumor types traditionally known to have poor outcomes. However, stimulating anticancer immune responses may also elicit an unusual pattern of immune-related adverse events (irAEs), different from those of conventional chemotherapy, likely due to a self-tolerance impairment featuring the production of autoreactive lymphocytes and autoantibodies, or a non-specific autoinflammatory reaction. Ionizing radiation has proven to promote both positive pro-inflammatory and immunostimolatory activities, and negative anti-inflammatory and immunosuppressive mechanisms, as a result of cross-linked interactions among radiation dose, the tumor microenvironment and the host genetic predisposition. Several publications argue in favor of combining immunotherapy and a broad range of radiation schedules, based on the recent evidence of superior treatment responses and patient survival. The synergistic modulation of the immune response by radiation therapy and immunotherapeutics, particularly those manipulating T-cell activation, may also affect the type and severity of irAEs, suggesting a relationship between the positive antitumor and adverse autoimmune effects of these agents. As yet, information on factors that may help to predict immune toxicity is still lacking. The aim of our work is to provide an overview of the biological mechanisms underlying irAEs and possible crosslinks with radiation-induced anticancer immune responses. We believe such an overview may support the optimization of immunotherapy and radiotherapy as essential components of multimodal anticancer therapeutic approaches. Challenges in translating these to clinical practice are discussed

Epileptogenesis and Tumorigenesis in Glioblastoma: Which Relationship?

Epilepsy is reported in 29–52% of patients with glioblastoma (GBM) and has an important role in the natural history of this tumor and patients’ life quality. Although GBM is less epileptogenic than lower-grade gliomas, seizures are usually more difficult to control with common antiseizure medications; drug resistance is found in 20% of cases. Recent studies suggest that seizures at the onset of GBM could be a possible favorable independent prognostic factor in patients. Moreover, a growing body of evidence shows that many molecular mechanisms that influence epileptogenesis often regulate GBM growth and invasiveness, sometimes favoring or counteracting the tumor, respectively. The better-characterized players include glutamate, gamma-aminobutyric acid, aquaporin-4, and hypoxia-activated molecules. However, currently available data on the molecular basis of epileptogenesis, tumorigenesis, and their relationship is incomplete or discordant and further research is urgently needed on this topic

Advantages of intraoperative implant for interstitial brachytherapy for accelerated partial breast irradiation either frail patients with early-stage disease or in locally recurrent breast cancer

Purpose: to describe the intraoperative multicatheter implantation technique for accelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy (HDR-BT). Secondarily, to evaluate outcomes and toxicity in a series of 83 patients treated with this technique at our institution. Material and methods: retrospective analysis of a series of patients treated with HDR-BT APBI after intraoperative multicatheter interstitial implant between November 2006 and June 2017 at our institution. We assessed cosmesis, toxicity, overall survival (OS), and disease-free survival (DFS). Results: eighty-three patients were included: 59 patients (71.1%) with primary early-stage breast cancer and 24 (28.9%) with locally recurrent breast cancer. Tumorectomy was performed in all cases, with intraoperative tumor margin assessment and sentinel node biopsy. Median age was 82 years (range, 44-92). The total prescribed dose was 32 Gy (8 treatment fractions) in 60 patients (72.3%), and 34 Gy (10 fractions) in 23 patients (27.7%). Median follow-up was 40 months (range, 1-136 months). Three-year OS and DFS in the recurrent and primary cancer groups were 87% vs. 89%, and 96 % vs. 97.8%, respectively. Five patients died from non-cancer related causes. No local relapses were observed. Rates of acute and late toxicity were low in both groups. The cosmesis was good or excellent in most of patients treated for primary disease; in patients who underwent salvage brachytherapy for local recurrence, cosmesis was good in 49 patients and fair in 6. Conclusions: this technique, although time-consuming, achieves good local disease control with a satisfactory toxicity profile in both early-stage and local recurrent breast cancer patients. It may be especially suitable for frail patients

Radiation-induced breast angiosarcoma: report of two patients after accelerated partial breast irradiation (APBI) and review of the literature

BACKGROUND: Angiosarcoma may rarely complicate radiotherapy of breast cancer. This so-called radiation-induced angiosarcoma (RIAS) occurs in less than 0.3% of patients that underwent breast conservation surgeries, usually years after completion of radiotherapy. CASE PRESENTATION: we introduce two cases of invasive ductal carcinoma who underwent lumpectomy and accelerated partial breast irradiation (APBI) as an alternative protocol to whole breast irradiation (WBI). They received adjuvant partial breast radiotherapy on tumor cavity for a total dose of 38.5 Gy in 10 fractions in 5 days using 3D-external-beam RT. In both cases, RIAS occurred eight years after radiotherapy, in the sub-cicatricial area in one patient and outside the irradiated area in the other one. They both underwent radical surgery and chemotherapy was performed in one patient. DISCUSSION: The underlying mechanism for development of RIAS is not well known, but its incidence seems to be increasing. RIAS after partial breast irradiation is very rare and has been reported in two cases so far. As it may be suggested in case 2, it is still a matter of debate if the risk of radiation-induced sarcoma is radiation-dose dependent. Although mastectomy is considered as a standard treatment, choice of treatment should be made according to the patient’s specifications. CONCLUSION: There are very few studies in the literature that report RIAS after APBI. Present study is the only one reporting two cases after the external 3D technique APBI. Prognosis of RIAS remains poor. Only a careful evaluation in a multidisciplinary context can offer to the patients the best result in terms of local control and surviva

Lattice radiation therapy in clinical practice: a systematic review

Purpose: Lattice radiation therapy (LRT) is an innovative type of spatially fractionated radiation therapy. It aims to increase large tumors control probability by administering ablative doses without an increased toxicity. Considering the rising number of positive clinical experiences, the objective of this work is to evaluate LRT safety and efficacy. Method: Reports about LRT clinical experience were identified with a systematic review conducted on four different databases (namely, Medline, Embase, Scopus, and Cochrane Library) through the August 2022. Only LRT clinical reports published in English and with the access to the full manuscript text were considered as eligible. The 2020 update version PRISMA statement was followed. Results: Data extraction was performed from 12 eligible records encompassing 7 case reports, 1 case series, and 4 clinical studies. 81 patients (84 lesions) with a large lesion ranging from 63.2 cc to 3713.5 cc were subjected to exclusive, hybrid, and metabolism guided LRT. Excluding two very severe toxicity with a questionable relation with LRT, available clinical experience seem to confirm LRT safety. When a complete response was not achieved 3-6 months after LRT, a median lesion reduction approximately ≥50 % was registered. Conclusion: This systematic review appear to suggest LRT safety, especially for exclusive LRT. The very low level of evidence and the studies heterogeneity preclude drawing definitive conclusions on LRT efficacy, even though an interesting trend in terms of lesions reduction has been described

Second breast-conserving therapy with interstitial brachytherapy (APBI) as a salvage treatment in ipsilateral breast tumor recurrence: a retrospective study of 40 patients

Purpose: breast-conserving treatment (BCT) have emerged as an alternative to mastectomy in patients with ipsilateral breast tumor recurrence (IBTR). We evaluated survival outcomes and treatment-related toxicity in a series of 40 patients with IBTR, who underwent tumorectomy plus interstitial brachytherapy (APBI) as a salvage treatment. Material and methods: retrospective analysis included 40 patients diagnosed with IBTR and treated with intraoperative (26 patients) or post-operative (14 patients) multicatheter brachytherapy for APBI at our institution between June 2002 and October 2017. We assessed cosmesis, toxicity, overall survival (OS), and cancer-specific survival (CSS). Results: tumorectomy was performed in all cases, including intraoperative tumor margin assessment and sentinel node biopsy. Median age was 65 years (range, 41-92). The total prescribed dose was 32 Gy (8 fractions) in 19 patients and 34 Gy (10 fractions) in 20 patients. One elderly patient (age 92) received a single fraction of 16 Gy. Median follow-up was 61.5 months (range, 6-153). A median of 14 tubes were inserted. Mean treated V100 was 115 cc. Two patients developed a second relapse at 3 and 5 years after salvage treatment: one patient underwent salvage mastectomy and remains alive 10 years after brachytherapy, and the second one developed both local relapse and bone metastasis. The disease is stable at present. Five-year OS and CSS rates were 85.3% and 97.5%, respectively. Two patients died from cancer-related causes. Acute and late toxicity rates were low; seven patients developed acute infectious mastitis. Late fibrosis > grade 3 and late mastitis were observed in 14 and 6 cases, respectively. Conclusions: second BCT with APBI as a salvage treatment in ipsilateral breast recurrence achieves good local disease control, with a satisfactory toxicity profile compared to mastectomy. This approach seems to be safe and effective, although more data from randomized trials are needed

Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6–12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11–52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival

Special stereotactic radiotherapy techniques: procedures and equipment for treatment simulation and dose delivery

Stereotactic radiotherapy (SRT) is a multi-step procedure with each step requiring extreme accuracy. Physician-dependent accuracy includes appropriate disease staging, multi-disciplinary discussion with shared decision-making, choice of morphological and functional imaging methods to identify and delineate the tumor target and organs at risk, an image-guided patient set-up, active or passive management of intra-fraction movement, clinical and instrumental follow-up. Medical physicist-dependent accuracy includes use of advanced software for treatment planning and more advanced Quality Assurance procedures than required for conventional radiotherapy. Consequently, all the professionals require appropriate training in skills for high-quality SRT. Thanks to the technological advances, SRT has moved from a “frame-based” technique, i.e. the use of stereotactic coordinates which are identified by means of rigid localization frames, to the modern “frame-less” SRT which localizes the target volume directly, or by means of anatomical surrogates or fiducial markers that have previously been placed within or near the target. This review describes all the SRT steps in depth, from target simulation and delineation procedures to treatment delivery and image-guided radiation therapy. Target movement assessment and management are also described.