Tumour Evolution and Seed and Soil Mechanism in Pancreatic Metastases of Renal Cell Carcinoma.
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ABSTRACT:
SUBMITTER: Sellner F
PROVIDER: S-EPMC8002056 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Previously documented arguments, in favor of the suspected impact of a seed and soil mechanism, in the development and progression of isolated pancreatic metastasis of renal cell carcinomas (isPM) are: (1) uniform and independent from the side of the primary tumor distribution of isPM within the pancreas and, (2) the similar survival rates for singular and multiple isPM. In addition, the present study adds new arguments that further confirm the importance of an seed and soil mechanism in isPM: (1) Within the singular isPM, the size of the metastasis does not affect the overall survival; (2) Within the group of multiple isPMs, the overall survival does not depend on the number of metastases; (3) For synchronous and metachronous isPM, survival rates are also not different, and (4) Within the group of metachronous isPM there is also no correlation between the overall survival and interval until metastases occurs. This unusual ineffectiveness of otherwise known risk factors of solid cancers can be explained plausibly by the hypothesis of a very selective seed and soil mechanism in isPM. It only allows embolized renal carcinoma cells in the pancreas to complete all steps required to grow into clinically manifest metastases. In all other organs, on the other hand, the body is able to eliminate the embolized tumor cells or at least put them into a dormant state for many years. This minimizes the risk of occult micrometastases in distant organs, which could later—after isPM treatment—grow into clinically manifest metastases, so that the prognosis of the isPM is only determined by an adequate therapy of the pancreatic foci, and prognostic factors, such as total tumor burden or interval until the occurrence of the isPM remain ineffective.
| S-EPMC7273884 | biostudies-literature
Project description:Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox's proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54-142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10-14). Median overall survival was 73 months (95% CI 61-86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78-204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36-11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94-2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43-5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30-0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate.
| S-EPMC4827845 | biostudies-literature
Project description:BACKGROUND:Treatment of pancreatic metastases (PM) from renal cell carcinoma (RCC) is still an issue between surgeons and oncologists, in the era of target-therapy. METHODS:Data from 26 patients undergoing resection of PM and extra-PM from RCC, with R0 intention were retrospectively analysed. No one received adjuvant chemotherapy. Patients were divided into two groups; Group A comprehends 14 patients who developed synchronous (5) or methacronous (9) extra-PM. Group B comprehends 12 patients that developed PM only. RESULTS:No intraoperative mortality was recorded. Complications occurred in 14 patients (53.8%), all but 2 (7.26%) were graded I and II according to Clavien-Dindo classification. Recurrences occurred in 8 patients (30.8%), of whom, 5 (62.5%) were submitted for further resections in other sites. Three-, five- and ten-year observed overall survival were respectively 88,5% [95%CI: 0,56 - 1,33], 76,9% [95%CI: 0,47 - 1,19] and 50% [95%CI: 0,20 - 1,03]. Disease-free survival was 65,4% [95%CI: 0,38 - 1,05], at 3 years, 57,7% [95%CI 0,323 - 0,952] at 5 years and 42,9% [95%CI 0,157 - 0,933], at 10 years. QoL analysis, through WHOQOL-BREF questionnaire, assessed at last available follow up revealed a mean score of 75,9 ± 11,6 on 100 points. CONCLUSION:Despite no significant differences in survival between patients affected by Pancreatic or Extra-Pancreatic metastases, PM patients seems to show better outcome when managed surgically. mRCC patients, eligible for radical metastasectomy, tend to have long survival rates, reduced recurrence rates and good QoL. STUDY REGISTRATION:This paper was registered retrospectively in ClinicalTrials.gov with Identification number: NCT03670992.
| S-EPMC7218538 | biostudies-literature
Project description:Renal cell carcinoma (RCC) is characterized by a particularly broad metastatic swath, and, enigmatically, when the pancreas is a destination, the disease is associated with improved survival. Intrigued by this observation, we sought to characterize the clinical behavior, therapeutic implications, and underlying biology. While pancreatic metastases (PM) are infrequent, we identified 31 patients across 2 institutional cohorts and show that improved survival is independent of established prognostic variables, that these tumors are exquisitely sensitive to antiangiogenic agents and resistant to immune checkpoint inhibitors (ICIs), and that they are characterized by a distinctive biology. Primary tumors of patients with PM exhibited frequent PBRM1 mutations, 3p loss, and 5q amplification, along with a lower frequency of aggressive features such as BAP1 mutations and loss of 9p, 14q, and 4q. Gene expression analyses revealed constrained evolution with remarkable uniformity, reduced effector T cell gene signatures, and increased angiogenesis. Similar findings were observed histopathologically. Thus, RCC metastatic to the pancreas is characterized by indolent biology, heightened angiogenesis, and an uninflamed stroma, likely underlying its good prognosis, sensitivity to antiangiogenic therapies, and refractoriness to ICI. These data suggest that metastatic organotropism may be an indicator of a particular biology with prognostic and treatment implications for patients.
| S-EPMC7205259 | biostudies-literature
Project description:Treatment for renal cell carcinoma (RCC) has improved dramatically over the last decade, shifting from high-dose cytokine therapy in combination with surgical resection of tumors to targeted therapy, immunotherapy, and combination therapies. However, curative treatment, particularly for advanced-stage disease, remains rare. Cell therapy as a "living drug" has achieved hematological malignancy cures with a high response rate, and significant research efforts have been made to facilitate its translation to solid tumors. Herein, we overview the cellular therapies for RCC focusing on allogeneic hematopoietic stem cell transplantation, T cell receptor gene-modified T cells, chimeric antigen receptor (CAR) T cells, CAR natural killer (NK) cells, lymphokine-activated killer (LAK) cells, γδ T cells, and dendritic cell vaccination. We have also included perspectives for using other recent approaches, such as CAR macrophages, dendritic cell-cytokine induced killer cells and regulatory CAR-T cells to shed light on preclinical development of cell therapy and advancing cell therapy into clinic to achieve cures for RCC.
| S-EPMC10775455 | biostudies-literature
Project description:Hepatocyte growth factor (HGF)/c-Met pathway is implicated in embryogenesis and organ development and differentiation. Germline or somatic mutations, chromosomal rearrangements, gene amplification, and transcriptional upregulation in MET or alterations in autocrine or paracrine c-Met signalling have been associated with cancer cell proliferation and survival, including in renal cell carcinoma (RCC), and associated with disease progression. HGF/c-Met pathway has been shown to be particularly relevant in tumors with bone metastases (BMs). However, the efficacy of targeting c-Met in bone metastatic disease, including in RCC, has not been proven. Therefore, further investigation is required focusing the particular role of HGF/c-Met pathway in bone microenvironment (BME) and how to effectively target this pathway in the context of bone metastatic disease.
| S-EPMC7527574 | biostudies-literature
Project description:In patients with renal cell carcinoma, brain metastasis is generally one of the poor prognostic factors. However, the recent introduction of molecular target therapy and immune checkpoint inhibitor has remarkably advanced the systemic treatment of metastatic renal cell carcinoma and prolonged the patients' survival. The pivotal clinical trials of those agents usually excluded patients with brain metastasis. The incidence of brain metastasis has been increasing in the actual clinical setting because of longer control of extra-cranial disease. Brain metastasis subgroup data from the prospective and retrospective series have been gradually accumulated about the risk classification of brain metastasis and the efficacy and safety of those new agents for brain metastasis. While the local treatment against brain metastasis includes neurosurgery, stereotactic radiosurgery, and conventional whole brain radiation therapy, the technology of stereotactic radiosurgery has been especially advanced, and the combination with systemic therapy such as molecular target therapy and immune checkpoint inhibitor is considered promising. This review summarizes recent progression of multimodality treatment of brain metastasis of renal cell carcinoma from literature data and explores the future direction of the treatment.
| S-EPMC7600559 | biostudies-literature
Project description:BackgroundBrain metastases (BM) pose a significant problem in patients with metastatic renal-cell carcinoma (mRCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management.Patients and methodsThe mRCC patients with BM treated with SRS were reviewed. Patient demographics, clinical history, and SRS treatment parameters were identified.ResultsAmong 268 patients with mRCC treated between 2006 and 2015, 38 patients were identified with BM. A total of 243 BM were treated with SRS with 1 to 26 BMs treated per SRS session (median, 2 BMs). The median (range) BM size was 0.6 (0.2-3.1) cm and median (range) SRS treatment dose was 18 (12-24) Gy. Treated BM local control rates at 1 and 2 years were 91.8% (95% confidence interval, 85.7-95.4) and 86.1% (95% confidence interval, 77.1-91.7), respectively. BM control declined for larger tumors. Survival after 1-year was 57.5% (95% CI 40.2-71.4) for all patients. Survival was not statistically different between patients with < 5 BM versus ≥ 5 BM. Survival was prognostic based on International Metastatic Renal Cell Carcinoma Database (IMDC) risk groups in patients with < 5 BM. Two patients experienced grade 3 radiation necrosis requiring surgical intervention.ConclusionSRS is effective in controlling BM in patients with mRCC. Over half of treated patients survive past a year, and no differences in survival were noted in patients with > 5 metastases. Prognostic risk categories based on systemic disease (IMDC) are predictive of survival in this BM population, with limited rates of symptomatic radiation necrosis.
| S-EPMC6563340 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma is a fatal malignancy with a five-year survival rate lower than 7%, and most patients dying within six months of diagnosis. The factors that contribute to the aggressiveness of the disease include, but are not limited to: late diagnosis, prompt metastasis to adjacent vital organs, poor response, and resistance to anticancer treatments. This malignancy is uniquely associated with desmoplastic stroma that accounts for 80% of tumor mass. Understanding the biology of stroma can aid the discovery of innovative strategies for eradicating this lethal cancer in the future. This review highlights the critical components in the stroma and how they interact with the cancer cells to convey the devastating tumor progression.
| S-EPMC5532629 | biostudies-other
Project description:Background:Patients with brain metastases (BM) from renal cell carcinoma (RCC) were considered to experience a poor prognosis. However, there is little knowledge on the risk factors for BM from RCC at diagnosis. This study was aimed at exploring the risk factors for patients with BM from RCC and the interaction among these risk factors. Methods:A total of 38759 cases of RCC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for BM from RCC were evaluated by univariate and multivariate logistic regression analyses. Interaction effect between age and tumor size was tested. Results:There was a significant difference in univariate analysis, including T stage, tumor size, grades III and IV, lymph node metastasis, bone metastasis, liver metastasis, lung metastasis, and surgery. There was a significant difference in multivariate analysis, including age, T stage, tumor size < 10?cm, grade IV, lymph node metastasis, bone metastasis, lung metastasis, and surgery. Patients older than 70 had 0.653-fold lower risk of developing BM compared with those younger than 70. Patients with tumor size ? 4?cm and <10?cm had higher risk of developing BM compared with those < 4?cm. The larger the tumor size, the higher the incidence of BM from RCC in those whose tumor size was less than 10?cm. An interaction test between the tumor size and age on brain metastasis was statistically significant in the crude analysis (P = 0.0114) and model II analysis (P = 0.0114) and model II analysis (P = 0.0114) and model II analysis (. Conclusion:Both tumor size and age were independent risk factors for brain metastases in patients with RCC. The impact of age on the risk of developing BM from RCC was limited to patients with tumor size ? 7?cm. Patients with a larger tumor size and younger age might have the higher risk of developing BM at diagnosis of RCC.
| S-EPMC7085365 | biostudies-literature