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Metastatic renal cell carcinoma (mRCC) carrying sarcomatoid features (sRCC) has aggressive biology and poor prognosis. First‐line immunotherapy (IO)‐based combinations have improved the outcome of clear cell RCC patients, including that of sRCC. Real‐world data confirming the adequate first‐line management of sRCC is largely lacking. We investigated the clinical features and the outcome of sRCC patients treated with IO‐based combinations within the ARON‐1 study population (NCT05287464). The primary objective was to define the incidence and baseline clinical characteristics of sRCC compared with non‐sRCC patients. The secondary objective was to describe the outcome of sRCC patients based on type of first‐line treatment (IO + IO vs. IO + tyrosin kinase inhibitor [TKI]). We identified 1362 mRCC patients with IMDC intermediate or poor risk, 226 sRCC and 1136 non‐sRCC. These two subgroups did not differ in terms of baseline characteristics. The median overall survival (OS) was 26.8 months (95%CI 21.6–44.2) in sRCC and 35.3 months (95%CI 30.2–40.4) in non‐sRCC patients (p =.013). The median progression‐free survival (PFS) was longer in non‐sRCC patients compared to sRCC (14.5 vs. 12.3 months, p =.064). In patients treated with first‐line IO + TKI the median OS was 34.4 months compared to 26.4 months of those who received IO + IO (p =.729). The median PFS was 12.4 months with IO + TKI and 12.3 months with IO + IO (p =.606). In conclusion, we confirm that sRCC are aggressive tumors with poor prognosis. IO‐based combinations improve survival outcomes of sRCC patients, regardless from the type of strategy (IO + IO versus IO + TKI) adopted. [ABSTRACT FROM AUTHOR]

Abstract Background Tumor microenvironment (TME) is a dynamic setting and changes in TILs and their subpopulations are potential candidates to influence the metastatic process. Aim of this pilot study is to describe the changes occurring between primary breast cancers and their paired metastases in terms of TILs composition. To assess if these changes influence the process of metastasis development, we used a control group of patients. Methods We retrospectively identified 18 Luminal patients, for whom primary and metastatic tissue were available (cases) and 18 paired-matched patients (controls), not relapsed after at least 9 years of follow-up, and we quantified TILs and their composition (i.e. T CD8+ and CD4+/FOXP3+). The presence of TILs was defined as ≥10%. Results Our results showed that the microenvironment composition of relapsed patients was poor of TILs (median = 5%, I-III quartiles = 0.6–5%), CD8+ (2.5%, 0–5%) and CD4+/FOXP3 + (0%, 0–0.6%) in the primary tumor. Comparable results were observed in their related metastases (TILs 3.8%, 0.6–5%; CD8+ 0%, 0–1.3%; CD4+/FOXP3+ 0%,0–1.9%). On the contrary, the microenvironment in the control group was richer of TILs (5%, 5–17.5%) in comparison to cases, both in primary tumor (p = 0.035) and related metastases (p = 0.018). Although CD8+ in controls were similar to cases at primary tumor (p = 0.6498), but not at metastasis (p = 0.0223), they expressed only one part on the TILs subpopulations (p = 0.0060), while TILs in the cases at primary tumor were almost completely CD8+ (p = 0.5034). Conclusions These findings suggest that the lack of activation of immune system in the primary tumor might influence the multifactor process of cancer progression.

Radiotherapy is a recommended procedure, in average, for 52% of cancer cases as one of the treatment forms, therefore, it is important for the clinical practice to investigate the affecting factors in dose distribution received by the patients, and for example, devices and treatment couch. With the introduction of treatments with modulated intensity techniques like IMRT and VMAT, the number of incidence fields used for patient treatment increased, which makes the couch’s dosimetric effect more significant in these modalities. The attenuation data acquisition referring to the treatment couches, as well as the TPS data evaluation, show as important parameters for the clinical practice because they show what happens with the dose delivery during the treatment, ensuring a better quality and safety to the treatments. This research presents experimental results evaluating the couch’s impact in the treatments by a study of perturbation in the distribution of surface dose, dose attenuation according to the gantry’s angle for the couches BrainLABTM, ExactTM and iBEAMTM. Then we propose better density values for the couches BrainLABTM and ExactTM for their inclusion in EclipseTM TPS. Lastly, we compare the dose difference considering the presence or not of couch in the planning. In conclusion, the beam’s attenuation increase by the couches and the doses alterations on the skin must be taken in consideration in the treatment planning process. It is of great relevance that each treatment center perform internal tests to determinate the best density values for available TPS.

The formalism used for barriers calculations is based on a conservative estimation of workload, use factor, and occupancy factor. IMRT techniques (Intensity Modulated Radiation Therapy) and VMAT (Volumetric Modulated Arc Therapy) are known for being superior to conventional techniques, but costly from the shielding standpoint, as they increase the number of monitor units used to deliver the same dose to the patient, increasing the leakage radiation produced and, consequently, the thickness of the secondary barriers. At InRad (Radiology Institute of HC-FMUSP) a 2100CD LINAC already installed was upgraded to perform IMRT/VMAT techniques, and the existing barrier was reassessed. The present study proposes a methodology for acquiring real workload data from the institution's management software (MOSAIQ®) to replace the initially estimated data and recalculate the thickness of the barriers, assessing the impact of the introduction of these techniques and understanding the profile of the treatments carried out at the institution over the years of 2010 to 2020. Through this methodology, a decrease in the workload of 15 MV was observed as the technique of modulated intensity with 6 MV was introduced, reducing the thicknesses calculated for primary barriers. However, no significant changes were observed in the thicknesses calculated for the secondary barriers, because despite the increase in the leakage workload of 6 MV, the total workload of 15 MV decreased. There was also a trend towards an increase in the number of patients treated with modulated intensity year after year, which went from 5% in 2016 to 67% in 2020.

Background. Vinorelbine (VRB) and capecitabine (CAPE) are demonstrated to be active in pretreated metastatic breast cancer patients. Different studies have demonstrated that the metronomic treatment is active with an acceptable toxicity profile. We designed a Phases I-II study to define the MTD of oral metronomic, VRB, and CAPE. Patients and Methods. Phase I: fixed dose of CAPE was 500 mg thrice a day, continuously. Level I of VRB was 20 mg/tot thrice a week for 3 weeks (1 cycle). Subsequent levels were 30 mg/tot and 40 mg/tot (Level III), respectively, if no Grades 3-4 toxicity were observed in the previous level. Phase II: further 32 patients received the MTD of VRB plus CAPE for a total of 187 cycles to confirm toxicity profile. Results. 12 patients were enrolled in Phase I and 22 in Phase II. Phase I: the MTD of VRB was 40 mg. Phase II: 187 cycles were delivered, observing 5.9% of Grades 3-4 toxicity. 31 patients are evaluable for efficacy, obtaining a clinical benefit rate of 58.1%. Conclusion. MTD of VRB with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the ongoing Phase II multicenter study.

Este artigo dedica-se, com base em fragmentos de um caso clínico, a discutir a contribuição dos traços mnêmicos filo e ontogenéticos para a formação de compromissos que acontecem diante do terror suscitado pela velhice. Concomitantemente, apresenta a viabilidade do amparo clínico como alternativa à ameaça de desamparo que emerge da consciência de finitude e salienta a complexidade e a importância do trabalho psíquico de envelhescência como condição fundamental à escuta na transferência.

Background. Vinorelbine (VRB) and capecitabine (CAPE) are demonstrated to be active in pretreated metastatic breast cancer patients. Different studies have demonstrated that the metronomic treatment is active with an acceptable toxicity profile. We designed a Phases I-II study to define the MTD of oral metronomic, VRB, and CAPE. Patients and Methods. Phase I: fixed dose of CAPE was 500 mg thrice a day, continuously. Level I of VRB was 20 mg/tot thrice a week for 3 weeks (1 cycle). Subsequent levels were30mg/tot and 40 mg/tot (Level III), respectively, if no Grades 3-4 toxicity were observed in the previous level. Phase II: further 32 patients received the MTD of VRB plus CAPE for a total of 187 cycles to confirm toxicity profile. Results. 12 patients were enrolled in Phase I and 22 in Phase II. Phase I: the MTD of VRB was 40 mg. Phase II: 187 cycles were delivered, observing 5.9% of Grades 3-4 toxicity. 31 patients are evaluable for efficacy, obtaining a clinical benefit rate of 58.1%. Conclusion. MTD of VRB with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the ongoing Phase II multicenter study. [ABSTRACT FROM AUTHOR]

The interaction between systolic and diastolic effects of inotropic drugs is an important subject which has not yet been fully clarified in the cardiological literature. The effects of the inotropic drugs k-strophanthidin and dobutamine on left ventricular (LV) relaxation and early filling phase were compared in patients with coronary artery disease (CAD) and preserved systolic function. Twenty-two patients were randomly divided into two groups; group I was infused with 0.0035mg. kg of k-strophanthidin for 10 min and group II with dobutamine at a rate of 10 fig. kg. min for 10 min. Both groups underwent simultaneous haemodynamic and echo 2D-Doppler evaluations at controlled heart rate. K-strophanthidin improved contractility indexes (peak of LV systolic pressure P<0.001, max dPldt+ P<0.05 and dPIdt P<0.01) and worsened T constant and LV lowest diastolic pressure, (LVLDP) (P<0.001 and P<0.05 respectively) without changing early transmitral filling parameters. Dobutamine induced a significant increase in contractility in group II but at the same time significantly improved LV relaxation variables (max dPIdt− P<0.01 and T constant P<0.001). In addition, dobutamine reduced LVLDP (P<0.05) and significantly increased LV early filling parameters. These results show that an acute administration of either k-strophanthidin or dobutamine enhances contractility, whereas these drugs have the opposite effect on the early diastolic phase. [ABSTRACT FROM PUBLISHER]

Cancer immunotherapy, largely represented by immune checkpoint inhibitors (ICI), has led to substantial changes in preclinical cancer research and clinical oncology practice over the past decade. However, the efficacy and toxicity profiles of ICIs remain highly variable among patients, with only a fraction achieving a significant benefit. New combination therapeutic strategies are being investigated, and the search for novel predictive biomarkers is ongoing, mainly focusing on tumor- and host-intrinsic components. Less attention has been directed to all the external, potentially modifiable factors that compose the exposome, including diet and lifestyle, infections, vaccinations, and concomitant medications, that could affect the immune system response and its activity against cancer cells. We hereby provide a review of the available clinical evidence elucidating the impact of host-extrinsic factors on ICI response and toxicity., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background. Vinorelbine (VRB) and capecitabine (CAPE) are demonstrated to be active in pretreated metastatic breast cancer patients. Different studies have demonstrated that the metronomic treatment is active with an acceptable toxicity profile. We designed a Phases I-II study to define the MTD of oral metronomic, VRB, and CAPE. Patients and Methods. Phase I: fixed dose of CAPE was 500 mg thrice a day, continuously. Level I of VRB was 20 mg/tot thrice a week for 3 weeks (1 cycle). Subsequent levels were 30 mg/tot and 40 mg/tot (Level III), respectively, if no Grades 3-4 toxicity were observed in the previous level. Phase II: further 32 patients received the MTD of VRB plus CAPE for a total of 187 cycles to confirm toxicity profile. Results. 12 patients were enrolled in Phase I and 22 in Phase II. Phase I: the MTD of VRB was 40 mg. Phase II: 187 cycles were delivered, observing 5.9% of Grades 3-4 toxicity. 31 patients are evaluable for efficacy, obtaining a clinical benefit rate of 58.1%. Conclusion. MTD of VRB with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the ongoing Phase II multicenter study.