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      Downstaging and Pathological Complete Response of Locally Recurrent Sarcomatoid Renal Cell Carcinoma under Pembrolizumab and Lenvatinib: A Case Report and Review of Literature

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          Abstract

          The advent of immune checkpoint inhibition opened new perspectives for patients with recurrent or metastasized renal cell carcinoma. In case of recurrent disease, surgical resection remains the most promising therapeutic option. Surgical resection is associated with improved overall survival and demonstrated curative potential given complete resection of metastases can be performed. This report presents the case of a patient with local recurrence of dedifferentiated sarcomatoid renal cell carcinoma approximately 1 year after initial open lumbar nephrectomy. After initial evaluation, surgical removal was deemed infeasible and an induction therapy with pembrolizumab and lenvatinib was initiated. After 3 months, corresponding to 5 cycles of pembrolizumab, the tumor showed a partial response on imaging control and was successfully resected en bloc. Histopathological examination of the specimen revealed no evidence of viable neoplastic cells. This is the first report describing a complete pathological response of a locally recurrent dedifferentiated sarcomatoid renal cell carcinoma after treatment with pembrolizumab and lenvatinib. Overall, the combination therapy was well tolerated with a maximum Common Terminology Criteria for Adverse Events Level of Two. These findings underline the potential of multimodal therapeutic strategies for recurrent renal cell carcinoma, such as induction therapies to downstage initially nonresectable masses, and highlight the need for prospective studies to allow for evidence-based treatment plans.

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          Most cited references15

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          Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma

          Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.
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            Epidemiology of Renal Cell Carcinoma

            Though renal cell carcinoma (RCC) accounts for 2% of global cancer diagnoses and deaths, it has more than doubled in incidence in the developed world over the past half-century, and today is the ninth most common neoplasm in the United States (US). While North America and Western Europe have the highest disease burden (with the Belarus highest in incidence), Latin America, Asia and Africa are projected to see an increase in incidence as nation’s transition to a Western lifestyle. Most cases of RCC are discovered incidentally on imaging, and survival is highly dependent on the stage at diagnosis, with the metastatic disease having only a 12% 5-year survival rate. Two-thirds of RCC diagnoses are made in men, and the average age of diagnosis in the US is 64. Those with genetic predispositions, namely von Hippel-Lindau disease, tend to be diagnosed 20 years earlier. RCC has a greater incidence among Hispanics and Native Americans, and a lower survival rate among African Americans in the US. Modifiable risk factors for RCC include smoking, obesity, poorly-controlled hypertension, diet and alcohol, and occupational exposures. Prevention strategies aimed at improving survival and reducing disparities include addressing lifestyle factors and access to regular healthcare among underserved populations and in developing nations, as well as more rigorous imaging guidelines to detect RCC at an earlier stage. A stronger understanding of global RCC epidemiology can facilitate prevention efforts, especially in developing nations and underserved communities where disease burden is predicted to rise in the coming decades.
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              Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial

              Background The extent to which response and survival benefits with immunotherapy-based regimens persist informs optimal first-line treatment options. We provide long-term follow-up in patients with advanced renal cell carcinoma (aRCC) receiving first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the phase 3 CheckMate 214 trial. Survival, response, and safety outcomes with NIVO+IPI versus SUN were assessed after a minimum of 42 months of follow-up. Methods Patients with aRCC were enrolled from October 16, 2014, through February 23, 2016. Patients stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and region were randomized to nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks for four doses, followed by nivolumab (3 mg/kg) every 2 weeks; or SUN (50 mg) once per day for 4 weeks (6-week cycle). Primary endpoints: overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) per independent radiology review committee in IMDC intermediate-risk/poor-risk patients. Secondary endpoints: OS, PFS, and ORR in the intention-to-treat (ITT) population and safety. Favorable-risk patient outcomes were exploratory. Results Among ITT patients, 550 were randomized to NIVO+IPI (425 intermediate/poor risk; 125 favorable risk) and 546 to SUN (422 intermediate/poor risk; 124 favorable risk). Among intermediate-risk/poor-risk patients, OS (HR, 0.66; 95% CI, 0.55–0.80) and PFS (HR, 0.75; 95% CI, 0.62–0.90) benefits were observed, and ORR was higher (42.1% vs 26.3%) with NIVO+IPI versus SUN. In ITT patients, both OS benefits (HR, 0.72; 95% CI, 0.61–0.86) and higher ORR (39.1% vs 32.6%) were observed with NIVO+IPI versus SUN. In favorable-risk patients, HR for death was 1.19 (95% CI, 0.77–1.85) and ORR was 28.8% with NIVO+IPI versus 54.0% with SUN. Duration of response was longer (HR, 0.46–0.54), and more patients achieved complete response (10.1%–12.8% vs 1.4%–5.6%) with NIVO+IPI versus SUN regardless of risk group. The incidence of treatment-related adverse events was consistent with previous reports. Conclusions NIVO+IPI led to improved efficacy outcomes versus SUN in both intermediate-risk/poor-risk and ITT patients that were maintained through 42 months’ minimum follow-up. A complete response rate >10% was achieved with NIVO+IPI regardless of risk category, with no new safety signals detected in either arm. These results support NIVO+IPI as a first-line treatment option with the potential for durable response. Trial registration number NCT02231749.
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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                CRO
                Case Reports in Oncology
                S. Karger AG (Basel, Switzerland )
                1662-6575
                30 October 2023
                Jan-Dec 2023
                30 October 2023
                : 16
                : 1
                : 1245-1252
                Affiliations
                [a ]Department of Urology, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany
                [b ]Department of Radiology, Neuroradiology and Nuclear Medicine, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany
                Author notes
                Correspondence to: Jascha Ell, jascha.ell@ 123456klinikum-nuernberg.de
                Article
                534000
                10.1159/000534000
                10616667
                37915993
                d2ffae7b-5fc2-42c9-aa77-67e0f6b39f69
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 13 April 2023
                : 4 September 2023
                : 2023
                Page count
                Figures: 2, References: 15, Pages: 8
                Funding
                No funding was received for this case report.
                Categories
                Case Report

                Oncology & Radiotherapy
                renal cell carcinoma,recurrence,immunotherapy,neoadjuvant therapy
                Oncology & Radiotherapy
                renal cell carcinoma, recurrence, immunotherapy, neoadjuvant therapy

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