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.
Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20-25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic ...options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9/19 papillary, 5/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7-11.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.
Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples ...and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1%–100% accuracy. We validated the score accuracies in an independent cohort (up to 18 mccRCC versus nine healthy) and verified that the scores normalized in eight patients with no evidence of disease. In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis.
Display omitted
•Coordinated regulation of glycosaminoglycan (GAG) biosynthesis is observed in ccRCC•The plasma and urine GAG profile is strongly altered in metastatic ccRCC•Three non-invasive GAG scores accurately predict the occurrence of metastatic ccRCC•The GAG scores normalize in patients with no evidence of disease
Gatto et al. computationally uncovered altered and coordinated regulation of glycosaminoglycan biosynthesis in clear cell renal cell carcinoma, resulting in altered metabolite levels in plasma and urine that, in turn, could be used to diagnose the occurrence of the disease.
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.
Androgen Receptor-Targeted Agents (ARTA) have dramatically changed the therapeutic landscape of metastatic Castration-Resistant Prostate Cancer (mCRPC), but 20-40% of these patients progress early ...after start of ARTA treatment. The present study investigated the potential utility of plasma cell-free microRNAs (cfmiRNAs) as prognostic markers by analyzing a prospective cohort of 31 mCRCP patients treated with abiraterone (
= 10) or enzalutamide (
= 21). Additional potential prognostic factors were extracted from clinical records and outcome was evaluated as overall survival (OS) and progression-free survival (PFS). cfmiRNAs were measured in plasma samples using quantitative real-time RT-PCR. Linear correlation among clinical factors and cfmiRNAs was assessed using the Spearman's rank correlation coefficient. The association with survival was studied using univariate and multivariate Cox proportional hazards models. Continuous variables were dichotomized with the cut points corresponding to the most significant relation with the outcome. Univariate analysis indicated that plasma levels of miR-21-5p, miR-141-3p and miR-223-3p, time to development of castration-resistance (tCRPC), and blood hemoglobin (Hb) levels strongly correlated with both PFS and OS. Multivariate analysis revealed that low plasma levels of miR-21, shorter tCRPC, and lower Hb values were independent factors predicting reduced PFS and OS. These findings suggest that the integrated analysis of cfmiRNAs, tCRPC, and Hb may provide a promising, non-invasive tool for the prognostic stratification of mCRPC patients treated with ARTA.
The prognosis of metastatic clear cell renal cell carcinoma (ccRCC) vastly improved since the introduction of antiangiogenic-targeted therapy. However, it is still unclear which biological processes ...underlie ccRCC aggressiveness and affect prognosis. Here, we checked whether a recently discovered systems biomarker based on plasmatic or urinary measurements of glycosaminoglycans (GAGs) aggregated into diagnostic scores correlated with ccRCC prognosis.
Thirty-one patients with a diagnosis of ccRCC (23 metastatic) were prospectively enrolled, and their urine and plasma biomarker scores were correlated to progression-free survival (PFS) and overall survival (OS) as either a dichotomous ("Low" vs. "High") or a continuous variable in a multivariate survival analysis.
The survival difference between "High"- vs. "Low"-scored patients was significant in the case of urine scores (2-year PFS rate = 53.3 vs. 100%,
= 3 × 10
and 2-year OS rate = 73.3 vs. 100%,
= 0.0078) and in the case of OS for plasma scores (2-year PFS rate = 60 vs. 84%,
= 0.0591 and 2-year OS rate = 66.7 vs. 90%,
= 0.0206). In multivariate analysis, the urine biomarker score as a continuous variable was an independent predictor of PFS hazard ratio (HR): 4.62, 95% CI: 1.66-12.83,
= 0.003 and OS (HR: 10.13, 95% CI: 1.80-57.04,
= 0.009).
This is the first report on an association between plasma or urine GAG scores and the prognosis of ccRCC patients. Prospective trials validating the prognostic and predictive role of this novel systems biomarker are warranted.
Immune-Oncology (IO) improves Overall Survival (OS) in metastatic Renal Cell Carcinoma (mRCC). The prognostic impact of previous Cytoreductive Nephrectomy (CN) and radical nephrectomy (RN), with ...curative intent, in patients treated with IO is not well defined. The aim of our paper is to evaluate the impact of previous nephrectomy on outcome of mRCC patients treated with IO.
287 eligible patients were retrospectively collected from 16 Italian referral centers adhering to the MeetUro association. Patients treated with IO as second and third line were included, whereas patients treated with IO as first line were excluded. Kaplan-Meier method and log-rank test were performed to compare Progression Free Survival (PFS) and OS between groups. In our analysis, both CN and RN were included. The association between nephrectomy and other variables was analyzed in univariate and multivariate setting using the Cox proportional hazard model.
246/287 (85.7%) patients had nephrectomy before IO treatment. Median PFS in patients who underwent nephrectomy (246/287) was 4.8 months (95%CI 3.9-5.7) vs 3.7 months (95%CI 1.9-5.5) in patients who did not it (HR log rank 0.78; 95%CI 0.53 to 1.15;
= 0.186). Median OS in patients who had previous nephrectomy (246/287) was 20.9 months (95%CI 17.6-24.1)
13 months (95%CI 7.7-18.2) in patients who did not it (HR log rank 0.504; 95%CI 0.337 to 0.755;
= 0.001). In the multivariate model, nephrectomy showed a significant association with OS (HR log rank 0.638; 95%CI 0.416 to 0.980), whereas gland metastases were still associated with better outcome in terms of both OS (HR log rank 0.487; 95%CI 0.279 to 0.852) and PFS (HR log rank 0.646; 95%CI 0.435 to 0.958).
IO treatment, in patients who had previously undergone nephrectomy, was associated with a better outcome in terms of OS. Further prospective trials would assess this issue in order to guide clinicians in real word practice.
Thyroid hormone impairment, represented as an alteration in levels of thyroid hormones and a lower fT3/fT4 ratio, has been correlated with a worse prognosis for both cancer and non-cancer patients. ...The role of baseline thyroid function in patients with metastatic renal cell carcinoma (mRCC) however, has not been studied yet.
We recorded clinical data, baseline biochemical results, and oncological outcomes from 10 Oncology Units in Italy. We stratified patients into three groups according to the fT3/fT4 ratio value and subsequently analyzed differences in progression-free survival (PFS) and overall survival (OS) in the three groups. We also performed univariate and multivariate analyses to find prognostic factors for PFS and OS.
We analyzed 134 patients treated with systemic treatment for mRCC. Median PFS in the low, intermediate, and high fT3/fT4 ratio group were 7.5, 12.1, and 21.7 months respectively (p<0.001); median OS in the three groups were 36.5, 48.6, and 70.5 months respectively (p =0.006). The low fT3/fT4 ratio maintained its prognostic role at the multivariate analysis independently from IMDC and other well-established prognostic factors. The development of iatrogenic hypothyroidism was not associated with a better outcome.
We found that baseline thyroid hormone impairment, represented by a low fT3/fT4 ratio, is a strong prognostic factor in patients treated for mRCC in first line setting and is independent of other parameters currently used in clinical practice.
Background:
Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an ...indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics.
Methods:
This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database.
Results:
59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival.
Conclusion:
In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.
Background
Veneto Institute of Oncology has activated a simultaneous care outpatient clinic (SCOC) in which cancer patients with advanced‐stage cancer are evaluated by oncologist and palliative care ...specialists. This cross‐sectional study investigated patients' perceptions of the quality of this service.
Materials and Methods
An ad‐hoc self‐administered questionnaire, developed by SCOC team, was used to assess the satisfaction of patients admitted at SCOC consultation. The questionnaire, in addition to the socio‐demographic questions, contains eight questions with the Likert scale: time dedicated, feel listened to, feel understood, feel free to speak openly and to express doubts and concerns, feeling about information and indication received, level of empathy of health care and quality of the relationship, level of professional/quality of performance and utility of consultation, and one open‐ended question. The questionnaire has been proposed to all 174 consecutively admitted patients at SCOC.
Results
One hundred and sixty‐two patients filled in the questionnaire: 66.7% were male, median age was 71 years, 88.3% had metastatic disease. The time dedicated to SCOC consultation was judged more than adequate (55%) or adequate (35%) by 90% of subjects. Patients completely satisfied about being listened to were 92.5%, with 80.9% being completely satisfied with understanding of their issues and 92% with the freedom to speak and express doubts. Usefulness of the SCOC was rated as excellent by 40% and good by 54.4% of patients. No statistically significant differences were observed in the responses to the questions by gender, age (< or ≥70 years old) and type of tumor.
Conclusion
Our study shows high levels of satisfactions after SCOC consultation in advanced cancer subjects. Patients' feedback confirmed that SCOC model was effective in helping them during their treatment journey and decision at the end of life. This study encouraged us to enhance our practice of SCOC consultation.
Implications for Practice
A joint evaluation of patients living with cancer by oncologist and palliative care team (SCOC‐embedded model), has shown to enhance patients' experience/satisfaction with care‐such as listening, understanding, receiving information, symptom control, and decision about future, independently of age, gender, and kind of tumor.
PDF
