The role of percutaneous tumour biopsies had gain importance in the management of renal cell carcinoma to provide diagnostic specimen for the patients with metastatic disease that could benefit a ...systemic treatment. Among the possible complications of this procedure, however, there is the risk of tumoral cells seeding along the biopsy’s tract; this complication, albeit being reported as anecdotal, could have devastating effects. Here we report a case of a young male who developed subcutaneous chest metastasis of renal cell carcinoma after a biopsy of a lung nodule. We subsequently reviewed other cases reported in literature
Background Nowadays, different therapeutic options are available for the first-line treatment of metastatic renal cell carcinoma (mRCC). Immuno-combinations are the standard first-line therapy in all ...mRCC patients regardless of the International Metastatic RCC Database Consortium (IMDC) risk category, even though TKI monotherapy is still a therapeutic option in selected patients. However, comparisons between the different first-line treatment strategies are lacking and few real-world data are available in this setting. For this reason, the regimen choice represents an important issue in clinical practice and the optimal treatment sequence remains unclear. Methods The REGAL study is a multicentric prospective observational study enrolling mRCC patients treated with first-line systemic therapy according to clinical practice in a real-world setting. A retrospective cohort of mRCC patients who received first-line systemic therapy from the 1st of January 2021 will also be included. The primary objective is to identify potential prognostic and predictive factors that could help guide the treatment choice; secondary objectives included the assessment of the prognostic performance of the novel prognostic Meet-URO score (IMDC score + neutrophil-to-lymphocyte ratio + bone metastases) compared with the IMDC score and the comparison between treatment strategies according to response and survival outcomes and toxicity profile. Discussion Considering the high number of therapeutic first-line strategies available for mRCC, the identification of clinical prognostic and predictive factors to candidate patients to a preferable systemic therapy is still an unmet clinical need. The Meet-URO 33 study aims to provide a large-scale real-world database on mRCC patients, to identify the clinical predictive and prognostic factors and the different performances between the ICI-based combinations according to response, survival and toxicity. Trial Registration CESC IOV 2023-78. Keywords: Metastatic renal cell carcinoma, Immunotherapy, Immune checkpoint inhibitor, Clinical practice, Real-world, IMDC score, Meet-URO score, Prospective, Retrospective
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Radionecrosis is a consequence of SRS (stereotactic radiosurgery) for brain metastases in 34% of cases, and if symptomatic (8%-16%), it requires therapy with corticosteroids and bevacizumab and, less ...frequently, surgery. Oncological indications are increasing and appropriate stereotactic adapted LINACs (linear accelerators) are becoming more widely available worldwide. Efforts are being made to treat brain radionecrosis in order to relieve symptoms and spare the use of active therapies.
Herein, we describe a 65-year-old female patient presenting with brain radionecrosis 6 months after stereotactic radiotherapy for two brain metastatic lesions. Being symptomatic with headache and slow cognitive-motor function, the patient received corticosteroids. Because of later lung progression, the patient took cabozantinib. An impressive reduction of the two brain radionecrosis areas was seen at the brain MRI 2 months after the initiation of the angiogenic drug.
The high incidence of radionecrosis (2/2 treated lesions) can be interpreted by the combination of SRS and previous ipilimumab that is associated with increased risk of radionecrosis. The molecular mechanisms of brain radionecrosis, and its exact duration in time, are poorly understood. We hypothesize that the antiangiogenic effect of cabozantinib may have had a strong effect in reducing brain radionecrosis areas.
In this clinical case, cabozantinib is associated with a fast and significant volume reduction of brain radionecrosis appearing after SRS and concomitant immunotherapy. This drug seems to show, like bevacizumab, clinical implications not only for its efficacy in systemic disease control but also in reducing brain radionecrosis. More research is needed to evaluate all molecular mechanisms of brain radionecrosis and their interaction with systemic therapies like third-generation TKIs.
Purpose
To evaluate adherence to abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
Methods
In an observational prospective cohort study, we ...monitored patients with mCRPC for their adherence to abiraterone or enzalutamide in the pre- or post-chemotherapy setting.
Results
Fifty-eight patients with median age of 76 years (range 56–94), age-adjusted Charlson comorbidity score of 10 (range, 4–15), and geriatric G8 score of 14 (range, 6–17) were enrolled. Twenty-two (38%) patients were treated with abiraterone and 36 (62%) with enzalutamide, while forty-two (72%) were in the pre-chemotherapy setting. Forty-seven patients (81%) had a caregiver. Based on the pill counting, a non-adherence rate of 4.8% and 6.2% was observed for the whole period and the first 3 months, respectively, without a statistically significant difference between abiraterone and enzalutamide cohorts. A lower non-adherence rate (1.3%) was reported by patients during the whole period, mainly due to a misperception (77%) and forgetfulness (19%). Non-adherence rate to the fulfilling of the clinical diary was 38% for the whole period. Non-adherence in the whole period was related to the radiological response (
p
= 0.03) and geriatric G8 score (
p
= 0.005). By the receiver operating characteristic (ROC) curve based on the radiological response, non-adherence cut-off was 1.87% (
p
= 0.04). By this non-adherence cut-off, the G8 cut-off was 14.75 (
p
= 0.0003).
Conclusion
Non-adherence to abiraterone or enzalutamide for mCRPC may have an impact on disease response and be related to patients’ frailty, suggesting their geriatric assessment and clinical interventions to monitor and increase their adherence.
Instrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually ...precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients' IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5-ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p < 0.01), and lower adherence to ARPIs whether assessed by pill counting (p = 0.01) or self-reported by the patient himself (p = 0.03). The combination of an IADL < 6 and the absence of a caregiver resulted in a significantly high risk of non-adherence to the ARPIs at the multivariable analysis (HR 9.23, 95% confidence interval 2.28-37.43, p = 0.01). IADL alongside the geriatric G8 scales represent essential tools to identify frail and less auto-sufficient patients who are extremely vulnerable particularly if not supported by a caregiver and have the highest risk of nonadherence to ARPIs.
Background: Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of cancer. Treatment recommendations are extrapolated from ccRCC and lack solid evidence. Here, we review advanced ...nccRCC patients treated at our institute. Patients and methods: We collected retrospective data on all advanced nccRCC pts treated at the Istituto Oncologico Veneto from January 2008. We compared overall response rate (ORR), progression free survival (PFS) and overall survival (OS) according to histological subtypes and type of systemic treatments. Kaplan-Meier method, log-rank test and Cox regression were used to estimate and compare PFS and OS. Results: Of 1370 RCC patients, 289 had a diagnosis of nccRCC and 121 were eligible for the analysis. Fifty-three pts showed papillary histology (pRCC), 15 chromophobe; 37 unclassified RCC (NOS-RCC), 16 other histologies. Pts with chromophobe and other hystologies showed poorer survival rates compared to pRCC and NOS-RCC (mOS 10.7 vs. 20.7 vs. 30.7, p = 0.34). Pts treated with combination regimens achieved a better OS (30.7 vs. 13.7, p = 0.10), PFS (12.7 vs. 6.4, p = 0.10) and ORR (42.4% vs. 13.9%, p = 0.002) than those treated with monotherapy. IMDC and Meet-URO score retained their prognostic value. Conclusion: Our retrospective real-life cohort of advanced nccRCC patients shows that immunotherapy-based combinations could improve ORR, PFS and OS compared to TKI monotherapy. Prospective trials for nccRCC patients utilizing novel therapies are ongoing and their results eagerly awaited.
Abstract
Background
Severe immune-related Adverse Events (irAEs) develop in 10–27% of patients treated with Immune-Oncology (IO) Powles (Lancet 391:748–757, 2018); Galsky (Lancet 395:1547–1557, ...2020); Haanen (Ann Oncol 28:119–142, 2017). The aim of our study was to evaluate efficacy and clinical outcome of metastatic renal cell carcinoma (mRCC) patients who stopped Immune Checkpoint Inhibitors (ICIs) due to early Grade (G) 3-G4 irAEs.
Methods
We retrospectively collected data from 204 mRCC patients treated with ICIs in 6 Italian referral centers adhering to the Meet-Uro group, between February 2017 and January 2020. To properly weight the results, patients who did not report early G3–G4 toxicities have been included as control group.
Primary endpoint was to evaluate 6 months Progression Free Survival (PFS) after early treatment interruption for Grade (G) 3–4 toxicities compared to the control group. Secondary endpoints were to evaluate Time to treatment failure (TTF) and overall survival (OS) in both groups. All statistical analyses were performed using SPSS software (version 19.00, SPSS, Chicago).
Results
18/204 (8.8%) patients had early treatment interruption for serious (G3-G4) irAEs. Early was defined as interruption of IO after only one or two administrations. Immune related nephritis and pancreatitis were the most common irAE that lead to treatment interruption. 6/18 patients received IO-IO combination whereas 12/18 patients antiPD1. In the study group, 12/18 (66.6%) were free from progression at 6 months since IO interruption, TTF was 1.6 months (95% CI 1.6–2.1), mPFS was 7.4 months (95% CI 3.16–11.6) and mOS was 15.5 months (5.1–25.8). In the control group 111/184 (60.3%) patients were free from progression at 6 months, TTF was 4.6 months (95% CI 3.5–5.6), mPFS was 4.6 months (95% CI 3.5–5.6) and mOS was 19.6 months (95% CI 15.1–24.0). In the overall population, mPFS was 5.0 months (95% CI 4.0–5.9) and mOS was 19.6 months (95% CI 15.1–24.0).
Conclusions
ICIs seem to maintain efficacy even after early interruption due to severe irAE.
Introduction
Immunotherapy with nivolumab (a monoclonal antibody that targets the programmed cell death protein 1, PD1) has become the standard treatment for patients with metastatic renal cell ...carcinoma (mRCC) after progression to single-agent tyrosine kinase inhibitors. However, the optimal duration of immunotherapy in this setting has not yet been established.
Patients and methods
We retrospectively reviewed all patients treated with nivolumab at our institution from January 2014 to December 2021 and identified those who discontinued treatment for reasons other than disease progression (PD). We then associated progression-free survival (PFS) and overall survival following treatment cessation with baseline clinical data.
Results
Fourteen patients were found to have discontinued treatment. Four patients (28.6%) ceased treatment due to G3/G4 toxicities, whereas the remaining ten (71.4%) opted to discontinue treatment in agreement with their referring clinicians. The median duration of the initial treatment with nivolumab was 21.7 months (7.5-37.3); during treatment, two patients (14.3%) achieved stable disease as the best response, and the remaining twelve (85.7%) a partial response. At a median follow-up time of 24.2 months after treatment discontinuation, 7 patients (50%) were still progression-free. The median PFS from the date of discontinuation was 19.8 months (15.2 - not reached); a radiological objective response according to RECIST and treatment duration of more than 12 months were associated with a longer PFS. Three patients were re-treated with Nivolumab after disease progression, all of whom achieved subsequent radiological stability.
Conclusion
In our experience, the majority of patients who discontinued treatment in the absence of PD were still progression-free more than 18 months after discontinuation. Patients whose initial treatment duration was less than 12 months or who did not achieve a radiological objective response had a greater risk of progression. Immunotherapy rechallenge is safe and seems capable of achieving disease control.
Cancer-related pain, usually associated with bone metastases, is a frequent and debilitating morbidity in patients with prostate cancer. To date there are only limited data regarding the prognostic ...role of pain in men with metastatic castration-sensitive prostate cancer (mCSPC). The objective of our analysis was to assess if the presence of pain can be considered an independent prognostic factor in mCSPC patients.
A retrospective analysis was performed on patients with mCSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. Patients were considered to have pain if this was reported within the patient's file or in case of a chronic analgesic therapy was found among the concomitant medications. Survivals were estimated by the Kaplan-Meier method, and compared across groups using the log-rank test. Cox proportional hazard models, stratified according to the baseline characteristics, were used to estimate hazard ratios for overall survival (OS). All the variables were significant if p < 0.05.
Data about pain were available for 365 cases and pain was present in 34.8% of patients. Pain was mainly associated with high value of prostate-specific antigen, metastatic bone extension regardless of the site, and lymph node involvement. mCSPC patients with pain had in most of the cases high-volume or Hr disease, and significant shorter OS (27.0 vs. 58.2 months, p < 0.001) and PFS (10.1 vs. 17.4 months, p < 0.001) compared to those without pain. The negative impact of pain on OS remained significant even if adjusted for CHAARTED or LATITUDE classification, and other significant baseline prognostic factors.
This analysis supports the poor prognostic role of cancer-related pain in the setting of mCSPC patients. A prospective validation is required.
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