Thoracic radiotherapy for renal cell carcinoma metastases.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 409-409
Author(s):  
Glenn Stewart ◽  
William Breen ◽  
Brad J. Stish ◽  
Sean Sunghun Park ◽  
Kenneth R. Olivier ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Lung Metastases ◽  
Kaplan Meier ◽  
Median Total Dose ◽  
Thoracic Radiation ◽  
Delay Progression

409 Background: For patients with metastatic renal cell carcinoma (RCC), metastasis-directed local therapies can delay progression and need to initiate/switch systemic therapy. We examined our experience treating lung or mediastinal metastases from RCC with radiotherapy (RT). Methods: We reviewed patients with lung or mediastinal metastases from RCC treated with RT. Overall survival (OS) and local control (LC) was measured from the start of RT using the Kaplan-Meier method. Results: Seventy-one patients were treated with RT for 89 lung or mediastinal metastases. Median follow-up was 2.0 years (range 0.02-11.4 years) after RT for surviving patients. Most patients were male (n=53, 74.6%). Median age was 58.4 years at initial diagnosis. Histology was most frequently clear cell carcinoma (n=62, 89.9%). At the time of treatment, 18 patients (25.4%) had 1-3 metastases, and the remainder (74.6%) had 4 or more metastases. Forty-one patients (57.5%) received systemic therapy prior to thoracic radiation. Initial systemic therapy was most commonly sunitinib (45%) or pazopanib (32.5%). Median time from starting systemic therapy to initiation of radiation was 2.0 years. Fifty-eight lung metastases and 31 mediastinal metastases were treated with a median 5 fractions (range 1-40), to a median total dose of 4800 cGy (range 400-7000), with a median fraction size of 500 cGy (range 150-2000). Thirty-three lesions were treated with concurrent systemic therapy, which was most commonly nivolumab (n=16). Of 89 treated lesions, 11 (12%) had local tumor recurrence, at a median of 1.6 years (range 0.4-2.9 years) after initiation of radiation. 1, 3, and 5 year MC (metastasis control) were 96.6%, 83.5% and 67.9%, respectively. Nine patients were treated with radiation in order to delay initiation of systemic therapy. Of these, 3 eventually received systemic therapy, initiated at a median 2.5 years after radiation. At last follow-up, 41 patients (57.7%) had died. Median OS was 2.6 years. Survival at 1, 3, and 5 years was 65.2%, 48.5%, and 38%, respectively. Conclusions: Radiation achieves high metastasis control rates for lung and mediastinal metastases from RCC, potentially delaying the need for systemic therapy.

Sunitinib dose escalation after disease progression in metastatic renal cell carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 458-458
Author(s):  
Jacques Raphael ◽  
Alia Thawer ◽  
Georg A. Bjarnason
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Skin Toxicity ◽  
Kaplan Meier ◽  
Best Response ◽  
Higher Doses

458 Background: Previous pharmacologic studies demonstrated that higher sunitinib ( S) exposure is associated with improved clinical outcomes in metastatic renal cell carcinoma (mRCC) patients. We aimed to assess the efficacy and toxicity of S dose escalation in mRCC patients progressing on the standard 50mg dose. Methods: A single institution retrospective review was conducted on mRCC patients, treated outside trials with a 50 mg S dose given on an individualized schedule between October 2009 and January 2016, who subsequently progressed on imaging. At progression, patients were dose escalated to 62.5 and 75mg on an individualized schedule if toxicity permitted. Median Progression and Overall Survival (PFS, OS) were analyzed using the Kaplan Meier method. PFS1 and 2 were defined as the time between the start of sunitinib and first progression and the time between dose escalation and second progression respectively. Results: Twenty-five eligible patients were identified, with a median follow-up of 40.3 months (11.1-66.6) and a mean age of 54 years (12.4). The majority of patients underwent cytoreductive surgery (92%) and were men (88%). Thirty two percent, 44%, and 24% had a good, intermediate, and poor prognostic Heng score respectively. At the 50 mg doses, 60% and 16% of patients had a partial response (PR) and stable disease (SD) respectively with a median time to progression (TTP) of 11.4 months (95% CI, 3-20.7). After progression, 36% and 28% had PR and SD on higher doses of S respectively with a TTP of 7.8 months (95% CI, 6.3-12.4). Three patients with progressive disease as best response on a 50 mg S dose achieved SD (2/3) or PR (1/3) after dose escalation. The median PFS1, PFS2, and OS were 6.1 months (95% CI, 2.3-19.4), 6.7 months (95% CI, 3.1-8.4), and 63.7 months (95% CI, 26-not reached) respectively. The most common adverse events after dose escalation were fatigue (56%), diarrhea (40%), and skin toxicity (28%). Conclusions: Patients with mRCC who progress on a 50 mg S dose, may derive a clinical benefit and prolonged survival from dose escalation with acceptable toxicity profiles. These results need to be confirmed in well-designed prospective studies with the aim to optimize the duration of benefit from S therapy.

Patterns of failure following surgical resection of renal cell carcinoma: implications for adjuvant local and systemic therapy.

1994 ◽  
Vol 12 (1) ◽  
pp. 206-212 ◽  
Author(s):  
R A Rabinovitch ◽  
M J Zelefsky ◽  
J J Gaynor ◽  
Z Fuks
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Renal Vein ◽  
Adjuvant Radiation ◽  
Patterns Of Failure ◽  
Pathologic Features ◽  
Increased Risk

PURPOSE This report is a patterns-of-failure analysis of resected renal cell carcinoma (RCC) performed to determine the relative incidences of local failure (LF) and distant failure, to identify the pathologic features predicting for each using a multivariate analysis, and to assess the relative impact of each form of failure on overall survival (OS). In this way, the potential value of and selection of patients for adjuvant local and/or systemic therapy can be better evaluated. MATERIALS AND METHODS The records of 172 patients with unilateral, nonmetastatic RCC who were treated with definitive surgery between 1978 and 1988, and who had a minimum follow-up duration of 1 year, were identified through the Memorial Sloan-Kettering tumor registry. Distribution by stage included T1, 10 patients; T2, 102; T3a, 32; T3b, 27; and T4, one. The incidences of positive lymph nodes (LNs) and positive margins were 5.8% and 6.4%, respectively. RESULTS LF developed in only six patients, yielding a 7-year actuarial incidence of 5%. In this subset, four patients developed distant metastases (DM), three occurring concurrently with or before LF. DM developed in 30 patients, yielding a 7-year actuarial incidence of 26%. Among the variables that had an impact on the development of DM according to univariate log-rank tests, only positive LNs (P = .026) and renal vein extension (P = .001) remained as significant independent prognosticators. The overall 7-year actuarial survival rate was 80%. Eleven patients died of RCC during follow-up, nine of whom (82%) died of metastatic disease. CONCLUSION LF is rare following surgical management of RCC, and shows no clear causal relationship with the development of DM. Patients die of DM, and not LF. These data do not support the role of adjuvant radiation therapy in this disease. Patients with LN involvement or renal vein extension have a significantly increased risk for developing DM, and are therefore appropriate candidates for trials investigating systemic therapy.

Efficacy of treatment beyond third-line (3L) in metastatic clear-cell renal cell carcinoma (mccRCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 647-647
Author(s):  
Annalisa Guida ◽  
Gwénaël Le Teuff ◽  
Carolina Alveosta Silva ◽  
Emeline Colomba Blameble ◽  
Flore Salviat ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Retrospective Data Analysis ◽  
Kaplan Meier ◽  
Practice Methods

647 Background: During the last decade, 10 agents have been approved for the treatment of patients (pts) with mccRCC, and guidelines have been developed up to 3L. The aim of the study is to describe the potential benefit of therapies beyond 3L in clinical practice Methods: Retrospective data analysis was performed using IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes beyond 3L in mccRCC. Kaplan Meier estimation was applied for progression free survival (PFS) and overall survival (OS) Results: Between 2005 and 2016, 825 (80%) pts had mccRCC and were treated with targeted therapies, of which 517 (63%) had 2L, 271 (33%) had 3L, 145 (18%) had 4L and 75 (9%) had 5L of therapy. Baseline characteristics and treatments are displayed in Table 1. With a median follow-up of 29 months (mo) (min: 20 max: 51), for patients receiving 4L, the median PFS is 5 mo (95%CI 4 – 6) and the median OS is 15.5 mo (95%CI 12 – 21). Pts with International Metastatic Renal Cell Cancer Database Consortium (IMDC) score favourable (18%), intermediate (59%), and poor risk (23%) at 4L initiation had a median OS of 24 mo (95%CI 11 – NR), 16 mo (95%CI 12.6 – 24), and 8 mo (95%CI 6 – 15), respectively (p < 0.0036). Partial response (PR) and stable disease (SD) were achieved in 13% and 56% of 122 evaluable pts. With a median follow-up of 16 mo (min: 13 max: 37) in 5L, the median PFS is 4.5 mo (95%CI 3 – 6) and the median OS is 19.5 mo (95%CI 11 - 28). Pts with a poor IMDC score risk at 5L initiation (33%) had a median OS of 7 mo (95%CI 3 – 10) (p < 0.0001). PR and SD were achieved in 16% and 52% of 55 evaluable pts in 5L Conclusions: The approved agents remain active as 4L or 5L options for mccRCC in pts who can reach this situation. Interestingly, both PFS and OS appear to be very similar in 4L and 5L as compared to 3L. Therefore, we believe that selected pts may derive benefit from these treatments beyond the barriers of regulatory or reimbursement approval [Table: see text]

Prognostic biomarkers of systemic inflammation in patients on active surveillance for metastatic renal cell carcinoma (mRCC): A biobank analysis.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 348-348
Author(s):  
Vishwani Chauhan ◽  
Jahangeer Malik ◽  
Aravindhan Sundaramurthy ◽  
Stefan N. Symeonides ◽  
Mark Stares
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Active Surveillance ◽  
Metastatic Renal Cell Carcinoma ◽  
Risk Score ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Time Period ◽  
Time To Initiation

348 Background: A subset of patients with metastatic renal cell carcinoma (mRCC) follow an indolent disease course. Given the toxicity and non-curative nature associated with systemic anti-cancer therapy (SACT), some patients may benefit from initial active surveillance (AS). However, selecting patients suitable for this approach is challenging. Biomarkers of systemic inflammation predict survival in mRCC, both independently and as part of the International Metastatic Database Consortium (IMDC) risk score. We sought to use these biomarkers to characterise the time to initiation of SACT (tSACT) in mRCC patients on AS. Methods: 126 mRCC patients clinically assessed and commenced on AS prior to any systemic therapy were retrospectively identified from a regional mRCC clinical database. Patients who underwent metastasectomy for oligometastatic disease at any time were excluded. The primary endpoint, tSACT, was defined as the time from radiological diagnosis of mRCC until SACT initiation, or death, or censorship if continuing AS at follow-up date. Inflammatory biomarkers from routine blood tests (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein (CRP), albumin) and the IMDC score, measured at the time of diagnosis of mRCC, were recorded. The relationship between these and tSACT was examined using Kaplan-Meier and Cox-regression methods. Results: 66 (52%) patients had commenced SACT. 17 (13.5%) had died without commencing SACT (median survival of the 17 was 40.4 months, range 9.1-130.2 months, and comorbidities may have affected fitness for starting therapy or led to all-cause mortality). 43 patients remained on AS, with minimum and median follow-up of 12.6 months and 39.6 months respectively. The median tSACT was 17.2 months (IQR 8.8-34.8 months). On univariate analysis, CRP and albumin were predictive of time on AS ( p= 0.01 and p= 0.049 respectively). On multivariate analysis, only CRP was independently associated with tSACT ( p= 0.035), stratifying tSACT from 9.1 months (CRP > 10) to 20.9 months (CRP≤10) ( p= 0.009). 111 (88.1%) patients were IMDC 0-1, while 12 (9.5%) and 3 (2.4%) were IMDC 2 or 3 and may have had comorbidities that influenced the initial AS decision. In our cohort the IMDC risk score did not predict time on AS. Conclusions: These results highlight that some patients with mRCC may undergo active surveillance for a marked time period before SACT initiation. We identify routine biomarkers of the systemic inflammatory response that predict time to systemic therapy. In particular CRP, a simple measure of inflammation, stratifies the time to initiation of SACT across a clinically significant time period. This simple, widely available test may help to objectively inform clinical decisions about AS in patients in mRCC. Additional experience is necessary to further define the risks and benefits of this approach.

scholarly journals An unusual outcome of papillary renal cell carcinoma with lung metastases: a case report and review of literature

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Emmanuel Owusu Ofori ◽  
Baba Alhaji Bin Alhassan ◽  
Edwina Ayaaba Ayabilah ◽  
Patrick Opoku Manu Maison ◽  
Alvin Asante-Asamani ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Lung Metastases ◽  
Papillary Renal Cell Carcinoma ◽  
Cancer Syndrome ◽  
Histologic Subtype ◽  
Papillary Rcc ◽  
Metastatic Rcc

Abstract Background Renal cell carcinoma (RCC) is a heterogeneous group of malignant epithelial tumors of the kidney. It accounts for more than 90% of all kidney cancers. However, papillary RCC is the second most common histologic subtype representing 10–15% of all RCCs. The mean age of presentation for papillary RCC ranges between 59 and 63 years but more importantly when RCC is diagnosed at a younger age, the possibility of an underlying hereditary kidney cancer syndrome should be considered. RCC potentially metastasizes to many different organs with lung being the commonest site accounting for 45.2%. The treatment for metastatic RCC is mostly multimodal for most patients. However, patients with untreated pulmonary metastases have been observed to have very poor prognosis with a 5-year overall survival rate of only 5% or even less and thus the need to report on the unusual outcome of our patient who had a metastatic disease. Case presentation The present study reports a papillary renal cell carcinoma with multiple lung metastases in a 31-year-old woman who presented with progressive right flank mass and pain with no chest symptoms. She underwent cytoreductive radical nephrectomy via a right subcostal incision. Patient, however, did not undergo metastasectomy nor palliative systemic therapy and was seen 5 years post-nephrectomy. Conclusion Our patient with metastatic RCC, without undergoing metastasectomy nor palliative systemic therapy, remained stable with 5-year progression-free survival post-cytoreductive nephrectomy.

506: A Risk-Adjusted Follow-up for Patients with Stage I and II Renal Cell Carcinoma

2007 ◽  
Vol 177 (4S) ◽  
pp. 169-169
Author(s):  
Quoc-Dien Trinh ◽  
Pierre I. Karakiewicz ◽  
Thierry Lebeau ◽  
Dan Lewinshtein ◽  
Elie Antebi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Stage I

scholarly journals Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and A Profile of Dysregulated microRNAs

2021 ◽  
Vol 22 (15) ◽  
pp. 7913
Author(s):  
Julia Oto ◽  
Raquel Herranz ◽  
Emma Plana ◽  
José Vicente Sánchez-González ◽  
Javier Pérez-Ardavín ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Diagnostic Value ◽  
Diagnostic Model ◽  
Low Grade ◽  
Non Invasive ◽  
Good Expression ◽  
Independent Cohort

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.

scholarly journals Hyperprogressive disease after radiotherapy combined with anti-PD-1 therapy in renal cell carcinoma: a case report and review of the literature

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Liu ◽  
Jingjing Piao ◽  
Zhiyang Shang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
General Condition ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Left Lung ◽  
The Third ◽  
Bidirectional Regulation ◽  
Hyperprogressive Disease

Abstract Background Studies have shown that immune checkpoint inhibitors (ICIs) have limited efficacy and can even increase tumour burden in short time periods. This is usually called hyperprogressive disease (HPD). To date, there are few reports regarding HPD; fewer have analysed the relationship between HPD and radiotherapy combined with ICIs, and their conclusions are controversial. Case presentation A 42-year-old woman was diagnosed with stage IV renal clear cell carcinoma. The patient had previously received sorafenib and pazopanib as first- and second-line therapies, respectively. She received radiotherapy combined with nivolumab. Eighteen days after administration of the third dose of nivolumab, the patient’s general condition deteriorated; this was associated with immune-related adverse events. Computed tomography showed that the diameter of left lung metastases had sharply increased. A biopsy of the lung metastasis showed no infiltration of lymphocytes. The patient’s general condition worsened and she died of the disease on the 70th day after administration of the third dose of nivolumab. Conclusions This report describes the development of HPD following the administration of radiotherapy combined with ICIs in a case of advanced renal cell carcinoma. The case indicates that radiotherapy may show bidirectional regulation effects on anti-tumour immune response. If the immunosuppressive function of radiotherapy is dominant, combined with ICIs, it could result in HPD.

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